NDRG1, a cell differentiation-associated factor, has recently emerged as a regulator ferroptosis. Nevertheless, its role in modulating ferroptosis within hepatocellular carcinoma (HCC) remains unchara Show more
NDRG1, a cell differentiation-associated factor, has recently emerged as a regulator ferroptosis. Nevertheless, its role in modulating ferroptosis within hepatocellular carcinoma (HCC) remains uncharacterized. The differential expression of NDRG1 and its prognostic value were analyzed in HCC using data from TCGA and GEO. Ferroptosis in HepG2 and Huh7 cells was assessed using flow cytometry, transmission electron microscopy, and propidium iodide staining following NDRG1 knockdown using shRNA. RNA-seq was performed to characterize the mRNA expression profiles in HepG2 cells, identifying differentially expressed mRNAs (DE-mRNAs) and NDRG1-related hub genes. NDRG1 was overexpressed in multiple malignant tumors, including HCC, and was associated with a significantly poor prognosis in HCC patients. A nomogram model integrating NDRG1 expression and clinical parameters demonstrated robust prognostic accuracy. NDRG1 knockdown potentiated erastin-induced alterations in Fe NDRG1 exhibits strong predictive value for HCC, and accelerates tumor progression by suppressing ferroptosis. Show less
Lifestyle improvement may help reverse prediabetes. Indicators such as Life's Essential 8 (LE8) and biological aging measures (phenotypic age, cardiovascular biological age) partially reflect metaboli Show more
Lifestyle improvement may help reverse prediabetes. Indicators such as Life's Essential 8 (LE8) and biological aging measures (phenotypic age, cardiovascular biological age) partially reflect metabolic status in prediabetes, but their predictive value for cardiovascular mortality and stroke in this population remains unclear. We analyzed data from 74,678 White participants with prediabetes in the UK Biobank, defined by either HbA1c (5.7-6.4%) or fasting glucose (6.1-6.9 mmol/L). Follow-up continued until October 10, 2023. Cox regression was used to examine associations between LE8, phenotypic age (PhenoAge), cardiovascular biological age (CBA), and outcomes of cardiovascular (CVD) mortality and stroke. Restricted cubic spline (RCS) models identified biological age risk thresholds. Mediation analysis assessed whether proteins such as CST3, EFEMP1, FES, IGFBP2, IGFBP6, LPA, PCSK9, and TIMP1 mediated these effects. Over a median follow-up of 13.4 years, 2263 participants died from CVD causes. Each 1-year increase in CBA or PhenoAge was associated with a ~ 10% higher risk of CVD mortality (CBA aHR = 1.10; PhenoAge aHR = 1.09; both P < 0.001), while each 1-point increase in LE8 score was linked to a 3% lower risk (HR = 0.97, P < 0.001). The risk biological ages for these two indicators were also identified: PhenoAge ≥ 58.52 years and CBA ≥ 62.42 years. Similar trends were observed for stroke. Mediation analysis revealed that CST3, TIMP1, IGFBP2, and IGFBP6 contributed to the biological pathways between aging/lifestyle and CVD outcomes. The combined LE8 and PhenoAge model showed the strongest predictive performance for CVD mortality (AUC = 0.716) and stroke (AUC = 0.638) over 15 years. LE8 combined with phenotypic age provides prognostic value for CVD outcomes in prediabetes. These findings highlight the potential of lifestyle modification and delayed biological aging in reversing prediabetes and underscore comorbidity-related proteins as promising therapeutic targets. Show less
The Roucongrong Pill (RCRP), originating from the historical General Medical Collection of Royal Benevolence, is frequently used to treat postmenopausal osteoporosis (PMOP). Despite its prevalent appl Show more
The Roucongrong Pill (RCRP), originating from the historical General Medical Collection of Royal Benevolence, is frequently used to treat postmenopausal osteoporosis (PMOP). Despite its prevalent application, the specific anti-osteoporotic mechanisms of RCRP remain to be elucidated. This study aims to elucidate the therapeutic mechanism of RCRP in the context of ovariectomy (OVX)-induced PMOP in rats. By employing an integrative approach, the research combines medicinal chemistry, gut microbiota (GM) profiling, metabolomics, MetOrigin traceability, network pharmacology, molecular docking, and molecular dynamics simulations to deliver a comprehensive analysis. Sprague-Dawley (SD) rats underwent bilateral OVX to establish a PMOP model. The therapeutic efficacy of RCRP was evaluated through bone metrics (BMD, bone strength, BV/TV, Tb.Sp), hematoxylin and eosin (H&E) histological assessment, and bone metabolism markers (OPG, BALP, TRACP-5b, β-CTX, RANKL). Fecal metabolomics and 16S rDNA sequencing were employed to assess the influence of RCRP on GM and metabolite profiles. Furthermore, MetOrigin facilitated the traceability analysis of relevant metabolites. Molecular docking identified potential RCRP compounds with anti-PMOP activity, while their stability and protein interactions were assessed through molecular dynamics simulations. Network pharmacology further confirms the targets of action. RCRP alleviated PMOP in rats, enhancing bone strength, cortical and trabecular BMD, BV/TV, and serum OPG levels, while reducing Tb.Sp, serum BALP, TRACP-5b, β-CTX, and RANKL concentrations. A total of twenty-six distinct metabolites were identified, of which ten-tribufos, sulfoacetic acid, betamethasone dipropionate, 9-oxooctadeca-10,12,15-trienoic acid, menatetrenone, piperlongumine, maltopentaose, enol-phenylpyruvate, catechol, pentaacetate, and (+)-2-methylpropanoic acid-exhibited correlations with six GM species: Turicibacter, Roseburia, Colidextribacter, Helicobacter, Odoribacter, and Lachnoclostridium, as determined by Spearman's correlation analysis. Notably, MetOrigin revealed the microbial metabolism of taurine and hypotaurine, along with host-specific steroid hormone synthesis. Computational docking studies demonstrated robust interactions between five RCRP-derived steroids (hydroxyecdysone, corticosterone, trilostane, 5α-androstan-3,6,17-trione, and cortisol) and key enzymes (estradiol 17α-dehydrogenase and UDP-glucuronosyltransferase), suggesting a potential enhancement of therapeutic efficacy against PMOP. Furthermore, molecular dynamics simulations indicated stable interactions between hydroxyecdysone and two proteins, with binding free energies of -67.427 kJ/mol and -156.948 kJ/mol, respectively. Through network pharmacology and molecular docking approaches, potential targets of these metabolites were identified, including estrogen receptors ESR1 and ESR2, dual specificity phosphatase 6 (DUSP6), sex hormone-binding globulin (SHBG), prostaglandin E receptor 4 (PTGER4), cannabinoid receptor 2 (CNR2), cathepsin K (CTSK), and androgen receptor (AR). RCRP effectively mitigates OVX-induced bone loss in PMOP rats by modulating GM and associated metabolites, along with their potential targets and key metabolic pathways, including taurine and hypotaurine metabolism, as well as steroid hormone biosynthesis. These findings offer new insights into the therapeutic mechanisms by which RCRP may alleviate PMOP. Show less
This study evaluated the efficacy and safety of tafolecimab in patients with type 2 diabetes (T2D) and hypercholesterolemia by a post-hoc analysis of pooled data from three phase 3 trials. Data from u Show more
This study evaluated the efficacy and safety of tafolecimab in patients with type 2 diabetes (T2D) and hypercholesterolemia by a post-hoc analysis of pooled data from three phase 3 trials. Data from up to 12 weeks were analyzed to assess the effects of tafolecimab 450 mg every four weeks (Q4W) in patients with T2D and hypercholesterolemia. The primary endpoint was the percentage change in low-density lipoprotein cholesterol (LDL-C) levels from baseline to week 12. Secondary endpoints included the proportion of participants achieving LDL-C levels below 1.8 mmol/L at weeks 12, the proportion of patients achieving LDL-C ≥ 50% reduction and LDL-C < 1.4 mmol/L, as well as percentage changes from baseline to week 12 in non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apo B), lipoprotein(a) [Lp(a)], and triglyceride (TG) levels. The reduction in LDL-C from baseline was significantly greater in patients receiving tafolecimab than in those receiving placebo (estimated treatment difference: - 64.02%, 95% confidence interval: [- 68.08%, - 59.96%], P < 0.0001). The proportion of patients achieving a reduction of over 50% and an absolute LDL-C value below 1.4 mmol/L was significantly higher in the tafolecimab group than that in the placebo group (P < 0.0001). Furthermore, a significantly greater proportion of patients in the tafolecimab group achieved LDL-C levels below 1.8 mmol/L at week 12 compared to the placebo group (P < 0.0001). The tafolecimab group also showed significant reductions in TG, non-HDL-C, apo B, and Lp(a) from baseline to week 12 compared to the placebo group (all P < 0.001). The incidence of adverse events was generally similar between the two groups. Tafolecimab 450 mg Q4W demonstrated a superior lipid-lowering efficacy and favorable safety profile compared to placebo. This suggests it could be a promising new treatment option for Chinese patients with T2D and hypercholesterolemia. Show less
Alzheimer's disease (AD) is a common progressive and irreversible neurodegenerative disease. AD accounts for 60%-70% of all dementia cases, ranking as the seventh leading cause of death globally. Huma Show more
Alzheimer's disease (AD) is a common progressive and irreversible neurodegenerative disease. AD accounts for 60%-70% of all dementia cases, ranking as the seventh leading cause of death globally. Human umbilical cord mesenchymal stem cells (hUC-MSCs) characterized by their abundant availability and low immunogenicity, have demonstrated significant therapeutic potential for AD in both preclinical studies and clinical trials. The use of exosomes can help mitigate the issues associated with cellular therapies. However, the clinical application of hUC-MSCs remains challenging due to their inability to effectively traverse the blood-brain barrier (BBB) and reach pathological sites. Therapeutic strategies utilizing exosomes derived from hUC-MSCs (Exos) have emerged as an effective approach for AD intervention. Here, we used ultrasound to construct multifunctional Exos (MsEVB@R/siRNA) for AD therapy. We obtained small interfering RNA for β-site precursor protein lyase-1 (BACE1 siRNA) and berberine for co-delivery into the brain. Berberine, a classical anti-inflammatory agent, effectively alleviates neuroinflammation in AD pathogenesis. BACE1 serves as the pivotal cleavage enzyme in amyloid β-protein (Aβ) formation, where silencing BACE1 synthesis through BACE1 siRNA significantly reduces Aβ production. In a 5xFAD mouse model, Exos selectively targeted microglial and neuronal cells after nasal delivery under the action of neural cell-targeting peptide rabies virus glycoprotein 29 (RVG29). BACE1 siRNA and berberine (BBR) loading enhanced the effectiveness of Exos in improving cognitive function, promoting nerve repair and regeneration, reducing inflammatory cytokine expression, and suppressing glial responses. BACE1 siRNA release was confirmed to reduce BACE1 expression and Aβ deposition. Concurrently, berberine effectively suppressed the release of inflammatory factors, thereby reducing neuroinflammation. In conclusion, the nasal delivery of engineered exosomes is a potentially effective method for treating AD. Show less
Interleukin-27 (IL-27), an Interleukin-12 (IL-12) family heterodimeric cytokine, plays a central yet complex role in immunoregulation within the intestinal mucosa, where its context-dependent actions Show more
Interleukin-27 (IL-27), an Interleukin-12 (IL-12) family heterodimeric cytokine, plays a central yet complex role in immunoregulation within the intestinal mucosa, where its context-dependent actions can promote both protective and pathogenic outcomes. Although its cellular sources, receptor structure (IL-27Rα/gp130 complex), and involvement in regulating key immune cells (e.g., T-cell subsets, macrophages, neutrophils) and epithelial functions are established, the precise mechanisms underlying its paradoxical effects-balancing homeostasis with inflammation-remain incompletely resolved. This review synthesizes current understanding of IL-27 biology to clarify its multifaceted role. Crucial insights into these dual functions have emerged from preclinical models, including murine colitis (e.g., DSS-, TNBS-induced), enteric infection (e.g., Toxoplasma gondii, Citrobacter rodentium), and colorectal cancer models. These studies demonstrate that IL-27 critically orchestrates gut immunity, maintaining homeostasis through antimicrobial defense and barrier enhancement while suppressing immunopathology. Conversely, its dysregulation drives chronic inflammation and carcinogenesis. Clinically, IL-27 expression correlates with disease activity in inflammatory bowel disease (IBD), colorectal cancer (CRC), and infections, highlighting its biomarker potential. Consequently, targeting the IL-27 pathway presents promising therapeutic avenues: augmenting signaling may mitigate IBD hyperinflammation, while inhibition could bolster antitumor immunity or resolve infection-driven pathology. Future research must prioritize defining context-specific IL-27 functions, optimizing delivery strategies, and integrating IL-27 targeting with existing biologics to translate its immunomodulatory potential into novel therapies for intestinal diseases. Show less
Juvenile hormone (JH) is important to maintain insect larval status; however, its cell membrane receptor has not been identified. Using the lepidopteran insect
The intrinsic heterogeneity and invasiveness of diffuse gliomas complicate accurate prognosis. Existing approaches are largely constrained by subtype specificity or limited analytical dimensions. To a Show more
The intrinsic heterogeneity and invasiveness of diffuse gliomas complicate accurate prognosis. Existing approaches are largely constrained by subtype specificity or limited analytical dimensions. To address this gap, a multi- dimension-based prognostic framework encompassing the full glioma spectrum was developed, accompanied by an analysis of the associated immune microenvironment. A total of 3,323 glioma samples from the SEER (n = 2181), CGGA (n = 807), and TCGA (n = 335) datasets were integrated. Differentially expressed genes were screened using the limma package, and a Lasso-Cox-based prognostic signature (Glioma-GDPM) was established. Clinical variables such as age, grade, and IDH mutation status were harmonized through propensity score matching to construct a multi-omics prognostic model (Glioma-GCDPM). GSEA, CIBERSORT-based immune infiltration analysis, and TIDE scoring were used to investigate the biological characteristics of different risk subgroups. Eleven key prognostic genes (such as PRAMEF2 and FADS1) and four clinical factors (age, tumor grade, IDH mutation, and 1p/19q codeletion) were identified. Glioma-GCDPM demonstrated favorable predictive ability in both the internal test cohort (AUC 0.81-0.86) and external validation sets (AUC 0.59-0.83). High-risk tumors exhibited greater invasiveness, with significant enrichment in cell cycle and proliferation-associated pathways. Additionally, a suppressed immune microenvironment was observed, reflected by elevated M2 macrophage infiltration and increased T cell dysfunction scores. The multi-omics model established in this study enables precise stratification of prognostic risk in diffuse glioma patients and reveals immunosuppressive features in high-risk individuals, providing a new basis for personalized treatment strategies. Show less
Ovarian cancer presents a significant treatment challenge due to its insidious nature and high malignancy. As autophagy is a vital cellular process for maintaining homeostasis, targeting the autophagi Show more
Ovarian cancer presents a significant treatment challenge due to its insidious nature and high malignancy. As autophagy is a vital cellular process for maintaining homeostasis, targeting the autophagic pathway has emerged as an avenue for cancer therapy. In the present study, we identify apolipoprotein B100 (ApoB100), a key modulator of lipid metabolism, as a potential prognostic biomarker of ovarian cancer. ApoB100 functioned as a tumor suppressor in ovarian cancer, and the knockdown of ApoB100 promoted ovarian cancer progression in vivo. Moreover, ApoB100 blocked autophagic flux, which was dependent on interfering with the lipid accumulation/endoplasmic reticulum (ER) stress axis. The effects of LFG-500, a novel synthetic flavonoid, on ApoB100 induction were confirmed using proteomics and lipidomics analyses. Herein, LFG-500 induced lipid accumulation and ER stress and subsequently blocked autophagy by upregulating ApoB100. Moreover, data from in vivo experiments further demonstrated that ApoB100, as well as the induction of the lipid/ER stress axis and subsequent blockade of autophagy, were responsible for the anti-tumor effects of LFG-500 on ovarian cancer. Hence, our findings support that ApoB100 is a feasible target of ovarian cancer associated with lipid-regulated autophagy and provide evidence for using LFG-500 for ovarian cancer treatment. Show less
Increasing evidence underscores the driving role of coding and non-coding variants in cancer development. Analyzing gene sets in biological processes offers deeper insights into the molecular mechanis Show more
Increasing evidence underscores the driving role of coding and non-coding variants in cancer development. Analyzing gene sets in biological processes offers deeper insights into the molecular mechanisms of carcinogenesis. Here, we developed geMER to identify candidate driver genes genome-wide by detecting mutation enrichment regions within coding and non-coding elements. We subsequently designed a pipeline to identify a core driver gene set (CDGS) that broadly promotes carcinogenesis across multiple cancers. CDGS comprising 25 genes for 25 cancers displayed instability in DNA aberrations. Variants within the TTN enrichment region may influence the folding of the I-set domain by altering local polarity or side-chain chemistry properties of amino acids, potentially disrupting its antigen-binding capacity in LUAD. Multi-omics analysis revealed that APOB emerged as a candidate oncogene in LIHC, whose genetic alterations within the enrichment region may activate key TFs, upregulate DNA methylation levels, modulate critical histone modifications, and enhance transcriptional activity in the HepG2 and A549 cell lines compared to Panc1. Additionally, CDGS mutation status was an independent prognostic factor for the pan-cancer cohort. High-risk patients tended to develop an immunosuppressive microenvironment and demonstrated a higher likelihood of responding to ICI therapy. Finally, we provided a user-friendly web interface to explore candidate driver genes using geMER ( http://bio-bigdata.hrbmu.edu.cn/geMER/ ). Show less
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective death of motor neurons in the spinal cord, brainstem, and motor cortex. This study investigates the ef Show more
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the selective death of motor neurons in the spinal cord, brainstem, and motor cortex. This study investigates the effects of simvastatin on the G93A-copper/zinc superoxide dismutase (G93ASOD1) transgenic mouse model of ALS. The experiment included three groups: C57BL/6 wild-type mice, C57BL/6J SOD1G93A mice treated with PBS (SOD1G93A + PBS), and C57BL/6J SOD1G93A mice treated with simvastatin (SOD1G93A + simvastatin). The primary endpoints were survival rates, body weight changes, performance in pole climbing and suspension tests, and neurological deficit scores. Pathological changes were assessed using hematoxylin and eosin staining, transmission electron microscopy, Nissl staining, and Masson staining. Proteomic and metabolomic analyses were performed to identify differentially expressed proteins (DEPs) and metabolites. Quantitative real-time polymerase chain reaction and western blotting were used to measure gene expression. Although there were no significant differences in survival rates, body weight, pole climbing, and suspension test performance, or neurological deficit scores between the SOD1G93A + simvastatin and SOD1G93A + PBS groups, simvastatin treatment improved axonal organization within the spinal cord, increased the number of neurons, and reduced cytoplasmic swelling and gastrocnemius fibrosis. A total of 47 DEPs and 13 differential metabolites were identified between the SOD1G93A + PBS and SOD1G93A + simvastatin groups. Notably, the expression levels of Apoa4 and Alb were elevated in the SOD1G93A + simvastatin group compared to the SOD1G93A + PBS group. Our results suggest that simvastatin may have potential therapeutic effects in ALS, likely involving the modulation of Apoa4 and Alb expression. Show less
Calcific aortic valve stenosis (CAVS) can lead to cardiac adverse outcomes; however, currently, no effective pharmacological interventions are available to prevent or delay disease progression. Emergi Show more
Calcific aortic valve stenosis (CAVS) can lead to cardiac adverse outcomes; however, currently, no effective pharmacological interventions are available to prevent or delay disease progression. Emerging evidence has identified significant associations between CAVS and key biomarkers, including Lp(a) (lipoprotein [a]), low-density lipoprotein cholesterol, and PCSK9 (proprotein convertase subtilisin/kexin type 9). However, robust evidence from randomized controlled trials is still lacking to substantiate these associations. The EPISODE (Effect of PCSK9 Inhibitors on Calcific Aortic Valve Stenosis) trial is a prospective, evaluator-blinded, randomized controlled trial designed to assess the therapeutic efficacy of PCSK9 inhibitors in patients with CAVS. A total of 160 patients with mild-to-moderate or asymptomatic severe CAVS will be randomly assigned to receive either statin monotherapy or a combination of statins and PCSK9 inhibitors. Participants will undergo follow-up assessments at 3-month intervals for 24 months, including transthoracic ultrasonic cardiogram, computed tomography, and quality-of-life evaluations using the EuroQol-5 Dimension-3 Level questionnaire. The primary end point is the annualized change in peak aortic jet velocity, whereas secondary end points encompass changes in aortic valve area, calcification score, incidence of heart valve surgery, and quality of life. Safety end points include all-cause mortality and cardiovascular events. The trial aims to evaluate the efficacy of PCSK9 inhibitors in modulating disease progression, reducing adverse cardiovascular events, and improving clinical outcomes in patients with CAVS. The anticipated findings are expected to provide critical insights for developing novel therapeutic strategies for early intervention in CAVS. URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04968509. Show less
Heparan sulfate (HS) is an anionic polysaccharide generated by all animal cells, but our understanding of its roles in human pluripotent stem cell (hPSC) self-renewal and differentiation is limited. W Show more
Heparan sulfate (HS) is an anionic polysaccharide generated by all animal cells, but our understanding of its roles in human pluripotent stem cell (hPSC) self-renewal and differentiation is limited. We derived HS-deficient hPSCs by disrupting the EXT1 glycosyltransferase. These EXT1 Show less
Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treat Show more
Acute respiratory distress syndrome (ARDS) is a common respiratory emergency, but current clinical treatment remains at the level of symptomatic support and there is a lack of effective targeted treatment measures. Our previous study confirmed that inhalation of hydrogen gas can reduce the acute lung injury of ARDS, but the application of hydrogen has flammable and explosive safety concerns. Drinking hydrogen-rich liquid or inhaling hydrogen gas has been shown to play an important role in scavenging reactive oxygen species and maintaining mitochondrial quality control balance, thus improving ARDS in patients and animal models. Coral calcium hydrogenation (CCH) is a new solid molecular hydrogen carrier prepared from coral calcium (CC). Whether and how CCH affects acute lung injury in ARDS remains unstudied. In this study, we observed the therapeutic effect of CCH on lipopolysaccharide (LPS) induced acute lung injury in ARDS mice. The survival rate of mice treated with CCH and hydrogen inhalation was found to be comparable, demonstrating a significant improvement compared to the untreated ARDS model group. CCH treatment significantly reduced pulmonary hemorrhage and edema, and improved pulmonary function and local microcirculation in ARDS mice. CCH promoted mitochondrial peripheral division in the early course of ARDS by activating mitochondrial thioredoxin 2 (Trx2), improved lung mitochondrial dysfunction induced by LPS, and reduced oxidative stress damage. The results indicate that CCH is a highly efficient hydrogen-rich agent that can attenuate acute lung injury of ARDS by improving the mitochondrial function through Trx2 activation. Show less
Sepsis is associated with high morbidity and high mortality and has strongly motivated intense studies into its mechanisms. Antibiotics, aimed to eradicate bacteria, have some impact on the immune sys Show more
Sepsis is associated with high morbidity and high mortality and has strongly motivated intense studies into its mechanisms. Antibiotics, aimed to eradicate bacteria, have some impact on the immune system due to anti-inflammatory properties. Tigecycline, an antibiotic of the glycylcycline class, is commonly used for severe infections. This study aimed to investigate tigecycline's mechanism on the inflammatory response of sepsis to find new targets for sepsis treatment. The objective included (i) to observe the changes in inflammatory factors in LPS (lipopolysaccharide) induced septic mice after tigecycline administration, (ii) to detect the effect of tigecycline on macrophages NF-κB (nuclear factor kappa B) signalling. For LPS-induced sepsis in mice and intervention with tigecycline, mice were first injected with tigecycline (6.5 mg/kg) via tail vein followed by LPS (15 mg/kg). Luminex analysis was performed on 16 mediators. NF-κB signalling pathway antibody chip detected the expression of target sites in macrophages of the LPS group and tigecycline + LPS group. Tigecycline has inhibitory effects on LPS-induced inflammatory response in septic mice, decreasing the concentrations of IL (interleukin)-6, IL-27, TNF-α (tumour necrosis factor-α), TNF RII, IFN-γ (interferon-gamma), CCL5/RANTES (CC Motif Chemokine Ligand) while increasing IL-6Rα, IL-10, and TWEAK (TNF-related weak inducer of apoptosis). Tigecycline downregulated phosphorylation levels of key sites JNK (c-Jun N-terminal kinase)1/2/3, p-p65 (s468) and p-p105/p50 (s907) in NF-κB signalling. Tigecycline may inhibit the excessive immune response induced by LPS in sepsis, which may cause a potential protective effect on the host through immune regulation. Show less
Heart failure (HF) is a serious cardiovascular condition resulting from abnormalities in multiple biological processes, affecting over 64 million people worldwide. We sought to expand our understandin Show more
Heart failure (HF) is a serious cardiovascular condition resulting from abnormalities in multiple biological processes, affecting over 64 million people worldwide. We sought to expand our understanding of the genetic basis of HF and more specific NICM subtype in the East Asian populations and evaluate the biological pathways underlying subclinical left ventricular dysfunction. We conducted a meta-analysis of genome-wide association studies (GWAS) for all-cause HF in the East Asian populations (N cases ~ 13,385) and a more precise definition of nonischemic cardiomyopathy (NICM) subtype in multi-ancestry populations (N cases~3,603). We identified a low-frequency East-Asian enriched coding variant near MYBPC3 and a NICM specific locus. Follow up analyses demonstrated male-specific HF association at the MYBPC3 locus, and highlighted SVIL as a candidate causal gene for NICM. Moreover, we demonstrated that SVIL deficiency aggravated cardiomyocyte hypertrophy, apoptosis and impaired cell viability in phenylephrine (PE)-treated H9C2 cells. In addition, the gene expression level of B-type natriuretic peptide (BNP) which was deemed as a hallmark for HF was further elevated by SVIL silencing in PE-stimulated H9C2 cells. RNA-sequencing analysis of H9C2 cells revealed that the function of SVIL might be mediated through pathways relevant to regulation and differentiation of heart muscle. These results enhance our understanding of the genetic architecture of HF in the East Asian populations, and provide important insight into the biological pathways underlying NICM and sex-specific relevance of the MYBPC3 locus that warrants further replication in another datasets. Show less
Hui Wang, Timothy S Chang, Beth A Dombroski+64 more · 2025 · Movement disorders : official journal of the Movement Disorder Society · Wiley · added 2026-04-24
The 17q21.31 region with various structural forms characterized by the H1/H2 haplotypes and three large copy number variations (CNVs) represents the strongest risk locus in progressive supranuclear pa Show more
Energy deprivation and metabolic rewiring of cardiomyocytes are widely recognized hallmarks of heart failure. Here, we report that HEY2 (a Hairy/Enhancer-of-split-related transcriptional repressor) is Show more
Energy deprivation and metabolic rewiring of cardiomyocytes are widely recognized hallmarks of heart failure. Here, we report that HEY2 (a Hairy/Enhancer-of-split-related transcriptional repressor) is upregulated in hearts of patients with dilated cardiomyopathy. Induced Hey2 expression in zebrafish hearts or mammalian cardiomyocytes impairs mitochondrial respiration, accompanied by elevated ROS, resulting in cardiomyocyte apoptosis and heart failure. Conversely, Hey2 depletion in adult mouse hearts and zebrafish enhances the expression of mitochondrial oxidation genes and cardiac function. Multifaceted genome-wide analyses reveal that HEY2 enriches at the promoters of genes known to regulate metabolism (including Ppargc1, Esrra and Cpt1) and colocalizes with HDAC1 to effectuate histone deacetylation and transcriptional repression. Consequently, restoration of PPARGC1A/ESRRA in Hey2- overexpressing zebrafish hearts or human cardiomyocyte-like cells rescues deficits in mitochondrial bioenergetics. Knockdown of Hey2 in adult mouse hearts protects against doxorubicin-induced cardiac dysfunction. These studies reveal an evolutionarily conserved HEY2/HDAC1-Ppargc1/Cpt transcriptional module that controls energy metabolism to preserve cardiac function. Show less
To investigate the clinical and pathological characteristics of patients with non-small cell lung cancer exhibiting coexistence of Clinical data, as well as histopathological, immunohistochemical, and Show more
To investigate the clinical and pathological characteristics of patients with non-small cell lung cancer exhibiting coexistence of Clinical data, as well as histopathological, immunohistochemical, and molecular pathological characteristics, of two patients harboring both Both patients were women aged 57 and 66 years. The two cases were diagnosed as invasive lung adenocarcinoma, and immunohistochemical staining showed that all tumor cells expressed CK7, Napsin A, TTF-1, and PD-L1. In Case 1, an Show less
Despite preclinical evidence for berberine's antidepressant potential, its pharmacological effects remain controversial.This study therefore systematically reviews animal research to clarify its mecha Show more
Despite preclinical evidence for berberine's antidepressant potential, its pharmacological effects remain controversial.This study therefore systematically reviews animal research to clarify its mechanisms and support future clinical trials. We searched PubMed, Embase, Web of Science, Cochrane Library, and OVID for studies on berberine in depression models up to March 20, 2025. Analysis used STATA 15.0 and Review Manager 5.4, with study quality assessed via SYRCLE's risk of bias tool. The meta-analysis included 18 studies (338animals). Overall, berberine significantly reduced depression-like behaviors in animal models.Specifically, BBR increased total locomotor activity in the open field test (SMD=2.79, 95% CI: 1.55, 4.02) and time spent in the center zone (SMD=2.49, 95% CI:1.61, 3.37), reduced immobility time in both the forced swim test and tail suspension test (SMD =-4.42, 95% CI:-5.77,-3.07; SMD=-4.46, 95% CI:-6.21, -2.71), increased sucrose intake in the sucrose preference test (SMD = 3.72, 95% CI: 2.37, 5.07), and reduced feeding latency in the novelty-suppressed feeding test (SMD=-5.72, 95% CI:-7.63, -3.82). However, BBR did not significantly alter the number of square crossings (SMD=1.36, 95%CI:-0.07 , 2.79) or rearing frequency (SMD=1.66, 95% CI: -0.29, 3.61) in the open field test. BBR also increased the levels of body weight, brain-derived neurotrophic factor, dopamine, serotonin, and norepinephrine,while reducing the levels of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6. Preclinical studies suggest that berberine may represent a promising therapeutic agent for the treatment of depressive disorders. Its antidepressant effects appear to be closely associated with the modulation of neurotransmitter levels,reduction of oxidative stress, and inhibition of inflammatory responses.However, methodological limitations may constrain these findings. Larger, more rigorous preclinical studies are needed for confirmation. https://inplasy.com/inplasy-2025-6-0002, identifier INPLASY202560002. Show less
Cang Li · 2025 · Bulletin of experimental biology and medicine · Springer · added 2026-04-24
The paper is aimed to screen the target molecules of miR-12 and to further explore the mechanism of GAS5 action in prostate cancer. The expression of GPRC5B in prostate cancer cell lines LNCaP, VCaP, Show more
The paper is aimed to screen the target molecules of miR-12 and to further explore the mechanism of GAS5 action in prostate cancer. The expression of GPRC5B in prostate cancer cell lines LNCaP, VCaP, 22RV1, DU145, and PC3 was measured by quantitative real-time PCR with reverse transcription (RT-qPCR) and variations in GPRC5B expression were analyzed after down-regulating GAS5 or silencing miR-12. CCK8 and plate clone experiments were performed to detect changes in proliferative activity and colony-forming capacity of prostate cancer cells after down-regulating GPRC5B. After transfection of prostate cancer cells with sh-GAS5 and/or miR-12 inhibitor, the changes in GPRC5B expression were evaluated with RT-qPCR and Western blotting. Our results showed that GPRC5B was highly expressed in prostate cancer cell lines. Down-regulating of GAS5 decreased GPRC5B expression, while silencing miR-12 increased it. CCK8 and plate clone experiments showed that expression of GPRC5B increased proliferative activity and clone formation ability of prostate cancer cells. RT-qPCR and Western blotting revealed that miR-12 inhibited the promoting effect of GAS5 on GPRC5B expression. Thus, GPRC5B is directly bound to miR-12. GAS5 promotes proliferation, migration, and invasion of prostate cancer cells and participates in malignant progression of tumors by suppressing miR-12-mediated regulation of GPRC5B expression. Show less
Studies showed that contaminants adhered to the surface of nano-polystyrene microplastics (NPs) have a toxicological effect. Juveniles tilapia were dispersed into four groups: the control group A, 75 Show more
Studies showed that contaminants adhered to the surface of nano-polystyrene microplastics (NPs) have a toxicological effect. Juveniles tilapia were dispersed into four groups: the control group A, 75 nm NPs exposed group B, 5 ng·L Show less
Atherosclerosis is the leading cause of cardiovascular disease-related morbidity and mortality. The traditional Chinese medicine Qingre Sanjie Formula (QRSJF), composed of Prunellae Spica, Sargassum, Show more
Atherosclerosis is the leading cause of cardiovascular disease-related morbidity and mortality. The traditional Chinese medicine Qingre Sanjie Formula (QRSJF), composed of Prunellae Spica, Sargassum, Fritillariae Thunbergii Bulbus, Leonuri Herba, and Forsythiae Fructus, has shown efficacy in treating cardiovascular diseases, although its mechanisms are unclear. This study aimed to explore the protective effects of QRSJF against atherosclerosis and the mechanisms involved. The composition of QRSJF was analyzed using Ultra Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry. An 8-week high-fat diet (HFD)-induced atherosclerosis model was established in ApoE Both low- and high-dose QRSJF effectively attenuated dyslipidemia and decreased serum inflammatory cytokine levels in HFD-fed ApoE QRSJF improves dyslipidemia and reduces atherosclerotic plaque in ApoE Show less
Diabetic retinopathy (DR) is a common complication of type II diabetes mellitus (T2DM) and a leading cause of blindness in the working population. Apolipoprotein levels have been reported to be associ Show more
Diabetic retinopathy (DR) is a common complication of type II diabetes mellitus (T2DM) and a leading cause of blindness in the working population. Apolipoprotein levels have been reported to be associated with the risk of DR. This study aimed to develop a predictive model for DR based on apolipoproteins (apoA and apoB) and menopausal status in Chinese Han women with T2DM and to evaluate the model's effectiveness. Data from 2339 T2DM women were collected between January 2018 and June 2022. Multilevel regression was used to explore the independent effect of apolipoproteins and interaction between apolipoproteins and menopausal status on DR and proliferative diabetic retinopathy (PDR). Receiver operating characteristic (ROC) analysis was performed to compare the fitting degree and predictive efficiency of different models. Results showed that both apoA and apoB were independent influencing factors for DR and PDR and interacted significantly with menopausal status. The interaction between apoA and menopausal status had a protective effect on DR [OR (95% CI) = 0.925 (0.858-0.996), P = 0.040] and PDR [OR (95% CI) = 0.937 (0.895-0.981), P = 0.006]. In contrast, the interaction between apoB and menopausal status was a risk factor for DR [OR (95% CI) = 1.684 (1.141-2.379), P = 0.008)] and PDR [OR (95% CI) = 3.377 (1.148-9.937), P = 0.027]. ROC analysis demonstrated that the interaction model outperformed models without interaction terms (P < 0.01). The area under the curve for the interaction model was 0.879 (95% CI 0.864-0.893) for DR and 0.930 (95% CI 0.915-0.945) for PDR. These findings suggest that the interaction model is highly efficient in predicting DR, particularly PDR, in Chinese Han women with T2DM. Show less
To identify distinct sleep quality profiles among patients undergoing maintenance hemodialysis (MHD) using latent profile analysis (LPA), and examine differences in perceived stigma across these sleep Show more
To identify distinct sleep quality profiles among patients undergoing maintenance hemodialysis (MHD) using latent profile analysis (LPA), and examine differences in perceived stigma across these sleep quality subtypes. From December 2024 to March 2025, a total of 334 MHD patients were recruited via convenience sampling from the nephrology departments of two tertiary hospitals in Xinjiang, China. Data were collected using structured questionnaires, including the Pittsburgh Sleep Quality Index (PSQI), the Self-Rating Depression Scale (SDS), and the Social Impact Scale (SIS), along with sociodemographic and clinical information. LPA was employed to identify latent subgroups of sleep quality based on PSQI components. Multinomial logistic regression was used to determine predictors of sleep profile membership. Differences in stigma scores across sleep profiles were analyzed using non-parametric equivalents. Three distinct sleep profiles were identified: Class 1 - "overall better sleep", Class 2 - "short sleep duration and low efficiency", and Class 3 - "poor sleep quality with high medication use". Multinomial logistic regression identified comorbid heart failure (OR=2.867, Patients with MHD exhibit heterogeneous patterns of sleep disturbance, which are associated with varying levels of perceived stigma. Those with the poorest sleep quality and highest reliance on medication experience the most pronounced stigma. Tailored interventions addressing sleep-related issues and psychosocial factors may help reduce stigma and improve patient well-being. Show less