Causal Associations with Arterial Stiffness and Sarcopenia: A Mendelian Randomization Analysis
Observational studies and clinical trials indicate a link between arterial stiffness (AS) and sarcopenia (SAR), yet the causal relationship between these remains unclear. The study aims to investigate the causal connection from AS to SAR by Mendelian randomization (MR). We analyzed Genome-Wide Association Studies data for AS indicators: pulse wave arterial stiffness index (PWASI) and pulse wave peak-to-peak time (PPT), and SAR indicators: low hand grip strength (LHGS), usual walking pace (UWP), moderate-to-vigorous physical activity levels (MVPA), and walk or cycle unassisted for 10 minutes. The inverse variance-weighted, MR-Egger, weighted mode, and weighted median were applied to MR. There is a bidirectional causal relationship between the AS and SAR. The PWASI has a causation with UWP (odds ratio [OR] = 0.97, 95% confidence interval [CI] = 0.94-0.99). The PPT has a causal association with MVPA (OR = 1.08, 95% CI = 1.002-1.144) and UWP (OR = 1.05, 95% CI = 1.017-1.096). The LHGS is causally associated with PPT (OR = 0.95, 95% CI = 0.91-0.98) and UWP has a causal association with PWASI (OR = 0.77, 95% CI = 0.65-0.90) and PPT (OR = 1.37, 95% CI = 1.17-1.60). The increased AS could reduce the motor ability slightly and the lower upper and lower limb strength could lead to the higher AS. This bidirectional causal relationship of the two may offer novel perspectives for advancing the understanding of the underlying mechanisms related to AS and muscle pathophysiology.
Effects of Predictive Nursing Process on Elderly Patients with Total Hip Arthroplasty
Elderly individuals represent a significant demographic undergoing total hip arthroplasty, with distinct risks and complications. The study aimed to determine whether predictive nursing, guided by risk assessment, could reduce these risks and improve patient outcomes. A total of 191 elderly patients undergoing total hip arthroplasty were included in the study, with 142 patients randomly assigned to either the control or observation groups. The control group received routine care, while the observation group received predictive nursing based on comprehensive risk assessment. Various assessment tools were employed to evaluate risks such as venous thrombosis, pressure injuries, falls, joint dislocation, infections, and psychological factors. The primary outcomes included functional improvement measured by the Harris Hip Score, Activities of Daily Living (ADL), anxiety levels, and patient satisfaction. Our study demonstrated that predictive nursing interventions, guided by comprehensive risk assessment, yielded significant reductions in postoperative complications, particularly deep vein thrombosis, in elderly patients undergoing total hip arthroplasty. In addition, patients who received predictive nursing care experienced notable benefits, including shorter hospital stays, heightened satisfaction levels, enhanced hip function, improved ADL scores, and reduced anxiety levels compared with those receiving standard care. The study underscores the substantial benefits of predictive nursing interventions guided by risk assessment in improving outcomes for elderly patients undergoing total hip arthroplasty, highlighting the potential of individualized nursing care to optimize postoperative recovery and enhance patient well-being.
Relationship of Serum Fibroblast Growth Factor 23, Hypoxia-Inducible Factor-1α, and Klotho with In-Stent Restenosis in Elderly Patients with Coronary Artery Disease after the Treatment of Percutaneous Coronary Intervention
In-stent restenosis (ISR) commonly occurs in elderly patients with coronary artery disease (CAD) after percutaneous coronary intervention. Atherosclerosis in elderly patients may be the leading cause of ISR. Therefore, we aim to explore the relationship between vascular calcification-associated factors and ISR occurrence. Elderly patients were enrolled according to standard inclusion and exclusion criteria. The serum fibroblast growth factor 23 (FGF23), hypoxia-inducible factor-1α (HIF-1α), and Klotho levels were determined using an enzyme-linked immunosorbent assay. The degree of coronary artery stenosis of the patients with CAD before operation was assessed using the Gensini score. The correlation was analyzed using Pearson analysis. The prediction value was evaluated using receiver operating characteristic (ROC) curve analysis. The patients with CAD were classified into the ISR group with 97 cases and the non-ISR (NISR) group with 349 cases. The Gensini score, serum FGF23, and HIF-1α levels increased while Klotho levels decreased in patients with CAD of the ISR group compared with those of the NISR group. Pearson analysis showed that FGF23 and HIF-1α positively correlated while Klotho negatively correlated to the Gensini score. ROC analysis showed all three factors could effectively predict the occurrence of ISR. Furthermore, the joint had a more effective prediction value for ISR occurrence. The dynamic analysis presented that the serum FGF23 and HIF-1α levels dramatically increased while Klotho levels decreased in patients with CAD after 1-year follow-up. Serum FGF23 and HIF-1α positively correlated while serum Klotho negatively correlated to ISR. Conclusively, these three factors effectively predicted the occurrence of ISR.
Luteolin Exhibits Anxiolytic and Antidepressant Potential in Parkinson's Disease Rat: Antioxidant and Anti-Inflammatory Effects
Parkinson's disease (PD) is accompanied by a complex array of nonmotor and motor manifestations. The exploration of anti-inflammatory and antioxidant active ingredient as potential therapeutic interventions in PD-associated mood alterations has gained significant attention. This study aimed to assess the antidepressant and anxiolytic properties of luteolin (LTN), a potent antioxidant and anti-inflammatory component, using a 6-hydroxydopamine (6-OHDA)-induced animal model of PD. Rats were administered LTN (10, 25, and 50 mg/kg, per oral) and fluoxetine (10 mg/kg/per oral) over a 28-day period. Behavioral tests were employed to estimate the depression- and anxiety-like behaviors. Rats treated with LTN exhibited significant improvement in 6-OHDA-induced mood alterations, as per behavioral tests. Additionally, LTN treatment led to increased hippocampal levels of catalase and superoxide dismutase, and a reduction in malondialdehyde. LTN downregulated the gene expression of nuclear factor kappa B (NF-κB)/nod-like receptor (NLR) pyrin domain-containing 3 (NLRP3) axis components, including NF-κB, NLRP3, ASC, and Caspase1 and reduced the protein level of pro-inflammatory cytokines, including interleukin (IL)-6, interleukin (IL)-1β, and tumor necrosis factor alpha (TNF-α), in addition to augmenting the protein levels of TNF-α, IL-1β, and IL-6. Furthermore, LTN exhibited an upregulatory effect on the anti-inflammatory cytokine IL-10 within the hippocampus of 6-OHDA-induced PD rats. Also, molecular docking showed higher affinity between LTN and NF-κB/NLRP3 axis components. These findings highlight the potential anxiolytic and antidepressant impacts of LTN through its antioxidant and anti-inflammatory mechanisms against 6-OHDA-induced alterations in a rat PD model.
Systems Pharmacology to Explore the Potential Mechanism of Ginseng Against Heart Failure
The aim of this study is to elucidate the pharmacological mechanism underlying the effects of Ginseng Radix et Rhizoma (ginseng) in heart failure (HF), providing a theoretical foundation for its clinical application. The potential mechanism of ginseng in the context of HF was investigated using systems pharmacology that combined network pharmacology, Gene Expression Omnibus (GEO) analysis, molecular docking, and experimental verification. Network pharmacology was employed to identify drug-disease targets. Core gene targets were subsequently subjected to enrichment analysis by integrating network pharmacology with GEO. Molecular docking was utilized to predict the binding affinities between identified targets and ginseng compounds. Furthermore, the therapeutic efficacy of ginseng was validated in an isoproterenol (ISO)-induced rat model of HF. The modulation of key signaling pathways by ginseng was confirmed through Western blot analysis. A total of 154 potential targets of ginseng in the treatment of HF were identified through network pharmacology analysis. The analysis of GSE71613 revealed that the PI3K-Akt pathway, reactive oxygen species, oxidative phosphorylation, MAPK signaling, and Ras signaling pathways are predominantly associated with patients with HF. By integrating the findings from network pharmacology and GEO analysis, ginsenoside Rg1 and ginsenoside Rb3 were identified as the potential components in ginseng, while and were recognized as key targets involved in the PI3K-AKT and AMPK pathways, respectively. Molecular docking analysis revealed a strong affinity between the potential components and the identified core targets. experiments indicated that the extract of ginseng (EPG) significantly ameliorated ISO-induced cardiac dysfunction by improving cardiac parameters such as cardiac left ventricular internal systolic diameter, left ventricular end-diastolic volume, left ventricular end systolic volume, and left ventricular ejection fraction, while also reducing malondialdehyde production. In addition, EPG was found to enhance superoxide dismutase activity and ATP levels, while concurrently reducing the levels of interleukin (IL)-1β, IL-6, and TNF-α. The extract also reduced myocardial oxygen consumption, inflammatory cell infiltration, and the number of damaged myocardial fibers. Moreover, EPG was observed to upregulate the expression of p-PI3K, p-AKT, p-AMPK, and Bcl-2, while downregulating the expression of p-NFκB, TGF-β, and Bax. The therapeutic effects of ginseng on HF are primarily mediated through the PI3K-Akt and AMPK pathways. Ginsenoside Rg1 and ginsenoside Rb3 have been identified as potential therapeutic agents for HF.
Continuing the Legacy: Understanding and Reducing Tissue Aging to Prevent Many Currently Incurable Diseases
Molecular Mechanisms of Dietary Bioactive Peptides in Treating Alzheimer's Disease and Mild Cognitive Impairment by Network Pharmacology and Molecular Docking Analysis
Emerging evidence suggests that bioactive peptides from various foods have therapeutic potentials in improving cognitive function in Alzheimer's disease (AD) and mild cognitive impairment (MCI). We aimed to explore the characteristics of these peptides and their mechanisms on AD/MCI using a network pharmacology approach. We compiled a dataset of cognition-enhancing peptides from literatures and identified shared targets between these peptides and AD/MCI using Swiss Target Predication, PharmMapper, OMIM, GeneCards, TTD, and Drugbank databases. We then performed functional enrichment analysis and constructed a gene-gene interaction network to identify key hub targets. Additionally, we investigated the transcription factors (TFs) and microRNAs (miRNAs) regulating these hub genes. Molecular docking and dynamic simulations were performed using AutoDock Vina and GROMACS. We identified 59 cognition-enhancing oligopeptides, typically short and rich in arginine. These peptides were predicted to interact with 222 potential targets relevant to AD/MCI, with functional pathways mainly involving neuroactive ligand-receptor interactions and inflammation. We identified 15 hub targets, regulated by 144 TFs and 95 miRNAs. Notably, peptides containing the "Trp-Tyr" sequence demonstrated strong binding affinities to many hub targets, especially matrix metalloproteinase-9. The findings provided valuable insights into the molecular mechanisms through which bioactive peptides may act against AD/MCI and highlight the potential of network pharmacology for future exploration of bioactive peptides from natural foods.
The Epigenetic Landscape: From Molecular Mechanisms to Biological Aging
Epigenetics, the study of heritable changes in gene expression that do not involve alterations to the deoxyribonucleic acid (DNA) sequence, plays a pivotal role in cellular function, development, and aging. This review explores key epigenetic mechanisms, including DNA methylation (DNAm), histone modifications, chromatin remodeling, RNA-based regulation, and long-distance chromosomal interactions. These modifications contribute to cellular differentiation and function, mediating the dynamic interplay between the genome and environmental factors. Epigenetic clocks, biomarkers based on DNAm patterns, have emerged as powerful tools to measure biological age and predict health span. This article highlights the evolution of epigenetic clocks, from first-generation models such as Horvath's multi-tissue clock to advanced second- and third-generation clocks such as DNAGrimAge and DunedinPACE, which incorporate biological parameters and clinical biomarkers for precise age estimation. Moreover, the role of epigenetics in aging and age-related diseases is discussed, emphasizing its impact on genomic stability, transcriptional regulation, and cellular senescence. Epigenetic dysregulation is implicated in cancer, genetic disorders, and neurodegenerative diseases, making it a promising target for therapeutic interventions. The reversibility of epigenetic modifications offers hope for mitigating age acceleration and enhancing health span through lifestyle changes and pharmacological approaches.
Relationship of α-Klotho with Frailty Index and Sarcopenia: A Bidirectional Mendelian Randomization Study
Previous studies have established associations between α-Klotho and frailty or sarcopenia; however, the causal nature of these relationships remains unclear. This study investigates the causal effects of α-Klotho on frailty and sarcopenia-related traits using Mendelian randomization (MR). Genetic instruments for circulating α-Klotho concentrations, frailty index (FI), low grip strength (LGS), appendicular lean mass (ALM), and walking pace were developed based on data from large genome-wide association studies. Two-sample MR analyses were performed, supplemented by sensitivity analyses to ensure the robustness of the findings. Reverse MR analyses were also conducted to explore potential reverse causation. The findings demonstrated an inverse causal relationship of circulating α-Klotho levels with FI ( = -0.020, 95% confidence interval [95% CI] = -0.036 to -0.004; = 0.017) and LGS ( = -0.033, 95% CI = -0.061 to -0.004; = 0.023). However, no causal relationship was observed between circulating α-Klotho levels and ALM or walking pace. Additionally, no evidence of reverse causation was identified between FI or sarcopenia-related traits and circulating α-Klotho levels. In conclusion, this MR analysis establishes an inverse causal relationship of circulating α-Klotho levels with both FI and LGS.
Dietary Restriction Attenuates Inflammation and Protects Mouse Skin from High-Dose Ultraviolet B Irradiation (doi: 10.1089/rej.2021.0022)
Parishin Alleviates Pulmonary Fibrosis by Reducing CD38 Levels in Naturally Aging Mice
Parishin, a natural compound, has demonstrated significant potential in mitigating age-related phenotypes and improving outcomes in age-associated diseases. Given that aging is a major risk factor for numerous chronic conditions, including pulmonary fibrosis, we investigated parishin's effects on cellular senescence and lung health. In our study, we treated mouse lung epithelial cells with parishin and observed a reduction in cellular senescence markers alongside an upregulation of sirtuin 1 (SIRT1). Building on these findings, we administered parishin to naturally aged mice. The treatment resulted in decreased pulmonary fibrosis and reduced DNA damage in lung tissue. Notably, we found that parishin treatment led to a reduction in Cluster of differentiation 38 (CD38) levels, concomitant with an increase in SIRT1 expression. These findings indicate that parishin may enhance lung function in aged mice, suggesting its potential as a therapeutic agent for treating age-related pulmonary disorders.
Related Factors with Vascular Dementia: A Two-Sample Mendelian Randomization Study
Pathogenesis of vascular dementia (VD) is still unclear, there are currently no effective prevention and treatment methods. We applied Mendelian randomization (MR) using summary statistics from large-scale GWAS of metabolites and VD to reveal the causal effect of metabolites on the VD. One set of genetics instrument was used for analysis, derived from publicly available genetic summary data. Which was 32 single-nucleotide polymorphisms robustly associated with metabolites. Inverse-variance weighted, weighted median method, MR-Egger regression, and MR Pleiotropy RESidual Sum and Outlier test were used for MR analyses. Strong evidence for a positive effect of metabolites, which means N6-threonylcarbamoyladenosine (tA) on VD was found in inverse-variance weighted (odds ratios [OR]: 0.667, 95% confidence interval [CI]: 0.548-0.812, < 0.001), MR-Egger (OR: 0.647, 95% CI: 0.458-0.913, = 0.019), and weighted median (OR: 0.650, 95% CI: 0.466-0.908, = 0.012). The MR analysis indicated that metabolites (tA) may be causally associated with a positive effect on VD.
Association Between Arterial Stiffness Index and Age-Related Diseases: A Mendelian Randomization Study
Arterial stiffness is an emerging indicator of cardiovascular risk, but its causal relationship with a variety of age-related diseases is unclear. The objective is to assess the causal relationship between arterial stiffness index (ASI) and age-related diseases by Mendelian randomization (MR) analysis. We obtained instrumental variables associated with age-related diseases from genome-wide association studies (GWAS) of 484,598 European individuals, and data for ASI were obtained from the UK Biobank GWAS of 127,127 participants. We used the inverse variance-weighted as the primary analysis method. In addition, several sensitivity analyses including MR-Egger, weighted-median (WM), Mendelian randomization pleiotropy residual sum and outlier, and Cochran's Q test were performed to test the robustness of the results. Reverse MR analysis was also performed to assess reverse causal relationships between age-related diseases and ASI. We verified the causal relationship between eight age-related diseases and ASI, of which cardiovascular disease ( = 0.19), gallbladder disease ( = 0.85), liver, biliary, or pancreas problem ( = 1.02), hypertension ( = 0.19), joint disorder ( = 0.53), and esophageal disorder ( = 2.10) elevated ASI. In contrast, hyperthyroidism or thyrotoxicosis ( = -2.17) and bowel problems ( = -1.83) may reduce ASI. This MR analysis reveals causal relationships between ASI and several age-related diseases. ASI is expected to be a potential indicator of health conditions for older populations.
Moxibustion Regulates the Expression of T Cells in Rheumatoid Arthritis Through Tim-3/Gal-9 Signaling Pathway
To observe the effects of moxibustion on T cells and T cell immunoglobulin and mucin-domain-containing molecule-3/galectin-9 (Tim-3/Gal-9) pathway in rats with rheumatoid arthritis (RA). To further explore the possible anti-inflammatory mechanism of moxibustion in the treatment of RA. Thirty Sprague Dawley rats were randomly divided into three groups, including a control group, an RA model group, and a moxibustion group. An RA model was created through the injection of Freund's complete adjuvant. In the moxibustion group, rats were treated with moxibustion at acupoints of "Shenshu" and "Zusanli." A total of three courses of treatment were conducted. Then the thickness of foot pad was measured, joint pathological changes were observed by hematoxylin-eosin (HE) staining, the proportion of CD4T and CD8T in peripheral blood was detected by flow cytometry, the expression levels of Tim-3 and Gal-9 in synovium were detected by polymerase chain reaction (PCR), and the expressions of CD4T and CD8T in synovium were detected by immunofluorescence. HE staining showed that the synovial tissue of the control group was smooth and neatly arranged without inflammatory cell infiltration. In the model group, the joint space was narrowed, the synovial tissue had congestion and edema, and a large number of inflammatory cells infiltrated. Compared with the model group, in the moxibustion group, the joint space narrowed with synovium hyperemia and edema, and the level of inflammatory cell infiltration decreased. Flow cytometry showed that compared with the model group, CD4T expression in the moxibustion group was downregulated, while CD8T expression was upregulated. PCR results showed that compared with the model group, the expressions of Tim-3 and Gal-9 in the moxibustion group were upregulated. Immunofluorescence results showed that compared with the model group, CD4T expression in the moxibustion group was decreased, while CD8T expression was increased. The results demonstrate that moxibustion not only suppressed the expression of CD4T but also promoted the expression of CD8T. The anti-inflammatory effect of moxibustion may be related to the regulation of T cell expression through the Tim-3/Gal-9 signaling pathway.
Comparison of Antioxidant Activities of Extracts According to Harvest Area
is a medicinal plant native to East Asia with its diverse therapeutic potentials. In particular, the antioxidant effect of this plant is well known, but there has been little research on the antioxidant effect according to different habitats or ages. In this study, we evaluated the proximate composition, mineral, saponin, rutin, total phenolic and flavonoid contents, and antioxidant activities of leaf extracts of plants cultivated from two different regions (New Zealand and Jeju Island, Korea) and of the same age (2-year-old plants). The assessment of proximate composition and total phenolic and flavonoid contents revealed significant variations in these parameters dependent on the cultivation region and age. The highest total phenol and total flavonoid contents were observed in from Jeju Island. In addition, the antioxidant activities of leaf extracts of from different cultivation regions and ages were assessed in terms of 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)free radical scavenging, total antioxidant capacity, and superoxide dismutase activity. The extract of from Jeju Island showed the highest antioxidant activity among the samples tested. These findings clearly indicate that both the cultivation region and plant age affect the phytochemical content and antioxidant activity of . Therefore, extracts of obtained from optimal harvest regions and ages could serve as promising natural antioxidant candidates with potential health benefits.
Causal Association of Sleep Traits with All-Cause and Cause-Specific Mortality: A Prospective Cohort and Mendelian Randomization Study
The study aimed to explore the association between different sleep traits and all-cause mortality as well as to validate causality in the association through mendelian randomization (MR). We analyzed 451,420 European ancestry participants from the UK Biobank. Multivariable-adjusted Cox proportional hazards model was conducted to evaluate the association between sleep traits and all-cause mortality. In MR analysis, the inverse variance weighting (IVW) method was applied as the primary analysis to investigate the causal association between sleep traits and mortality. During a median follow-up period of 12.68 years, 34,397 individuals died. Observational analyses showed the multivariate-adjusted hazard ratio (HR) and 95% confidence intervals (CIs) for short sleep, long sleep, early chronotype, daytime sleepiness, daytime napping, and insomnia with mortality, 1.246 (1.195, 1.298), 1.735 (1.643, 1.831), 0.931 (0.909, 0.953), 1.276 (1.212, 1.344), 1.299 (1.254, 1.346), and 1.117 (1.091, 1.142) (All < 0.0001). Based on UK Biobank, MR analysis indicated the association between daytime napping and an increased risk of all-cause mortality (odd ratio [OR]: 1.219, 95% CI: 1.071-1.387, = 0.003), which may be largely attributable to cancer disease mortality (OR: 1.188, 95% CI: 1.009-1.399, = 0.039). We found no causal association between sleep duration, short sleep, long sleep, chronotype, daytime sleepiness, insomnia, and mortality risk. The causal associations between sleep traits and all-cause mortality risk were directionally replicated in FinnGen. Our findings suggest a potential causal association between daytime napping and increased risk of all-cause mortality in middle-aged and older persons. The finding could have important implications for evaluating daytime napping habits to decrease the risk of mortality.
Transition of Physical, Psychological, and Cognitive Frailty and Its' Associated Determinants in Malaysian Older Adults: A 5-Year Follow-up Study
Frailty, a multifaceted syndrome, affects approximately 26% of older adults globally, yet there are limited data on the prevalence and longitudinal impact of frailty subtypes. Therefore, in this study, we aim to determine the prevalence of physical, psychological, and cognitive frailty, transitions between subtypes, and associated health determinants among Malaysian community-dwelling older adults. This study is part of the longitudinal aging study in Malaysia (LRGS Ageless and TUA). We assessed 815 older adults in 2014, with successful follow-up of 402 participants (mean age: 67.08 ± 5.38 years) after 5 years. Frailty subtypes were assessed at baseline, and transitions were evaluated at the 5-year mark. At baseline, the prevalence of older adults categorized as robust, physical frailty, cognitive frailty, and psychological frailty was 26.7%, 36.3%, 12.1%, and 16.7%, respectively, with 8.1% exhibiting concurrent psychological and cognitive frailty. Follow-up results showed that 22.9% remained robust, 46.8% experienced no change, 24.9% deteriorated (adversed), and 5.5% improved (reversed). Logistic regression analysis identified living alone ( < 0.001), increased body fat percentage ( < 0.05), increased waist circumference ( < 0.05), reduced fat-free mass ( < 0.05), decreased lower limb flexibility ( < 0.05), and declined cardiorespiratory fitness ( < 0.05) as significant predictors of frailty deterioration. Higher Mini Mental State Examination (MMSE) scores and improved Timed Up and Go and Chair Stand test results ( < 0.05) were significantly associated with the reversal of frailty subtypes ( < 0.05). Younger older adults ( < 0.001), males ( < 0.05), those with lower WHO Disability Scale scores ( < 0.05), and higher MMSE scores ( < 0.05) were significantly less likely to develop frailty subtypes. Intervention strategies that focus on combined physical, cognitive, and psychosocial functions are crucial for both reversing and preventing the progression of frailty subtypes in older adults.
Sarcopenia Is Associated with Neoplasm of Bone and Articular Cartilage: Findings from Mendelian Randomized Study
Exploring the causal relationship between sarcopenia and neoplasm of bone and articular cartilage (NBAC) by bidirectional Mendelian randomization (MR). Genome-wide association study (GWAS) data on sarcopenia-associated traits including appendicular lean mass, low handgrip strength (including criteria from the European Working Group on Sarcopenia in Older People and the Foundation for the National Institutes of Health), and usual walking speeds were obtained from the UK Biobank. GWAS data for NBAC (benign and malignant) were provided by the Finnish Genetic Database. Three different methods of MR analysis, including inverse-variance weighted, Mendelian randomized Egger regression, and weighted median methods, were utilized. MR analysis showed that high appendicular lean mass was positively associated with the risk of developing benign NBAC (odds ratio and 95% confidence interval = 1.236 (1.026,1.489), = 0.025). At the same time, there is no statistically significant association was found between traits related to sarcopenia and malignant neoplasm of bone and articular cartilage. There was also no reverse causal correlation between NBAC and traits related to sarcopenia. In European populations, better appendicular lean body mass is positively associated with the risk of benign neoplasm of bone and articular cartilage, representing the possibility that sarcopenia may be a protective factor against neoplasm of bone and articular cartilage.
Wedelolactone Attenuates Liver Fibrosis and Hepatic Stellate Cell Activation by Suppressing the Hippo Pathway
Liver fibrosis is a commonly observed pathological phenomenon that occurs during the progression of various types of chronic liver diseases. The Hippo pathway is closely associated with the pathogenesis of liver fibrosis. Previous studies have shown that wedelolactone (WED) has a significant antihepatic fibrosis effect, whereas the target and mechanism underlying WED remain elusive. In this study, we found that WED significantly alleviated liver fibrosis and injury by inhibiting the expression of Yes-associated protein (YAP) and tafazzin (TAZ). In an model, WED suppressed the activation of hepatic stellate cells (HSCs) induced by transforming growth factor (TGF-β1), as well as the mRNA and protein expression of α-smooth muscle actin (α-SMA), YAP, and TAZ. The allosteric regulation of YAP by WED was confirmed using MD and cellular thermal shift assay. Moreover, specific knockdown or inhibition of YAP did not enhance the suppressive effect of WED on HSC activation or protein expression associated with fibrosis. These findings demonstrated that the administration of WED effectively alleviated liver fibrosis by suppressing the Hippo/YAP/TAZ pathways. In addition, YAP activity may be regulated by WED via allosteric regulation.
Tripartite Motif-Containing Protein 65 Promotes Proliferation and Inhibits Ferroptosis in Prostate Cancer via Enhancing NKD Inhibitor of WNT Signaling Pathway 2 Ubiquitination
As a typical E3 ligase, tripartite motif-containing 65 (TRIM65), is implicated in the modulation of biological processes, such as metastasis, proliferation, and apoptosis. However, the function of TRIM65 in prostate cancer (PCa) and its potential mechanism have not yet been excavated. In this work, we affirmed Tripartite motif-containing protein 65 (TRIM65) as a new oncogene in PCa, which accelerated PCa cell proliferation and impeded cell ferroptosis. , depletion of TRIM65 inhibited PCa tumorigenesis and metastasis. Mechanically, our findings uncovered that TRIM65 enhances NKD inhibitor of WNT signaling pathway 2 (NKD2) degradation via the ubiquitin-proteasome signaling. TRIM65 facilitated proliferation and restricted ferroptosis via downregulating NKD2 levels. Moreover, TRIM65 activated the wingless-integrated/β-catenin pathway in PCa cells via inhibiting NKD2. Taken together, these data uncovered that TRIM65 controls PCa proliferation, and ferroptosis and regulates the Wnt/β-catenin signaling via directly targeting NKD2 for ubiquitination degradation. Our study provides insights into the multifaceted regulatory role of TRIM65 in the development of PCa, laying the foundation for exploring new therapeutic approaches.
Only Some Paths Lead to Longer Healthier Life and How to Find Them