Higher Magnesium Depletion Score Increases the Risk of All-cause and Cardiovascular Mortality in Hypertension Participants.

The magnesium depletion score (MDS) is a novel index utilized for evaluating body magnesium status. The present study intended to explore the association of MDS with mortality among hypertension (HTN) participants. In this cohort study, we utilized data from the National Health and Nutrition Examination Survey (NHANES) covering the years 2003 to 2018. MDS levels were categorized into three groups (lower: MDS = 0-1; middle: MDS = 2; higher: MDS = 3-5). Kaplan-Meier curves were employed to illustrate survival differences between groups with varying MDS levels. The relationship between MDS and mortality was assessed through weighted multivariate Cox regression models. Subgroup analyses, along with sensitivity analyses, were also conducted to further explore and validate the findings. This study encompassed 12,485 participants, recording 2537 all-cause deaths and 707 cardiovascular deaths. The Kaplan-Meier curves revealed that the higher MDS group had the highest rates of all-cause and cardiovascular death. (P < 0.001). Controlling for all confounding variables, participants belonging to the higher MDS group demonstrated a substantially elevated risk of mortality in comparison to the lower MDS group (all-cause mortality: hazard ratio (HR) = 1.31, 95% confidence interval (CI) 1.10-1.54; cardiovascular mortality: HR = 1.63, 95% CI 1.19-2.22). There were no interaction factors found in subgroup analyses that affected the relationship between MDS and mortality, except for cardiovascular disease. The findings were confirmed to be robust through further sensitivity analyses. Higher MDS levels independently predict an elevated risk of mortality among US adults with HTN. Therefore, MDS may serve as a cost-effective and widely available prognostic marker for HTN.

Regulatory role of BNP in the spinal center of rats with nonbacterial prostatitis.

BACKGROUND: A growing body of evidence has shown that activating spinal cord glial cells (typically astrocytes and microglial cells) is closely related to hyperpathia and persistent pain. OBJECTIVE: To investigate the expression of GFAP and CR3/CD11b in cornu dorsale medullae spinalis of rats with nonbacterial prostatitis, to explore the therapeutic efficacy and action mechanism of intrathecal injection of BNP alleviating chronic neuropathic pain. METHODS: Eighteen male SPF SD rats were randomly divided into sham operation control group, nonbacterial prostatitis group (NBP) and intrathecal injection BNP group, the NBP model was established by intraprostatic injection of CFA, and the spinal cord of L6-S1 segment was extracted seven days after intrathecal injection of BNP; The expression of GFAP and CR3/CD11b in dorsal horn of spinal cord were detected by immunofluorescence and Western blot. RESULTS: The cumulative optical density values of GFAP and CR3/CD11b immunofluorescence assay in the NBP group were higher than those in the sham operation group, with statistical significance (p⁢ï⁢»â¢ 0.01); The expression of GFAP and CR3/CD11b in intrathecal injection BNP group were lower than those in NBP group, the differences were statistically significant (p⁢ï⁢»â¢ 0.01). Western blot results showed that the expression of GFAP and CR3/CD11B in NBP group were higher than those in sham operation group, with statistical significance (p⁢ï⁢»â¢ 0.05). The expression of GFAP and CR3/CD11B in intrathecal injection BNP group were lower than those in NBP group, the differences were statistically significant (p⁢ï⁢»â¢ 0.05). CONCLUSION: Intrathecal injection of BNP can down-regulate the expressions of GFAP and CR3/CD11b in L6-S1 spinal cord of NBP rat model and to further inhibit chronic pain caused by NBP.

M2 macrophage-derived exosomal miR-25-3p improves high glucose-induced podocytes injury through activation autophagy via inhibiting DUSP1 expression.

Diabetic nephropathy (DN) is the primary reason of chronic kidney disease. The aim of our study is to explore the role and action mechanism of M2 macrophage-derived exosomes in high glucose (HG)-induced podocytes injury. Here, 30 mmol/L of HG was used to induce podocytes injury. Annexin V-FITC/PI double staining was performed to measure podocytes apoptosis, and western blot was carried out to ensure proteins expression. The shape of exosomes was identified using TEM. Besides, the expression of miR-25-3p was determined by qRT-PCR, FAM-labeled miR-25-5p combined with DiI-labeled exosomes were utilized to explore the uptake of podocytes to exosomes. Relationship between miR-25-3p and DUSP family members was ensued by luciferase activity assay. In the beginning, we found that M2 macrophage ameliorated HG-induced podocytes apoptosis and epithelial-mesenchymal transition through secreting exosomes. Subsequently, highly expressed miR-25-3p was found in M2 macrophage-derived exosomes that effectively improved HG-induced podocytes injury. Furthermore, inhibition of miR-25-3p in M2 macrophage inefficiently repressed HG-induced podocytes injury, thus we proposed that M2 macrophage attenuated podocytes injury through secreting exosomal miR-25-3p. Then, we used an autophagy inhibitor to stimulate podocytes, and demonstrated that M2 macrophage-derived exosomal miR-25-3p improved HG-induced podocytes injury through activating autophagy. Finally, DUSP1 was proved to be a downstream target and mediated the inhibition of exosomal miR-25-3p to HG-induced podocytes injury. Our results indicated that M2 macrophage could improve HG-induced podocytes injury via secreting exosomal miR-25-3p to activate autophagy of the cells through suppressing DUSP1 expression. We proved a newly potential therapy strategy for DN treatment.

Role of Nampt overexpression in a rat model of Hashimoto's thyroiditis and its mechanism of action.

The present study was designed to investigate the role of nicotinamide phosphoribosyltransferase (Nampt) overexpression in a rat model of Hashimoto's thyroiditis (HT) and its mechanism of action. A rat model of HT was constructed, and the HT rats were injected with an adenoviral expression vector carrying the Nampt gene. The expression of Nampt and Toll-like receptor 4 (TLR4) in thyroid tissues was examined using immunohistochemistry (IHC), RT-qPCR and western blot analyses. Serum anti-thyroglobulin antibodies (TGAb) and anti-thyroid peroxidase antibodies (TPOAb) were measured using chemiluminescence method. Hematoxylin and eosin (H&E) and IHC staining of the rat thyroid tissues showed destroyed thyroid follicles and monocyte infiltration, as well as increased Nampt expression in the thyroid tissues of rats with HT. Furthermore, it was found that Nampt overexpression led to increased severity of inflammatory infiltration in thyroid tissues and increased levels of TPOAb in the serum of HT rats; however, the serum TGAb level was not affected by Nampt overexpression. In addition, Nampt overexpression promoted TLR4 expression in HT rats. In conclusion, it was demonstrated that Nampt was strongly expressed in the capillary region of HT rats thyroid tissues. The Nampt mRNA level was increased but the Nampt protein level was decreased in the thyroid tissues of rats with HT. Nampt overexpression has a promotive effect on HT progression, and this effect was related to TLR4. This study suggests that inhibition of Nampt activity may be valuable in the treatment of HT.

miR­124 regulates the osteogenic differentiation of bone marrow­derived mesenchymal stem cells by targeting Sp7.

MicroRNAs (miRNAs) are novel key regulators of cellular differentiation. miR­124 has been reported to regulate osteogenic differentiation of bone marrow­derived mesenchymal stem cells (BMSCs). However, the specific mechanisms involved have not yet been fully elucidated. The present study aimed to investigate the effect of miR­124 on osteogenic differentiation of BMSCs and its underlying mechanisms. In the present study, it was found that alkaline phosphatase (ALP) activity, osteocalcin (OC) secretion, and the protein levels of osterix (Sp7) and runt­related transcription factor 2 (Runx2) were significantly increased, whereas the expression of miR­124 was decreased in a time­dependent manner during osteogenic differentiation of BMSCs. Following overexpression of miR­124 via transfection of miR­124 mimics in BMSCs, Runx2 protein expression and ALP activity were significantly decreased. By contrast, inhibition of miR­124 expression led to an increase in ALP activity and Runx2 expression. Sp7 expression was suppressed in BMSCs transfected with miR­124 mimics while increased when miR­124 expression was inhibited, indicating that miR­124 regulates the expression of Sp7. Moreover, a luciferase reporter assay further verified that Sp7 is the direct target of miR­124. Finally, the effect of miR­124 inhibitor on promoting the differentiation of BMSCs was abolished following treatment with a small interfering RNA targeting Sp7. Taken together, the present study demonstrates that miR­124 inhibits the osteogenic differentiation of BMSCs by targeting Sp7.

Obesity-associated family with sequence similarity 13, member A (FAM13A) is dispensable for adipose development and insulin sensitivity.

BACKGROUND: Obesity and its associated morbidities represent the major and most rapidly expanding world-wide health epidemic. Recent genome-wide association studies (GWAS) reveal that single nucleotide polymorphism (SNP) variant in the Family with Sequence Similarity 13, Member A (FAM13A) gene is strongly associated with waist-hip ratio (WHR) with adjustment for body mass index (BMI) (WHRadjBMI). However, the function of FAM13A in adipose development and obesity remains largely uncharacterized. METHODS: The expression of FAM13A in adipose tissue depots were investigated using lean, genetic obese and high fat diet-induced obese (DIO) animal models and during adipocyte differentiation. Stromal vascular cells (SVCs) or 3T3-L1 cells with gain and loss of function of FAM13A were used to determine the involvement of FAM13A in regulating adipocyte differentiation. Adipose development and metabolic homeostasis in Fam13a-/- mice were characterized under normal chow and high fat diet feeding. RESULTS: Murine FAM13A expression was nutritionally regulated and dramatically reduced in epididymal and subcutaneous fat in genetic and diet-induced obesity. Its expression was enriched in mature adipocytes and significantly upregulated during murine and human adipogenesis potentially through a peroxisome proliferator-activated receptor-gamma (PPARγ)-dependent mechanism. However, Fam13a-/- mice only exhibited a tendency of higher adiposity and were not protected from DIO and insulin resistance. While Fam13a-/- SVCs maintained normal adipogenesis, overexpression of FAM13A in 3T3-L1 preadipocytes downregulated ß-catenin signaling and rendered preadipocytes more susceptible to apoptosis. Moreover, FAM13A overexpression largely blocked adipogenesis induced by a standard hormone cocktail, but adipogenesis can be partially rescued by the addition of PPARγ agonist pioglitazone at an early stage of differentiation. CONCLUSIONS: Our results suggest that FAM13A is dispensable for adipose development and insulin sensitivity. Yet the expression of FAM13A needs to be tightly controlled in adipose precursor cells for their proper survival and downstream adipogenesis. These data provide novel insights into the link between FAM13A and obesity.

[Effects of glimepiride and metformin on free fatty acid in patients with Type 2 diabetes mellitus].

OBJECTIVE: To investigate the effect of glimepiride and metformin on free fatty acid (FFA) in patients with Type 2 diabetes mellitus and to further study the relationship between free fatty acid and insulin resistance in patients with Type 2 diabetes mellitus. METHODS: A prospective and case-control study was conducted. Ninty-four patients with Type 2 diabetes mellitus (35-70 year-old) were divided into 3 groups: glimepiride treated group (n=33), metformin treated group (n=29) and glimepiride plus metformin treated group (n=32). These patients were followed up for 6 months. Free fatty acids were measured by using an enzymatic colorimetry. RESULTS: The concentration of FFA didn't significantly change in the glimepiride treated group at the end of treatment, but it obviously decreased in the metformin treated group and in the glimepiride plus metformin treated group (P < 0.05 and P < 0.001, respectively). The decrease of FFA in the glimepiride plus metformin treated group was more obvious than that in the glimepiride treated group (P < 0.05). The fasting serum FFA concentration is positively related to HOMA-IR( homeostasis model assessment-insulin resistance) and the choice of drugs by stepwise regression analysis. CONCLUSION: Metformin alone or metformin plus glimepiride can decrease FFA levels, body weight index, blood glucose and insulin resistance. FFA level can reflect the index of insulin resistance to some degree.