To explore the promoting effect of ginsenoside Rb3 (Rb3) on osteogenesis in periodontitis environment, and to explain its mechanism.

Human periodontal ligament stem cells (hPDLSCs) were cultured by tissue block method and identified by flow cytometry. Cell counting kit-8 (CCK8) method and calcein acetoxymethyl ester/propidium iodide staining were used to detect the effect of Rb3 on the viability of hPDLSCs cells. In vitro cell experiments were divided into control group, 10 μg/mL lipopolysaccharides (LPS) group, 10 μg/mL LPS+100 μmol/L Rb3 group and 10 μg/mL LPS+200 μmol/L Rb3 group. Alkaline phosphatase (ALP) staining was used to detect the ALP activity of hPDLSCs in each group after osteogenesis induction. The expression of hPDLSCs interleukin-6 (IL-6), interleukin-8 (IL-8), runt-related transcription factor 2 (RUNX2) and transforming growth factor-β (TGF-β)genes in each group after osteogenesis was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) method. Western blot was used to detect the protein expression of hPDLSCs phosphorrylated extracellular signal-regulated kinase (p-ERK) in each group. Sprague-Dawley rats were randomly divided into the control group, ligation group and ligation+Rb3 group. The left molar-maxillary tissue was subjected to micro-computed tomography (micro-CT) scanning. After the scanning, the left molar-maxilla was made into periodontal tissue sections. Hematoxylin-eosin (HE) staining was used to detect the infiltration and loss of adhesion of inflammatory cells. Masson staining was used to detect the destruction of gingival collagen fibers. Immunofluorescence staining was used to detect the protein expression of RUNX2 and p-ERK. The expression of TGF-β in rat gingival tissue was detected by qRT-PCR. The protein expression of IL-6 in peripheral serum of rats was detected by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to detect the proportion of Treg cells in rat heart blood. The experimental data were statistically analyzed by Graph Pad Prism10.1.2 software.

Rb3 had no effect on the cell activity of hPDLSCs. The results of qRT-PCR and ALP staining showed that Rb3 could inhibit the gene expression of IL-6 and IL-8 in inflammatory hPDLSCs, promote TGF-β gene and promote the osteogenic differentiation of inflammatory hPDLSCs. Western blot showed that Rb3 inhibited the protein expression of inflammatory hPDLSCs p-ERK. The results from micro-CT, Masson staining, and HE staining demonstrated that Rb3 promotes alveolar bone formation in rats with periodontitis, while simultaneously inhibiting the destruction of periodontal fibrous tissue, reducing attachment loss, and suppressing inflammatory cell infiltration. The results of flow cytometry showed that Rb3 could promote the differentiation of Treg cells in peripheral blood of periodontitis rats. The results of ELISA and qRT-PCR showed that Rb3 could inhibit the protein expression of IL-6 and promote the gene expression of TGF-β in periodontitis rats. Immunofluorescence results showed that Rb3 could promote the protein expression of RUNX2 and inhibit the protein expression of p-ERK in periodontitis rats.

Rb3 can reduce the inflammatory reaction of periodontal tissues in periodontitis rats, and promote the osteogenic differentiation of hPDLSCs by regulating p-ERK pathways.

Periodontitis (PDS) is one of the most common and crippling systemic diseases. It is a chronic inflammatory condition that leads to the loss of periodontal attachment, resulting in tooth loss. In addition to its effects on oral health and nutrition, PDS is closely linked to other systemic conditions such as diabetes mellitus (DM), cardiovascular diseases (CVD), and rheumatoid arthritis (RA). The active role of inflammation and oxidation in systemic health, as well as their relationship with periodontal therapy, has been investigated. This review explores the evidence on how periodontal therapy and dietary lifestyle can help reduce chronic inflammation, limit oxidation, and prevent related pathologies. Nonsurgical periodontal therapy (NSPT) and nutrition have been extensively discussed as potential contributors to positive clinical outcomes by resolving inflammatory pathogenic pathways. NSPT, foods, and dietary supplements represent therapeutic strategies that address the underlying mechanisms of chronic inflammation and oxidation at various stages. A key finding from this review is that periodontal treatment, in conjunction with nutritional counseling, can improve clinical outcomes in PDS, DM, CVD, and RA. However, for NSPT, nutrition, and dietary composition to be effective, they should be integrated into a sustainable, long-term lifestyle.

Periodontal disease is a chronic inflammatory condition that destroys the tooth-supporting structures due to the host's immune response to microbial biofilms. Traditional periodontal treatments, such as scaling and root planing, pharmacological interventions, and surgical procedures, have significant limitations, including difficulty accessing deep periodontal pockets, biofilm recolonization, and the development of antibiotic resistance. In light of these challenges, natural bioactive compounds derived from plants, herbs, and other natural sources offer a promising alternative due to their anti-inflammatory, antioxidant, antimicrobial, and tissue-regenerative properties. This review focuses on the molecular mechanisms through which bioactive compounds, such as curcumin, resveratrol, epigallocatechin gallate (EGCG), baicalin, carvacrol, berberine, essential oils, and Gum Arabic, exert therapeutic effects in periodontal disease. Bioactive compounds inhibit critical inflammatory pathways like NF-κB, JAK/STAT, and MAPK while activating protective pathways such as Nrf2/ARE, reducing cytokine production and oxidative stress. They also inhibit the activity of matrix metalloproteinases (MMPs), preventing tissue degradation and promoting healing. In addition, these compounds have demonstrated the potential to disrupt bacterial biofilms by interfering with quorum sensing, targeting bacterial cell membranes, and enhancing antibiotic efficacy.Bioactive compounds also modulate the immune system by shifting the balance from pro-inflammatory to anti-inflammatory responses and promoting efferocytosis, which helps resolve inflammation and supports tissue regeneration. However, despite the promising potential of these compounds, challenges related to their poor bioavailability, stability in the oral cavity, and the absence of large-scale clinical trials need to be addressed. Future strategies should prioritize the development of advanced delivery systems like nanoparticles and hydrogels to enhance bioavailability and sustain release, alongside long-term studies to assess the effects of these compounds in human populations. Furthermore, combining bioactive compounds with traditional treatments could provide synergistic benefits in managing periodontal disease. This review aims to explore the therapeutic potential of natural bioactive compounds in managing periodontal disease, emphasizing their molecular mechanisms of action and offering insights into their integration with conventional therapies for a more comprehensive approach to periodontal health.

Diabetic periodontitis (DP) is a commonly co-occurring complication in diabetes patients characterized by advanced gum disease and bone resorption. Conventional treatment modalities often fail to adequately address the underlying biological disruptions caused by diabetes. The use of traditional medicinal formulas Kouqiangjie Formula (KQJF) potentially offers novel therapeutic approaches for DP, but its detailed regulatory mechanisms remain unclear.

This study aims to investigate the impacts of KQJF on osteoblastic activity and inflammatory responses in a rat model and in vitro pre-osteoblast cultures under conditions mimicking DP, focusing on the involvement of the miR-29a-3p-Dkk-1/Wnt/β-catenin signaling pathway.

Using network pharmacological analysis, micro-CT, histological staining, and an array of molecular biology methodologies including Western blotting, RT-qPCR, and immunofluorescence, we investigated the systemic and cellular responses to KQJF treatment. Both in vivo (rat model) and in vitro (MC3T3-E1 pre-osteoblasts) models subjected to high glucose and lipopolysaccharide (HG + LPS) stress were used to simulate DP conditions.

Network pharmacological analyses, incorporating protein-protein interactions and pathway enrichment, disclosed that KQJF interacts with pathways crucial for inflammation and bone metabolism. Experimentally, KQJF significantly preserved alveolar bone architecture, reduced osteoclast activity, and dampened inflammatory cytokine production in DP rats. In pre-osteoblasts, KQJF enhanced cell viability, promoted cell cycle progression, and decreased apoptosis. At the molecular level, KQJF treatment upregulated miR-29a-3p and downregulated Dkk-1, thereby activating the Wnt/β-catenin pathway. The interventional studies with miR-29a-3p antagonists and Dkk-1 knockdown further confirmed the regulatory role of the miR-29a-3p/Dkk-1 axis in mediating the effects of KQJF.

KQJF mitigates the deleterious effects of DP by enhancing osteoblastic activity and reducing inflammatory responses, predominantly through the modulation of the miR-29a-3p-Dkk-1/Wnt/β-catenin signaling pathway. These discoveries underscore the therapeutic promise of KQJF in managing bone and inflammatory complications of DP, offering insights into its mechanism, and supporting its use in clinical settings.

Pulmonary fibrosis significantly contributes to the pathogenesis of acute respiratory distress syndrome (ARDS), markedly increasing patient mortality. Despite the established anti-fibrotic effects of mesenchymal stem cells (MSCs), numerous challenges hinder their clinical application. A recent study demonstrated that microvesicles (MVs) from MSCs (MSC-MVs) could attenuate ARDS-related pulmonary fibrosis and enhance lung function via hepatocyte growth factor mRNA transcription. This discovery presents a promising strategy for managing ARDS-associated pulmonary fibrosis. This article initially examines the safety and efficacy of MSCs from both basic science and clinical perspectives, subsequently exploring the potential and obstacles of employing MSC-MVs as a novel therapeutic approach. Additionally, it provides perspectives on future research into the application of MSC-MVs in ARDS-associated pulmonary fibrosis.

Tissue engineering envisions functional substitute creation for damaged tissues. Insulin-like growth factor-1 (IGF-1) plays roles in bone marrow mesenchymal stem cell (BMSC) osteogenic differentiation (OD), and we investigated its specific mechanism. BMSCs were cultured and OD was induced. Surface antigens (CD105, CD90, CD44, CD45, CD34) were identified by flow cytometry. Adipogenic, chondrogenic, and osteogenic differentiation abilities of BMSCs were observed. BMSCs were cultured in osteogenic medium containing 80 ng/mL IGF-1 for 3 weeks. Alkaline phosphatase activity, calcification level, osteogenic factor (runt related protein 2 [RUNX2], osteocalcin [OCN], osterix [OSX]), total (t-) ERK1/2 and phosphorylated- (p-) ERK1/2 levels, and SRY-related high-mobility-group box 4 (SOX4) levels were assessed by alkaline phosphatase staining and Alizarin Red staining, Western blot, and reverse transcription-quantitative polymerase chain reaction. The mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) pathway inhibitor (PD98059) was used to inhibit the MAPK/ERK pathway in IGF-1-treated BMSCs. Small interfering-SOX4 was transfected into BMSCs to down-regulate SOX4. IGF-1 increased alkaline phosphatase activity, cell calcification, and osteogenic factor (RUNX2, OCN, OSX) levels in BMSCs, indicating that IGF-1 induced rat BMSC OD. SOX4, and p-ERK1/2 and t-ERK1/2 levels were elevated in IGF-1-induced BMSCs, which were annulled by PD98059. PD98059 partly averted IGF-1-induced rat BMSC OD. SOX4 levels, alkaline phosphatase activity, cell calcification, and osteogenic factor (RUNX2, OCN, OSX) levels were reduced after SOX4 down-regulation, showing that downregulation of SOX4 averted the effect of IGF-1 on inducing rat BMSC OD. IGF-1 induced rat BMSC OD by stimulating SOX4 via the MAPK/ERK pathway.

To investigate the protective effect of resveratrol on intestinal barrier in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse models and its mechanism for regulating TLR4/MyD88/NF-κB signaling to protect dopaminergic neurons.

Fifty-two C57BL/6J mice were randomized into control group (n= 12), MPTP group (n=14), MPTP + resveratrol (30 mg/kg) group (n=13), and MPTP + resveratrol (90 mg/kg) group (n=13), and mouse models were established by intraperitoneal MPTP (30 mg/kg) injection for 7 days in the latter 3 groups. Behavioral tests were conducted to evaluate the effect of resveratrol on motor symptoms of the mice. Western blotting was used to detect the expression of TH, α-syn, ZO-1, Claudin-1, TLR4, MyD88, and NF-κB in the brain tissues of the mice. Immunohistochemistry, immunofluorescence, ELISA and transmission electron microscopy were used to verify the effect of resveratrol for suppressing inflammation and protecting the intestinal barrier.

Compared with those in the normal control group, the mice in MPTP group showed significant changes in motor function, number of dopaminergic neurons, neuroinflammation, levels of LPS and LBP, and expressions of tight junction proteins in the intestinal barrier. Resveratrol treatment significantly improved motor function of the PD mice (P < 0.01), increased the number of neurons and TH protein expression (P < 0.05), down-regulated the expressions of GFAP, Iba-1, and TLR4, lowered fecal and plasma levels of LPS and LBP (P < 0.05), restored the expression levels of ZO-1 and Claudin-1 (P < 0.01), and down-regulated the expressions of TLR4, MyD88, and NF-κB in the colon tissue (P < 0.05). The mice with resveratrol treatment at 30 mg/kg showed normal morphology of the tight junction complex with neatly and tightly arranged intestinal villi.

Resveratrol repairs the intestinal barrier by inhibiting TLR4/MyD88/NF-κB signaling pathway-mediated inflammatory response, thereby improving motor function and neuropathy in mouse models of MPTP-induced PD.

Periodontitis (PD) is a chronic inflammatory disease of the periodontium characterized by the formation of gingival pockets and gingival recession. The local inflammatory environment can lead to the destruction of the extracellular matrix and subsequent bone loss. The pathophysiology of PD involves interactions between genetic predisposition, lifestyle, environmental factors, the oral microbiota condition, systemic health disorders, innate and adaptive immune responses, and various host defenses. The review highlighted the importance of the oral cavity condition in systemic health. Thus, a correlation between harmful oral microbiota and cardiovascular disease (CVD)/diabetes/ arthritis, etc, progressions through inflammation and bacterial translocation was highlighted. Antecedents increase an individual's risk of developing PD, trigger initiate microbe-host immunologic responses, and mediators sustain inflammatory interactions. Generally, this review explores the antecedents, triggers, and mediators along the pathophysiological continuum of PD. An analysis of modern approaches to treating periodontitis, including antibiotics for systemic and local use, was carried out. The potential role of natural ingredients such as herbal extracts, phytoconstituents, propolis, and probiotics in preventing and treating PD was highlighted.

Resveratrol is a stilbenoid from red grapes that possesses a strong antioxidant activity. Resveratrol has been shown to have anticancer activity, making it a promising drug for the treatment and prevention of numerous cancers. Several in vitro and in vivo investigations have validated resveratrol's anticancer capabilities, demonstrating its ability to block all steps of carcinogenesis (such as initiation, promotion, and progression). Additionally, resveratrol has been found to have auxiliary pharmacological effects such as anti-inflammatory, cardioprotective, and neuroprotective activity. Despite its pharmacological properties, several obstacles, such as resveratrol's poor solubility and bioavailability, as well as its adverse effects, continue to be key obstacles to drug development. This review critically evaluates the clinical trials to date and aims to develop a framework to develop resveratrol into a clinically viable drug.