Objective: The purpose of this review is to examine M. pubescens's pharmacological, phytochemical, and toxicological properties. Furthermore, the study intends to explore and disseminate all relevant facts and information regarding this species' chemical compounds and medicinal uses. Materials and Methods: This investigation was conducted using a range of scholarly resources, including ScienceDirect, Scopus, PubMed, and Google Scholar. Plantlist.org was used to verify the correct plant names. The bibliographic material retrieved was used to interpret, analyze, and document the findings of this inquiry. Results: This plant is commonly used in conventional medicine due to its high content of phytochemicals. These chemical compounds, known as secondary metabolites, include phenols, flavonoids, terpenes, alkaloids, and tannins, and are associated with medicinal properties. These chemicals are ideal for modern medicinal use because of their antibacterial, antioxidant, antifungal, antiinflammatory, antidiabetic, and antihypertensive activities. As our scientific understanding of their biological properties deepens, plant secondary metabolites are increasingly being used as medicines and food additives for flavoring and cooking. Discussion: This study provides a thorough analysis of the pharmacological and medicinal properties of M. pubescens. Despite this, studies in the literature have shown that M. pubescens is a valuable medicinal resource with a range of pharmacological properties. It is a strong candidate for research and the development of new therapeutic treatments because it has demonstrated a variety of pharmacological traits that support its traditional use. Conclusion: This review focuses on the distribution, chemistry, and principal applications of M. pubescens, identifying potential research and the exploration of medicinal uses through clinical trials.
The severe acute respiratory syndrome coronavirus SARS-CoV-2, which causes COVID-19, has attracted the interest of the scientific community since 2019. In fact, in the majority of cases, COVID-19 results in a mildly symptomatic disease that needs no treatment. However, patients with comorbidities have an increased risk of severe manifestations of COVID-19. Although research progress in the field has been successfully accomplished, novel therapeutic strategies are still required. Treatment efforts are needed against the severe manifestations of the disease, such as the severe respiratory distress syndrome. The tripeptide glutathione could be a promising therapeutic approach against COVID-19. Glutathione is a multitarget agent that exhibits antiviral activity against SARS-CoV-2 and modulates the host response to SARS-CoV-2. Oxidative stress and glutathione deficiency have been implicated in the pathophysiology of severe COVID-19 disease. Thus, a possible therapeutic strategy could be the enhancement of the antioxidant defenses of the host through the treatment with nonenzymatic antioxidants. Apart from functioning as a scavenging agent, glutathione plays a central role in cellular signalling. As a redox regulator, glutathione also acts as a signalling molecule, thus modulating innate and T cell immunity, with implications for SARS-CoV-2 infection. Existing clinical data, although limited, provide evidence that the modulation of glutathione levels could be a preventive or adjunctive therapeutic strategy against SARS-CoV-2 infection.
BACKGROUND:Neutrophil extracellular traps (NETs) participate in thrombosis, inflammation, and cardiovascular remodeling, yet whether NET-related genes (NRGs) are associated with atrial fibrillation (AF) risk across multiple molecular layers remains unclear. This study used a multiomics Mendelian randomization framework to prioritize NRGs supported by methylation, expression, and protein quantitative trait loci (QTL) data. METHODS:Genome-wide significant cis instruments (P < 5 × 10-8) were obtained for 90 methylation QTLs (mQTLs), 100 expression QTLs (eQTLs), and 38 protein QTLs (pQTLs) mapped to 137 literature- curated NRG entries. Summary-data-based Mendelian randomization (SMR) coupled with the heterogeneity in dependent instruments (HEIDI) test was applied using whole-blood mQTL data (n = 1,980), eQTLGen blood eQTL data (n = 31,684), and deCODE plasma pQTL data (n = 35,559). AF outcome data were obtained from a meta-analysis including 60,620 cases and 970,216 controls of European ancestry. RESULTS:At the methylation level, 21 CpG-feature associations across 13 genes remained significant after HEIDI filtering and false discovery rate (FDR) correction. Expression-level analysis identified eight significant gene-AF associations, whereas protein-level analysis identified seven significant features representing five unique proteins. Cross-omics integration prioritized C3, MAPK3, and STAT3 as Tier 1 genes, CTSC, LPAR3, and THBD as Tier 2 genes, and fourteen additional genes as Tier 3 candidates. C3 showed risk-increasing protein-level associations together with multiple significant CpG signals, whereas MAPK3 and STAT3 showed directionally protective expression/protein or methylation/protein patterns. DISCUSSION:The cross-omics convergence on C3, MAPK3, and STAT3 is consistent with complement activation, immune-fibrotic signaling, and cytokine-regulatory pathways implicated in AF biology, but the findings should be interpreted as genetic prioritization rather than definitive intervention-ready causality. CpG-level heterogeneity at the C3 locus and the blood/plasma origin of the QTL resources further support a cautious interpretation. Modest colocalization support and the unresolved possibility of pQTL sample overlap further support this cautious, hypothesis-generating interpretation. CONCLUSION:Multi-omics SMR prioritizes C3, MAPK3, and STAT3 as the most consistently supported NET-related genes associated with AF risk. These findings provide a framework for atrialtissue replication and mechanistic validation of NET-related pathways in AF.
Food is indispensable for survival, yet it originates from biological matter derived from other living organisms. Food macromolecules are almost always structurally different from those of the host and may therefore be regarded as foreign biological material. This observation leads to what is defined here as the Food Paradox: food sustains life but initially represents non-self biological material. Digestion resolves this paradox by breaking down food macromolecules to universal molecular units compatible with host metabolism. From this perspective, the Food Paradox is proposed as a conceptual framework linking digestion, gut microbiota, intestinal barrier function, and, eventually, chronic inflammatory diseases. Under physiological conditions, digestion transforms foreign biological material into metabolically compatible nutrients, while the intact intestinal barrier prevents microbes, microbial products, and incompletely digested food molecules from entering the systemic circulation. However, imbalanced dietary patterns may alter gut microbiota composition, promote dysbiosis and intestinal inflammation, and impair intestinal barrier integrity. Increased intestinal permeability may allow microbial components and only partially digested food fragments to reach systemic circulation, thereby eventually contributing to systemic chronic low-grade inflammation.
Introduction: Immune checkpoint inhibitors (ICIs) are a revolutionary class of drugs for the treatment of various malignancies by harnessing the immune system to eliminate cancer cells. However, their antitumor efficacy is accompanied by a spectrum of immune-mediated adverse effects, including endocrine disorders. Among them, diabetes mellitus, though rare compared to thyroid dysfunction, is a serious complication due to its abrupt onset and high risk of life-threatening diabetic ketoacidosis. Methods: This article presents several clinical cases of ICI-induced diabetes mellitus with an emphasis on the clinical presentation, biochemical assessment, and the importance of early recognition. Results: Each of the patients in this clinical case series was admitted to the hospital on an emergency basis with significant hyperglycaemia and ketonuria. Given the established insulin deficiency (low C-peptide levels), after stabilization with intravenous insulin and rehydration, they were switched to maintenance therapy with subcutaneous administration of basal and rapid-acting insulin. Discussion: The management of immune-mediated diabetes mellitus requires an individualized approach, considering the rapid progression to insulin dependence, the oncologic status of the patient, and the need for continuation of immunotherapy. Conclusion: Early identification through regular glucose monitoring and rapid insulin initiation are crucial for effective management of ICI-induced diabetes mellitus. Comprehensive care requires close cooperation between oncology and endocrinology teams, individualized follow-up, and lifelong insulin therapy.
BACKGROUND:As key medicinal targets, ginseng and Angelica sinensis have demonstrated potential efficacy in the treatment of Premature Ovarian Failure (POF). This study identified the key targets and further explored their potential causal links with POF using Mendelian randomization (MR) analysis. METHOD:This study integrated network pharmacology and transcriptomic data to identify novel POFassociated targets using differential expression analysis, Protein-Protein Interaction (PPI) network construction, machine learning algorithms, and expression validation. Additionally, it performed gene set enrichment analysis (GSEA), immune infiltration analysis, and single-cell RNA sequencing to investigate the potential biological roles of these targets in POF. RESULTS:HSD17B1, MAPK14, and CDC7 were identified as the key targets related to ginseng and Angelica sinensis in POF. HSD17B1 and CDC7 were downregulated, while MAPK14 was upregulated, and these targets were enriched in immune- and metabolism-related pathways. MAPK14 was strongly correlated with γδ T cells (cor = 0.82, P < 0.05). Single-cell analysis identified nine ovarian cell subpopulations. MR analysis indicated that HSD17B1 was associated with an increased risk of female infertility [FINN-b-N14 FEMALEINFERT: odds ratio (OR) = 1.175, 95% confidence interval (CI) = 1.064-1.298; FINN-b-N14 FIANOV: OR = 1.459, 95% CI = 1.154-1.845; P < 0.05]. DISCUSSION:These findings indicate that ginseng and Angelica sinensis might modulate steroidogenesis, immune responses, and granulosa-cell function, with HSD17B1, MAPK14, and CDC7 identified as candidate biomarkers, warranting further mechanistic exploration in POF. CONCLUSION:This study identified three key targets (HSD17B1, MAPK14, and CDC7) associated with ginseng and Angelica sinensis that may be involved in the pathogenesis of POF and may serve as candidate markers for subsequent mechanistic exploration.
Introduction: Quercitrin (QC) is a dietary flavonoid glycoside with diverse pharmacological activities, yet a review on its cellular signaling mechanisms remains lacking. This review aims to synthesize and rigorously assess existing evidence concerning the modulatory influence of QC on essential signaling pathways and its therapeutic effects. Methods: A literature search was performed using Web of Science, Medline, and Embase databases. The synthesis of 25 original experimental studies evaluating QC as a pure compound with specific effects on signaling pathways was reported. Results: QC potentially inhibited pro-inflammatory signaling pathways, including NF-κB, p38 MAPK, JNK, and Jak/Stat, while activating cytoprotective pathways such as Nrf2 and Wnt/β- catenin. Notably, evidence demonstrated context-dependent bidirectional regulation of PI3K/Akt and ERK signaling, with QC suppressing pathological hyperactivation during inflammation while restoring impaired signaling under oxidative stress, metabolic dysfunction, and tissue injury. These molecular actions contributed to anti-inflammatory, antioxidant, chondroprotective, neuroprotective, metabolic, and anticancer effects. Discussion: Current evidence suggests that QC functions as a context-dependent homeostatic regulator rather than a simple pathway activator or inhibitor. Its ability to differentially modulate signaling networks according to disease context may explain its broad therapeutic potential across multiple pathological conditions. Conclusion: Preclinical evidence supports QC as a multi-target signaling modulator with promising therapeutic potential. However, its clinical translation remains limited by insufficient pharmacokinetic data and the absence of well-designed human studies. Future standardized pharmacokinetic investigations and clinical trials are warranted to establish its efficacy and safety.
INTRODUCTION/OBJECTIVE:Diabetic Nephropathy (DN) is the main cause of End-Stage Renal Disease (ESRD) worldwide. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important molecular target for regulating oxidative stress and inflammation in DN. This study aims to quantitatively map the global research landscape of Nrf2 in diabetic nephropathy using bibliometric methods, identifying key contributors, thematic evolution, and emerging trends with implications for drug target development. METHODS:Bibliometric analysis was conducted using the Web of Science Core Collection database. Publications from 2000 to 2025 were systematically examined using the "bibliometrix" package in R, CiteSpace, and VOSviewer, with a focus on publication trends, countries and institutions, journal impact, and keyword development. RESULTS:In total, 465 papers from authors affiliated with 647 institutions, spanning 2,413 researchers and 45 nations, have been identified as meeting the inclusion criteria. China leads in publications (TP = 321) and citations (TC = 9603). Jilin University has the most publications (n = 79). The most influential journals are Free Radical Biology and Medicine and Frontiers in Pharmacology. The keyword cluster analysis identified five main research clusters, including: (1) Oxidative Stress; (2) Cellular Processes Affected by Oxidative Stress; (3) Signalling Pathways and Fibrosis; (4) Diabetic Complications; and (5) Genetics and Signalling Mechanisms. The recent burst of keywords such as "stress" and "protects" highlights the evolving research frontiers. DISCUSSION:This analysis confirms that the main contributors to this field are worthy of attention because of their contributions to major research hotspots. A noteworthy trend is that research has shifted from focusing solely on oxidative stress to encompassing integrated mechanisms such as autophagy, inflammation, and cellular protection. CONCLUSION:This analysis reveals a thematic shift from oxidative stress to autophagy and inflammation, highlighting evolving opportunities for Nrf2-targeted drug development in DN.
Introduction: Disruption of skeletal homeostasis poses substantial risks to aging populations. Naringin, a flavonoid from Citrus paradisi and Drynariae Rhizoma, shows promise as a multitarget therapeutic agent for bone disorders. Methods: This review systematically examines published literature on naringin's mechanisms in bone metabolism, analyzing signaling pathways, cellular interactions, and delivery systems through comprehensive database searches. Results: As a prodrug, naringin must be hydrolyzed to its active aglycone, naringenin. Naringenin promotes osteogenesis via Wnt/β-catenin, BMP-2/Smad, and the naringenin-activated estrogen receptor pathway while inhibiting osteoclastogenesis through RANKL/RANK/OPG modulation. Naringin demonstrates dual functionality by protecting normal bone tissue while inducing ferroptosis in osteosarcoma cells. Discussion: Naringin's pleiotropic effects address multiple pathological processes in skeletal disorders, including inflammation, oxidative stress, and metabolic dysregulation. Its interaction with gut microbiota and systemic metabolic pathways provides additional therapeutic benefits. Conclusion: Naringin represents a promising natural therapeutic candidate for skeletal diseases. Key clinical translation gaps include the absence of fracture‑endpoint trials, insufficient bioavailability solutions, and unknown long‑term safety in humans. Future research should focus on advanced delivery systems and well‑designed randomized controlled trials.
OBJECTIVES:Metabolic dysfunction-associated fatty liver disease (MAFLD) is a prevalent chronic liver condition lacking approved pharmacological therapies. Erchen Decoction (EC), a classic traditional Chinese medicine prescription, possesses the therapeutic effects of strengthening the spleen, resolving dampness, and eliminating phlegm. This study aims to investigate the therapeutic potential and underlying mechanisms of EC against MAFLD. METHODS:The anti-MAFLD efficacy of EC was evaluated using a high-fat diet (HFD)-induced rat model and palmitic acid-stimulated AML12 cells. Therapeutic outcomes were assessed by measuring body and liver weights, serum biochemical parameters, and hepatic histological changes. The regulatory effects of EC on endoplasmic reticulum stress (ERS) were analyzed via immunohistochemistry, Western blotting, and qRT-PCR. Furthermore, MFN2 knockdown was employed to verify whether EC alleviates MAFLD via the MFN2 pathway. RESULTS:EC administration significantly ameliorated hepatic steatosis and injury in both in vivo and in vitro models. Mechanistically, EC upregulated the expressions of MFN2 and its splicing variant ERMIT2, thereby suppressing the activation of ERS-related signaling molecules, including PERK, eIF2α, and ATF4. Consequently, EC mitigated ERS, reduced lipid accumulation, and hindered MAFLD progression. DISCUSSION:The findings highlight the critical role of the MFN2/ERMIT2 signaling axis in regulating endoplasmic reticulum stress during MAFLD pathogenesis. By restoring this organelle tethering complex, EC effectively buffers calcium handling, maintains global ER homeostasis, and mitigates lipotoxic hepatocyte injury, offering a novel pharmacological rationale for its traditional application in metabolic disorders. CONCLUSION:EC exerts significant protective effects against MAFLD by upregulating the MFN2/ERMIT2 axis and suppressing the PERK, eIF2α, and ATF4 ERS pathway. This regulation suggests a restorative effect on calcium handling, maintains ER homeostasis, and reduces hepatocyte injury, highlighting EC as a promising therapeutic candidate for MAFLD.
BACKGROUND:Nonalcoholic fatty liver disease (NAFLD) is characterized by profound metabolic reprogramming. Recent evidence suggests that lactate, beyond its role as a metabolic waste product, may modulate histone lactylation, linking metabolic stress to the epigenetic regulation of disease progression. However, the specific lactate-related gene (LRG) signatures driving NAFLD remain to be elucidated. METHODS:We integrated transcriptomic mining of the GSE164760 dataset with in vivo validation to decode the LRG landscape. Differentially expressed LRGs were identified using strict thresholds and subsequently intersected with the GeneCards database. Functional enrichment (GO/KEGG) and Protein-Protein Interaction (PPI) networks were constructed to screen for hub genes. Key biomarkers were subsequently corroborated in a high-fat diet (HFD)- induced rat NAFLD model via Western blotting. RESULTS:A total of 98 differentially expressed LRGs were identified, which were primarily enriched in molecular catabolism and xenobiotic stress responses. From this network, eight pivotal hub genes were distilled: CREBBP, EP300, HDAC1, HIF1A, PARP1, SIRT1, STAT3, and TP53. Diagnostic modeling demonstrated their predictive value, with AUC scores ranging from 0.60 to 0.81, among which PARP1 and STAT3 exhibited high diagnostic potential (AUC > 0.80). Experimental validation in the rat model confirmed the disruption of this metabolic-epigenetic regulatory module, revealing significant dysregulation in protein expression that reflects a compensatory stress response to lipotoxicity. DISCUSSION:These findings bridge the gap between metabolic lipotoxicity and epigenetic regulation, suggesting that lactylation acts as a critical driver in NAFLD pathogenesis. CONCLUSION:This study delineates a preliminary, hypothesis-generating lactate-associated gene signature in NAFLD, highlighting a complex regulatory network governing hepatocyte metabolic plasticity and survival. These eight core biomarkers offer promising tissue-based targets for mechanistic intervention, though further validation in peripheral blood is required to establish their non-invasive diagnostic utility.
Introduction: Tripterygium wilfordii Hook.f. (TwHF), A traditional Chinese medicine has been historically used for treating inflammatory conditions such as osteoarthritis (OA) and rheumatoid arthritis (RA), owing to its potent anti-inflammatory and immunomodulatory properties. Notably, OA is now recognized as a whole-joint disorder driven not merely by mechanical wear and tear, but by complex pathophysiological processes involving immune response dysregulation and localized metabolic disturbances. Despite its therapeutic potential, the clinical application of TwHF remains constrained by significant multi-organ toxicity and a narrow therapeutic window. This review aims to summarize the therapeutic mechanisms, toxicity profile, and clinical evidence of TwHF and its active components in OA treatment, and to discuss strategies for mitigating toxicity and future research directions. Methods: A systematic search was performed across multiple electronic databases, including PubMed and Web of Science, up to February 2026, to identify studies on TwHF and its components in OA. The process followed PRISMA guidelines using keywords including “Tripterygium wilfordii,” “osteoarthritis,” and “toxicity.” Included studies focused on TwHF and OA pharmacology, toxicity, or clinical outcomes; those with insufficient data were excluded. Data on authors, year, findings, and conclusions were extracted and synthesized narratively by themes. Results: TwHF active components demonstrate potent anti-inflammatory and chondroprotective effects in cellular and animal OA models. However, they also cause dose-dependent hepatotoxicity, nephrotoxicity, and immunosuppression. Strategies like drug combination, targeted delivery, and metabolic modulation can reduce toxicity. Clinical evidence in OA remains limited and lowquality, whereas more robust data support its use in rheumatoid arthritis. Discussion: TwHF presents a compelling therapeutic profile for OA due to its multi-faceted anti- inflammatory and immunomodulatory actions, primarily mediated by its active constituents through a multi-targeted approach. However, its promise is tempered by significant safety concerns, particularly hepatotoxicity and nephrotoxicity, and a lack of conclusive efficacy data from robust clinical trials in OA.Future research should prioritize high-quality RCTs, deeper investigation into toxicity mechanisms, development of safer derivatives, and establishment of predictive biomarkers. Conclusion: While TwHF holds promise for OA treatment due to its multimodal anti-inflammatory mechanisms, its toxicity and insufficient clinical evidence necessitate further high-quality trials, precise therapeutic targeting, and safer formulation development for safe clinical integration.
Introduction: Osteoporosis (OP) is a common skeletal disease mainly caused by the imbalance between bone formation and bone resorption. Dysfunction and senescence of bone marrow mesenchymal stem cells (BMSCs) are critical pathogenic factors for OP, resulting in impaired osteogenic differentiation, increased adipogenic shift, and enhanced susceptibility to inflammation and oxidative stress. Therefore, the purpose of this review is to systematically synthesize current evidence on how Icariin (ICA)—a major bioactive flavonoid from Epimedium—exhibits therapeutic potential against OP by targeting BMSC senescence and regulating multiple underlying signaling networks. Methods: This narrative review systematically synthesized preclinical and mechanistic evidence regarding Icariin-mediated regulation of BMSC function in osteoporosis. Relevant cellular, animal, pharmacological, and mechanistic studies were reviewed, with emphasis on BMSC senescence, osteogenic/adipogenic lineage commitment, oxidative stress, inflammation, and major signaling pathways, including Wnt/β-catenin, Notch, BMP/Runx2/Osx, MAPK, and OPG/RANK/RANKL. Results: ICA can promote osteogenic differentiation and inhibit osteoclastogenesis by regulating multiple signaling pathways simultaneously. ICA activates the Wnt/β-catenin pathway to enhance the stability of β-catenin and its downstream transcriptional programs, modulates Notch signaling through regulating the activity of DLL1, Jagged1, and NICD, and promotes the BMP/Runx2/Osx axis, which favors osteoblast lineage commitment. Additionally, it controls the activity of MAPK (ERK, p38, JNK) and restores bone homeostasis by managing the OPG/RANK/RANKL system, leading to reduced osteoclastogenesis and decreased production of inflammatory cytokines. In addition to regulating lineage commitment, ICA alleviates BMSC senescence by reducing oxidative stress, DNA damage, mitochondrial dysfunction, and SASP-associated microenvironmental deterioration. Discussion: Collectively, these effects promote osteogenesis, maintain stem cell vitality, and mitigate OP-induced bone loss. The hierarchy, crosstalk, and cell-type specificity of ICA-targeted signaling networks require further elucidation to facilitate clinical translation. Conclusion: Preclinical evidence suggests ICA is a promising natural compound with the potential to mitigate OP progression by comprehensively regulating BMSC functions and bone remodeling pathways. Future research needs to focus on rigorous clinical trials and single-cell-level studies to determine the specific BMSC subpopulations responsive to ICA and optimize its therapeutic application.
INTRODUCTION:Genetic polymorphisms affecting oxidative stress and lipid metabolism contribute to type 2 diabetes (T2D). The role of oxidized low-density lipoprotein receptor 1 (OLR1) rs11053646 single nucleotide polymorphism (SNP) in the Saudi population remains unclear. This study aimed to assess its association with T2D risk in Saudi adults. METHODS:A tertiary hospital-based case-control study was conducted among 143 Saudi adults (≥18 years) in Riyadh from November 2019 to January 2020, including 79 individuals with T2D (fasting blood glucose ≥7 mmol/L) and 64 normoglycemic controls (<5.6 mmol/L). Genomic DNA was extracted from peripheral blood, and the OLR1 rs11053646 SNP was genotyped using PCR-RFLP. Genotype distributions were tested for Hardy-Weinberg equilibrium (HWE). Logistic regression models adjusted for age, sex, and body mass index were used to estimate odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS:Genotype distribution in controls conformed to HWE (p=0.14). The GG genotype was predominant, while the CC genotype was absent. GC frequency was slightly higher in T2D cases, but not statistically significant. Allele distributions were comparable between groups. Adjusted analysis showed no significant association with T2D risk (OR=0.41, p=0.14). DISCUSSION:OLR1 rs11053646 SNP was not significantly association with T2D risk in this Saudi cohort. The absence of the CC genotype and small sample size may have limited statistical power to detect potential associations. CONCLUSION:OLR1 rs11053646 SNP does not appear to be associated with T2D risk in Saudi adults. Larger studies are required to confirm these findings.
INTRODUCTION:Recognizing the risk factors associated with Ischemic Stroke (IS) is essential for its prevention. Currently, there are no studies exploring the causal link between antibodymediated immune responses and IS. This Mendelian Randomization (MR) study further examines whether a causal relationship exists between antibody-mediated immune responses and IS, and offers evidence supporting causality. METHOD:Data on antibody-mediated immune responses came from 9,724 subjects (European ethnicity) as the research participants and who collected their serum samples for microbiological serological analysis. By employing a multiplex antigen detection technique, the total antibody concentrations against various antigens in the samples were systematically measured. IS data were acquired from the MEGASTROKE consortium, which provides stroke-related summary data based on genomewide association studies, encompassing 40,585 stroke patients and 406,111 control individuals (European ethnicity). MR analysis was conducted to estimate the associations between antibodymediated immune responses (exposure) and IS (outcome) risk. RESULTS:The inverse variance weighted analysis revealed that 26 antibody-mediated immune responses were associated with IS in three subtypes in genetic prediction. There is an effect of anti- Chlamydia trachomatis, anti-cytomegalovirus, anti-human herpesvirus, varicella-zoster virus, anti- Merkel cell polyomavirus, Epstein-Barr virus, anti-Helicobacter pylori, anti-JC polyomavirus, and anti-Toxoplasma antibodies on the three subtypes of IS in genetic prediction. DISCUSSION:In large-artery atherosclerosis and small-vessel stroke, a high antibody level may be accompanied by direct endothelial cell invasion and vascular inflammation. In cardioembolic stroke, however, high antibody levels may instead reflect efficient viral latency maintenance with reduced systemic inflammation or hypercoagulability associated with cardiogenic embolism. In addition, different antigenic components (momp A vs. total IgG) against C. pneumoniae showed opposite associations. CONCLUSION:The research provides new genetic evidence for the complex role of antibody-mediated immune responses in the etiology of stroke, suggesting that pathogen-specific immune responses may serve as differentiated risk markers and potential intervention targets for different subtypes of stroke.
BACKGROUND:People with Acute Pancreatitis (AP) who also have Metabolic Dysfunctionassociated Fatty Liver Disease (MAFLD) are more likely to experience worse consequences. However, the mechanisms that link MAFLD and AP are not fully understood. Our study identified shared biomarkers utilizing bioinformatics and machine learning techniques. METHODS:We selected datasets for AP and MAFLD from the GEO database. Differentially Expressed Genes (DEGs) were identified from the AP dataset. Weighted Gene Co-expression Network Analysis (WGCNA) was conducted on the MAFLD dataset to identify the module highly correlated with the disease. Subsequently, we obtained shared genes by taking the intersection of the DEGs and the module genes. The shared genes were analyzed for GO and KEGG enrichment. A Protein-Protein Interaction (PPI) network and machine learning techniques were used to identify diagnostic genes, which were evaluated for diagnostic efficacy using ROC curves. RESULTS:The AP dataset yielded 454 upregulated and 380 downregulated DEGs. WGCNA identified 715 module genes in MAFLD, producing 42 shared genes. Enrichment analyses implicated inflammatory responses, calcium signaling, and lipopolysaccharide-related immune pathways. FPR1 and S100A9 emerged as the final diagnostic candidates, with AUC values exceeding 0.7 across all datasets. DISCUSSION:FPR1 and S100A9 are involved in immune activation, inflammatory signaling, and oxidative stress, suggesting roles in the pathogenesis of both AP and MAFLD. MAFLD may indirectly worsen AP severity through inflammatory and lipid pathways. CONCLUSION:FPR1 and S100A9 are promising common biomarkers for AP and MAFLD, and may provide important insights into common mechanisms and therapeutic opportunities.
OBJECTIVE:Research has found that paraoxonase 1 (PON1) is closely related to cardiovascular disease, but the relationship between circulating PON1 levels and coronary artery stenosis (CAS) in patients with diabetes remains unclear. METHODS:This study is a single-center, retrospective cross-sectional study that includes 34 patients with diabetes mellitus (DM) and 118 patients with DM and CAS (DM+CAS). All study participants were from Beijing Luhe Hospital, affiliated with Capital Medical University. In this study, data regarding demographic characteristics, medication history, and key laboratory parameters were collected. The concentration of plasma PON1 was quantified using an enzyme-linked immunosorbent assay (ELISA) kit. Multiple logistic regression models were employed to evaluate the connection between PON1 levels and the presence of CAS among patients with diabetes. Additionally, the diagnostic performance of PON1 levels for diabetes combined with CAS was evaluated utilizing the receiver operating characteristic (ROC) curve and the area under the curve (AUC). RESULTS:Compared with patients in the diabetes group, plasma PON1 levels were significantly lower in diabetic patients with CAS. To evaluate the correlation between PON1 levels and CAS among individuals with diabetes, three logistic regression models were developed. As a continuous variable, higher PON1 levels were found to be inversely related to CAS risk in all models. In tertile-stratified analyses, compared with T1, all other tertiles exhibited significantly reduced risk of CAS. The ROC curve demonstrated that the unadjusted AUC of PON1 levels was 0.662 (95% CI 0.561-0.762, p = 0.004), while the fully adjusted model yielded an AUC of 0.833 (95% CI: 0.758-0.908, p < 0.001). DISCUSSION:Plasma PON1 levels were significantly decreased and independently associated with CAS in diabetic patients. Circulating PON1 alone showed moderate diagnostic efficiency, whereas its predictive accuracy was greatly improved when combined with clinical covariates. The findings are limited by single-center enrollment, a small sample size, and a lack of subgroup analysis for stenosis severity. Moreover, only PON1 protein levels were examined, with no detection of PON1 enzymatic activity. Further large-scale multicenter prospective studies are needed to validate these results and clarify the clinical utility of PON1. CONCLUSION:Circulating PON1 levels are negatively correlated with CAS in diabetic patients. While PON1 alone has limited diagnostic value, its combination with clinical covariates significantly improves risk discrimination.
INTRODUCTION:This study aims to investigate the influence of age and gender on the efficacy of metabolic surgery in patients with obesity with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS:This is a prospective cohort study. A total of 95 patients with obesity and T2DM who underwent metabolic surgery between June 2022 and October 2024 were enrolled. Patients were divided into four groups based on their age and gender as follows: young (<35 years) men, young women, middle-aged (35-55 years) men and middle-aged women. Body mass index (BMI) data, glycated haemoglobin (HbA1c) levels and gastrointestinal peptide hormone (e.g. glucagon- like peptide-1 (GLP-1), peptide YY (PYY) and ghrelin (GHRL)) levels, as well as Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale (HAM-D) scores, were collected preoperatively and at 1, 3 and 6 months postoperatively. Gastrointestinal peptide hormone levels were measured using enzyme-linked immunosorbent assay, and anxiety and depression statuses were assessed using online questionnaires. Data were analysed using repeated measures analysis of variance, paired t-tests, analysis of covariance and multiple linear regression, with adjustments for baseline BMI, diabetes duration and surgical type (laparoscopic sleeve gastrectomy vs Roux-en-Y gastric bypass) where appropriate. RESULTS:Both BMI and HbA1c levels decreased significantly in all groups postoperatively, with a greater reduction observed in the younger groups compared with the middle-aged groups at the 6- month timepoint (adjusted p < 0.01). The percentage of total weight loss was lower in women than in men (mean difference: 2.8%, 95% confidence interval: 1.1-4.5, p = 0.03). Among gastrointestinal peptide hormones, GLP-1, PYY and cholecystokinin (CCK) significantly increased, whereas GHRL, insulin (INS) and leptin significantly decreased postoperatively. The increase in GLP-1 was more pronounced in the younger groups than in the middle-aged groups (r = -0.312, p < 0.05). Hamilton Anxiety Rating Scale scores were negatively correlated with INS (r = -0.297, p < 0.05) and positively correlated with GHRL (r = 0.286, p < 0.05), whereas HAM-D scores were negatively correlated with CCK (r = -0.258, p < 0.05). Multivariate analysis revealed that younger age (β = -0.251, p = 0.004), female gender (β = 0.178, p = 0.041), and higher HAM-A scores (β = 0.327, p = 0.002) were independent factors influencing the significant changes observed in gastrointestinal hormone levels. DISCUSSION:Individualised treatment plans based on patient age, gender and psychological status should be developed in clinical practice, and lifestyle and psychological interventions should be developed further to improve surgical outcomes and maintain the long-term efficacy of metabolic surgery. CONCLUSION:Metabolic surgery is effective in patients with obesity with T2DM, with younger patients experiencing greater metabolic improvement.
Introduction: Growth Hormone (GH) therapy for deficiency carries potential cancer risks with unclear causality. This Mendelian randomization study investigated the relationship between genetically predicted GH levels and cancer risk across 16 types. Methods: We selected genetic variants strongly associated with serum GH levels from published GWAS as instrumental variables. The primary analysis employed inverse-variance weighted MR, supplemented by MR-Egger regression. Sensitivity analyses, including MR-PRESSO and pleiotropy tests, were conducted to evaluate robustness. Mediation analysis was performed to assess the contribution of specific metabolites. Results: Genetic instruments for GH were derived from genome-wide association studies. Analyses suggested GH may be a risk factor for breast cancer, prostate cancer, and malignant lymphoma, and potentially a protective factor for oral/oropharyngeal cancer and skin cancer. Sensitivity analyses partially supported robustness, though notable limitations were present for some outcomes. Mediation analysis revealed that isovalerylglycine (mediating 34.12%) and the proline/trans-4- hydroxyproline ratio (28.40%) partially explained GH's effect on breast cancer, while the histidine/ glutamine ratio mediated 36.28% of GH's effect on prostate cancer. Discussion: These findings demonstrate tissue-specific effects of GH on carcinogenesis, partially mediated through metabolic pathways. Results suggest careful risk-benefit assessment in GH therapy and suggest metabolite monitoring could help mitigate cancer risk in susceptible individuals. Conclusion: This Mendelian randomization study provides genetic evidence suggesting a potential causal role of GH exposure and the development of specific cancers, partially mediated by certain metabolites. GH shows both promoting and protective effects depending on the cancer type, with important implications for clinical management. The findings highlight the potential value of exploring risk-stratified approaches in GH replacement therapy and suggest further investigation into metabolic interventions to modulate GH-related cancer risk.
INTRODUCTION:Characterized as an idiopathic primary myocardial disorder, dilated cardiomyopathy (DCM) predominantly affects children and elderly adults. However, a lack of specific clinical symptoms and reliable biomarkers impedes timely diagnosis and rational clinical management of DCM. METHODS:Whole-genome expression profiles (GSE120895, GSE9800) were retrieved from the Gene Expression Omnibus database via the GEOquery R package. A series of bioinformatic methods were employed, including DEG, GSVA, WGCNA, GO/KEGG enrichment, PPI, and immune infiltration analysis. Key biomarkers were validated by qRT-PCR in a Doxorubicin (DOX)-induced DCM model. RESULTS:In total, 629 differentially expressed genes (DEGs) were screened out between DCM and control groups. Combined analysis of DEGs and WGCNA outputs identified 13 hub genes overlapping with oxidative stress-associated gene modules. Receiver Operating Characteristic (ROC) curve analyses confirmed that these hub genes exhibit favorable diagnostic efficiency for DCM. Functional enrichment results showed that these genes are mainly enriched in transmembrane transport and nucleotide metabolism pathways. Immune infiltration analysis indicated significantly elevated infiltration levels of five immune cell subsets in DCM myocardial tissues. In vivo experiments verified the significant upregulation of five core hub genes in DOX-induced DCM mice. By screening hub genes with diagnostic potency based on public transcriptome datasets and validating their expression alterations in a DOX-induced DCM animal model, this study provides partial experimental evidence to support the above bioinformatic outcomes. DISCUSSION:Through integrative analysis of multiple datasets and molecular biology validation, this study provides robust evidence supporting the involvement of these hub genes in DCM pathogenesis. Although validation was limited to a single murine model, the findings lay the groundwork for future mechanistic studies and clinical exploration of these candidate genes. CONCLUSION:Hub genes including MVP, WISP1, FCN1, AMPD3, RARRES1, FTL, and KRT14 possess promising auxiliary diagnostic potential, which provides novel clues for subsequent clinical evaluation research on DCM.
