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Maher S, Atta S, Kamel M, A. Hammam O, Okasha H. Therapeutic Potential and Mechanistic Insights of a Novel Synthetic α-Lactalbumin-Derived Peptide for the Treatment of Liver Fibrosis. J Clin Exp Hepatol 2025; 15:102488. [PMID: 39868009 PMCID: PMC11755051 DOI: 10.1016/j.jceh.2024.102488] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 12/09/2024] [Indexed: 01/28/2025] Open
Abstract
Background Liver fibrosis is a serious global health issue, but current treatment options are limited due to a lack of approved therapies capable of preventing or reversing established fibrosis. Aim This study investigated the antifibrotic effects of a synthetic peptide derived from α-lactalbumin in a mouse model of thioacetamide (TAA)-induced liver fibrosis. Methods In silico analyses were conducted to assess the physicochemical properties, pharmacophore features, and docking interactions of the peptide. Mice with induced fibrosis were treated with three different doses of the synthetic peptide (2.5, 5, or 10 μg/kg, twice weekly for 8 weeks). Immunohistochemistry, antioxidant enzyme levels, IGF-1 levels, and expression of fibrosis-related genes were assessed. Results Peptide interacted with human prothrombin's many sites with varying binding affinities. Besides, ligand similarity analysis identified 26 thrombin inhibitors with high Tanimoto scores. The peptide exhibited antifibrotic effects with dose-dependent improvements. The upregulated expression of IGF-1 in all treated groups compared with the pathological untreated group. In contrast, fibrotic markers such as TIMP, PDGF-α, and TGF-β were upregulated in the untreated pathological group but downregulated in the peptide-treated groups. The assessment of IGF-1 concentration in sera demonstrated that the peptide-treated groups exhibited an increase in IGF-1 levels. Histopathological examination of peptide-treated groups showed normal hepatic architecture with hepatocytes arranged in thin plates. Immunohistochemical results of high dose peptide-treated group showed a few numbers of positive αSMA with mild proliferating cell nuclear antigen expression. Conclusion The synthetic α-lactalbumin peptide shows promise as an antifibrotic therapy. Its safety and effectiveness are supported by in silico and in vivo analyses. The peptide's pharmacophore characteristics and potential as a thrombin inhibitor combine with its ability to downregulate fibrotic markers and maintain liver tissue integrity. These findings concluded the potential of this peptide as a promising therapeutic candidate for liver fibrosis, warranting further investigation.
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Affiliation(s)
- Sara Maher
- Immunology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Shimaa Atta
- Immunology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Manal Kamel
- Immunology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Olfat A. Hammam
- Pathology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Hend Okasha
- Biochemistry and Molecular Biology Department, Theodor Bilharz Research Institute, Giza, Egypt
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Alessandri G, Mancabelli L, Fontana F, Lepore E, Forte G, Burratti M, Ventura M, Turroni F. Disclosing α-lactalbumin impact on the intestinal and vaginal microbiota of women suffering from polycystic ovary syndrome. Microb Biotechnol 2024; 17:e14540. [PMID: 39364592 PMCID: PMC11450379 DOI: 10.1111/1751-7915.14540] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Accepted: 07/17/2024] [Indexed: 10/05/2024] Open
Abstract
Polycystic ovary syndrome (PCOS) is one of the most widespread endocrinopathy affecting women of reproductive age with detrimental effects on life quality and health. Among several mechanisms involved in its aetiopathogenesis, recent studies have also postulated the involvement of the vaginal and intestinal microbiota in the development of this disorder. In this study, an accurate insight into the microbial changes associated with PCOS was performed through a pooled-analysis highlighting that this syndrome is characterized by intestinal and vaginal dysbiosis with a reduction of beneficial microorganisms and a higher proportion of potential pathogens. Based on this observation, we evaluated the ability of a milk-derived protein exerting positive outcomes in the management of PCOS, that is, α-lactalbumin (α-LA), to recover PCOS-related dysbiosis. In vitro experiments revealed that this protein improved the growth performances of members of two health-promoting bacterial genera, that is, Bifidobacterium and Lactobacillus, depleted in both intestinal and vaginal microbiota of PCOS-affected women. In addition, α-LA modulated the taxonomic composition and growth performances of the microbial players of the complex intestinal and vaginal microbiota. Finally, an in vivo pilot study further corroborated these observations. The oral administration of α-LA for 30 days to women with PCOS revealed that this protein may have a role in favouring the growth of health-promoting bacteria yet limiting the proliferation of potential pathogens. Overall, our results could pave the way to the use of α-LA as a valid compound with 'prebiotic effects' to limit/restore the PCOS-related intestinal and vaginal dysbiosis.
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Affiliation(s)
- Giulia Alessandri
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental SustainabilityUniversity of ParmaParmaItaly
| | - Leonardo Mancabelli
- Department of Medicine and SurgeryUniversity of ParmaParmaItaly
- Microbiome Research HubUniversity of ParmaParmaItaly
| | - Federico Fontana
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental SustainabilityUniversity of ParmaParmaItaly
| | | | | | | | - Marco Ventura
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental SustainabilityUniversity of ParmaParmaItaly
- Microbiome Research HubUniversity of ParmaParmaItaly
| | - Francesca Turroni
- Laboratory of Probiogenomics, Department of Chemistry, Life Sciences, and Environmental SustainabilityUniversity of ParmaParmaItaly
- Microbiome Research HubUniversity of ParmaParmaItaly
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Yamada N, Kobayashi K, Nagira A, Toshimitsu T, Sato A, Kano H, Hojo K. The Beneficial Effects of Regular Intake of Lactobacillus paragasseri OLL2716 on Gastric Discomfort in Healthy Adults: A Randomized, Double-Blind, Placebo-Controlled Study. Nutrients 2024; 16:3188. [PMID: 39339788 PMCID: PMC11434869 DOI: 10.3390/nu16183188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2024] [Revised: 08/24/2024] [Accepted: 09/19/2024] [Indexed: 09/30/2024] Open
Abstract
We investigated the effects of Lactobacillus paragasseri OLL2716 on gastrointestinal symptoms in healthy adults with gastric complaints. In this randomized, double-blind, placebo-controlled trial, 174 healthy Japanese adults were randomly assigned to an OLL2716 or placebo group, and each group consumed 85 g of yogurt containing L. paragasseri OLL2716 or placebo yogurt daily for 12 weeks. The primary endpoint was the change in gastric symptoms from baseline as per the participants' questionnaires at 6 and 12 weeks. The secondary endpoints were changes from baseline in the short-form Nepean Dyspepsia Index (SF-NDI), the Gastrointestinal Symptom Rating Scale (GSRS), and the Council on Nutrition Appetite Questionnaire-Japanese (CNAQ-J) scores at 6 and 12 weeks. The primary endpoint data showed that the changes in "epigastric pain" at 6 and 12 weeks were significantly decreased in the OLL2716 group compared with those in the placebo group. Additionally, the changes in "epigastric pain syndrome-like symptoms" were significantly decreased in the OLL2716 group compared with those in the placebo group at 6 weeks. The SF-NDI items that improved at 6 weeks were "irritable, tense, or frustrated", "enjoyment of eating or drinking", and "tension", which are sub-scales related to mental stress. The items "Over-all" in the GSRS and "feeling hungry" in the CNAQ-J significantly improved in the OLL2716 group compared with the placebo group at 12 weeks. The results suggest that regular intake of L. paragasseri OLL2716 may improve both gastric discomfort and mental stress in healthy adults with gastric complaints, such as postprandial fullness or early satiety.
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Affiliation(s)
- Naruomi Yamada
- Health Science Research Unit, Division of Research and Development, Meiji Co., Ltd., Tokyo 192-0919, Japan; (N.Y.); (A.N.); (T.T.); (A.S.)
| | - Kyosuke Kobayashi
- Wellness Science Labs, Meiji Holdings Co., Ltd., Tokyo 192-0919, Japan; (K.K.); (H.K.)
| | - Akika Nagira
- Health Science Research Unit, Division of Research and Development, Meiji Co., Ltd., Tokyo 192-0919, Japan; (N.Y.); (A.N.); (T.T.); (A.S.)
| | - Takayuki Toshimitsu
- Health Science Research Unit, Division of Research and Development, Meiji Co., Ltd., Tokyo 192-0919, Japan; (N.Y.); (A.N.); (T.T.); (A.S.)
| | - Asako Sato
- Health Science Research Unit, Division of Research and Development, Meiji Co., Ltd., Tokyo 192-0919, Japan; (N.Y.); (A.N.); (T.T.); (A.S.)
| | - Hiroshi Kano
- Wellness Science Labs, Meiji Holdings Co., Ltd., Tokyo 192-0919, Japan; (K.K.); (H.K.)
| | - Kenichi Hojo
- Health Science Research Unit, Division of Research and Development, Meiji Co., Ltd., Tokyo 192-0919, Japan; (N.Y.); (A.N.); (T.T.); (A.S.)
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Yang L, Wang M, Mo L, Yang Y, Cui Y, Wu Y. The relationship between sarcopenia and related bioindicators and changes after intensive lifestyle intervention in elderly East-China populations. BMC Musculoskelet Disord 2024; 25:704. [PMID: 39227842 PMCID: PMC11370020 DOI: 10.1186/s12891-024-07835-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 08/29/2024] [Indexed: 09/05/2024] Open
Abstract
BACKGROUND As populations live longer, there is a progressive increase in chronic degenerative diseases, particularly those related to the musculoskeletal system. Sarcopenia is characterized by loss of skeletal muscle mass, muscle strength, and loss of physical function. It is a common disease in older adults associated with various adverse health outcomes. There is a lack of bioindicators to screen for sarcopenia. Albumin and lymphocyte counts are commonly used to assess the degree of malnutrition, and blood routine, lipids, and thyroid function are relatively easy to obtain as part of a routine physical examination. Therefore, finding blood markers that can screen for sarcopenia is essential. Our primary aim was to explore whether the bioindicators of body composition, lymphocytes, albumin, lipids, and thyroid hormones are associated with sarcopenia, and a secondary aim was to investigate changes in these indicators after an intensive lifestyle intervention preliminarily. METHODS 60 subjects were selected from Runda and Bailian community health centers in Suzhou, China. They underwent body composition analysis and tested lymphocyte, albumin, lipid, and thyroid hormone levels. The 30 sarcopenia subjects underwent a 3-month intensive lifestyle intervention program. At the end of the intervention, we rechecked the bioindicators. Statistical analyses were performed in IBM SPSS v26.0. RESULTS The blood indices of sarcopenia subjects were generally lower in albumin, non-high-density lipoprotein cholesterol (non-HDL-C), and free triiodothyronine (FT3). Body mass index (BMI)(r = 0.6266, p < 0.0001), fat-free mass (r = 0.8110, p < 0.0001), basal metabolism (r = 0.7782, p < 0.0001), and fat mass (r = 0.3916, p = 0.0020) were positively correlated with appendicular skeletal muscle index (ASMI). Higher BMI and FT3 were associated with lower odds of sarcopenia, while higher fat mass was associated with higher odds of sarcopenia. After a 3-month intensive intervention, sarcopenia subjects had a significant increase in BMI, ASMI, lymphocyte, and albumin levels, and an increase in FT3, but with a non-significant difference (p = 0.342). CONCLUSIONS Low BMI, FT3, and high fat mass were associated with sarcopenia. Intensive lifestyle intervention can significantly improve ASMI, BMI, lymphocytes, albumin, and FT3 in sarcopenia subjects, which is favorable for delaying the progression of sarcopenia. TRIAL REGISTRATION This study was retrospectively registered on ClinicalTrials.gov, registration number NCT06128577, date of registration: 07/11/2023.
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Affiliation(s)
- Lijun Yang
- Department of Geriatric Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, Jiangsu, China
| | - Minhong Wang
- Department of Geriatric Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, Jiangsu, China
| | - Liya Mo
- Department of Geriatric Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, Jiangsu, China
| | - Yunlong Yang
- Department of Geriatric Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, Jiangsu, China
| | - Yan Cui
- Department of Geriatric Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, Jiangsu, China
| | - Yonghua Wu
- Department of Geriatric Medicine, The Affiliated Suzhou Hospital of Nanjing Medical University (Suzhou Municipal Hospital), Suzhou, Jiangsu, China.
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Dhar H, Verma S, Dogra S, Katoch S, Vij R, Singh G, Sharma M. Functional attributes of bioactive peptides of bovine milk origin and application of in silico approaches for peptide prediction and functional annotations. Crit Rev Food Sci Nutr 2024; 64:9432-9454. [PMID: 37218679 DOI: 10.1080/10408398.2023.2212803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
Bovine milk peptides are the protein fragments with diverse bioactive properties having antioxidant, anticarcinogenic, other therapeutic and nutraceutical potentials. These peptides are formed in milk by enzymatic hydrolysis, gastrointestinal digestion and fermentation processes. They have significant health impact with high potency and low toxicity making them a suitable natural alternative for preventing and managing diseases. Antibiotic resistance has increased the quest for better peptide candidates with antimicrobial effects. This article presents a comprehensive review on well documented antimicrobial, immunological, opioid, and anti-hypertensive activities of bovine milk peptides. It also covers the usage of computational biology tools and databases for prediction and analysis of the food-derived bioactive peptides. In silico analysis of amino acid sequences of Bos taurus milk proteins have been predicted to generate peptides with dipeptidyl peptidase IV inhibitory and ACE inhibitory properties, making them favorable candidates for developing blood sugar lowering drugs and anti-hypertensives. In addition to the prediction of new bioactive peptides, application of bioinformatics tools to predict novel functions of already known peptides is also discussed. Overall, this review focuses on the reported as well as predicted biologically active peptide of casein and whey proteins of bovine milk that can be utilized to develop therapeutic agents.
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Affiliation(s)
- Hena Dhar
- Department of Microbiology, School of Biosciences, RIMT University, Mandi Gobindgarh, India
| | - Subhash Verma
- Department of Veterinary Microbiology, Dr. G.C. Negi College of Veterinary & Animal Sciences, CSK Himachal Pradesh Agricultural University, Palampur, India
| | - Sarita Dogra
- PGIMR, Postgraduate Institute of Medical Education & Research, Chandigarh, India
| | - Shailja Katoch
- Department of Veterinary Microbiology, Sardar Vallabh Bhai Patel University of Agriculture and Technology, Meerut, India
| | - Rishika Vij
- Department of Veterinary Physiology & Biochemistry, Dr. G.C. Negi College of Veterinary & Animal Sciences, CSK Himachal Pradesh Agricultural University, Palampur, India
| | - Geetanjali Singh
- Department of Veterinary Physiology & Biochemistry, Dr. G.C. Negi College of Veterinary & Animal Sciences, CSK Himachal Pradesh Agricultural University, Palampur, India
| | - Mandeep Sharma
- Department of Veterinary Microbiology, Dr. G.C. Negi College of Veterinary & Animal Sciences, CSK Himachal Pradesh Agricultural University, Palampur, India
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Si L, Guo X, Bera H, Chen Y, Xiu F, Liu P, Zhao C, Abbasi YF, Tang X, Foderà V, Cun D, Yang M. Unleashing the healing potential: Exploring next-generation regenerative protein nanoscaffolds for burn wound recovery. Asian J Pharm Sci 2023; 18:100856. [PMID: 38204470 PMCID: PMC10777420 DOI: 10.1016/j.ajps.2023.100856] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2023] [Revised: 09/15/2023] [Accepted: 10/07/2023] [Indexed: 01/12/2024] Open
Abstract
Burn injury is a serious public health problem and scientists are continuously aiming to develop promising biomimetic dressings for effective burn wound management. In this study, a greater efficacy in burn wound healing and the associated mechanisms of α-lactalbumin (ALA) based electrospun nanofibrous scaffolds (ENs) as compared to other regenerative protein scaffolds were established. Bovine serum albumin (BSA), collagen type I (COL), lysozyme (LZM) and ALA were separately blended with poly(ε-caprolactone) (PCL) to fabricate four different composite ENs (LZM/PCL, BSA/PCL, COL/PCL and ALA/PCL ENs). The hydrophilic composite scaffolds exhibited an enhanced wettability and variable mechanical properties. The ALA/PCL ENs demonstrated higher levels of fibroblast proliferation and adhesion than the other composite ENs. As compared to PCL ENs and other composite scaffolds, the ALA/PCL ENs also promoted a better maturity of the regenerative skin tissues and showed a comparable wound healing effect to Collagen spongeⓇ on third-degree burn model. The enhanced wound healing activity of ALA/PCL ENs compared to other ENs could be attributed to their ability to promote serotonin production at wound sites. Collectively, this investigation demonstrated that ALA is a unique protein with a greater potential for burn wound healing as compared to other regenerative proteins when loaded in the nanofibrous scaffolds.
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Affiliation(s)
- Liangwei Si
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang l10016, China
| | - Xiong Guo
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang l10016, China
| | - Hriday Bera
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang l10016, China
- Dr. B. C. Roy College of Pharmacy and Allied Health Sciences, Durgapur, 713206, India
| | - Yang Chen
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang l10016, China
| | - Fangfang Xiu
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang l10016, China
| | - Peixin Liu
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang l10016, China
| | - Chunwei Zhao
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang l10016, China
| | - Yasir Faraz Abbasi
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang l10016, China
| | - Xing Tang
- Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China
| | - Vito Foderà
- Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen O, Denmark
| | - Dongmei Cun
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang l10016, China
| | - Mingshi Yang
- Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang l10016, China
- Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen O, Denmark
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Xiao J, Ma J, Khan MZ, Alugongo GM, Chen T, Liu S, Li S, Cao Z. Unlocking the potential of milk whey protein components in colorectal cancer prevention and therapy. Crit Rev Food Sci Nutr 2023; 64:12961-12998. [PMID: 37846905 DOI: 10.1080/10408398.2023.2258970] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2023]
Abstract
Extensive research from large prospective cohort studies and meta-analytical investigations over recent decades have consistently indicated that dairy foods have protective effects, reducing the risk of colorectal cancer. Most of the literature has explored the potential role of milk minerals and vitamins in managing colorectal cancer. Yet, there is a paucity of a comprehensive summary of the anticancer attributes of milk protein components and their underlying mechanisms of action. Recent advancements have spotlighted the potential of whey proteins, including β-lactoglobulin, α-lactalbumin, serum albumin, and lactoferrin, as promising candidates for both the prevention and treatment of colorectal cancer. Notably, whey proteins have demonstrated a more pronounced capacity for suppressing carcinogen-induced tumors when compared to casein. Their strong binding affinity enables them to serve as effective carriers for small molecules or drugs targeting colon cancer therapy. Furthermore, numerous studies have underscored the anti-inflammatory and antioxidant prowess of whey proteins in cancer prevention. Additionally, whey proteins have been shown to trigger apoptosis, hinder tumor cell proliferation, and impede metastasis. This comprehensive review, therefore, not only substantiates the significance of incorporating whey protein components into a balanced daily diet but also underscores their potential in safeguarding against the onset and progression of colorectal cancer.
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Affiliation(s)
- Jianxin Xiao
- State Key Laboratory of Animal Nutrition and Feeding, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural University, Beijing, China
- Key Laboratory of Low Carbon Culture and Safety Production in Cattle in Sichuan, Animal Nutrition Institute, Sichuan Agricultural University, Chengdu, China
| | - Jiaying Ma
- State Key Laboratory of Animal Nutrition and Feeding, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Muhammad Zahoor Khan
- Faculty of Veterinary and Animal Sciences, University of Agriculture Dera Ismail Khan, Khyber Pakhtunkhwa, Pakistan
| | - Gibson Maswayi Alugongo
- State Key Laboratory of Animal Nutrition and Feeding, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Tianyu Chen
- State Key Laboratory of Animal Nutrition and Feeding, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Shuai Liu
- State Key Laboratory of Animal Nutrition and Feeding, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Shengli Li
- State Key Laboratory of Animal Nutrition and Feeding, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural University, Beijing, China
| | - Zhijun Cao
- State Key Laboratory of Animal Nutrition and Feeding, Beijing Engineering Technology Research Center of Raw Milk Quality and Safety Control, College of Animal Science and Technology, China Agricultural University, Beijing, China
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Liu E, Yang M, Li Q, Cheng Q, Wang Y, Ye L, Tian F, Ding H, Ling Y, Xia M, Ji ZS, Li W. Antitumor activity of a whey peptide-based enteral diet in C26 colon tumor-bearing mice. J Food Sci 2023; 88:4275-4288. [PMID: 37615996 DOI: 10.1111/1750-3841.16724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2023] [Revised: 06/07/2023] [Accepted: 07/14/2023] [Indexed: 08/25/2023]
Abstract
The antitumor effects of a whey peptide-based enteral diet, whose main components are whey peptides and yogurt fermented by Lactobacillus delbureckii subsp. bulgaricus 2038 and Streptococcus thermophilus 1131, were investigated in mice. Our results indicated that the tumor weight in C26 carcinoma-transplanted mice was significantly smaller at day 16 post-implantation in the whey peptide-based enteral diet group (1.36 ± 0.54 g) than in the control group (1.83 ± 0.89 g) (p < 0.05). The whey peptide-based enteral diet group exhibited higher tumor cell apoptosis, lower cell proliferation, and inactive angiogenesis indicating by higher degree of TUNEL, lower positive rates of Ki-67, VEGF, and CD34 than control group. It also attenuated inflammatory cell infiltration of spleen and liver as indicated by the decreased spleen index (10.89 ± 2.06 vs. 12.85 ± 2.92, p < 0.05) and increased liver index (58.09 ± 11.37 vs. 53.19 ± 6.67, p < 0.05) in the whey peptide-based enteral diet group than the control diet group. These results proved the inhibitory effect of the whey peptide-based enteral diet on tumor growth, which might be attributed to the whey peptides component. PRACTICAL APPLICATION: A whey peptide-based enteral diet (MEIN® ), containing cheese whey and multiple nutrients, was selected to verify the anti-tumor effect by animal experiments. The tumor weight growth, tumor cell proliferation, inflammatory cell infiltration of spleen and liver in tumor model mice was significantly attenuated by the whey peptide-based enteral diet, that might be attributed to its whey peptides component. These results provided an additive direction for cancer therapy and need a further study including clinical trials.
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Affiliation(s)
- Enuo Liu
- College of Food Sciences and Technology, Shanghai Ocean University, Shanghai, China
- NHC Key Laboratory of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Fudan University, Shanghai, China
| | - Mingjun Yang
- NHC Key Laboratory of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Fudan University, Shanghai, China
| | - Qilin Li
- College of Food Sciences and Technology, Shanghai Ocean University, Shanghai, China
- NHC Key Laboratory of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Fudan University, Shanghai, China
| | - Qianqian Cheng
- NHC Key Laboratory of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Fudan University, Shanghai, China
| | - Yuzhu Wang
- NHC Key Laboratory of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Fudan University, Shanghai, China
| | - Luyi Ye
- NHC Key Laboratory of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Fudan University, Shanghai, China
| | - Fang Tian
- NHC Key Laboratory of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Fudan University, Shanghai, China
| | - Hao Ding
- Shanghai Tongyuan Food Science and Technology Co., Ltd., Shanghai, China
| | - Yiqun Ling
- Department of Nutrition, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Minjie Xia
- NHC Key Laboratory of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Fudan University, Shanghai, China
| | - Zai-Si Ji
- NHC Key Laboratory of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Fudan University, Shanghai, China
- Shanghai Tongyuan Food Science and Technology Co., Ltd., Shanghai, China
| | - Weihua Li
- NHC Key Laboratory of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Fudan University, Shanghai, China
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Kamenov Z, Gateva A, Dinicola S, Unfer V. Comparing the Efficacy of Myo-Inositol Plus α-Lactalbumin vs. Myo-Inositol Alone on Reproductive and Metabolic Disturbances of Polycystic Ovary Syndrome. Metabolites 2023; 13:717. [PMID: 37367875 DOI: 10.3390/metabo13060717] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2023] [Revised: 05/29/2023] [Accepted: 05/30/2023] [Indexed: 06/28/2023] Open
Abstract
Despite the beneficial effect of myo-inositol on metabolic, hormonal, and reproductive parameters of polycystic ovary syndrome (PCOS) patients, 28% to 38% could be resistant to this treatment. The combination with the milk protein α-lactalbumin can be a useful therapeutic approach to overcome inositol resistance and achieve ovulation in these women. This open-label prospective study aimed to compare the effects of supplementing myo-inositol plus α-lactalbumin vs myo-inositol alone on reproductive and metabolic abnormalities in PCOS. A total of 50 anovulatory women with a PCOS diagnosis were randomly assigned to receive myo-inositol alone or a combination of myo-inositol and α-lactalbumin for three months. Anthropometric measures, hormonal levels, and menstrual cycle duration were collected at baseline and after treatment. The therapy with myo-inositol plus α-lactalbumin improved both ovulation rate and menstrual cycle duration more than myo-inositol alone. The body weight was significantly reduced in women receiving myo-inositol plus α-lactalbumin, while patients in the myo-inositol group experienced no change. In addition, the improvement of hyperandrogenism was more prominent in patients treated with myo-inositol plus α-lactalbumin. The benefits of associating myo-inositol and α-lactalbumin clearly make this combination a true edge in the management of PCOS.
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Affiliation(s)
- Zdravko Kamenov
- Department of Internal Medicine, University Hospital "Alexandrovska", Clinic of Endocrinology and Metabolism, Medical University, 1431 Sofia, Bulgaria
- The Experts Group on Inositol in Basic and Clinical Research (EGOI), 00161 Rome, Italy
| | - Antoaneta Gateva
- Department of Internal Medicine, University Hospital "Alexandrovska", Clinic of Endocrinology and Metabolism, Medical University, 1431 Sofia, Bulgaria
| | - Simona Dinicola
- The Experts Group on Inositol in Basic and Clinical Research (EGOI), 00161 Rome, Italy
- Systems Biology Group Lab, 00161 Rome, Italy
| | - Vittorio Unfer
- The Experts Group on Inositol in Basic and Clinical Research (EGOI), 00161 Rome, Italy
- Systems Biology Group Lab, 00161 Rome, Italy
- UniCamillus-Saint Camillus International University of Health Sciences, 00131 Rome, Italy
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Guarnieri G, Iervolino M, Cavallone S, Unfer V, Vianello A. The "Asthma-Polycystic Ovary Overlap Syndrome" and the Therapeutic Role of Myo-Inositol. Int J Mol Sci 2023; 24:ijms24086959. [PMID: 37108123 PMCID: PMC10138395 DOI: 10.3390/ijms24086959] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 04/03/2023] [Accepted: 04/07/2023] [Indexed: 04/29/2023] Open
Abstract
Asthma is a heterogeneous inflammatory disease characterized by abnormalities in immune response. Due to the inherent complexity of the disease and the presence of comorbidities, asthma control is often difficult to obtain. In asthmatic patients, an increased prevalence of irregular menstrual cycles, infertility, obesity, and insulin resistance has been reported. Given that these conditions are also common in patients with polycystic ovary syndrome (PCOS), we propose the definition of "asthma-PCOS overlap syndrome" to indicate a medical condition which shares characteristics of both diseases. The aim of this review is to analyze the links between asthma and PCOS and evaluate the therapeutic role of myo-inositol, a natural compound currently utilized in patients with PCOS, in the management of asthma patients.
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Affiliation(s)
- Gabriella Guarnieri
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy
| | | | | | - Vittorio Unfer
- Systems Biology Group Laboratory, 00163 Rome, Italy
- The Experts Group on Inositol in Basic and Clinical Research (EGOI), 00161 Rome, Italy
| | - Andrea Vianello
- Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padova, 35128 Padova, Italy
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11
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Zhao Q, Li K, Jiang K, Yuan Z, Xiao M, Wei G, Zheng W, Wang X, Huang A. Proteomic approach-based comparison of metabolic pathways and functional activities of whey proteins derived from Guishan and Saanen goat milk. J Dairy Sci 2023; 106:2247-2260. [PMID: 36870847 DOI: 10.3168/jds.2022-22404] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 10/21/2022] [Indexed: 03/06/2023]
Abstract
Guishan goats, a unique goat breed in Yunnan Province, have a long history and representation, but their whey protein and function remain unclear. In this study, we carried out a quantitative analysis of the Guishan and Saanen goat whey proteome using a label-free proteomic approach. A total of 500 proteins were quantified from the 2 kinds of goat whey proteins, including 463 common proteins, 37 uniquely expressed whey proteins (UEWP), and 12 differentially expressed whey proteins (DEWP). Bioinformatics analysis indicated that UEWP and DEWP were mainly involved in cellular and immune system processes, membrane, and binding. In addition, UEWP and DEWP in Guishan goats participated primarily in metabolism and immune-related pathways, whereas Saanen goat whey proteins were associated mostly with environmental information processing-related pathways. Guishan goat whey promoted the growth of RAW264.7 macrophages more than Saanen goat whey, and significantly reduced the production of nitric oxide in lipopolysaccharide-stimulated RAW264.7 cells. This study provides a reference for further understanding these 2 goat whey proteins and finding functional active substances from them.
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Affiliation(s)
- Qiong Zhao
- College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, Yunnan, China
| | - Kunlin Li
- College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, Yunnan, China
| | - Kexin Jiang
- College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, Yunnan, China
| | - Ziyou Yuan
- College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, Yunnan, China
| | - Menglin Xiao
- College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, Yunnan, China
| | - Guangqiang Wei
- College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, Yunnan, China
| | - Wentao Zheng
- College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, Yunnan, China
| | - Xuefeng Wang
- College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, Yunnan, China
| | - Aixiang Huang
- College of Food Science and Technology, Yunnan Agricultural University, Kunming 650201, Yunnan, China.
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12
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Positive Effects of α-Lactalbumin in the Management of Symptoms of Polycystic Ovary Syndrome. Nutrients 2022; 14:nu14153220. [PMID: 35956395 PMCID: PMC9370664 DOI: 10.3390/nu14153220] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 07/29/2022] [Accepted: 08/03/2022] [Indexed: 11/18/2022] Open
Abstract
To date, the involvement of α-Lactalbumin (α-LA) in the management of polycystic ovary syndrome (PCOS) refers to its ability to improve intestinal absorption of natural molecules like inositols, overcoming the inositol resistance. However, due to its own aminoacidic building blocks, α-LA is involved in various biological processes that can open new additional applications. A great portion of women with PCOS exhibit gastrointestinal dysbiosis, which is in turn one of the triggering mechanisms of the syndrome. Due to its prebiotic effect, α-LA can recover dysbiosis, also improving the insulin resistance, obesity and intestinal inflammation frequently associated with PCOS. Further observations suggest that altered gut microbiota negatively influence mental wellbeing. Depressive mood and low serotonin levels are indeed common features of women with PCOS. Thanks to its content of tryptophan, which is the precursor of serotonin, and considering the strict link between gut and brain, using α-LA contributes to preserving mental well-being by maintaining high levels of serotonin. In addition, considering women with PCOS seeking pregnancy, both altered microbiota and serotonin levels can induce later consequences in the offspring. Therefore, a deeper knowledge of potential applications of α-LA is required to transition to preclinical and clinical studies extending its therapeutic advantages in PCOS.
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13
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Lactoferrin and Its Potential Impact for the Relief of Pain: A Preclinical Approach. Pharmaceuticals (Basel) 2021; 14:ph14090868. [PMID: 34577568 PMCID: PMC8468947 DOI: 10.3390/ph14090868] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 08/21/2021] [Accepted: 08/25/2021] [Indexed: 02/08/2023] Open
Abstract
Pain is one of the most disabling symptoms of several clinical conditions. Neurobiologically, it is classified as nociceptive, inflammatory, neuropathic and dysfunctional. Opioids and nonsteroidal anti-inflammatory drugs (NSAIDs) are conventionally prescribed for the treatment of pain. Long-term administration of opioids results in the loss of analgesic efficacy, leading to increased dosage, tolerance, and addiction as the main drawbacks of their use, while the adverse effects of NSAIDs include gastric ulcer formation, intestinal bleeding, acute kidney injury, and hepatotoxicity. Lactoferrin is an iron-binding, anti-inflammatory glycoprotein that displays analgesic activities associated, in part, by interacting with the low-density lipoprotein receptor-related protein (LRP), which may result in the regulation of the DAMP-TRAF6-NFκB, NO-cGMP-ATP K+-sensitive channel and opioid receptor signaling pathways. This review summarizes and discusses for the first time the analgesic effects of lactoferrin and its presumable mechanisms based on pre-clinical trials. Given its anti-nociceptive and anti-inflammatory properties, lactoferrin may be used as an adjunct to enhance the efficacy and to decrease the tolerogenic effects of canonical therapeutic drugs prescribed for pain treatment.
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14
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Koh FH, Chua JMW, Tan JLJ, Foo FJ, Tan WJ, Sivarajah SS, Ho LML, Teh BT, Chew MH. Paradigm shift in gastrointestinal surgery − combating sarcopenia with prehabilitation: Multimodal review of clinical and scientific data. World J Gastrointest Surg 2021; 13:734-755. [PMID: 34512898 PMCID: PMC8394378 DOI: 10.4240/wjgs.v13.i8.734] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2021] [Revised: 05/08/2021] [Accepted: 07/12/2021] [Indexed: 02/06/2023] Open
Abstract
A growing body of evidence has demonstrated the prognostic significance of sarcopenia in surgical patients as an independent predictor of postoperative complications and outcomes. These included an increased risk of total complications, major complications, re-admissions, infections, severe infections, 30 d mortality, longer hospital stay and increased hospitalization expenditures. A program to enhance recovery after surgery was meant to address these complications; however, compliance to the program since its introduction has been less than ideal. Over the last decade, the concept of prehabilitation, or “pre-surgery rehabilitation”, has been discussed. The presurgical period represents a window of opportunity to boost and optimize the health of an individual, providing a compensatory “buffer” for the imminent reduction in physiological reserve post-surgery. Initial results have been promising. We review the literature to critically review the utility of prehabilitation, not just in the clinical realm, but also in the scientific realm, with a resource management point-of-view.
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Affiliation(s)
- Frederick H Koh
- Division of Surgery, Sengkang General Hospital, Singapore 544886, Singapore
| | - Jason MW Chua
- Institute of Molecular and Cell Biology, Agency for Science Technology and Research, Singapore 138673, Singapore
| | - Joselyn LJ Tan
- Institute of Molecular and Cell Biology, Agency for Science Technology and Research, Singapore 138673, Singapore
| | - Fung-Joon Foo
- Division of Surgery, Sengkang General Hospital, Singapore 544886, Singapore
| | - Winson J Tan
- Division of Surgery, Sengkang General Hospital, Singapore 544886, Singapore
| | | | - Leonard Ming Li Ho
- Division of Surgery, Sengkang General Hospital, Singapore 544886, Singapore
| | - Bin-Tean Teh
- Duke-NUS Graduate Medical School, National Cancer Centre Singapore, Singapore 169610, Singapore
| | - Min-Hoe Chew
- Division of Surgery, Sengkang General Hospital, Singapore 544886, Singapore
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15
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Chatterton DEW, Aagaard S, Hesselballe Hansen T, Nguyen DN, De Gobba C, Lametsch R, Sangild PT. Bioactive proteins in bovine colostrum and effects of heating, drying and irradiation. Food Funct 2021; 11:2309-2327. [PMID: 32108849 DOI: 10.1039/c9fo02998b] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Bovine colostrum (BC) contains bioactive proteins, such as immunoglobulin G (IgG), lactoferrin (LF) and lactoperoxidase (LP). BC was subjected to low-temperature, long-time pasteurization (LTLT, 63 °C, 30 min) or high-temperature, short-time pasteurization (HTST, 72 °C, 15 s) and spray-drying (SD), with or without γ-irradiation (GI, ∼14 kGy) to remove microbial contamination. Relative to unpasteurized liquid BC, SD plus GI increased protein denaturation by 6 and 11%, respectively, increasing to 19 and 27% after LTLT and to 48% after HTST, with no further effects after GI (all P < 0.05). LTLT, without or with GI, resulted in 15 or 29% denaturation of IgG, compared with non-pasteurized BC, and 34 or 58% for HTST treatment (all P < 0.05, except LTLT without GI). For IgG, only GI, not SD or LTLT, increased denaturation (30-38%, P < 0.05) but HTST increased denaturation to 40%, with further increases after GI (60%, P < 0.05). LTLT and HTST reduced LP levels (56 and 81% respectively) and LTLT reduced LF levels (21%), especially together with GI (47%, P < 0.05). Denaturation of BSA, β-LgA, β-LgB and α-La were similar to IgG. Methionine, a protective amino acid against free oxygen radicals, was oxidised by LTLT + GI (P < 0.05) while LTLT and HTST had no effect. Many anti-inflammatory proteins, including serpin anti-proteinases were highly sensitive to HTST and GI but preserved after LTLT pasteurization. LTLT, followed by SD is an optimal processing technique preserving bioactive proteins when powdered BC is used as a diet supplement for sensitive patients.
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Affiliation(s)
| | - Sasha Aagaard
- Department of Food Science, University of Copenhagen, DK-1958, Denmark. and Comparative Pediatrics and Nutrition, Department of Veterinary Clinical and Animal Sciences, Denmark
| | | | - Duc Ninh Nguyen
- Comparative Pediatrics and Nutrition, Department of Veterinary Clinical and Animal Sciences, Denmark
| | - Cristian De Gobba
- Department of Food Science, University of Copenhagen, DK-1958, Denmark.
| | - René Lametsch
- Department of Food Science, University of Copenhagen, DK-1958, Denmark.
| | - Per T Sangild
- Comparative Pediatrics and Nutrition, Department of Veterinary Clinical and Animal Sciences, Denmark
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16
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Luoyizha W, Zeng B, Li H, Liao X. A Preliminary Study of Proteomic Analysis on Caseins and Whey Proteins in Donkey Milk from Xinjiang and Shandong of China. EFOOD 2021. [DOI: 10.2991/efood.k.210222.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022] Open
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17
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α-Lactalbumin, Amazing Calcium-Binding Protein. Biomolecules 2020; 10:biom10091210. [PMID: 32825311 PMCID: PMC7565966 DOI: 10.3390/biom10091210] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 08/14/2020] [Accepted: 08/17/2020] [Indexed: 02/06/2023] Open
Abstract
α-Lactalbumin (α-LA) is a small (Mr 14,200), acidic (pI 4–5), Ca2+-binding protein. α-LA is a regulatory component of lactose synthase enzyme system functioning in the lactating mammary gland. The protein possesses a single strong Ca2+-binding site, which can also bind Mg2+, Mn2+, Na+, K+, and some other metal cations. It contains several distinct Zn2+-binding sites. Physical properties of α-LA strongly depend on the occupation of its metal binding sites by metal ions. In the absence of bound metal ions, α-LA is in the molten globule-like state. The binding of metal ions, and especially of Ca2+, increases stability of α-LA against the action of heat, various denaturing agents and proteases, while the binding of Zn2+ to the Ca2+-loaded protein decreases its stability and causes its aggregation. At pH 2, the protein is in the classical molten globule state. α-LA can associate with membranes at neutral or slightly acidic pH at physiological temperatures. Depending on external conditions, α-LA can form amyloid fibrils, amorphous aggregates, nanoparticles, and nanotubes. Some of these aggregated states of α-LA can be used in practical applications such as drug delivery to tissues and organs. α-LA and some of its fragments possess bactericidal and antiviral activities. Complexes of partially unfolded α-LA with oleic acid are cytotoxic to various tumor and bacterial cells. α-LA in the cytotoxic complexes plays a role of a delivery carrier of cytotoxic fatty acid molecules into tumor and bacterial cells across the cell membrane. Perhaps in the future the complexes of α-LA with oleic acid will be used for development of new anti-cancer drugs.
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18
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Della Corte L, Foreste V, Barra F, Gustavino C, Alessandri F, Centurioni MG, Ferrero S, Bifulco G, Giampaolino P. Current and experimental drug therapy for the treatment of polycystic ovarian syndrome. Expert Opin Investig Drugs 2020; 29:819-830. [PMID: 32543238 DOI: 10.1080/13543784.2020.1781815] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects 8-13% of reproductive-age women. Irregular periods, hirsutism, or infertility are the most common clinical presentations of patients affected by PCOS. This syndrome is also linked to metabolic abnormalities such as type 2 diabetes, insulin resistance and obesity. The optimal therapeutic approach is still unknown. AREAS COVERED This narrative review offers an overview of the literature on current and experimental pharmacological options for treating PCOS and highlights ongoing clinical trials. Several electronic databases were searched and current research registers were analyzed to the present year. The papers selected for this review were critically analyzed, and all data available were summarized, organized, and explored to derive key information. EXPERT OPINION The main goal of PCOS treatment is to obtain a metabolic and hormonal balance. Optimal PCOS therapy should be direct to the reproductive abnormalities and the entire spectrum of endocrine and metabolic complications that appear to have a long-term negative impact on PCOS patient health, as in post-menopausal period. The discovery of new mechanisms in PCOS pathogenesis will offer the possibility of testing new drug classes.
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Affiliation(s)
- Luigi Della Corte
- Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples "Federico II" , Naples, Italy
| | - Virginia Foreste
- Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples "Federico II" , Naples, Italy
| | - Fabio Barra
- Academic Unit of Obstetrics and Gynecology, IRCCS Ospedale Policlinico San Martino , Genoa, Italy.,Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (Dinogmi), University of Genoa , Genoa, Italy
| | - Claudio Gustavino
- Unit of Obstetrics and Gynecology, IRCCS Ospedale Policlinico San Martino , Genoa, Italy
| | - Franco Alessandri
- Unit of Obstetrics and Gynecology, IRCCS Ospedale Policlinico San Martino , Genoa, Italy
| | | | - Simone Ferrero
- Academic Unit of Obstetrics and Gynecology, IRCCS Ospedale Policlinico San Martino , Genoa, Italy.,Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (Dinogmi), University of Genoa , Genoa, Italy
| | - Giuseppe Bifulco
- Department of Neuroscience, Reproductive Sciences and Dentistry, School of Medicine, University of Naples "Federico II" , Naples, Italy
| | - Pierluigi Giampaolino
- Department of Public Health, School of Medicine, University of Naples Federico II , Naples, Italy
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19
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Li HY, Li P, Yang HG, Yao QQ, Huang SN, Wang JQ, Zheng N. Investigation and comparison of the protective activities of three functional proteins-lactoferrin, α-lactalbumin, and β-lactoglobulin-in cerebral ischemia reperfusion injury. J Dairy Sci 2020; 103:4895-4906. [PMID: 32229112 DOI: 10.3168/jds.2019-17725] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Accepted: 01/22/2020] [Indexed: 01/05/2023]
Abstract
The objective of this study was to evaluate the protection conferred by lactoferrin, α-lactalbumin, and β-lactoglobulin in cerebral ischemia reperfusion (I/R) injury. Rat pheochromocytoma (PC12) cells were used to construct an oxygen and glucose deprivation model in vitro, and ICR mice underwent carotid artery "ligation-relaxation" to construct a cerebral I/R injury model in vivo. The levels of toll-like receptor 4 (TLR4) and downstream factors including nuclear factor-κB, tumor necrosis factor-α, and IL-1β were measured. Metabonomics detection and data mining were conducted to identify the specific metabolic sponsor of the 3 proteins. The results showed that lactoferrin, α-lactalbumin, and β-lactoglobulin protected neurons from cerebral I/R injury by increasing the level of bopindolol and subsequently inhibiting the TLR4-related pathway to different degrees; β-lactoglobulin had the strongest activity of the 3 proteins. In summary, this study is the first to investigate and compare the protective effects of lactoferrin, α-lactalbumin, and β-lactoglobulin in a cerebral stroke model. The results implicate TLR4 as a novel target of the 3 bioactive proteins to prevent cerebral I/R injury.
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Affiliation(s)
- Hui-Ying Li
- Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China
| | - Peng Li
- Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China; Key Laboratory of Quality and Safety Risk Assessment for Dairy Products, Ministry of Agriculture and Rural Affairs, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China
| | - Huai-Gu Yang
- Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China
| | - Qian-Qian Yao
- Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China
| | - Sheng-Nan Huang
- Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China
| | - Jia-Qi Wang
- Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China.
| | - Nan Zheng
- Institute of Animal Sciences of Chinese Academy of Agricultural Sciences, Beijing 100193, P. R. China.
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20
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Facchinetti F, Appetecchia M, Aragona C, Bevilacqua A, Bezerra Espinola MS, Bizzarri M, D'Anna R, Dewailly D, Diamanti-Kandarakis E, Hernández Marín I, Kamenov ZA, Kandaraki E, Laganà AS, Monastra G, Montanino Oliva M, Nestler JE, Orio F, Ozay AC, Papalou O, Pkhaladze L, Porcaro G, Prapas N, Soulage CO, Stringaro A, Wdowiak A, Unfer V. Experts' opinion on inositols in treating polycystic ovary syndrome and non-insulin dependent diabetes mellitus: a further help for human reproduction and beyond. Expert Opin Drug Metab Toxicol 2020; 16:255-274. [PMID: 32129111 DOI: 10.1080/17425255.2020.1737675] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2019] [Accepted: 02/28/2020] [Indexed: 01/05/2023]
Abstract
Introduction: This Experts' opinion provides an updated scientific support to gynecologists, obstetricians, endocrinologists, nutritionists, neurologists and general practitioners on the use of Inositols in the therapy of Polycystic Ovary Syndrome (PCOS) and non-insulin dependent (type 2) diabetes mellitus (NIDDM).Areas covered: This paper summarizes the physiology of Myo-Inositol (MI) and D-Chiro-Inositol (DCI), two important molecules present in human organisms, and their therapeutic role, also for treating infertility. Some deep differences between the physiological functions of MI and DCI, as well as their safety and intestinal absorption are discussed. Updates include new evidence on the efficacy exerted in PCOS by the 40:1 MI/DCI ratio, and the innovative approach based on alpha-lactalbumin to overcome the decreased therapeutic efficacy of Inositols in some patients.Expert opinion: The evidence suggests that MI, alone or with DCI in the 40:1 ratio, offers a promising treatment for PCOS and NIDDM. However, additional studies need to evaluate some still unresolved issues, such as the best MI/DCI ratio for treating NIDDM, the potential cost-effectiveness of reduced gonadotropins administration in IVF due to MI treatment, or the benefit of MI supplementation in ovulation induction with clomiphene citrate in PCOS patients.
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Affiliation(s)
- Fabio Facchinetti
- Department of Obstetrics and Gynecology and Pediatrics, University of Modena and Reggio Emilia, Modena, Italy
| | - Marialuisa Appetecchia
- Oncological Endocrinology Unit, Regina Elena National Cancer Institute - IRCCS, Rome, Italy
| | - Cesare Aragona
- Systems Biology Group Lab, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Arturo Bevilacqua
- Department of Dynamic and Clinical Psychology, Sapienza University of Rome, Rome, Italy
| | | | - Mariano Bizzarri
- Systems Biology Group Lab, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Rosario D'Anna
- Unit of Gynecology and Obstetrics, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Messina, Italy
| | - Didier Dewailly
- Faculty of Medicine, University of Lille, Lille, France
- INSERM, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Jean-Pierre Aubert Research Centre, Lille, France
| | | | - Imelda Hernández Marín
- Human Reproduction Department, Hospital Juárez de México, México City Mexico
- Facultad de Medicina, Universidad Nacional Autónoma De México (UNAM), México City, México
| | - Zdravko A Kamenov
- Department of Internal Medicine, Medical University of Sofia, Sofia, Bulgaria
| | - Eleni Kandaraki
- Department of Endocrinology & Diabetes, HYGEIA Hospital, Marousi, Athens, Greece
| | - Antonio Simone Laganà
- Department of Obstetrics and Gynecology, "Filippo Del Ponte" Hospital, University of Insubria, Varese, Italy
| | - Giovanni Monastra
- Systems Biology Group Lab, Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | | | - John E Nestler
- Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA, USA
| | - Francesco Orio
- Department of Endocrinology, "Parthenope" University of Naples, Italy
| | - Ali Cenk Ozay
- Faculty of Medicine, Department of Obstetrics and Gynecology, Near East University, Nicosia Cyprus
- Near East University, Research Center of Experimental Health Sciences, Nicosia, Cyprus
| | - Olga Papalou
- Department of Endocrinology & Diabetes, HYGEIA Hospital, Marousi, Athens, Greece
| | - Lali Pkhaladze
- Department of Gynecological Endocrinology, Ioseb Zhordania Institute of Reproductology, Tbilisi, Georgia
| | | | - Nikos Prapas
- 3rd Department of OB-GYNAE, Aristotle University of Thessaloniki, Thessaloniki Greece
- IVF Laboratory, IAKENTRO Fertility Centre, Thessaloniki, Greece
| | | | - Annarita Stringaro
- National Center for Drug Research and Evaluation - Italian National Institute of Health, Rome, Italy
| | - Artur Wdowiak
- Diagnostic Techniques Unit, Medical University of Lublin, Poland
| | - Vittorio Unfer
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
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21
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Fukawa A, Baba S, Iwasawa K, Yamaguchi M, Hosono A. Dietary α-Lactalbumin protects against thioacetamide-induced liver cirrhosis by maintaining gut-liver axis function in rats. Biosci Biotechnol Biochem 2020; 84:171-177. [DOI: 10.1080/09168451.2019.1660613] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
ABSTRACT
We tested the hypothesis that α-lactalbumin inhibits the disruption of intestinal barrier function and liver cirrhosis by restoring gut-liver axis function in thioacetamide (TAA) -treated rats. Rat diets were supplemented with α-lactalbumin replacing 50% of dietary protein. After consuming α-lactalbumin for one week, rats were intraperitoneally injected with TAA twice a week for 14 weeks. The α-lactalbumin-enriched diet significantly inhibited the elevation of plasma alanine aminotransferase, aspartate aminotransferase, and hyaluronic acids. The supplement significantly reduced plasma lipopolysaccharide levels and increased occludin mRNA level. Hepatic fibrosis and regenerative nodules was developed and intestinal villi were shortened by TAA; α-Lactalbumin attenuated these histopathological changes. These results indicated that α-lactalbumin improved intestinal barrier function, suppressing endotoxin levels. These data also suggested that α-lactalbumin ameliorated the impairment of the gut-liver axis by TAA, inhibiting the development of liver cirrhosis.
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Affiliation(s)
- Akika Fukawa
- Food Microbiology and Function Research Laboratories, R&D Div., Meiji Co., Ltd, Hachioji, Japan
| | - Shunsuke Baba
- Food Microbiology and Function Research Laboratories, R&D Div., Meiji Co., Ltd, Hachioji, Japan
| | - Kaori Iwasawa
- Food Microbiology and Function Research Laboratories, R&D Div., Meiji Co., Ltd, Hachioji, Japan
| | - Makoto Yamaguchi
- Food Microbiology and Function Research Laboratories, R&D Div., Meiji Co., Ltd, Hachioji, Japan
| | - Akira Hosono
- College of Bioresource Sciences, Nihon University, Fujisawa, Japan
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22
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Sumi K, Ashida K, Nakazato K. Resistance exercise with anti-inflammatory foods attenuates skeletal muscle atrophy induced by chronic inflammation. J Appl Physiol (1985) 2020; 128:197-211. [DOI: 10.1152/japplphysiol.00585.2019] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Chronic inflammation (CI) can contribute to muscle atrophy and sarcopenia. Resistance exercise (RE) promotes increased and/or maintenance of skeletal muscle mass, but the effects of RE in the presence of CI are unclear. In this study, we developed a novel animal model of CI-induced muscle atrophy and examined the effect of acute or chronic RE by electrical stimulation. CI was induced in young female Lewis rats by injection with peptidoglycan-polysaccharide (PG-PS). Extracellular signal-regulated kinase (ERK), p70S6 kinase (p70S6K), 4E binding protein 1 (4E-BP1), Akt, and Forkhead box O1 (FOXO1) phosphorylation levels increased in gastrocnemius (Gas) muscle from normal rats subjected to acute RE. After acute RE in CI rats, increased levels of phosphorylated ERK, p70S6K, and 4E-BP1, but not Akt or FOXO1, were observed. Chronic RE significantly increased the Gas weight in the exercised limb relative to the nontrained opposing limb in CI rats. Dietary supplementation with anti-inflammatory agents, eicosapentaenoic/docosahexaenoic acid and α-lactalbumin attenuated CI-induced muscle atrophy in the untrained Gas and could promote RE-induced inhibition of atrophy in the trained Gas. In the trained leg, significant negative correlations ( r ≤ −0.80) were seen between Gas weights and CI indices, including proinflammatory cytokines and white blood cell count. These results indicated that the anabolic effects of RE are effective for preventing CI-induced muscle atrophy but are partially attenuated by inflammatory molecules. The findings also suggested that anti-inflammatory treatment together with RE is an effective intervention for muscle atrophy induced by CI. Taken together, we conclude that systemic inflammation levels are associated with skeletal muscle protein metabolism and plasticity. NEW & NOTEWORTHY This study developed a novel chronic inflammation (CI) model rat demonstrating that resistance exercise (RE) induced activation of protein synthesis signaling pathways and mitigated skeletal muscle atrophy. These anabolic effects were partially abrogated likely through attenuation of Akt/Forkhead box O1 axis activity. The degree of skeletal muscle atrophy was related to inflammatory responses. Dietary supplementation with anti-inflammatory agents could enhance the anabolic effect of RE. Our findings provide insight for development of countermeasures for CI-related muscle atrophy, especially secondary sarcopenia.
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Affiliation(s)
- Koichiro Sumi
- Food Microbiology and Function Research Laboratories, R&D Division, Meiji Co., Ltd., Hachiouji, Tokyo, Japan
| | - Kinya Ashida
- Food Microbiology and Function Research Laboratories, R&D Division, Meiji Co., Ltd., Hachiouji, Tokyo, Japan
| | - Koichi Nakazato
- Department of Exercise Physiology, Nippon Sports Science University, Setagaya-ku, Tokyo, Japan
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Kim DH, Chun SH, Oh NS, Lee JY, Lee KW. Anti-inflammatory activities of Maillard reaction products from whey protein isolate fermented by Lactobacillus gasseri 4M13 in lipopolysaccharide-stimulated RAW264.7 cells. J Dairy Sci 2019; 102:7707-7716. [PMID: 31326176 DOI: 10.3168/jds.2018-15774] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2018] [Accepted: 05/28/2019] [Indexed: 01/14/2023]
Abstract
Maillard reaction products formed from whey protein isolate (WPI) and sugar have been shown to have an anti-inflammatory effect in vitro. Here, we incubated WPI and galactose (GWA) in an aqueous solution at 65°C for 24 h to produce a glycated conjugate, which was then fermented using Lactobacillus gasseri 4M13 to obtain the fermented product (F-GWA). We demonstrated that F-GWA had an anti-inflammatory effect on lipopolysaccharide (LPS)-stimulated RAW264.7 cells. It reduced both LPS-stimulated nitric oxide production and LPS-stimulated increases in the gene expression levels of tumor necrosis factor-α and cyclooxygenase-2 in a dose-dependent manner. Furthermore, F-GWA inhibited the LPS-induced phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase, members of the mitogen-activated protein kinase family. The glycation process was evaluated by measuring fluorescence intensity and the furosine concentration during the Maillard reaction to form GWA. The protein modifications of WPI were analyzed using MALDI-TOF tandem mass spectrometry. We found that the combination of the Maillard reaction and L. gasseri 4M13 fermentation increased the prebiotic properties of GWA as well as organic acid production, compared with the nonreacted WPI and galactose.
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Affiliation(s)
- Da Hyun Kim
- Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea
| | - Su-Hyun Chun
- Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea
| | - Nam Su Oh
- R&D Center, Seoul Dairy Cooperative, Ansan, Kyunggi 15407, Republic of Korea
| | - Ji Young Lee
- Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea
| | - Kwang-Won Lee
- Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, Republic of Korea.
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Li CW, Yu K, Shyh-Chang N, Li GX, Jiang LJ, Yu SL, Xu LY, Liu RJ, Guo ZJ, Xie HY, Li RR, Ying J, Li K, Li DJ. Circulating factors associated with sarcopenia during ageing and after intensive lifestyle intervention. J Cachexia Sarcopenia Muscle 2019; 10:586-600. [PMID: 30969486 PMCID: PMC6596393 DOI: 10.1002/jcsm.12417] [Citation(s) in RCA: 164] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Accepted: 01/27/2019] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Ageing, chronic diseases, prolonged inactivity, and inadequate nutrition pose a severe threat to skeletal muscle health and function. To date, experimental evidence suggests that ageing-related subclinical inflammation could be an important causative factor in sarcopenia. Although inflammatory signalling has been implicated in the pathogenesis of experimental animal models of sarcopenia, few studies have surveyed the clinical association between circulating factors and muscle mass in patients before and after lifestyle interventions. In this study, we evaluated whether proinflammatory cytokines are associated with the onset of sarcopenia, which circulating factors are associated with the severity of sarcopenia, and how these factors change after lifestyle interventions in sarcopenic elderly persons. METHODS A total of 56 elderly subjects (age ≥ 60 years) with sarcopenia and 56 elderly non-sarcopenic subjects, who met entry criteria and had given informed consent, were selected from the Peking Union Medical College Hospital multicentre prospective longitudinal sarcopenia study for testing relevant circulating factors. Thirty-two elderly subjects from the sarcopenic cohort completed a 12 week intensive lifestyle intervention programme with whey supplements (30 g/day) and a personalized resistance training regimen. The levels of proinflammatory cytokines and metabolic hormones, pre-intensive and post-intensive lifestyle interventions, were measured. RESULTS The sarcopenic group was significantly older (72.05 ± 6.54 years; P < 0.001), more likely to be inactive and female (57.1% of all sarcopenic patients), and had a higher prevalence of type 2 diabetes (16% higher risk). Compared with non-sarcopenic subjects, serum interleukin (IL)-6, IL-18, tumour necrosis factor-α (TNF-α), TNF-like weak inducer of apoptosis (TWEAK), and leptin were significantly higher, while insulin growth factor 1, insulin, and adiponectin were significantly lower in sarcopenic patients (all P < 0.05). Logistic regression analyses revealed that high levels of TNF-α (>11.15 pg/mL) and TWEAK (>1276.48 pg/mL) were associated with a 7.6-fold and 14.3-fold increased risk of sarcopenia, respectively. After adjustment for confounding variables, high levels of TWEAK were still associated with a 13.4-fold increased risk of sarcopenia. Intensive lifestyle interventions led to significant improvements in sarcopenic patients' muscle mass and serum profiles of TWEAK, TNF-α, IL-18, insulin, and adiponectin (all P < 0.05). CONCLUSIONS High levels of the inflammatory cytokines TWEAK and TNF-α are associated with an increased risk of sarcopenia, while the metabolic hormones insulin growth factor 1, insulin, and adiponectin are associated with a decreased risk of sarcopenia in our Chinese patient cohort. Intensive lifestyle interventions could significantly improve muscle mass, reduce inflammation, and restore metabolic hormone levels in sarcopenic patients. This trial was registered at clinicaltrials.gov as NCT02873676.
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Affiliation(s)
- Chun-Wei Li
- Department of Clinical Nutrition and Department of Health Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Dongcheng District, Beijing, China.,Department of General Surgery and Clinical Nutrition, TianJin Union Medical Center, Hongqiao District, Tianjin, China
| | - Kang Yu
- Department of Clinical Nutrition and Department of Health Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Dongcheng District, Beijing, China
| | - Ng Shyh-Chang
- Institute of Stem cell and Regeneration, Chinese Academy of Sciences, Chaoyang District, Beijing, China.,State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.,University of Chinese Academy of Sciences, Beijing, China
| | - Guo-Xun Li
- Department of General Surgery and Clinical Nutrition, TianJin Union Medical Center, Hongqiao District, Tianjin, China
| | - Ling-Juan Jiang
- Department of Central Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Dongcheng District, Beijing, China
| | - Song-Lin Yu
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Dongcheng District, Beijing, China
| | - Long-Yu Xu
- Department of Sport Physiatry, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Dongcheng District, Beijing, China
| | - Rong-Ji Liu
- Department of Pharmacy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Dongcheng District, Beijing, China
| | - Zi-Jian Guo
- Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Dongcheng District, Beijing, China
| | - Hai-Yan Xie
- Department of Health Care, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Dongcheng District, Beijing, China
| | - Rong-Rong Li
- Department of Clinical Nutrition and Department of Health Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Dongcheng District, Beijing, China
| | - Jie Ying
- Department of Clinical Nutrition and Department of Health Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Dongcheng District, Beijing, China
| | - Kang Li
- Department of Vascular Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Dongcheng District, Beijing, China
| | - Dong-Jing Li
- Department of Health Care, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Dongcheng District, Beijing, China
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Hikosaka S, Goto E, Tabayashi N, Matsumura T. Effects of air temperature before harvest on the concentration of human adiponectin in transgenic strawberry fruits. PLANT BIOTECHNOLOGY (TOKYO, JAPAN) 2019; 36:21-27. [PMID: 31275045 PMCID: PMC6566012 DOI: 10.5511/plantbiotechnology.19.0128a] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/15/2018] [Accepted: 01/28/2019] [Indexed: 06/09/2023]
Abstract
Transgenic ever-bearing strawberry (Fragaria×ananassa Duch. 'HS 138') was cultivated in a closed plant production system to produce functional proteins that can enhance human immune functions. We investigated the effects of air temperature before harvest on fruit growth and the concentration of human adiponectin (hAdi) at harvest in transgenic strawberry. During the different stages of maturity (mature white and immature green stages), hAdi-expressing plants were exposed to four air temperature treatments (15, 20, 25, and 30°C) under 24-h illumination provided by fluorescent lamps. Fruits were harvested at the mature red stage. The number of days to the mature red stage decreased with increasing air temperature, being the least at 30°C. Fruit total soluble protein (TSP) concentration increased with decreasing air temperature, particularly at 15°C, whereas fruit hAdi concentration tended to be higher under the 30°C treatment than under any other of the temperature treatments. There was no significant relationship between fruit fresh weight at harvest time and hAdi concentration within treatments, nor between the number of days to harvest and hAdi or TSP concentration. Although there were no significant differences in fruit hAdi content among treatments, hAdi production rate was the highest at 30°C because of the shortest duration to harvest. These results indicate that a higher air temperature promoted fruit maturation and accelerated the production of functional hAdi proteins in the fruit. For hAdi-expressing strawberry plants, exposure to 30°C may reduce energy consumption (lighting and air conditioning) for functional protein production under controlled environments.
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Affiliation(s)
- Shoko Hikosaka
- Graduate School of Horticulture, Chiba University, 648 Matsudo, Matsudo, Chiba 271-8510, Japan
| | - Eiji Goto
- Graduate School of Horticulture, Chiba University, 648 Matsudo, Matsudo, Chiba 271-8510, Japan
| | - Noriko Tabayashi
- Agroscience Research Laboratories, Hokusan Co., Ltd., 27-4 Kitanosato, Kitahiroshima, Hokkaido 061-1111, Japan
| | - Takeshi Matsumura
- Bioproduction Research Institute, National Institute of Advanced Industrial Science and Technology, Hokkaido, Hokkaido, 2-17-2-1 Tsukisamu-Higashi, Toyohira-ku, Sapporo, Hokkaido 062-8517, Japan
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Carrillo W, Monteiro KM, Spindola H, Ramos M, de Carvalho JE. Antiulcerative and Antinociceptive Activities of Casein and Whey Proteins. J Med Food 2018; 21:605-611. [PMID: 29466063 DOI: 10.1089/jmf.2017.0090] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- Wilman Carrillo
- Research Institute of Food Science, CIAL (CSIC-UAM), Cantoblanco Campus, Autonomous Univeristy of Madrid, Madrid, Spain
- Laboratory of Functional Foods, Faculty of Foods Science and Engineering, Technical University of Ambato, Ambato, Ecuador
- Research Department Faculty of Health and Human Sciences, Bolivar State University, Guaranda, Ecuador
| | | | | | - Mercedes Ramos
- Research Institute of Food Science, CIAL (CSIC-UAM), Cantoblanco Campus, Autonomous Univeristy of Madrid, Madrid, Spain
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Montanino Oliva M, Buonomo G, Calcagno M, Unfer V. Effects of myo-inositol plus alpha-lactalbumin in myo-inositol-resistant PCOS women. J Ovarian Res 2018; 11:38. [PMID: 29747700 PMCID: PMC5944130 DOI: 10.1186/s13048-018-0411-2] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2018] [Accepted: 05/01/2018] [Indexed: 12/15/2022] Open
Abstract
Background Myo-inositol (MI), successfully used in polycystic ovary syndrome (PCOS), was administered with α-LA to exploit its action of favouring the passage of other molecules through biological barriers, and also considering its anti-inflammatory effect. Methods PCOS patients, according to the Rotterdam ESHRE–ASRM criteria, with anovulation and infertility > 1 year, were included in this open and prospective study. The preliminary phase was aimed at determining a set of MI-resistant PCOS patients. This treatment involved 2 g MI, taken twice per day by oral route, for three months. The Homeostasis Model Assessment (HOMA) index and MI plasma levels were measured. In the main phase, previously selected MI-resistant patients received the same daily amount of MI plus 50 mg α-LA twice a day, for a further three months. Ovulation was assessed using ultrasound examination on days 12, 14 and 20 of the cycle. The HOMA index, lipid, hormone and MI plasma levels were detected at baseline and at the end of this phase. Results Thirty-seven anovulatory PCOS subjects were included in the study. Following MI treatment, 23 of the 37 women (62%) ovulated, while 14 (38%) were resistant and did not ovulate. In the latter group, MI plasma levels did not increase. These MI-resistant patients underwent treatment in the main phase of the study, receiving MI and α-LA. After this combined treatment, 12 (86%) of them ovulated. Their MI plasma levels were found to be significantly higher than at baseline; also, a hormone and lipid profile improvement was recorded. Conclusion The combination of MI with α-LA allowed us to obtain significant progress in the treatment of PCOS MI-resistant patients. Therefore, this new formulation was able to re-establish ovulation, greatly increasing the chances of desired pregnancy. Trial Registration Clinical trial registration number: NCT03422289 (ClinicalTrials.gov registry).
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Affiliation(s)
- Mario Montanino Oliva
- Department of Woman Health and Reproductive Medicine, Santo Spirito Hospital, 00193, Rome, Italy.
| | - Giovanna Buonomo
- Department of Woman Health and Reproductive Medicine, Santo Spirito Hospital, 00193, Rome, Italy
| | - Marco Calcagno
- Department of Woman Health and Reproductive Medicine, Santo Spirito Hospital, 00193, Rome, Italy
| | - Vittorio Unfer
- Faculty of Medicine and Psychology, Department of Developmental and Social Psychology, Sapienza University, 00185, Rome, Italy
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Uchida M, Kobayashi O. Novel effect of α-lactalbumin on the yohimbine-induced hot flush increase of the tail skin temperature in ovariectomized rats. Biosci Biotechnol Biochem 2018; 82:862-868. [PMID: 29504865 DOI: 10.1080/09168451.2018.1444976] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
5-Hydroxytryptamine (5-HT) and noradrenaline have been thought to play important roles in the mechanism of hot flush. Then, to clarify the relation between serotonergic and adrenergic nervous systems on the mechanism of hot flush, the effect of paroxetine, 5-HT reuptake inhibitor (SSRI) was evaluated on the yohimbine-induced hot flush increase of tail skin temperature in ovariectomized female rats. Yohimbine (adrenaline α2 antagonist) significantly increased the tail skin temperature in course of time. Clonidine (adrenaline α2 agonist) significantly attenuated this effect. Paroxetine also significantly inhibited the increase of tail skin temperature by yohimbine. α-Lactalbumin having SSRI activity in vitro study also significantly inhibited the increase of tail skin temperature, but not significantly decreased the initial temperature. This difference may explain the different mechanism between paroxetine (SSRI) and α-lactalbumin, suggesting new mechanism of hot flush.
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Affiliation(s)
- Masayuki Uchida
- Food Science & Technology Research Laboratories, R&D Division, Meiji Co., Ltd., Tokyo, Japan
| | - Orie Kobayashi
- Food Science & Technology Research Laboratories, R&D Division, Meiji Co., Ltd., Tokyo, Japan
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Li X, Yuan S, Huang M, Gao J, Wu Z, Tong P, Yang A, Chen H. Identification of IgE and IgG epitopes on native Bos d 4 allergen specific to allergic children. Food Funct 2018; 7:2996-3005. [PMID: 27273451 DOI: 10.1039/c6fo00416d] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Alpha-lactalbumin (ALA) is one of the major allergens in cow's milk. However, research on its conformational epitopes has been relatively limited. In our study, specific antibodies against cow's milk ALA were purified from eight children by two-step affinity chromatography. Subsequently, mimotopes against IgG and IgE were biopanned from Ph.D.-12 and Ph.D.-C7C, respectively. Based on the mimotopes, linear epitopes were defined with the UniProt alignment tool. Conformational epitopes were computed using the Pepitope Server. Six IgE and seven IgG linear epitopes were identified. Meanwhile, five IgE and three IgG conformational epitopes were revealed with PyMOL. The results showed that common residues were identified in both IgE and IgG epitopes and some residues of the conformational epitopes were composed of linear epitopes on bovine α-lactalbumin. The results indicated that the data could be used for developing hypoallergenic dairy products on the basis of epitopes and providing a diagnostic tool for the assessment of patients who are allergic to cow's milk.
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Affiliation(s)
- Xin Li
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, P.R.China and School of Food Science & Technology, Nanchang University, Nanchang 330047, P.R.China
| | - Shuilin Yuan
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, P.R.China and School of Food Science & Technology, Nanchang University, Nanchang 330047, P.R.China
| | - Meijia Huang
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, P.R.China and School of Food Science & Technology, Nanchang University, Nanchang 330047, P.R.China
| | - Jinyan Gao
- School of Food Science & Technology, Nanchang University, Nanchang 330047, P.R.China
| | - Zhihua Wu
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, P.R.China and Jiangxi-OAI Joint Research Institute, Nanchang University, Nanchang 330047, P.R.China.
| | - Ping Tong
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, P.R.China and School of Food Science & Technology, Nanchang University, Nanchang 330047, P.R.China
| | - Anshu Yang
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, P.R.China and Jiangxi-OAI Joint Research Institute, Nanchang University, Nanchang 330047, P.R.China.
| | - Hongbing Chen
- State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, P.R.China and Jiangxi-OAI Joint Research Institute, Nanchang University, Nanchang 330047, P.R.China.
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Dietaryα-lactalbumin induced fatty liver by enhancing nuclear liver X receptorαβ/sterol regulatory element-binding protein-1c/PPARγexpression and minimising PPARα/carnitine palmitoyltransferase-1 expression and AMP-activated protein kinaseαphosphorylation associated with atherogenic dyslipidaemia, insulin resistance and oxidative stress in Balb/c mice. Br J Nutr 2017; 118:914-929. [DOI: 10.1017/s000711451700232x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
AbstractThe effect and the role played by dietaryα-lactalbumin (α-LAC) on hepatic fat metabolism are yet to be fully elucidated. We reported previously thatα-LAC intake induced atherogenic dyslipidaemia in Balb/c mice. The aim of the present study was to investigate if this atherogenic effect could be due to a possibleα-LAC-induced hepatic steatosis. We examine the ability of dietaryα-LAC to induce liver steatosis, identifying the molecular mechanisms underlying hepatic lipid metabolism in association with the lipid profile, peripheral insulin resistance (IR) and changes in the hepatic oxidative environment. Male Balb/c mice (n6) were fed with diets containing either chow or 14 %α-LAC for 4 weeks. Theα-LAC-fed mice developed abdominal adiposity and IR. Moderate liver steatosis with increased TAG and NEFA contents was correlated with atherogenic dyslipidaemia. There was increased nuclear expression of liver X receptorαβ(LXRαβ), sterol regulatory element-binding protein-1c (SREBP-1c) and PPARγtranscription factors and of the cytosolic enzymes acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase involved in the hepaticde novolipogenesis. The opposite was found for the nuclear receptor PPARαand the mitochondrial enzyme carnitine palmitoyltransferase-1 (CPT-1), leading to reduced fatty acidβ-oxidation (FAO). These changes were associated with a significant decrease in both p-Thr172-AMP-activated protein kinaseα(AMPKα) (inactivation) and p-Ser79-ACC1 (activation) and with a more oxidative liver environment increasing lipid peroxidation and protein oxidation and reducing GSH:GSSG ratio in theα-LAC-fed mice. In conclusion, 4 weeks of 14 %α-LAC feeding induced liver steatosis associated with atherogenic dyslipidaemia, IR and oxidative stress by enhancing nuclear LXRαβ/SREBP-1c/PPARγexpression and diminishing PPARα/CPT-1 expression and AMPKαphosphorylation shifting the hepatic FAO toward fatty acid synthesis in Balb/c mice.
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Dube N, Nimgulkar C, Bharatraj DK. Validation of therapeutic anti-inflammatory potential of Arjuna Ksheera Paka - A traditional Ayurvedic formulation of Terminalia arjuna. J Tradit Complement Med 2017; 7:414-420. [PMID: 29034188 PMCID: PMC5634724 DOI: 10.1016/j.jtcme.2016.11.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2016] [Revised: 09/25/2016] [Accepted: 11/03/2016] [Indexed: 01/13/2023] Open
Abstract
Arjuna Ksheera Paka (AKP), a traditional Ayurvedic formulation of Terminalia arjuna (T. arjuna) bark powder is used for its cardioprotective effects. However, its anti-inflammatory efficacy remained unexplored. In the present study, AKP was prepared in cow milk (as per standard Ayurvedic procedure) and compared with standard hydroalcoholic extract (HA) of T. arjuna. The extracts were analyzed for gross phytoconstituents levels, and their antioxidant activity was assayed by DPPH free radical scavenging activity and inhibition of lipid peroxidation. The in vivo anti-inflammatory activity of AKP and HA was studied in carrageenan-induced hind paw biphasic edema in C57BL/6 mice (at 200, 400 and 800 mg/kg BW). The percentage extraction yield of AKP was two folds higher than HA implying that the phytoconstituents in AKP were diluted by a factor of 0.5. The total polyphenol content of HA was (3.8 times) higher than AKP and the antioxidant activity of HA was also higher compared to AKP. Both the extracts, however, showed significant (p < 0.05) anti-inflammatory activity in reducing paw edema in mice. The efficacy of HA was more than AKP at early phase of inflammation, whereas, in the late phase of inflammation AKP was more efficacious and equipotent to HA. Thus, regardless of low in vitro antioxidant activity, AKP exhibited potential in vivo anti-inflammatory activity. The higher efficacy of AKP could be due to the presence of milk solids. These milk solids may act as adjuvants to T. arjuna's phytoconstituents, contributing to their sustained bioavailability, leading to higher in vivo anti-inflammatory efficacy at lower drug concentrations.
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Affiliation(s)
| | | | - Dinesh Kumar Bharatraj
- Food and Drug Toxicology Research Centre, National Institute of Nutrition (NIN), Indian Council of Medical Research (ICMR), Hyderabad-500 007, Telangana, India
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The analgesic activities of Stauntonia brachyanthera and YM 11 through regulating inflammatory mediators and directly controlling the sodium channel prompt. Sci Rep 2017; 7:7574. [PMID: 28790377 PMCID: PMC5548894 DOI: 10.1038/s41598-017-07095-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Accepted: 06/22/2017] [Indexed: 12/30/2022] Open
Abstract
The analgesic studies on Stauntonia brachyanthera, a traditional Chinese folk medicine used to treat headache, pains and inflammatory diseases in local areas, showed that the EtOH extracts (EESB) and the characteristic ingredient YM11 could significantly inhibit the acetic acid-induced writhing responses by 43.1% and 78.95%, and decrease the xylene-induced ear edemas by 48.9% and 21.4%, respectively. EESB could significantly increase pain threshold of mice in hot-plate test, but the effect of YM11 was not obviously. Further study in formalin test showed the inhibitory effect of YM11 in 2nd phase was more significant than that in 1st phase, revealed the peripheral analgesic activity of YM11. The ELISA and Western Blot analysis suggested that the analgesic mechanisms of YM11 were related to the inhibitions of the expressions of TNF-α, IL-1β and IL-6, and down-regulations of Nav1.8 protein in the left side of L4–6 DRG regulated by MAPKs, in which the levels of p-ERK, p-JNK and p-p38 were all decreased. In addition, the electrophysiological experiments indicated YM11 could reduce the Nav1.8 currents by 46.01% in small-diameter DRG neurons. Therefore, the analgesic activity of S. brachyanthera might be based on the regulation of inflammatory mediators and the directly control of the sodium channel prompt.
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Fukawa A, Kobayashi O, Yamaguchi M, Uchida M, Hosono A. Bovine milk-derived α-lactalbumin prevents hepatic fibrosis induced by dimethylnitrosamine via nitric oxide pathway in rats. Biosci Biotechnol Biochem 2017; 81:1941-1947. [PMID: 28752795 DOI: 10.1080/09168451.2017.1356215] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
The present study was designed to evaluate the hepatoprotective potential of α-lactalbumin (αLA) against dimethylnitrosamine (DMN)-induced toxic insults in the rat liver. The liver damage was induced in rats by the repeated administration of DMN (10 mg/kg, i.p.) on three consecutive days per week for three weeks. The rats were maintained on either a standard AIN-93 M or αLA-enriched diet starting one week before the DMN injection until the termination of the experiment. The DMN treatment produced a progressive increase in the plasma markers (aspartate aminotransferase, alanine aminotransferase, total bililbin, hyarulonic acid, and matrix metalloproteinase-2) in 28 days after the first DMN injection. Dietary treatment with αLA significantly reduced the DMN-induced damage toward normalcy. NＧ-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, significantly attenuated the hepatoprotective effect of αLA. These findings show that αLA has a marked suppressive effect on hepetic fibrosis through a nitric oxide-mediated mechanism.
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Affiliation(s)
- Akika Fukawa
- a Food Science Research Labs, R&D Division , Meiji Co., Ltd. , Odawara , Japan
| | - Orie Kobayashi
- a Food Science Research Labs, R&D Division , Meiji Co., Ltd. , Odawara , Japan
| | - Makoto Yamaguchi
- a Food Science Research Labs, R&D Division , Meiji Co., Ltd. , Odawara , Japan
| | - Masayuki Uchida
- a Food Science Research Labs, R&D Division , Meiji Co., Ltd. , Odawara , Japan
| | - Akira Hosono
- b College of Bioresource Sciences , Nihon University , Fujisawa , Japan
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Efficacy and safety of a compound supplement containing glucosamine, chondroitin, and five bioactive ingredients in volunteers with knee joint pain. ACTA ACUST UNITED AC 2017. [DOI: 10.1016/j.pmu.2016.10.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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Dideriksen K, Boesen A, Kristiansen J, Magnusson S, Schjerling P, Holm L, Kjaer M. Skeletal muscle adaptation to immobilization and subsequent retraining in elderly men: No effect of anti-inflammatory medication. Exp Gerontol 2016; 82:8-18. [DOI: 10.1016/j.exger.2016.05.009] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2016] [Revised: 05/13/2016] [Accepted: 05/23/2016] [Indexed: 12/25/2022]
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Nishizawa M, Saigusa M, Saeki H. Conjugation with alginate oligosaccharide via the controlled Maillard reaction in a dry state is an effective method for the preparation of salmon myofibrillar protein with excellent anti-inflammatory activity. FISHERIES SCIENCE 2016; 82:357-367. [DOI: 10.1007/s12562-015-0959-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/07/2015] [Accepted: 12/07/2015] [Indexed: 01/02/2025]
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Saigusa M, Nishizawa M, Shimizu Y, Saeki H. In vitro and in vivo anti-inflammatory activity of digested peptides derived from salmon myofibrillar protein conjugated with a small quantity of alginate oligosaccharide. Biosci Biotechnol Biochem 2015; 79:1518-27. [PMID: 25884412 DOI: 10.1080/09168451.2015.1031075] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Abstract
Salmon myofibrillar protein (Mf) was investigated as a source of edible anti-inflammatory products. Peptides produced by stepwise digestion of Mf (without carbohydrate) with pepsin and trypsin had little effect on the secretion of inflammation-related compounds from lipopolysaccharide-stimulated RAW 264.7 macrophage cells. However, peptides prepared from Mf conjugated with alginate oligosaccharide (AO; 19 μg/mg protein) (dMSA) through the Maillard reaction in the presence of sorbitol significantly reduced the secretion of the pro-inflammatory mediators nitric oxide, tumor necrosis factor (TNF)-α and interleukin (IL)-6, as well as mRNA expression of TNF-α, IL-6, inducible nitric oxide synthase and cyclooxygenase-2. Additionally, dMSA inhibited acute inflammation in a carrageenan-induced model of paw edema in mice, but had no effect on natural killer cell cytotoxic activity or macrophage phagocytosis. These results suggest that fish Mf conjugated with AO may be a potential food material with anti-inflammatory function.
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Affiliation(s)
- Musashi Saigusa
- Graduate School of Fisheries Sciences, Hokkaido University, Hakodate, Japan
| | - Mizuho Nishizawa
- Graduate School of Fisheries Sciences, Hokkaido University, Hakodate, Japan
| | - Yutaka Shimizu
- Faculty of Fisheries Sciences, Hokkaido University, Hakodate, Japan
| | - Hiroki Saeki
- Faculty of Fisheries Sciences, Hokkaido University, Hakodate, Japan
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Yamaguchi M, Takai S, Hosono A, Seki T. Bovine milk-derived α-lactalbumin inhibits colon inflammation and carcinogenesis in azoxymethane and dextran sodium sulfate-treated mice. Biosci Biotechnol Biochem 2014; 78:672-9. [PMID: 25036966 DOI: 10.1080/09168451.2014.890034] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Cyclooxygenase-2 is expressed early in colon carcinogenesis and plays crucial role in the progress of the disease. Recently, we found that α-lactalbumin had anti-inflammatory activity by inhibiting cyclooxygenase-2. In experiment 1, we investigated the effects of α-lactalbumin on the colon carcinogenesis initiated with azoxymethane (AOM) followed by promotion with dextran sodium sulfate (DSS) in mice. Dietary treatment with α-lactalbumin decreased fecal occult blood score at 3 days after DSS intake. α-Lactalbumin also decreased the colon tumor at week 9. In experiment 2, AOM-treated mice were sacrificed at 7 days after DSS intake. The plasma and colon prostaglandin E2 (PGE2) levels in AOM/DSS-treated mice were higher than those in the DSS-treated mice without initiation by AOM. α-Lactalbumin decreased PGE2 in both plasma and colon. These results suggest that α-lactalbumin effectively inhibited colon carcinogenesis, and the inhibition may be due to the decreased PGE2 by inhibiting cyclooxygenase-2 at cancer promotion stages.
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Affiliation(s)
- Makoto Yamaguchi
- a Food Science Research Labs, R&D Division, Meiji Co., Ltd. , Odawara , Japan
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Mangé A, Tuaillon E, Viljoen J, Nagot N, Bendriss S, Bland RM, Newell ML, Van de Perre P, Solassol J. Elevated concentrations of milk β2-microglobulin are associated with increased risk of breastfeeding transmission of HIV-1 (Vertical Transmission Study). J Proteome Res 2013; 12:5616-25. [PMID: 24144106 DOI: 10.1021/pr400578h] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
Abstract
There is increasing evidence to support a relationship between human immunodeficiency virus (HIV-1) transmission through breastfeeding and milk host factors. We analyzed skim milk proteome to further determine the contribution of host factors to the risk of mother-to-child transmission of HIV-1. Quantitative mass spectrometry analysis was performed on nine case-control pairs of HIV+ transmitter/nontransmitter mothers, and specific biochemical assays on two selected proteins were assessed in an independent validation set of 127 samples. 33 identified proteins were differentially expressed between HIV+ transmitter and nontransmitter mothers. Among them, β2-microglobulin was significantly higher in the maternal transmitter than in the nontransmitter groups (p value = 0.0007), and S100A9 was significantly higher in the early maternal transmitter cases (before 4 months of age) compared with the nontransmitters (p value = 0.004). β2-Microglobulin correlated with milk and plasma HIV viral load and CD4+ cell count, whereas S100A9 correlated with the estimated timing of infection of the infant through breastfeeding. Finally, β2-microglobulin concentration in milk could accurately predict the risk of HIV-1 postnatal transmission by breastfeeding (p value < 0.0001, log-rank test). In conclusion, milk β2-microglobulin and S100A9 are host factors that are found to be associated with mother-to-child transmission of HIV-1.
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Affiliation(s)
- Alain Mangé
- University of Montpellier 1 , EA 2415, 641 av. du Doyen Gaston Giraud, 34093 Montpellier, France
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Tavares T, Spindola H, Longato G, Pintado M, Carvalho J, Malcata F. Antinociceptive and anti-inflammatory effects of novel dietary protein hydrolysate produced from whey by proteases of Cynara cardunculus. Int Dairy J 2013. [DOI: 10.1016/j.idairyj.2013.05.010] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
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Chatterton DE, Nguyen DN, Bering SB, Sangild PT. Anti-inflammatory mechanisms of bioactive milk proteins in the intestine of newborns. Int J Biochem Cell Biol 2013; 45:1730-47. [DOI: 10.1016/j.biocel.2013.04.028] [Citation(s) in RCA: 251] [Impact Index Per Article: 20.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2013] [Revised: 04/25/2013] [Accepted: 04/28/2013] [Indexed: 01/04/2023]
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Sashihara T, Nagata M, Mori T, Ikegami S, Gotoh M, Okubo K, Uchida M, Itoh H. Effects of Lactobacillus gasseri OLL2809 and α-lactalbumin on university-student athletes: a randomized, double-blind, placebo-controlled clinical trial. Appl Physiol Nutr Metab 2013; 38:1228-35. [PMID: 24195623 DOI: 10.1139/apnm-2012-0490] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Strenuous exercise reduces immune cell function and increases the risk of respiratory and gastrointestinal infections. In addition, it affects mood state and causes physical fatigue. Athletes require both mental and physical conditioning to execute good performance. In this study, we conducted a randomized, double-blind, placebo-controlled clinical trial to evaluate the immunopotentiation and fatigue-alleviation effects of Lactobacillus gasseri OLL2809 (LG2809) and α-lactalbumin (αLA) in university-student athletes after strenuous exercise. A total of 44 university students who performed strenuous exercise daily were separated into 3 groups to receive a 4-week course of placebo, 100 mg LG2809, or 100 mg LG2809 in combination with 900 mg αLA, respectively. Before and after each dietary treatment, the subjects performed strenuous cycle ergometer exercise for 1 h. Before and after each exercise session, blood samples and visual analogue scale scores for fatigue were obtained. In addition, the mood of each subject before and after the dietary treatment was evaluated using the Profile of Mood States (POMS) questionnaire. LG2809 ingestion was effective in preventing reduced natural killer cell activity due to strenuous exercise and elevating mood from a depressed state. In addition, LG2809 + αLA was found to alleviate minor resting fatigue, which was supported objectively by the significant reduction in the serum reactive oxygen metabolites and transforming growth factor β1 levels. These effects could be helpful for athletes to maintain mental and physical condition.
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Affiliation(s)
- Toshihiro Sashihara
- Food Science Institute, Division of Research and Development, Meiji Corporation, 540 Naruda, Odawara, Kanagawa 250-0862, Japan.
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Couch Y, Anthony DC, Dolgov O, Revischin A, Festoff B, Santos AI, Steinbusch HW, Strekalova T. Microglial activation, increased TNF and SERT expression in the prefrontal cortex define stress-altered behaviour in mice susceptible to anhedonia. Brain Behav Immun 2013; 29:136-146. [PMID: 23305936 DOI: 10.1016/j.bbi.2012.12.017] [Citation(s) in RCA: 146] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/31/2012] [Revised: 12/14/2012] [Accepted: 12/21/2012] [Indexed: 01/03/2023] Open
Abstract
A chronic stress paradigm comprising exposure to predation, tail suspension and restraint induces a depressive syndrome in C57BL/6J mice that occurs in some, but not all, animals. Here, we sought to extend our behavioural studies to investigate how susceptibility (sucrose preference<65%) or resilience (sucrose preference>65%) to stress-induced anhedonia affects the 5HT system and the expression of inflammation-related genes. All chronically stressed animals, displayed increased level of anxiety, but susceptible mice exhibited an increased propensity to float in the forced swim test and demonstrate hyperactivity under stressful lighting conditions. These changes were not present in resilient or acutely stressed animals. Compared to resilient animals, susceptible mice showed elevated expression of tumour necrosis factor alpha (TNF) and the 5-HT transporter (SERT) in the pre-frontal area. Enhanced expression of 5HT(2A) and COX-1 in the pre-frontal area was observed in all stressed animals. In turn, indoleamine-2,3-dioxygenase (IDO) was significantly unregulated in the raphe of susceptible animals. At the cellular level, increased numbers of Iba-1-positive microglial cells were also present in the prefrontal area of susceptible animals compared to resilient animals. Consequently, the susceptible animals display a unique molecular profile when compared to resilient, but anxious, animals. Unexpectedly, this altered profile provides a rationale for exploring anti-inflammatory, and possibly, TNF-targeted therapy for major depression.
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Affiliation(s)
- Yvonne Couch
- Department of Pharmacology, Oxford University, Mansfield Road, Oxford, UK
| | - Daniel C Anthony
- Department of Pharmacology, Oxford University, Mansfield Road, Oxford, UK.
| | - Oleg Dolgov
- Department of Molecular Cell Biology, Max-Planck Institute of Biophysical Chemistry, Göttingen, Germany; Institute of Normal Physiology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, Russia
| | - Alexander Revischin
- Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow, Russia
| | | | - Ana Isabel Santos
- Department of Physiology, Medical Faculty, New University of Lisbon, Campo Martires da Patria, Lisbon, Portugal
| | - Harry W Steinbusch
- Department of Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands
| | - Tatyana Strekalova
- Department of Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands
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Kishta OA, Iskandar M, Dauletbaev N, Kubow S, Lands LC. Pressurized whey protein can limit bacterial burden and protein oxidation in Pseudomonas aeruginosa lung infection. Nutrition 2013; 29:918-24. [PMID: 23395602 DOI: 10.1016/j.nut.2012.11.009] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2012] [Revised: 10/06/2012] [Accepted: 11/18/2012] [Indexed: 12/27/2022]
Abstract
BACKGROUND Lung infection caused by Pseudomonas aeruginosa is associated with an exuberant inflammatory response, oxidative stress, and lung damage. Whey protein is a rich source of cysteine, and anti-inflammatory and immune-enhancing peptides. Anti-inflammatory and antioxidant properties of whey are augmented by hyperbaric pressure treatment. In this study, we tested whether dietary supplementation with pressurized whey protein enhances the host ability to clear P. aeruginosa infection compared with native (i.e., unpressurized) whey. METHODS Using a minimally invasive, non-lethal model of murine (female C57Bl/6) model of P. aeruginosa infection (mucoid strain embedded in agar beads), we studied kinetics of infection, inflammation, and oxidative stress at d 1, 3, and 7 postinfection. A parallel set of mice were fed for 4 wk a semipurified diet containing either native or pressurized whey and subsequently infected with P. aeruginosa. In these mice, the parameters mentioned previously were studied at d 1 and 3 postinfection. RESULTS Infection with P. aeruginosa resulted in inflammation and protein oxidation sustained beyond bacterial clearance. Animals that were fed pressurized whey had fewer bacteria at day 3 than mice on native whey. Weight loss or broncho-alveolar lavage cell content were comparable. Airway protein oxidation was attenuated, whereas airway leukocyte bacterial killing ability and oxidative burst in response to opsonized bacteria were increased in the pressurized whey-fed animals. CONCLUSIONS Use of nutritionally derived substances with anti-inflammatory and antioxidant properties, such as pressurized whey, aids in limiting airway bacterial infection, particularly, under conditions of ongoing oxidative stress.
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Affiliation(s)
- Osama A Kishta
- Division of Pediatric Respiratory Medicine, Montreal Children's Hospital-McGill University Health Centre, Montreal, QC, Canada
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Sugawara K, Takahashi H, Kashiwagura T, Yamada K, Yanagida S, Homma M, Dairiki K, Sasaki H, Kawagoshi A, Satake M, Shioya T. Effect of anti-inflammatory supplementation with whey peptide and exercise therapy in patients with COPD. Respir Med 2012; 106:1526-34. [DOI: 10.1016/j.rmed.2012.07.001] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2012] [Revised: 06/30/2012] [Accepted: 07/02/2012] [Indexed: 12/17/2022]
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Kume H, Okazaki K, Yamaji T, Sasaki H. A newly designed enteral formula containing whey peptides and fermented milk product protects mice against concanavalin A-induced hepatitis by suppressing overproduction of inflammatory cytokines. Clin Nutr 2011; 31:283-9. [PMID: 22119211 DOI: 10.1016/j.clnu.2011.10.012] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2011] [Revised: 09/29/2011] [Accepted: 10/26/2011] [Indexed: 01/16/2023]
Abstract
BACKGROUND & AIMS We previously reported that whey protein derived from cow milk suppressed inflammation in a variety of animal models. We developed a newly designed enteral formula using peptides prepared from whey protein and fermented milk product and investigated its ability to suppress inflammation in concanavalin A-induced hepatitis in mice. METHODS C57BL/6 mice were fed a standard formula, AIN-93M, or enteral formula for 14 days, and then were intravenously administered concanavalin A. Inflammatory cytokines in plasma, liver, and spleen and markers of hepatic function in plasma were assessed at various time points. Livers were assessed for necrosis and apoptosis. RESULTS After concanavalin A treatment, plasma aspartate aminotransaminase, alanine aminotransferase, TNF-α, IL-6, and IFN-γ levels were significantly lower in mice fed enteral formula than in those fed standard formula or AIN-93M. Liver TNF-α and IFN-γ, and spleen IL-6 and IFN-γ levels were lower in enteral formula-fed mice than in standard formula-fed mice 2 h after concanavalin A treatment. Necrosis and apoptosis were suppressed in the livers of enteral formula-fed mice. CONCLUSIONS The new enteral formula is a potent novel immune-modulating diet that prevents aggravation of local inflammation by modulating systemic cytokine levels.
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Affiliation(s)
- Hisae Kume
- Nutrition Research Dept., Food Science Research Labs, Meiji Co Ltd, 540 Naruda, Odawara, Kanagawa 250-0862, Japan.
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Hunter DC, Brown R, Green T, Thomson C, Skeaff M, Williams S, Todd JM, Lister CE, McGhie T, Zhang J, Martin H, Rippon P, Stanley R, Skinner MA. Changes in markers of inflammation, antioxidant capacity and oxidative stress in smokers following consumption of milk, and milk supplemented with fruit and vegetable extracts and vitamin C. Int J Food Sci Nutr 2011; 63:90-102. [DOI: 10.3109/09637486.2011.601286] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Uchida M, Ohshiba Y, Mogami O. Novel Dipeptidyl Peptidase-4–Inhibiting Peptide Derived From β-Lactoglobulin. J Pharmacol Sci 2011; 117:63-6. [DOI: 10.1254/jphs.11089sc] [Citation(s) in RCA: 84] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022] Open
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Early enteral nutrition with whey protein or casein in elderly patients with acute ischemic stroke: a double-blind randomized trial. Nutrition 2010; 27:440-4. [PMID: 21167685 DOI: 10.1016/j.nut.2010.02.013] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2009] [Revised: 02/20/2010] [Accepted: 02/25/2010] [Indexed: 11/23/2022]
Abstract
OBJECTIVE The aim of this study was to investigate the effects of an early enteral formula containing whey protein, in comparison to a standard enteral formula containing casein as the protein source, on the levels of glutathione and inflammatory markers in aged patients with acute ischemic stroke. METHODS Thirty-one elderly patients (12 males and 19 females; median age = 74 [range,65-90] y old) with ischemic stroke were randomized to receive early nasogastric feeding (35 kcal/kg/d and 1.2 g of protein/kg/d) with either a formula containing polymeric [corrected] casein (casein group, n =16) or another isocaloric and isonitrogenous formula containing hydrolyzed whey protein (WP group, n = 15) for 5 d. The primary endpoints of the study were the changes in the serum levels of glutathione peroxidase, C-reactive protein (CRP), and interleukin 6 (IL-6). RESULTS Twenty-five patients completed the study (10 in the WP group and 15 in the casein group). Mortality was similar between groups (33%; P = 1.00) and was associated with higher serum IL-6 (73.7 ± 24.7 versus 16.6 ± 2.4 pg/dL; P = 0.04) and CRP (82.0 ± 35.6 versus 48.3 ± 14.5 mg/L; P = 0.02) levels. Albumin levels dropped from the first to the fifth feeding day only in the casein group (P < 0.01). Serum IL-6 decreased (62.7 ± 47.2 to 20.6 ± 10.3 pg/dL; P = 0.02) and glutathione increased (32.2 ± 2.1 to 39.9 ± 6.8 U/G Hb; P = 0.03) only in the WP group. Serum IL-6 was lower (P = 0.03) and glutathione was higher (P = 0.03) in whey protein-fed patients than in the casein group. CONCLUSION Enteral formula containing whey protein may decrease inflammation and increase antioxidant defenses in elderly patients with ischemic stroke, compared to casein-containing formula.
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