Search Results (11,058)

Background/Objectives: Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) is intended to restore reparative signaling in diabetic wounds, yet its efficacy and the contribution of delivery systems remain uncertain. This systematic review evaluated its preclinical efficacy, mechanistic responses, safety, risk of bias, certainty, and attribution of effects. Methods: Following PRISMA 2020 and an OSF-registered protocol, PubMed, Embase, Scopus, Web of Science, and ScienceDirect were searched from inception to 29 July 2026 for controlled in vivo diabetic wound studies. Compatible outcomes were pooled using random-effects models with restricted maximum-likelihood estimation and Hartung–Knapp adjustment. Non-poolable findings were synthesized using attribution-specific effect direction maps. Risk of bias and certainty were assessed with SYRCLE and preclinical GRADE, respectively. Results: Twenty-nine studies were included from 3844 records. For percentage wound closure at days 10–12, three studies comprising 113 animals yielded a favorable but imprecise pooled estimate (mean difference: 12.94 percentage points; 95% CI: −0.34 to 26.23; p = 0.052; I² = 54.6%). Two studies comprising 45 animals suggested a non-significant 4.28-day reduction in time to complete closure (95% CI: −27.98 to 19.42). In the exploratory effect direction synthesis, directly attributable macroscopic healing showed a favorable direction in 17 of 22 studies and was the only domain meeting the prespecified 70% concordance threshold; four of these studies had confirmed unit-of-analysis concerns, and other reparative domains were heterogeneous. Formulation-level comparisons met the same exploratory threshold across four reparative domains, but the isolated contribution of rhPDGF-BB could not be determined. Safety reporting was sparse. Certainty for the primary outcome was very low. Conclusions: Directly attributable comparisons showed a predominantly favorable study-level pattern for macroscopic wound healing in the exploratory synthesis, but the pooled effects were imprecise and inconclusive. Formulation-level comparisons suggested broader reparative activity, although the independent contribution of rhPDGF-BB could not be isolated. Better controlled and clinically representative studies are required before confident translation. Full article

Aging is a major risk factor for chronic diseases, driving an urgent need for effective geroprotectors. Repurposing psychotropic agents offers an efficient strategy to accelerate anti-aging therapeutics development. In this study, we investigated the effects of pimozide (a diphenylbutylpiperidine-class antipsychotic) on aging in Caenorhabditis elegans and elucidated the underlying mechanisms. The results demonstrated that 0.1 μM pimozide significantly extends nematode lifespan, increasing mean, median, and maximum lifespans by 44.3%, 50.0%, and 39.8%, respectively. Furthermore, pimozide improves healthspan, as evidenced by reduced age-related lipofuscin accumulation, preserved locomotor function, and decreased paralysis incidence. Moreover, pimozide-treated nematodes showed enhanced resistance to heat, ultraviolet and oxidative stress, concomitant with reduced endogenous reactive oxygen species levels. Transcriptomic profiling and biochemical validation reveal that pimozide markedly upregulates collagen gene expression and increases hydroxyproline content, indicating enhanced collagen synthesis. Mechanistically, pimozide promotes the nuclear localization of SKN-1, and its beneficial effects on lifespan extension and collagen synthesis are SKN-1-dependent, as these effects are abolished in skn-1 mutants. Collectively, our findings demonstrate that pimozide promotes longevity and healthspan by activating skn-1, which is accompanied by enhanced collagen synthesis, providing a preclinical proof of concept for its potential repurposing as a geroprotector. Full article

Scutellaria barbata D. Don (SBD) has been widely investigated for antitumor activity, but its immune- and tumor microenvironment (TME)-related mechanisms remain fragmented. This study synthesized preclinical evidence on SBD and contextualized the findings using network pharmacology. A scoping review was conducted according to established scoping review methodology and PRISMA-ScR guidance. Preclinical in vitro and in vivo cancer studies published between January 2016 and December 2025 were searched in PubMed, Embase, CENTRAL, and OASIS. Network pharmacology analysis was performed using TCMSP, SwissTargetPrediction, ImmPort, GeneCards, STRING, Cytoscape, MCODE, DAVID, GO, and KEGG analyses. Fifty-six preclinical studies were included. SBD extracts, fractions, polysaccharides, diterpenoids, flavonoids, and isolated constituents suppressed cancer cell proliferation, induced cell-cycle arrest, promoted apoptosis and ferroptosis, modulated autophagy, induced endoplasmic reticulum stress-associated cell death, inhibited migration, invasion, angiogenesis, and metastasis, and enhanced chemosensitivity across diverse cancer models. Immune- and TME-related effects included activation of natural killer cells and CD8⁺ T cells, reduction in regulatory T cells, T helper 17 cells, myeloid-derived suppressor cells, and M2-like tumor-associated macrophage polarization, modulation of cytokine and inflammatory signaling, and regulation of epithelial–mesenchymal transition, matrix remodeling, angiogenesis, and metastatic niche formation. Network pharmacology identified 32 active candidate compounds, 408 predicted targets, and 152 immune/TME-overlapping targets. Protein–protein interaction and enrichment analyses highlighted AKT1, TNF, SRC, EGFR, and BCL2 as candidate hub targets and implicated PI3K-Akt, MAPK, Ras, EGFR tyrosine kinase inhibitor resistance, and proteoglycans in cancer. SBD-derived interventions showed antitumor, immunomodulatory, and TME-remodeling activities across diverse preclinical models. The integrated findings identify recurrent biological processes and candidate molecular targets, while differences in preparation, chemical characterization, dose, and experimental design limit direct comparison across studies. This framework supports further mechanistic, pharmacokinetic, and translational evaluation of chemically characterized SBD preparations and candidate compounds. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by epidermal barrier dysfunction, immune dysregulation, and increased oxidative stress. The current treatment strategies include topical corticosteroids, calcineurin inhibitors, and systemic immunomodulators. However, long-term use of steroids and other immunomodulators has unwanted side effects, and therefore recent interest has shifted towards complementary natural therapeutic approaches. Several studies indicate that natural plant-based antioxidants may help prevent AD. Specifically, a few studies demonstrated the significance of fat-soluble vitamins (A, D, E, and K) in controlling AD, owing to their strong roles in antioxidant defense, immune regulation, and maintenance of epidermal barrier integrity. In this review, we discussed recent evidence demonstrating the significant biological and therapeutic roles of fat-soluble vitamins in AD. We also discussed how vitamins A, D, E, and K may influence multiple mechanisms involved in AD pathogenesis and their potential as adjuvant therapy. Based on limited preclinical and clinical data, additional well-designed mechanistic and clinical trials are needed to establish their therapeutic efficacy in treating AD. Full article

Tumors of the spine and spinal cord, including primary and metastatic vertebral tumors, intramedullary gliomas, and refractory intradural lesions, are challenging to treat because curative local therapy is limited by the eloquent, nonregenerating neural tissue surrounding them. Oncolytic virotherapy may offer a rational alternative by combining tumor-selective oncolysis with the induction of systemic antitumor immunity, while sparing normal neural cells. This review summarizes the current field of oncolytic viruses, including adenovirus, herpes simplex virus, reovirus, and others, in the context of spinal and spinal cord tumors. Clinical data in the spine remain scarce; however, the rationale is based on histological evidence from sarcomas and other tumors, extensive glioma experience, including diffuse intrinsic pontine glioma, and preclinical activity in nerve sheath and meningioma models. We discuss the telomerase-specific oncolytic adenovirus OBP-301 and its derivatives, whose hTERT-driven replication provides histology-agnostic tumor selectivity, while sparing the telomerase-silent spinal cord. This telomerase dependence, however, limits activity against tumors that maintain telomeres through the alternative lengthening of telomeres (ALT) pathway, such as many osteosarcomas and some spinal cord astrocytomas. We also discuss delivery and safety within the confined spinal canal, combination strategies, and future directions, such as extracellular vesicle-mediated delivery and biomarker-guided patient selection. Although clinical translation to the spine will require dedicated preclinical and early-phase studies, virotherapy represents a promising, mechanistically grounded modality for these therapeutically challenging tumors. Full article

Traditional Chinese medicine (TCM) polysaccharides are important active components of traditional Chinese medicine, and their anti-inflammatory, immunomodulatory, and mucosal barrier protective effects have attracted widespread attention. Since most traditional Chinese medicine polysaccharides are difficult to be completely digested and absorbed in the gastrointestinal tract, their interventional effects on respiratory diseases may be closely related to the selective utilization by gut microorganisms and the regulation of the gut–lung axis. Therefore, the structural and functional interactions between traditional Chinese medicine polysaccharides and gut microbiota have gradually become an important direction in traditional Chinese medicine pharmacology and microecology research. This review mainly explores two core questions: first, how traditional Chinese medicine polysaccharides that can act on the gut–lung axis drive candidate gut bacteria and metabolic networks; second, how polysaccharide-driven candidate bacteria and metabolic networks regulate pulmonary infection, allergic inflammation, chronic airway injury, and fibrosis through the intestinal mucosal barrier, immune cell reprogramming, and cross-organ signal transmission. Accordingly, this narrative mechanistic review examines selected preclinical studies on traditional Chinese medicine polysaccharides regulating the gut–lung axis, focusing on summarizing the continuous mechanisms by which different polysaccharides promote the proliferation of related microbial communities and metabolite production through selective feeding of gut microorganisms, stabilize intestinal mucosal immunity, and exert pulmonary interventional effects. This review aims to deepen the understanding of the interaction mechanisms among traditional Chinese medicine polysaccharides, microorganisms, and the host, provide some reference for establishing a mechanistic evidence framework for gut–lung axis research and screening potential active polysaccharides with relevant structures and microbiota effects. Full article

Introduction: Animal models of cardiac dysfunction and heart failure play important roles in preclinical study and drug discovery. Cardiovascular disease and metabolic dysfunction-associated steatohepatitis (MASH) are closely associated metabolic disorders that frequently coexist in individuals with obesity and metabolic syndrome. However, the mechanisms linking diet-induced metabolic stress to cardiac dysfunction and hepatic pathology remain understudied. Method: In this study, six-week-old C57Bl/6J male mice were fed standard normal chow or a Gubra Amylin NASH (GAN) diet for six months to investigate the concurrent cardiac and hepatic manifestations. Results: Our results indicated that GAN diet-fed mice developed early cardiac dysfunction characterized by reduced ejection fraction (EF) and impaired diastolic function, as indicated by increased E/A and E/E′ ratios. These cardiac changes were accompanied by worsening hepatic pathology, including elevated total cholesterol (TC) and liver injury markers such as ALT, AST and ALP. By 6 months, mice developed pronounced fibrotic remodeling and inflammation in both the heart and liver, as confirmed by histopathological and gene expression analyses. Metabolic assessments further demonstrated a decreased respiratory exchange ratio (RER) in GAN diet-fed mice, particularly during the dark cycle, suggesting enhanced lipid utilization and decreased metabolic flexibility. In addition, reduced oxygen consumption, carbon dioxide production, and locomotor activity suggested impaired energy expenditure and reduced physical activity levels. Conclusion: Collectively, our findings demonstrate that chronic GAN diet feeding induces early cardiac dysfunction accompanied by progressive MASH-like hepatic pathology, with inflammation and fibrotic remodeling developing in both the heart and liver. These findings establish GAN diet feeding as a useful model for investigating the concurrent cardiac and hepatic consequences of chronic metabolic stress. Full article

Cholesterol is increasingly recognized as a regulator of hematolymphoid malignancy biology, by influencing tumor proliferation, immune function, and therapeutic response. This review summarizes current evidence regarding the relationship between cholesterol metabolism and hematologic malignancies, integrating mechanistic studies with retrospective and emerging prospective clinical data. Cholesterol contributes to immune dysfunction by promoting CD8⁺ T-cell exhaustion within the tumor microenvironment. Clinical studies have reported associations between serum lipid profiles, statin use, and outcomes across multiple hematologic malignancies, although findings remain heterogeneous and are largely derived from retrospective analyses. Preclinical studies demonstrate that statins disrupt cholesterol-dependent signaling and inhibit tumor growth, whereas retrospective clinical studies generally support the safety of statin use and suggest possible therapeutic benefits in some lymphoma subtypes. Clinically, low high-density lipoprotein cholesterol (HDL) has been associated with advanced disease across multiple hematological malignancies. However, prospective, interventional data remain limited. Collectively, this review highlights the possible relationship between cholesterol metabolism and hematologic malignancy biology, with a focus on potential impacts on disease related outcomes. Full article

Porcine endometritis, primarily resulting from mixed bacterial infections, adversely impacts sow reproductive performance and leads to substantial economic losses in the pig farming sector. Traditional antibiotic treatment is limited due to bacterial resistance and drug residue issues. Curcumin (Cur) possesses inherent antibacterial and anti-inflammatory properties; however, its use is restricted due to limited water solubility and low bioavailability. In this work, dominant pathogens were isolated and identified from vaginal swabs collected from 48 sows with clinical endometritis via 16S rRNA sequencing, followed by antibiotic susceptibility assessment. Cur-loaded ZIF-8 nanoparticles (Cur@ZIF-8) were synthesized for non-antibiotic therapeutic exploration against porcine endometritis. Physicochemical characterizations revealed that Cur@ZIF-8 possessed a hydrodynamic particle size of 106.2 nm, a curcumin loading efficiency of 10.8%, and an encapsulation efficiency of 86.4%. The nanoparticles exhibited uniform morphology, favorable dispersibility, and showed a moderate increase in curcumin release under acidic conditions. Hemolysis assays and mouse toxicity tests confirmed the favorable biocompatibility of Cur@ZIF-8 without obvious toxic effects. In vitro antibacterial evaluations demonstrated that Cur@ZIF-8 exerted potent bactericidal effects, with the minimum inhibitory concentration (MIC) against Proteus mirabilis determined to be 12.5 μg/mL. Consistent with clinical findings, Proteus mirabilis, Staphylococcus aureus, and Escherichia coli were confirmed as the major causative agents of porcine endometritis, which frequently occurred as mixed infections, and these clinical isolates exhibited prominent multi-drug resistance to common antibiotics. Using the isolated dominant clinical strains, we established mouse endometritis models and performed in vivo therapeutic evaluations via uterine bacterial load enumeration, histopathological observation, and immunofluorescence detection of macrophage polarization. The results demonstrated that Cur@ZIF-8 markedly mitigated uterine pathological injury, reduced intrauterine bacterial burden, and alleviated inflammatory infiltration. A decreased semi-quantitative histopathological inflammation score was observed in uterine tissues after Cur@ZIF-8 intervention. Mechanistically, Cur@ZIF-8 remodels the uterine inflammatory microenvironment through the modulation of macrophage polarization, achieving combined antibacterial and anti-inflammatory functions. Collectively, in vivo experiments in mouse endometritis models verified that the Cur@ZIF-8 nanoplatform produces antibacterial and anti-inflammatory effects and exhibits excellent biosafety and biocompatibility. This preclinical study offers a promising non-antibiotic nanotherapeutic candidate and provides an alternative strategy to reduce antibiotic consumption and combat antimicrobial resistance in livestock production; nevertheless, further systematic validation in sow models is still needed to support its practical clinical application for porcine endometritis control. Full article

Ulcerative colitis (UC) remains difficult to control in a substantial proportion of patients despite an expanding range of advanced therapies. Interleukin-7 (IL-7) is a homeostatic cytokine that supports lymphocyte survival, persistence and intestinal trafficking through signalling via IL-7 receptor-α (IL-7Rα; CD127), providing a rationale for selective pathway inhibition in chronic intestinal inflammation. This narrative review examines the biology of IL-7/IL-7R signalling in inflammatory bowel disease (IBD) and summarises the preclinical, translational and clinical development of lusvertikimab, a humanised monoclonal antibody targeting IL-7Rα. MEDLINE was searched from inception to 31 July 2026, supplemented by reference-list screening, trial registries, conference proceedings and regulatory sources. Experimental studies show that IL-7 supports the persistence of colitogenic effector-memory T cells and contributes to innate immune activation. Human translational data demonstrate enrichment of IL-7R pathway activity in treatment-refractory IBD, association with anti-TNF non-response, and IL-7-mediated upregulation of the gut-homing integrin α4β7. Preclinical IL-7R blockade attenuated experimental colitis, reduced intestinal T-cell trafficking and altered inflammatory responses in UC tissue. In a first-in-human study, lusvertikimab produced sustained receptor occupancy and suppression of IL-7-associated gene expression without broad lymphocyte depletion. In the phase II CoTikiS trial, lusvertikimab improved Modified Mayo Score versus placebo, with significant pooled endoscopic improvement but no significant pooled differences in clinical or endoscopic remission. Early safety findings were reassuring. Selective IL-7Rα blockade therefore represents a biologically distinct therapeutic strategy in UC, although larger controlled studies, biomarker validation and clarification of dose selection and long-term safety are required to define its clinical role and whether combination strategies warrant future evaluation in selected patients. Full article

Oral diseases remain widespread, while concerns about antimicrobial resistance, microbiome disruption, and adverse effects from prolonged antiseptic use encourage interest in plant-based approaches. This structured narrative review synthesises literature published predominantly from 2010 to 2026, including mechanistic, in vitro, biofilm, preclinical, clinical, and formulation studies addressing medicinal plants, isolated phytochemicals, and plant-derived oral healthcare products. We examine how these interventions may influence oral health through mechanisms extending beyond direct bacterial killing. We synthesise evidence on major phytochemical classes, including polyphenols, terpenoids, alkaloids, sulfur compounds, and glycosides, together with their effects on biofilms, quorum sensing, inflammation, oxidative stress, and tissue repair. We also assess clinical evidence for botanical formulations and emerging delivery systems designed to improve stability and local retention. Current evidence indicates that several plant-derived compounds can inhibit biofilm formation, interfere with bacterial virulence, modulate inflammatory signalling, and support tissue recovery. Green tea, pomegranate, cranberry, turmeric, neem, aloe vera, mangosteen, and propolis show promising clinical or experimental activity, although evidence strength varies considerably among plants and formulations. Nanoemulsions, lipid-based carriers, and mucoadhesive systems may improve phytochemical stability and local exposure, but clinical validation remains limited. Overall, phytotherapy appears most useful as an adjunct to established oral hygiene rather than a replacement for conventional care. Standardized extracts, well-characterized formulations, microbiome-based outcomes, long-term clinical trials, and clearer regulatory pathways remain essential before wider clinical adoption. Full article

Background/Objectives: Sarcopenia contributes to frailty and functional decline in older adults; however, effective adjunctive strategies remain limited. Heat-killed Bifidobacterium breve B-3 (B-3HK), a postbiotic, has shown muscle-related effects in preclinical studies; however, clinical evidence in patients with established sarcopenia is scarce. This pilot trial aimed to evaluate these clinical effects. Methods: In this 24-week randomized, double-blind, placebo-controlled trial, adults aged 50–89 years with Asian Working Group for Sarcopenia (AWGS) 2019-defined sarcopenia received B-3HK (2 × 10¹⁰ cells/day) or placebo daily. The primary outcome was the change in knee extension strength at week 24. Secondary outcomes included body composition measured using bioelectrical impedance analysis (BIA), dual-energy X-ray absorptiometry (DXA), physical performance, Eating Assessment Tool-10 (EAT-10), serum biomarkers, gut microbiota, and safety. Secondary outcomes were exploratory with nominal p-values and no adjustment for multiple comparisons. Results: Fifty participants were randomized, and 49 were included in the full analysis set. Compared with placebo, B-3HK did not significantly improve knee extension strength. Exploratory analyses showed between-group differences favoring B-3HK in the BIA-derived skeletal muscle mass index, limb muscle mass, EAT-10 score, and serum insulin-like growth factor-1 and 25-hydroxyvitamin D levels. These differences were primarily driven by the attenuation of the decline in the placebo group and were not corroborated by DXA-derived indices or functional outcomes. The gut microbiota composition did not differ between groups. No serious adverse events were observed. Conclusions: B-3HK did not improve muscle strength in patients with sarcopenia. Exploratory analyses identified nominal between-group differences in body composition and endocrine outcomes; however, these findings were unadjusted for multiplicity and should be regarded as hypothesis-generating rather than confirmatory evidence of efficacy. These data may help inform the design of future adequately powered trials, but confirmation is required before any therapeutic benefit can be inferred. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and a leading cause of advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. The disease develops through the interaction of multiple interconnected pathophysiological mechanisms, including insulin resistance, dysregulated lipid metabolism, oxidative stress, mitochondrial and endoplasmic reticulum dysfunction, chronic inflammation, gut–liver axis disruption, and progressive fibrogenesis. Betaine, a naturally occurring methyl donor, has been investigated as a potential therapeutic agent because of its diverse metabolic and cytoprotective effects. This review summarizes current knowledge on the mechanisms by which betaine may influence MASLD development and progression. Preclinical studies indicate that betaine improves insulin sensitivity and hepatic lipid homeostasis, reduces oxidative and endoplasmic reticulum stress, preserves mitochondrial function, mitigates inflammatory signaling, and limits hepatic fibrosis. In addition, growing evidence suggests that betaine contributes to the maintenance of gut–liver axis homeostasis, further supporting its beneficial effects on liver function. Although these findings are consistent across preclinical models, clinical evidence remains limited, and the therapeutic efficacy of betaine in patients with MASLD has not yet been established. Further well-designed clinical trials are required to determine its clinical value, optimal therapeutic strategy, and potential role in the management of MASLD. Full article

Oxidative stress is a well-recognized contributor to male reproductive dysfunction, yet discussion of this mechanism has focused almost exclusively on sperm damage. This focus overlooks the somatic and stromal networks that support testicular development, steroidogenesis, tissue architecture, and erectile function. Platelet-derived growth factor receptor alpha (PDGFRα) is expressed in heterogeneous interstitial and progenitor-enriched populations and has established roles in testicular development. This narrative review examines the evidence on PDGFRα in male reproductive tissues and considers the potential relevance of redox mechanisms identified predominantly in other organ systems. Genetic studies show that Pdgfa deficiency impairs the postnatal establishment of the adult Leydig-cell population, whereas Pdgfra deficiency disrupts fetal testis cord organization and Leydig-cell differentiation. Studies of the adult testis document receptor localization and, in cell-based models, downstream signaling capacity. Preclinical work has further identified PDGFRα-positive cavernosal fibroblasts associated with vascular remodeling in erectile dysfunction, although a receptor-specific function for these cells remains unproven. We propose that PDGFR-associated redox signaling may shape stromal responses to injury in the testis and penis; however, direct evidence for this mechanism in male reproductive tissue is currently lacking. Testing this hypothesis will require cell-resolved measurements of receptor phosphorylation and localized reactive oxygen species, together with lineage-restricted, receptor-specific perturbation. Establishing whether such a pathway exists could open a mechanistic link between oxidative stress and stromal, rather than purely germ-cell, contributions to male reproductive dysfunction—with implications for both testicular endocrine failure and vasculogenic erectile dysfunction. Full article

Regular consumption of dietary flavonoids and phenolic compounds has been associated with a reduced risk of disease development and progression. In this regard, syringic acid, a hydroxybenzoic acid, is present in fruits and vegetables and plays a vital role in disease prevention. It exhibits therapeutic potential for various chronic diseases through diverse molecular mechanisms, including modulation of cellular and molecular pathways, regulation of inflammation and oxidative stress responses, and maintenance of cellular and tissue architecture. In addition, syringic acid has been shown to modulate gene expression and enzyme activities associated with various chronic diseases. Moreover, preclinical studies, including both in vitro and in vivo investigations, have evidenced that it has significant hepatoprotective, antidiabetic, neuroprotective, cardioprotective, and other beneficial effects. Furthermore, its role in synergistic studies aimed at increasing the efficacy of other compounds/drugs has also been reported. Advances in nanotechnology-based formulations have also improved their stability, bioavailability, and therapeutic efficacy, thereby expanding their potential biomedical applications. This review aimed to compile information on its sources, role in different pathogeneses, nanoformulations, and synergistic effects with other drugs. Despite its significant role in preclinical studies, further research is needed to optimize dosage regimens and mechanisms of action, develop novel delivery systems, and conduct comprehensive clinical studies to translate its potential into disease management. Full article