Search Results (10,761)

Type 2 diabetes mellitus (T2DM) is a global health challenge characterized by insulin resistance and pancreatic β-cell dysfunction. While human umbilical cord mesenchymal stem cells (HUCMSCs) show therapeutic potential, their efficacy can be limited by the harsh in vivo microenvironment. 20(R)-Rg3, a ginsenoside with anti-inflammatory and antioxidant properties, may enhance HUCMSCs’ function, but the combined effect and mechanism of this “cell-molecule” strategy remain unclear. This study aimed to investigate the therapeutic effects and underlying mechanisms of a combination therapy using 20(R)-Rg3 and HUCMSCs in a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM mouse model. Diabetic mice were treated with PBS, HUCMSCs alone, or HUCMSCs pre-treated with 20(R)-Rg3. Fasting blood glucose and body weight were monitored. Insulin resistance was assessed via oral glucose tolerance tests (OGTTs) and intraperitoneal insulin tolerance tests (IPITTs). Serum biochemical parameters (lipids, liver and kidney function, insulin, C-peptide) were analyzed. Histopathological examination (H&E, PAS) of the liver, kidney, and pancreas was performed, alongside immunofluorescence for islet hormones. Transcriptomic analysis (RNA-seq) was conducted on HUCMSCs with or without 20(R)-Rg3 pretreatment to elucidate potential signaling pathways. Results demonstrated that the combination significantly reduced hyperglycemia and improved insulin sensitivity more effectively than HUCMSCs alone. It also ameliorated dyslipidemia, enhanced liver and kidney function, promoted glycogen synthesis, and facilitated pancreatic islet “regeneration”. Transcriptomic analysis indicated that the synergistic effect is primarily mediated through activation of the PI3K/Akt signaling pathway. These findings suggest that 20(R)-Rg3 potentiates the therapeutic efficacy of HUCMSCs, providing a promising combinatorial strategy for T2DM treatment. Full article

UVB radiation present in sunlight is the main pro-oxidative and pro-inflammatory factor that reaches human skin cells, including keratinocytes. Therefore, protective compounds eliminating the negative impact of UVB radiation are constantly being sought. This study aimed to estimate the effect of the lipid extract of microalgae Nannochloropsis oceanica (N.o.) on UVB-irradiated keratinocytes. A proteomic approach was used to estimate the proteomic profile of in vitro-treated keratinocytes. The results indicated 270 proteins had significantly altered expression in UVB-irradiated keratinocytes, while the treatment of cells with N.o. extract partially restored the levels of these proteins. Moreover, changes in protein structure resulting from the binding of glutathione (GSH) and thioredoxin (Trx) were also observed. Most of the GSH-modified proteins were involved in GSH or prostaglandin metabolism, while Trx-modified proteins were molecules related to Trx metabolism, as well as antioxidant and anti-inflammatory signaling. The treatment of cells with N.o. extract contributed to reversing the changes in the level of modification in individual proteins. It can be suggested that the lipid components of the microalgae N.o. extract protect keratinocytes against changes in metabolism induced by UVB radiation, modulating the antioxidant and pro-inflammatory responses of cells at the GSH and Trx-based signaling levels. Full article

Background: Psoriasis is a chronic inflammatory skin disease driven by keratinocyte hyperproliferation and immune dysregulation. Despite the availability of biologics and immunosuppressants, recurrence and adverse effects remain major limitations. Myricetin (Myr), a natural flavonoid with well-documented anti-inflammatory and immunomodulatory properties, has shown promise in inflammatory disorders; however, its efficacy and mechanisms in psoriasis have not been fully elucidated. Methods: The therapeutic effects of topical Myr (0.5–2%) were evaluated in an imiquimod (IMQ)-induced psoriatic mouse model. Network pharmacology and molecular docking were employed to predict potential targets, followed by validation using histological analysis, cytokine profiling, qPCR, and Western blotting. Results: Network analysis identified 52 overlapping targets between Myr and psoriasis, including TNF, PTGS2, MMP9, and EGFR, with enrichment in TNF, IL-17, and PI3K/AKT signaling pathways. Myr treatment significantly alleviated IMQ-induced erythema, scaling, and epidermal thickening, improved skin-barrier function, and reduced the expression of IL-6, IL-17A, and TNF-α. Molecular docking showed strong binding affinities of Myr with TNF, PTGS2, MMP9, and EGFR. Western blotting confirmed that Myr suppressed EGFR and AKT phosphorylation and downregulated Mmp9, Ptgs2, and Tnf expression. Conclusions: Myr exerts multi-target anti-psoriatic effects by inhibiting the EGFR/AKT axis and inflammatory mediators, highlighting its potential as a safe and effective natural therapeutic agent for psoriasis. Full article

Background/Objectives: Parkinson’s disease (PD) is the second most common neurodegenerative disease (NDD), marked by the progressive loss of dopaminergic neurons in the substantia nigra that causes motor dysfunction. Growing evidence indicates that neuroinflammation plays a crucial role in the onset and progression of PD, though the exact mechanisms are still unclear. In this study, we examined the anti-inflammatory and neuroprotective effects of 4-[3-oxo-3-(2-trifluoromethyl-phenyl)-propyl]-morpholinium chloride (OTPM), a fluoxetine derivative and selective serotonin reuptake inhibitor, in both lipopolysaccharide (LPS)-stimulated BV-2 microglial cells and an MPTP-induced mouse model of PD. Methods: C57BL/6 mice were orally administered OTPM (10 mg/kg b.w.) for 7 days and intraperitoneally injected with MPTP (20 mg/kg b.w.) for one day, with four injections at 2 h intervals. Bradykinesia was assessed using the Y-maze and Pole tests. Protein and mRNA levels were examined in vitro and in vivo using Western blotting and RT-PCR. Immunofluorescence was used to assess microglial and astrocyte activation. Results: In vitro, OTPM significantly decreased nitric oxide (NO) production (p < 0.001) and suppressed the protein and mRNA expression of iNOS (p < 0.001), COX-2 (p < 0.001), and pro-inflammatory cytokines, including IL-β (p < 0.001), IL-6 (p < 0.001), and TNF-α (p < 0.01), in LPS-activated BV-2 microglia. Further mechanistic studies showed that OTPM inhibited NF-κB phosphorylation and blocked its nuclear translocation, thereby reducing inflammatory signaling. In vivo, treatment with OTPM (10 mg/kg for 7 days) significantly reduced the MPTP-induced activation of microglia (MAC-1) and astroglia (GFAP) in the brain and improved behavioral deficits associated with PD, as assessed in the Y-maze and pole tests. Conclusions: Overall, these results reveal that OTPM has strong anti-neuroinflammatory and neuroprotective properties, suggesting its potential as a new therapeutic candidate for PD and other disorders associated with neuroinflammation. Full article

Background: Numerous degenerative diseases are brought on by inflammation and oxidative stress. Metabolites from plants contain anti-inflammatory and antioxidant properties. Indigenous and understudied, Thottea sivarajanii is a significant ethnobotanical herb. It is native to the Western Ghats and belongs to the Aristolochiaceae family. Objectives: The current study investigated the antioxidant and anti-inflammatory properties of T. sivarajanii leaf methanol extract (TSL) and the insights provided by phytochemical analysis. Methods: The HRLC–MS/MS (Q-TOF) study is used for the phytochemical analysis. The antioxidant efficacy is evaluated in terms of DPPH and ABTS radical scavenging, and reducing power (FRAP assay). In vitro anti-inflammatory efficacy was evaluated on RAW 264.7 cells challenged with lipopolysaccharide (LPS). Result: The HRLC–MS/MS (Q-TOF) study indicated the presence of bioactive molecules such as ursolic acid, Daidzein 4’,7-diglucoside, Calophyllin B, and Berbamine, etc. The results showed in vitro antioxidant capacity in DPPH, and ABTS, radical scavenging, and ferric-reducing activities with respective IC₅₀ and EC₅₀ values of 184.5 ± 2.4, 24.15 ± 0.13, and 4.94 ± 0.32 µg/mL, respectively. LPS significantly stimulated the production of IL-1β, IL-6, and TNF-α in RAW 264.7 cells (p < 0.001). Treatment with TSL reduced levels of IL-1β and IL-6 from 776.1 ± 11.4 and 1678.1 ± 12.4 to 195.4 ± 9.2 and 465.4 ± 11.8 pg/mg protein. It also reduced NO levels from 91.4 ± 1.3 to 30.8 ± 1.7 µM/mg protein while reducing TNF-α levels from 2041.2 ± 15.1 to 1037.5 ± 15.4 pg/mg protein. Conclusions: This work contributes to the growing evidence supporting the pharmacological importance of the underexplored Thottea sivarajanii, highlighting this species as a promising candidate for natural antioxidant and anti-inflammatory agents. Full article

Introduction/Objective: Dental extractions are among the most common oral surgical procedures worldwide, with postoperative pain representing a significant clinical concern. Cannabidiol (CBD), a non-intoxicating phytocannabinoid with analgesic and anti-inflammatory properties, has recently gained attention as a potential adjunct for managing acute dental pain. To explore its clinical utility to generate preliminary feasibility, we conducted the Simple Tooth Extraction with Analgesic Phytocannabinoid (SWAP) pilot trial to evaluate the preliminary efficacy and safety of oral CBD at two concentrations (17 mg/mL and 37 mg/mL) compared with placebo and standard ibuprofen/acetaminophen therapy following simple extractions. Materials and Methods: Eight adults were randomized equally to four arms (n = 2 per arm) CBD 17 mg/mL, CBD 37 mg/mL, placebo, or treatment-as-usual (TAU; ibuprofen/acetaminophen). CBD/placebo groups received 0.5 mL every 4–6 h as needed for 7 days, while TAU followed the non-opioid regimen. The primary endpoint was pain intensity (0–10 Numeric Rating Scale) captured via ecological momentary assessment (EMA) over 72 h. Secondary endpoints included worst pain, rescue medication use, adherence, tolerability, and qualitative feedback. Results: All participants completed follow-up with >75% EMA adherence. Because of the very small sample (n = 8), results are descriptive only. Baseline imbalance was observed; the CBD 17 mg/mL group reported substantially lower pre-extraction pain than other groups, limiting interpretability. Pain trajectories diverged by group: CBD 37 mg/mL showed the lowest ratings, paralleling TAU; CBD 17 mg/mL and placebo showed limited efficacy. Conclusions: This pilot suggests that higher-concentration CBD (37 mg/mL) may provide analgesia comparable to standard non-opioid therapy. Within this small feasibility cohort, higher-concentration CBD (37 mg/mL) appeared to produce pain patterns qualitatively similar to standard non-opioid therapy. Findings should be interpreted as exploratory only. A fully powered randomized trial incorporating biomarker endpoints and a taste-matched placebo is warranted. Full article

Background: Asthma exhibits marked heterogeneity both clinically and at the molecular phenotypic level, requiring specifically targeted treatments to block the key pathways of the disease. Monoclonal-antibody-based biologics targeted at critical inflammatory pathways of T2 inflammation such as IL-5, IL-5R, IL-4, and IL-13 are increasingly regarded as effective treatments for severe refractory eosinophilic asthma. Methods: This review provides an update on the potential of straightforward and reproducible biomarkers to aid in the selection of the biologic-based therapy most likely to be effective in patients with severe or refractory eosinophilic asthma based on English-language original articles in PubMed or MedLine. Results: Monoclonal-antibody-based biologic therapies have revolutionised severe asthma management, enabling reductions in symptoms that include exacerbations, discontinuation of oral corticosteroids, improved lung function, and enhanced quality of life. Significant clinical effects with anti-IL-5 or -IL-4/13 monoclonal antibodies are more likely to be seen when simple predictive biomarkers such as serum periostin, fractional exhaled nitric oxide (FENO), or blood eosinophil counts are used to aid in the identification of those patients with severe refractory eosinophilic asthma who are most likely to benefit from biologic therapies. Conclusions: Biologic-based therapy aimed at T2 inflammation benefits patients with severe eosinophilic asthma, particularly when guided by biomarkers that do not require direct sampling of the airways to target therapy, who are most likely to benefit from these treatments, with good safety profiles for these therapies. Full article

Calcium pyrophosphate deposition (CPPD) disease is a consequence of the immune response to the pathological accumulation of calcium pyrophosphate (CPP) crystals within joints. This clinically heterogeneous condition can cause significant disability, yet its management remains poorly defined. New discoveries are reshaping the therapeutic landscape beyond conventional anti-inflammatory agents—which remain the cornerstone of care—justifying this review on current standard of care and treatment advances in CPPD disease. We first address the two theoretical management goals, namely inflammation control and crystal dissolution—with attempts to address the latter having failed thus far. We then summarize the evidence supporting conventional anti-inflammatory treatments and review insights into the pathophysiology of CPPD disease, which are driving the development of novel therapeutic strategies. These include the current use of biologics (IL-1 and IL-6 inhibitors) to control inflammation and highlight the need to explore new pathways to inhibit crystal formation (e.g., selective NPP1 blockers). We present the treatments in the development pipeline for CPPD disease (including JAK inhibitors), and the therapies currently undergoing clinical trials in gout for which findings could be extended to CPPD disease given their shared pathophysiology (e.g., NLRP3 inhibitors). To support and improve research on CPPD disease treatments, clinical trial design needs to be standardized, incorporating the recent ACR/EULAR classification criteria for accurate diagnosis, careful phenotypic stratification to ensure homogeneous patient groups (although this point requires consensus), and validated core outcome domains currently being developed by the OMERACT. Full article

Oral and oropharyngeal squamous cell carcinomas (OSCC and OPSCC), two major sub-types of Head and Neck cancer, remain associated with significant morbidity and exhibit poor prognosis, with limited response to conventional therapies in advanced stages. Recent therapeutic strategies have increasingly focused on molecular targets involved in tumor proliferation, angiogenesis, and immune evasion. This overview provides a concise synthesis of targeted therapies under investigation or already in clinical use, including monoclonal antibodies against epidermal growth factor receptor (EGFR) (e.g., cetuximab) and immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab), as well as inhibitors of programmed cell death protein 1 (PD-1) and its ligand (PD-L1) or agents targeting angiogenic and intracellular signaling pathways such as VEGF and mTOR. Alongside these novel agents, growing interest surrounds the repurposing of established pharmacological agents which appear to modulate tumor-related inflammation, metabolic dysregulation, and epithelial-to-mesenchymal transition. Metformin and statins, for instance, have demonstrated anti-proliferative and pro-apoptotic effects in preclinical OSCC models. Notably, recent evidence suggests that regular use of nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, may improve survival specifically in patients with PIK3CA-altered Head and Neck tumors, potentially through modulation of the COX-2/PGE2 axis. Although prospective evidence remains limited and somewhat heterogeneous, existing preclinical and observational studies suggest that these agents may improve survival and reduce treatment-related toxicity, further pointing to the relevance of molecular stratification in guiding future repurposing strategies. This article aims to map the current therapeutic landscape, highlighting both established molecular targets and emerging repositioned drugs in the management of OSCC and OPSCC. Full article

Background/Objectives: Wound management remains a clinical challenge, particularly in chronic and refractory conditions. Ozone, due to its antimicrobial, anti-inflammatory, and tissue-regenerative properties, has emerged as promising adjuvant therapy. This integrative re-view aimed to critically analyze the therapeutic effects, routes of administration, benefits, and limitations of ozone in wound treatment. Methods: The review followed the Joanna Briggs In-stitute methodology and the PRISMA 2020 guidelines. Studies were identified through compre-hensive search in the SCOPUS, CINAHL Ultimate, MEDLINE Ultimate, and MedicLatina data-bases, with no time restrictions. Inclusion criteria encompassed primary studies involving adults (≥18 years) with wounds treated with ozone. The methodological quality of the selected studies was assessed using the tools recommended by JBI. Results: Nine reports published between 2019 and 2025 met the inclusion criteria. The findings consistently demonstrated clinical benefits of ozone therapy, including accelerated wound healing, pain reduction, and infection control. The forms of application included ozonated water, ozonated olive oil, and gaseous ozone. However, heterogeneity was observed in ozone concentration, frequency, and treatment duration. The methodological quality of the included studies ranged from moderate to high. Conclusions: The available evidence indicates that ozone may represent promising adjuvant treatment for certain types of wounds; however, the quality and independence of the existing studies are limited, and the lack of standardized protocols as well as methodological variability restrict the generalizability of the findings. Therefore, more robust clinical trials are needed to strengthen the evidence base and support its clinical implementation. Full article

Chronic pain is a pervasive global health issue that significantly impairs quality of life and remains inadequately managed by current therapeutic options. Traditional pharmacological treatments often offer limited relief and are associated with significant side effects, highlighting the urgent need for safer and more effective alternatives. Among emerging strategies, mesenchymal stem cell (MSC)-derived secretome, an acellular product composed of bioactive molecules such as cytokines, growth factors and extracellular vesicles, has gained increasing attention for its potent anti-inflammatory, neuroprotective and immunomodulatory properties. Unlike whole-cell therapies, secretome-based interventions offer advantages, including lower immunogenicity, higher safety and easier standardization and storage. Preclinical studies demonstrated that MSC secretome effectively alleviates pain-like behavior across various models of neuropathic, inflammatory and degenerative pain, primarily through neuroimmune modulation and glial cell reprogramming. In vitro experiments confirm its role in promoting neuronal survival, regulating opioid receptor expression and modulating (neuro)inflammatory responses. Preliminary clinical evidence supports its analgesic efficacy in conditions such as osteoarthritis, chronic low back pain and post-surgical pain, with a favorable safety profile and promising therapeutic outcomes. However, challenges remain, including variabilities in secretome composition, lack of standardized production protocols and absence of large-scale clinical trials. Despite these limitations, MSC secretome therapy represents a transformative approach in pain medicine. Continued research efforts are essential to optimize formulation, dosing and delivery strategies, as well as to clarify the regulatory landscape. With further validation, the MSC secretome could emerge as a novel, scalable and clinically viable solution for the management of chronic pain, bridging critical gaps in current treatment paradigms. Full article

Background: Infectious bronchitis virus (IBV) poses a significant threat to poultry health, and exploring effective antiviral agents is of considerable importance. This study aimed to investigate the antiviral activity of baicalin against IBV and its underlying immunomodulatory mechanisms. Methods: The antiviral effect of baicalin was evaluated in chicken embryo kidney cells using various treatment schedules. Viral replication was assessed through nucleocapsid protein expression and viral titers. Mechanistic studies involved analysis of key signaling pathways, IRF3 knockdown experiments, and proteasomal degradation assays. Results: Baicalin (20 µg/mL) significantly inhibited IBV replication, with optimal efficacy observed when administered at 2 h post-infection. The compound demonstrated time-dependent regulation of antiviral and inflammatory pathways, enhancing the MDA5-MAVS-STAT1 axis and IFN-β signaling at late infection stage while showing biphasic modulation of NF-κB pathway. IRF3 was identified as essential for both anti-inflammatory and antiviral effects. Baicalin enhanced IκBα stability by inhibiting its proteasomal degradation. Conclusions: Baicalin suppresses IBV replication through coordinated enhancement of type I interferon response and temporal regulation of NF-κB pathway, with IRF3 serving as a key regulatory molecule. These findings provide mechanistic support for baicalin’s potential as an anti-IBV therapeutic agent. Full article

Background/Objectives: Sodium polynucleotide (PN) injection has recently been considered as a potential intra-articular therapy for knee osteoarthritis (OA); however, there is limited evidence regarding the long-term consistency of repeated PN cycles. To evaluate the clinical effectiveness of repeated intra-articular PN injections after the initial 6 months of therapy in patients with knee OA, using nationwide claims data. Methods: We conducted a retrospective cohort study using data from the Korea Health Insurance Review and Assessment Service collected between 2020 and 2023. Patients who received PN injections for knee OA were classified into two groups based on the treatment cycle: Group 1 (single cycle) and Group 2 (re-administration). Surgical outcomes and symptomatic indicators, including pain-related hospital visits, arthrocentesis, nonsteroidal anti-inflammatory drug prescriptions, and antidepressant prescriptions, were analyzed. Results: A total of 142,322 patients were included in this study. Readministration of PN was associated with significantly lower rates of total knee arthroplasty (2.31% vs. 4.92%, p < 0.0001) and delayed time to surgery (252.0 vs. 176.6 days, p < 0.0001). Similar trends were observed for hemiarthroplasty, with a lower incidence (0.28% vs. 0.55%, p < 0.0001) and longer time to surgery (240.7 vs. 162.2 days, p < 0.0001) in the readministration group. All groups showed a timewise reduction in pain-related hospital visits and instances of arthrocentesis. Safety outcomes were not assessed in this claim-based dataset. Conclusions: Repeated cycles of PN injections provide sustained clinical benefits and may effectively delay the need for surgical intervention in patients with knee OA, supporting their possible role as a long-term conservative treatment option. Radiographic severity and safety outcomes were unavailable in this claims dataset, limiting the adjustment for baseline OA severity and restricting causal interpretation. Full article

Arthrospira platensis (commonly known as Spirulina platensis) is a blue-green microalga increasingly used in skincare due to its antioxidant and dermo-protective properties, primarily attributed to components such as phycocyanin and carotenoids. However, the intense blue color of phycocyanin can limit its cosmetic appeal. In this study, we investigated the antioxidant, anti-inflammatory, skin lightening and photoprotective activity of Elixspir^®, a novel light-colored aqueous extract of Spirulina, using both 2D and 3D skin cell models. We demonstrated that Elixspir^® exerts strong antioxidant and cytoprotective effects by reducing intracellular ROS levels and modulating cellular thiol redox state. Its anti-pigmentation potential was supported by tyrosinase inhibition, while anti-inflammatory activity was principally due to ability to reduce PGE2 levels. Finally, we demonstrated an unprecedented photoprotective effect of Elixspir^®, highlighting its potential as a novel active ingredient for skin defense against environmental stressors. Overall, these results provide a molecular-level understanding of Elixspir^® multifunctional bioactivity and support its application as a skin-lightening, anti-inflammatory, antioxidant, and photoprotective ingredient in the formulation of innovative skin anti-aging treatments. Full article

Zoledronic acid (ZA), a nitrogen-containing bisphosphonate, is widely used to treat osteoporosis and bone metastases. However, its clinical application is limited by adverse effects, notably bisphosphonate-related osteonecrosis of the jaw (BRONJ), which is associated with cytotoxicity in oral mucosal cells. Polydeoxyribonucleotide (PDRN), a salmon sperm-derived DNA polymer with regenerative and anti-inflammatory properties, has shown therapeutic potential in tissue repair; however, its ability to mitigate ZA-induced cytotoxicity remains poorly understood. Here, we investigated the molecular mechanisms of ZA-induced toxicity in HGF-1 cells, a human gingival fibroblast line, and evaluated the protective effects of PDRN. ZA treatment (50 µM, 48 h) significantly inhibited HGF-1 cell growth, accompanied by reduced phosphorylation of protein kinase B (PKB) and signal transducer and activator of transcription 3 (STAT-3), along with increased phosphorylation of TANK-binding kinase 1 (TBK1). TBK1 silencing restored cell growth under ZA exposure, whereas silencing PKB or STAT-3 further suppressed cell growth even without ZA. Co-treatment with PDRN (100 µg/mL) effectively prevented and reversed ZA-induced HGF-1 cytotoxicity. Mechanistically, PDRN inhibited ZA-induced TBK1 phosphorylation and partially restored PKB phosphorylation, though it did not reverse the reduction in p-STAT-3. Additionally, ZA significantly elevated intracellular reactive oxygen species (ROS) levels at 8 h, which were attenuated by PDRN. The antioxidant N-acetylcysteine (NAC) similarly reduced ZA-induced ROS and p-TBK1 levels and improved cell growth, although it had limited effects on p-PKB at 8 h. Importantly, delayed PDRN treatment following ZA exposure reversed ZA-induced cell growth inhibition and TBK1 activation in a dose- and time-dependent manner. In summary, these findings demonstrate that ZA suppresses HGF-1 cell growth through ROS production, TBK1 activation, and inhibition of PKB and STAT-3, whereas PDRN counteracts these effects primarily by suppressing TBK1 activation and oxidative stress. Full article