Rejuvenation research最新文献

Dendropanax morbifera Léveille 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 D. morbifera 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 D. morbifera from Jeju Island. In addition, the antioxidant activities of leaf extracts of D. morbifera 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 D. morbifera 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 D. morbifera. Therefore, extracts of D. morbifera obtained from optimal harvest regions and ages could serve as promising natural antioxidant candidates with potential health benefits.

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. In vivo, 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.

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.

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.

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 FN1 and PRKAA2 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. In vivo 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.

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.

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.

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 (t⁶A) on VD was found in inverse-variance weighted (odds ratios [OR]: 0.667, 95% confidence interval [CI]: 0.548-0.812, p < 0.001), MR-Egger (OR: 0.647, 95% CI: 0.458-0.913, p = 0.019), and weighted median (OR: 0.650, 95% CI: 0.466-0.908, p = 0.012). The MR analysis indicated that metabolites (t⁶A) may be causally associated with a positive effect on VD.

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 in vitro 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.