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Murgo E, Colangelo T, Bellet MM, Malatesta F, Mazzoccoli G. Role of the Circadian Gas-Responsive Hemeprotein NPAS2 in Physiology and Pathology. BIOLOGY 2023; 12:1354. [PMID: 37887064 PMCID: PMC10603908 DOI: 10.3390/biology12101354] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/22/2023] [Revised: 10/14/2023] [Accepted: 10/20/2023] [Indexed: 10/28/2023]
Abstract
Neuronal PAS domain protein 2 (NPAS2) is a hemeprotein comprising a basic helix-loop-helix domain (bHLH) and two heme-binding sites, the PAS-A and PAS-B domains. This protein acts as a pyridine nucleotide-dependent and gas-responsive CO-dependent transcription factor and is encoded by a gene whose expression fluctuates with circadian rhythmicity. NPAS2 is a core cog of the molecular clockwork and plays a regulatory role on metabolic pathways, is important for the function of the central nervous system in mammals, and is involved in carcinogenesis as well as in normal biological functions and processes, such as cardiovascular function and wound healing. We reviewed the scientific literature addressing the various facets of NPAS2 and framing this gene/protein in several and very different research and clinical fields.
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Affiliation(s)
- Emanuele Murgo
- Department of Medical Sciences, Division of Internal Medicine and Chronobiology Laboratory, Fondazione IRCCS “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, Italy;
| | - Tommaso Colangelo
- Department of Medical and Surgical Sciences, University of Foggia, Viale Pinto 1, 71100 Foggia, Italy;
- Cancer Cell Signaling Unit, Fondazione IRCCS “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, Italy
| | - Maria Marina Bellet
- Department of Medicine and Surgery, University of Perugia, P.le L. Severi 1, 06132 Perugia, Italy;
| | - Francesco Malatesta
- Department of Biochemical Sciences “Alessandro Rossi Fanelli”, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 Rome, Italy
| | - Gianluigi Mazzoccoli
- Department of Medical Sciences, Division of Internal Medicine and Chronobiology Laboratory, Fondazione IRCCS “Casa Sollievo della Sofferenza”, 71013 San Giovanni Rotondo, Italy;
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Cao XM, Kang WD, Xia TH, Yuan SB, Guo CA, Wang WJ, Liu HB. High expression of the circadian clock gene NPAS2 is associated with progression and poor prognosis of gastric cancer: A single-center study. World J Gastroenterol 2023; 29:3645-3657. [PMID: 37398880 PMCID: PMC10311614 DOI: 10.3748/wjg.v29.i23.3645] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Revised: 03/16/2023] [Accepted: 05/04/2023] [Indexed: 06/16/2023] Open
Abstract
BACKGROUND The prognostic assessment of patients after surgical resection of gastric cancer (GC) patients is critical. However, the role of the circadian clock gene NPAS2 expression in GC remains unknown.
AIM To explore the relationship between NPAS2 and the survival prognosis of GC patients and clarify its role in evaluating GC prognosis.
METHODS The tumor tissues and clinical data of 101 patients with GC were collected retrospectively. Immunohistochemical staining (IHC) was used to detect the expression of NPAS2 protein in GC and adjacent tissues. Univariate and multivariate Cox regression analysis was used to determine the independent prognostic factors of GC, and a nomogram prediction model was established. The receiver operating characteristic (ROC) curve, the ROC area under the curve, the calibration curve, and C-index were used to evaluate the predictive effectiveness of the model. Kaplan Meier analysis was used to compare the risk stratification of subgroups according to the median score in the nomogram model of each patient.
RESULTS Microarray IHC analysis showed that the positive rate of NPAS2 protein expression in GC tissues was 65.35%, which was significantly higher than 30.69% in adjacent tissues. The high expression of NPAS2 was correlated with tumor-node-metastasis (TNM) stage (P < 0.05), pN stage (P < 0.05), metastasis (P < 0.05), venous invasion (P < 0.05), lymphatic invasion (P < 0.05), and lymph node positive (P < 0.05) of GC. Kaplan Meier survival analysis showed that the 3-year overall survival (OS) of patients with high NPAS2 expression was significantly shortened (P < 0.0001). Univariate and multivariate COX regression analysis showed that TNM stage (P = 0.009), metastasis (P = 0.009), and NPAS2 expression (P = 0.020) were independent prognostic factors of OS in GC patients for 3 years. The nomogram prediction model based on independent prognostic factors has a C-Index of 0.740 (95%CI: 0.713-0.767). Furthermore, subgroup analysis showed that the 3-year OS time of the high-risk group was significantly lower than that of the low-risk group (P < 0.0001).
CONCLUSION NPAS2 is highly expressed in GC tissues and is closely related to worse OS in patients. Therefore, the evaluation of NPAS2 expression may be a potential marker for GC prognosis evaluation. Notably, the nomogram model based on NPAS2 can improve the accuracy of GC prognosis prediction and assist clinicians in postoperative patient management and decision-making.
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Affiliation(s)
- Xiao-Meng Cao
- Department of General Surgery, Gansu Provincial Hospital of TCM, Lanzhou 730050, Gansu Province, China
- The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou 730030, Gansu Province, China
| | - Wen-Di Kang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Tian-Hong Xia
- Clinical Medicine College, Ningxia Medical University, Clinical Medicine college, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Shao-Bin Yuan
- The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou 730030, Gansu Province, China
| | - Chang-An Guo
- Department of Emergency, Lanzhou University Second Hospital, Lanzhou 730030, Gansu Province, China
| | - Wen-Jie Wang
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou 730030, Gansu Province, China
| | - Hong-Bin Liu
- Department of General Surgery, The 940th Hospital of Joint Logistics Support Force of Chinese People's Liberation Army, Lanzhou 730050, Gansu Province, China.
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Shibuya Y, Hokugo A, Okawa H, Kondo T, Khalil D, Wang L, Roca Y, Clements A, Sasaki H, Berry E, Nishimura I, Jarrahy R. Therapeutic downregulation of neuronal PAS domain 2 ( Npas2) promotes surgical skin wound healing. eLife 2022; 11:e71074. [PMID: 35040776 PMCID: PMC8789286 DOI: 10.7554/elife.71074] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2021] [Accepted: 01/14/2022] [Indexed: 11/13/2022] Open
Abstract
Attempts to minimize scarring remain among the most difficult challenges facing surgeons, despite the use of optimal wound closure techniques. Previously, we reported improved healing of dermal excisional wounds in circadian clock neuronal PAS domain 2 (Npas2)-null mice. In this study, we performed high-throughput drug screening to identify a compound that downregulates Npas2 activity. The hit compound (Dwn1) suppressed circadian Npas2 expression, increased murine dermal fibroblast cell migration, and decreased collagen synthesis in vitro. Based on the in vitro results, Dwn1 was topically applied to iatrogenic full-thickness dorsal cutaneous wounds in a murine model. The Dwn1-treated dermal wounds healed faster with favorable mechanical strength and developed less granulation tissue than the controls. The expression of type I collagen, Tgfβ1, and α-smooth muscle actin was significantly decreased in Dwn1-treated wounds, suggesting that hypertrophic scarring and myofibroblast differentiation are attenuated by Dwn1 treatment. NPAS2 may represent an important target for therapeutic approaches to optimal surgical wound management.
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Affiliation(s)
- Yoichiro Shibuya
- Regenerative Bioengineering and Repair Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of MedicineLos AngelesUnited States
- Weintraub Center for Reconstructive BiotechnologyLos AngelesUnited States
- Department of Plastic and Reconstructive Surgery, Faculty of Medicine, University of TsukubaTsukubaJapan
| | - Akishige Hokugo
- Regenerative Bioengineering and Repair Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of MedicineLos AngelesUnited States
- Weintraub Center for Reconstructive BiotechnologyLos AngelesUnited States
| | - Hiroko Okawa
- Weintraub Center for Reconstructive BiotechnologyLos AngelesUnited States
- Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of DentistryMiyagiJapan
| | - Takeru Kondo
- Weintraub Center for Reconstructive BiotechnologyLos AngelesUnited States
- Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of DentistryMiyagiJapan
| | - Daniel Khalil
- Regenerative Bioengineering and Repair Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of MedicineLos AngelesUnited States
| | - Lixin Wang
- Regenerative Bioengineering and Repair Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of MedicineLos AngelesUnited States
| | - Yvonne Roca
- Regenerative Bioengineering and Repair Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of MedicineLos AngelesUnited States
| | - Adam Clements
- Regenerative Bioengineering and Repair Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of MedicineLos AngelesUnited States
| | - Hodaka Sasaki
- Weintraub Center for Reconstructive BiotechnologyLos AngelesUnited States
| | - Ella Berry
- Regenerative Bioengineering and Repair Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of MedicineLos AngelesUnited States
| | - Ichiro Nishimura
- Weintraub Center for Reconstructive BiotechnologyLos AngelesUnited States
| | - Reza Jarrahy
- Regenerative Bioengineering and Repair Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of MedicineLos AngelesUnited States
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Peng LU, Bai G, Pang Y. Roles of NPAS2 in circadian rhythm and disease. Acta Biochim Biophys Sin (Shanghai) 2021; 53:1257-1265. [PMID: 34415290 DOI: 10.1093/abbs/gmab105] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Indexed: 11/14/2022] Open
Abstract
NPAS2, a circadian rhythm gene encoding the neuronal PAS domain protein 2 (NPAS2), has received widespread attention because of its complex functions in cells and diverse roles in disease progression, especially tumorigenesis. NPAS2 binds with DNA at E-box sequences and forms heterodimers with another circadian protein, brain and muscle ARNT-like protein 1 (BMAL1). Nucleotide variations of the NPAS2 gene have been shown to influence the overall survival and risk of death of cancer patients, and differential expression of NPAS2 has been linked to patient outcomes in breast cancer, lung cancer, non-Hodgkin's lymphoma, and other diseases. Here, we review the latest advances in our understanding of NPAS2 with the aim of drawing attention to its potential clinical applications and prospects.
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Affiliation(s)
- L u Peng
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Gaigai Bai
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250012, China
| | - Yingxin Pang
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250012, China
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Duan J, Greenberg EN, Karri SS, Andersen B. The circadian clock and diseases of the skin. FEBS Lett 2021; 595:2413-2436. [PMID: 34535902 PMCID: PMC8515909 DOI: 10.1002/1873-3468.14192] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 09/11/2021] [Accepted: 09/13/2021] [Indexed: 02/06/2023]
Abstract
Organisms have an evolutionarily conserved internal rhythm that helps them anticipate and adapt to daily changes in the environment. Synchronized to the light-dark cycle with a period of around 24 hours, the timing of the circadian clock is set by light-triggering signals sent from the retina to the suprachiasmatic nucleus. Other inputs, including food intake, exercise, and temperature, also affect clocks in peripheral tissues, including skin. Here, we review the intricate interplay between the core clock network and fundamental physiological processes in skin such as homeostasis, regeneration, and immune- and stress responses. We illustrate the effect of feeding time on the skin circadian clock and skin functions, a previously overlooked area of research. We then discuss works that relate the circadian clock and its disruption to skin diseases, including skin cancer, sunburn, hair loss, aging, infections, inflammatory skin diseases, and wound healing. Finally, we highlight the promise of circadian medicine for skin disease prevention and management.
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Affiliation(s)
- Junyan Duan
- Center for Complex Biological Systems, University of California, Irvine, CA 92697
| | - Elyse Noelani Greenberg
- Department of Biological Chemistry, University of California, Irvine, CA 92697
- Department of Medicine, Division of Endocrinology, School of Medicine, University of California, Irvine, CA 92697
| | - Satya Swaroop Karri
- Department of Biological Chemistry, University of California, Irvine, CA 92697
| | - Bogi Andersen
- Center for Complex Biological Systems, University of California, Irvine, CA 92697
- Department of Biological Chemistry, University of California, Irvine, CA 92697
- Department of Medicine, Division of Endocrinology, School of Medicine, University of California, Irvine, CA 92697
- Institute for Genomics and Bioinformatics, University of California, Irvine, CA 92697
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Zhu J, Hao S, Zhang X, Qiu J, Xuan Q, Ye L. Integrated Bioinformatics Analysis Exhibits Pivotal Exercise-Induced Genes and Corresponding Pathways in Malignant Melanoma. Front Genet 2021; 11:637320. [PMID: 33679872 PMCID: PMC7930906 DOI: 10.3389/fgene.2020.637320] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Accepted: 12/21/2020] [Indexed: 02/03/2023] Open
Abstract
Malignant melanoma represents a sort of neoplasm deriving from melanocytes or cells developing from melanocytes. The balance of energy and energy-associated body composition and body mass index could be altered by exercise, thereby directly affecting the microenvironment of neoplasm. However, few studies have examined the mechanism of genes induced by exercise and the pathways involved in melanoma. This study used three separate datasets to perform comprehensive bioinformatics analysis and then screened the probable genes and pathways in the process of exercise-promoted melanoma. In total, 1,627 differentially expressed genes (DEGs) induced by exercise were recognized. All selected genes were largely enriched in NF-kappa B, Chemokine signaling pathways, and the immune response after gene set enrichment analysis. The protein-protein interaction network was applied to excavate DEGs and identified the most relevant and pivotal genes. The top 6 hub genes (Itgb2, Wdfy4, Itgam, Cybb, Mmp2, and Parp14) were identified, and importantly, 5 hub genes (Itgb2, Wdfy4, Itgam, Cybb, and Parp14) were related to weak disease-free survival and overall survival (OS). In conclusion, our findings demonstrate the prognostic value of exercise-induced genes and uncovered the pathways of these genes in melanoma, implying that these genes might act as prognostic biomarkers for melanoma.
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Affiliation(s)
- Jun Zhu
- Administrative Office, Shanghai Basilica Clinic, Shanghai, China
| | - Suyu Hao
- Shuangwu Information Technical Company Ltd., Shanghai, China
| | - Xinyue Zhang
- School of Education, Hangzhou Normal University, Hangzhou, China
| | - Jingyue Qiu
- School of Physical Science and Engineering, East China University of Science and Technology, Shanghai, China
| | - Qin Xuan
- School of Sports Science and Engineering, East China University of Science and Technology, Shanghai, China
| | - Liping Ye
- Department of Clinical Nursing, Minhang Hospital, Fudan University, Shanghai, China
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Benna C, Rajendran S, Spiro G, Menin C, Dall'Olmo L, Rossi CR, Mocellin S. Gender-specific associations between polymorphisms of the circadian gene RORA and cutaneous melanoma susceptibility. J Transl Med 2021; 19:57. [PMID: 33549124 PMCID: PMC7866430 DOI: 10.1186/s12967-021-02725-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 01/28/2021] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND Melanoma is the deadliest of skin cancers and has an increasing annual incidence worldwide. It is a multi-factorial disease most likely arising from both genetic predisposition and environmental exposure to ultraviolet light. Genetic variability of the components of the biological circadian clock is recognized to be a risk factor for different type of cancers. Moreover, two variants of a clock gene, RORA, have been associated with melanoma patient's prognosis. Our aim is to test the hypothesis that specific single nucleotide polymorphisms (SNPs) of the circadian clock genes may significantly influence the predisposition to develop cutaneous melanoma or the outcome of melanoma patients. METHODS We genotyped 1239 subjects, 629 cases of melanoma and 610 healthy controls in 14 known SNPs of seven selected clock genes: AANAT, CLOCK, NPAS2, PER1, PER2, RORA, and TIMELESS. Genotyping was conducted by q-PCR. Multivariate logistic regression was employed for susceptibility of melanoma assessment, modeled additively. Subgroup analysis was performed by gender. For the female subgroup, a further discrimination was performed by age. For prognosis of melanoma assessment, multivariate Cox proportional hazard regression was employed. The Benjamini-Hochberg method was utilized as adjustment for multiple comparisons. RESULTS We identified two RORA SNPs statistically significant with respect to the association with melanoma susceptibility. Considering the putative role of RORA as a nuclear steroid hormone receptor, we conducted a subgroup analysis by gender. Interestingly, the RORA rs339972 C allele was associated with a decreased predisposition to develop melanoma only in the female subgroup (OR 0.67; 95% CI 0.51-0.88; P = 0.003) while RORA rs10519097 T allele was associated with a decreased predisposition to develop melanoma only in the male subgroup (OR 0.62; 95% CI 0.44-0.87; P = 0.005). Moreover, the RORA rs339972 C allele had a decreased susceptibility to develop melanoma only in females aged over 50 years old (OR 0.67; 95% CI 0.54-0.83; P = 0.0002). None of the studied SNPs were significantly associated with the prognosis. CONCLUSIONS Overall, we cannot ascertain that circadian pathway genetic variation is involved in melanoma susceptibility or prognosis. Nevertheless, we identified an interesting relationship between melanoma susceptibility and RORA polymorphisms acting in sex-specific manner and which is worth further future investigation.
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Affiliation(s)
- Clara Benna
- Department of Surgery Oncology and Gastroenterology, University of Padova, Padova, Italy. .,First Surgical Clinic, Azienda Ospedaliera Padova, Padova, Italy.
| | - Senthilkumar Rajendran
- Department of Surgery Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Giovanna Spiro
- Department of Surgery Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Chiara Menin
- Immunology and Diagnostic Molecular Oncology Unit, Veneto Institute of Oncology (IOV - IRCCS), Padova, Italy
| | - Luigi Dall'Olmo
- Department of Surgery Oncology and Gastroenterology, University of Padova, Padova, Italy.,Surgical Oncology Unit, Veneto Institute of Oncology (IOV-IRCCS), Padova, Italy
| | - Carlo Riccardo Rossi
- Department of Surgery Oncology and Gastroenterology, University of Padova, Padova, Italy.,Surgical Oncology Unit, Veneto Institute of Oncology (IOV-IRCCS), Padova, Italy
| | - Simone Mocellin
- Department of Surgery Oncology and Gastroenterology, University of Padova, Padova, Italy.,Surgical Oncology Unit, Veneto Institute of Oncology (IOV-IRCCS), Padova, Italy
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Sasaki H, Hokugo A, Wang L, Morinaga K, Ngo JT, Okawa H, Nishimura I. Neuronal PAS Domain 2 (Npas2)-Deficient Fibroblasts Accelerate Skin Wound Healing and Dermal Collagen Reconstruction. Anat Rec (Hoboken) 2019; 303:1630-1641. [PMID: 30851151 DOI: 10.1002/ar.24109] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2018] [Revised: 12/11/2018] [Accepted: 12/17/2018] [Indexed: 01/17/2023]
Abstract
The circadian clock, which consists of endogenous self-sustained and cell-autonomous oscillations in mammalian cells, is known to regulate a wide range of peripheral tissues. The unique upregulation of a clock gene, neuronal PAS domain protein 2 (Npas2), observed along with fibroblast aging prompted us to investigate the role of Npas2 in the homeostasis of dermal structure using in vivo and in vitro wound healing models. Time-course healing of a full-thickness skin punched wound exhibited significantly faster wound closure in Npas2-/- mice than wild-type (WT) C57Bl/6J mice. Dorsal skin fibroblasts isolated from WT, Npas2+/-, and Npas2-/- mice exhibited consistent profiles of core clock gene expression except for Npas2 and Per2. In vitro behavioral characterizations of dermal fibroblasts revealed that Npas2-/- mutation was associated with increased proliferation, migration, and cell contraction measured by floating collagen gel contraction and single-cell force contraction assays. Npas2 knockout fibroblasts carrying sustained the high expression level of type XII and XIV FAICT collagens and synthesized dermis-like thick collagen fibers in vitro. Confocal laser scanning microscopy demonstrated the reconstruction of dermis-like collagen architecture in the wound healing area of Npas2-/- mice. This study indicates that the induced Npas2 expression in fibroblasts may interfere with skin homeostasis, wound healing, and dermal tissue reconstruction, providing a basis for novel therapeutic target and strategy. Anat Rec, 2019. © 2019 Wiley Periodicals, Inc.
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Affiliation(s)
- Hodaka Sasaki
- Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry, Los Angeles, California.,Department of Oral and Maxillofacial Implantology, Tokyo Dental College, Tokyo, Japan
| | - Akishige Hokugo
- Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry, Los Angeles, California.,Regenerative Bioengineering and Repair Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Lixin Wang
- Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry, Los Angeles, California.,Regenerative Bioengineering and Repair Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Kenzo Morinaga
- Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry, Los Angeles, California.,Department of Oral Rehabilitation, Section of Oral Implantology, Fukuoka Dental College, Fukuoka, Japan
| | - John T Ngo
- Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry, Los Angeles, California
| | - Hiroko Okawa
- Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry, Los Angeles, California.,Division of Molecular and Regenerative Prosthodontics, Tohoku University Graduate School of Dentistry, Sendai, Japan
| | - Ichiro Nishimura
- Weintraub Center for Reconstructive Biotechnology, UCLA School of Dentistry, Los Angeles, California
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Shostak A. Human Clock Genes and Cancer. CURRENT SLEEP MEDICINE REPORTS 2018. [DOI: 10.1007/s40675-018-0102-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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