SIRT3 rs11246020 Polymorphism Associated Postprandial Triglyceride Dysmetabolism.

Purpose: Energy metabolism is regulated by SIRT3, no research has been done on the connection between lipid metabolism in the oral fat test and SIRT3 polymorphism. Thus, we conducted a case-control study to investigate the connection between postprandial lipid and SIRT3 polymorphism. Patients and Methods: 402 non-obese Chinese subjects were enrolled and their postprandial lipid response to oral fat tolerance test (OFTT) was observed to understand the relationship between rs11246020 gene and postprandial triglyceride metabolism. Results: In a binary logic regression model, a protective effect of the T allele of the rs11246020 SIRT3 for postprandial hypertriglyceridemia was shown (OR=0.417, 95% CI = 0.219-0.794, p=0.008). Compared to the CC genotype, individuals with the TT+CT variant of the rs11246020 SIRT3 gene demonstrated significantly lower levels of homeostasis model assessment of insulin resistance (HOMA-IR) (p=0.04), postprandial plasma glucose (PPG) (p=0.037), fasting plasma glucose (FPG) (p=0.02), and 4-hour triglyceridemia (Tg) (p=0.032). Conclusion: The C allele of rs11246020 SIRT3 gene may be a risk factor to increased possibility of postprandial triglyceridemia after an oral fat test, which involved in the mechanism of glucose and insulin metabolism.

TG: A Mediator of the Relationship of Serum Uric Acid to Creatinine Ratio and Nonalcoholic Fatty Liver Disease in Non-Obese Patients with Type 2 Diabetes.

Background: The study estimated the association between NAFLD and SUA/Cr in Chinese non-obese patients with type 2 diabetes mellitus (T2DM) and also investigated mediating effect of TG. Methods: All patients were divided into NAFLD group (n = 420) and non-NAFLD group (n = 347). The differences of biochemical indicators between the two groups were compared. The link between SUA/Cr and other parameters was checked through Spearman correlation analysis. Differences in the incidence rate of NAFLD between SUA/Cr and TG 3 tertile subgroups were tested by chi-squared. To explore the independent influence of SUA/Cr and TG on NAFLD, logistic regression was performed. The predictive value of SUA/Cr and SUA/Cr combined with BMI for NAFLD was analyzed using ROC curves. In addition, to confirm whether TG has a mediating effect on the link of SUA/Cr and NAFLD, we conducted a mediating analysis. Results: NAFLD group had higher SUA/Cr values than individuals without NAFLD (P < 0.01). SUA/Cr was linked with TC and TG (r = 0.081, 0.215 respectively). NAFLD prevalence increased progressively from quartile 1 to quartile 3 of SUA/Cr (44% vs 57% vs 62%). Prevalence of NAFLD increased from quartile 1 to quartile 3 of TG (35.8% vs 58.7% vs 69.9%). Analysis of the logistic regression revealed that SUA/Cr and TG were statistically linked with NAFLD. The ROC curve pointed out that the area under the curve (AUC), sensitivity and specificity of SUA/Cr were 0.59, 0.629 and 0.522, respectively. The AUC, sensitivity and specificity for SUA/Cr combined with BMI were 0.719, 0.644 and 0.677, separately. The mediation analysis showed a statistically direct effect of SUA/Cr on NAFLD (ß=0.148, 95% CI: 0.0393, 0.2585). The function of SUA/Cr on NAFLD partially mediated by TG (ß=0.1571, 95% CI: 0.0704, 0.2869). Conclusion: SUA/Cr was significantly associated with NAFLD in non-obese T2DM patients, and TG partially mediated this association. SUA/Cr can be applied to predict for NAFLD.

Neuroprotective Effects of Bifidobacterium animalis subsp. lactis NJ241 in a Mouse Model of Parkinson's Disease: Implications for Gut Microbiota and PGC-1α.

Intestinal dysbiosis plays a critical role in the pathogenesis of Parkinson's disease (PD), and probiotics have emerged as potential modulators of central nervous system function through the microbiota-gut-brain axis. This study aimed to elucidate the anti-inflammatory effects and underlying mechanisms of the probiotic strain Bifidobacterium animalis subsp. lactis NJ241 (NJ241) in a mouse model of PD induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The impact of NJ241 was comprehensively assessed in PD mice through behavioral tests, immunofluorescence, Western blotting, enzyme-linked immunosorbent assay (ELISA), 16S rRNA sequencing, and short-chain fatty acid (SCFA) detection. NJ241 exhibited notable efficacy in mitigating MPTP-induced weight loss, gastrointestinal dysfunction, and behavioral deficits in mice. Furthermore, it demonstrated protected against MPTP-induced dopaminergic neuron death and inhibited the activation of glial cells in the substantia nigra (SN). NJ241 demonstrated the ability to normalized dysbiosis in the intestinal microbiota and elevate SCFA levels in PD mice. Additionally, NJ241 reversed MPTP-induced reductions in colonic GLP-1 levels and the expression of GLP-1R and PGC-1α in the SN. Notably, GLP-1R antagonists partially reversed the inhibitory effects of NJ241 on the activation of glial cells in the SN. In summary, NJ241 exerts a neuroprotective effect against MPTP-induced neuroinflammation by enhancing intestinal GLP-1 levels and activating nigral PGC-1α signaling. These findings provide a rationale for the exploration and development of probiotic-based therapeutic strategies for PD.

Geriatric nutritional risk index is correlated with islet function but not insulin resistance in elderly patients with type 2 diabetes: A retrospective study.

The geriatric nutritional risk index (GNRI) is a simple nutritional assessment tool that can predict poor prognosis in elderly subjects. The aim of this study was to evaluate the association between GNRI and both islet function and insulin sensitivity in patients with type 2 diabetes mellitus. This research carries significant implications for the integrated treatment and nutritional management of this patient population. A total of 173 patients with type 2 diabetes mellitus, aged 60 years or older, who were hospitalized in the Endocrinology Department at Hebei General Hospital from February 2018 to June 2021, were selected as the research subjects. These subjects were divided into 4 groups according to the quartile of their GNRI values: T1 (GNRI < 99.4, n = 43), T2 (99.4 ≤ GNRI < 103, n = 43), T3 (103 ≤ GNRI < 106.3, n = 43), and T4 (GNRI ≥ 106.3, n = 44). Glucose, insulin, and C-peptide concentrations were tested at 0, 30, 60, 120, and 180 minutes during a 75 g oral glucose tolerance test. The homeostasis model assessment for insulin resistance and the homeostasis model assessment for ß cell function index were calculated. As the GNRI value increased, the levels of total protein, albumin, hemoglobin, alanine transaminase, aspartate aminotransferase, and 25-hydroxyvitamin D increased significantly. The area under the curve for blood glucose decreased significantly across the 4 groups, while the AUCs for insulin and C-peptide showed an overall increasing trend. ß Cell function index increased significantly with the increase of GNRI; meanwhile, both the early-phase insulin secretion index and the late-phase insulin secretion index increased significantly. Although there was an increasing trend, homeostasis model assessment for insulin resistance did not change significantly among the 4 groups. This study indicates that elderly type 2 diabetes patients with higher nutritional risk have worse islet function, while insulin sensitivity is not associated with nutritional risk.

Hyperibone J exerts antidepressant effects by targeting ADK to inhibit microglial P2X7R/TLR4-mediated neuroinflammation.

INTRODUCTION: The antidepressant properties of Hypericum species are known. Hyperibone J, a principal component found in the flowers of Hypericum bellum, exhibited in vitro anti-inflammatory effects. However, the antidepressant effects and mechanisms of Hyperibone J remain to be elucidated. Adenosine kinase (ADK) is upregulated in epilepsy and depression and has been implicated in promoting neuroinflammation. OBJECTIVES: This study aimed to explore the impact of Hyperibone J on neuroinflammation-mediated depression and the mechanism underlying this impact. METHODS: This study employed acute and chronic in vivo depression models and an in vitro LPS-induced depression model using BV-2 microglia. The in vivo antidepressant efficacy of Hyperibone J was assessed through behavioral assays. Techniques such as RNA-seq, western blot, qPCR and ELISA were utilized to elucidate the direct target and mechanism of action of Hyperibone J. RESULTS: Compared with the model group, depression-like behaviors were significantly alleviated in the Hyperibone J group. Furthermore, Hyperibone J mitigated hippocampal neuroinflammation and neuronal damage. RNA-seq suggested that Hyperibone J predominantly influenced inflammation-related pathways. In vitro experiments revealed that Hyperibone J reversed the LPS-induced overexpression and release of inflammatory factors. Network pharmacology and various molecular biology experiments revealed that the potential binding of Hyperibone J at the ASN-312 site of ADK diminished the stability and protein expression of ADK. Mechanistic studies revealed that Hyperibone J attenuated the ADK/ATP/P2X7R/Caspase-1-mediated maturation and release of IL-1ß. The study also revealed a significant correlation between Tlr4 expression and depression-like behaviors in mice. Hyperibone J downregulated ADK, inhibiting Tlr4 transcription, which in turn reduced the phosphorylation of NF-κB and the subsequent transcription of Nlrp3, Il-1b, Tnf, and Il-6. CONCLUSION: Hyperibone J exerted antineuroinflammatory and antidepressant effects by binding to ADK in microglia, reducing its expression and thereby inhibiting the ATP/P2X7R/Caspase-1 and TLR4/NF-κB pathways. This study provides experimental evidence for the therapeutic potential of Hypericum bellum.

Reoperation for ipsilateral local recurrence following prior nephron-sparing surgery: innovative surgical insights from a high-volume urological center with cross-sectional study.

BACKGROUND: The main aim of this study was to examine the perioperative results of reoperations and suggest novel surgical approaches. Based on a substantial number of robotic and laparoscopic nephron-sparing surgery (NSS), we aim to propose novel surgical strategies that offer practical recommendations to surgeons. METHODS: Renal cell carcinoma patients with ipsilateral recurrent tumors, without evidence of metastasis, and who underwent primary NSS at our center between 2013 and 2023 were enrolled in this study, and all received the second time surgery. We conducted an analysis to evaluate perioperative outcomes and observed trends over a decade. Additionally, based on the findings from this study, we developed our surgical strategies. RESULTS: In the past decade, our center has successfully conducted a total of 2546 surgeries for renal cell carcinoma, out of which this study includes 15 patients who met the specified criteria. For reoperation, robotic-assisted surgery was applied in 5 cases (33.3%), laparoscopic surgery in 6 cases (40%), and open surgeries in 4 cases (26.7%). While 4 (26.7%) patients underwent NSS while radical nephrectomy was performed on 11 patients (73.3%). The median operative time was 215 minutes (IQR: 135-300), and the median estimated blood loss was 50 ml (IQR: 50-100). The median length of postoperative hospitalization was 6 days (IQR: 5-9). Furthermore, there has been a yearly increase in the application of robotic-assisted NSS at our institution. CONCLUSION: Reoperation following the pNSS is a secure and effective surgical approach. We introduce novel surgical strategies for primary surgery and reoperation, which offer valuable insights to surgeons in current study.