BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

We investigated the impact and predictive value of bladder function in patients with benign prostatic hyperplasia (BPH) on the efficacy of transurethral prostatectomy. Symptomatic, imaging, and urodynamic data of patients who underwent transurethral prostatectomy at West China Hospital of Sichuan University (Chengdu, China) from July 2019 to December 2021 were collected. Follow-up data included the quality of life (QoL), International Prostate Symptom Score (IPSS), and IPSS storage and voiding (IPSS-s and IPSS-v). Moreover, urinary creatinine (Cr), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and prostaglandin estradiol (PGE2) were measured in 30 patients with BPH and 30 healthy participants. Perioperative indicators were determined by subgroup analyses and receiver operating characteristic (ROC) curve analysis. Among the 313 patients with BPH included, patients with severe micturition problems had more improvements but higher micturition grades postoperatively than those with moderate symptoms. Similarly, good bladder sensation, compliance, and detrusor contractility (DC) were predictors of low postoperative IPSS and QoL. The urinary concentrations of BDNF/Cr, NGF/Cr, and PGE2/Cr in patients were significantly higher than those in healthy participants (all P < 0.001). After evaluation, only DC was significantly related to both urinary indicators and postoperative recovery of patients. Patients with good DC, as predicted by urinary indicators, had lower IPSS and IPSS-v than those with reduced DC at the 1st month postoperatively (both P < 0.05). In summary, patients with impaired bladder function had poor recovery. The combined levels of urinary BDNF/Cr, NGF/Cr, and PGE2/Cr in patients with BPH may be valid predictors of preoperative bladder function and postoperative recovery.

China ; History of Medicine ; Medicine/standards*

Objective:To evaluate the role of basolateral amygdala (BLA)-prelimbic cortex (PL) brain-derived neurotrophic factor (BDNF) in perioperative neurocognitive disorders (PND) and its relationship with tyrosine kinase B (TrkB) receptors in mice.Methods:Forty-eight clean-grade healthy C57BL/6J mice, aged 6 months, weighing 25-30 g, were divided into 4 groups ( n=12 each) using a random number table method: control group (group C), surgery group (group S), BDNF overexpression in BLA group (group B) and BDNF overexpression in BLA+ ANA-12 injection in PL group (group A). In group S, at 30 min after the end of training session of fear conditioning system, exploratory laparotomy was performed.In group B, recombinant adenovirus 0.3 μl was injected in BLA, fear conditioning test was performed 3 weeks later, and exploratory laparotomy was performed at 30 min after the end of the training session of fear conditioning system.In group A, recombinant adenovirus 0.3 μl was injected in BLA, catheterization was performed in PL, the fear conditioning test used performed 3 weeks later, TrkB receptor antagonist ANA-12 0.25 μg was given in PL starting from 30 min before training session, and exploratory laparotomy was performed at 30 min after training session.Test session was started at 24 h after the end of training session of fear conditioning system, and the percentage of time spent freezing was calculated in all groups.At 30 min after the end of the behavioral test, the expression of BDNF in brain areas, phosphorylated TrkB (p-TrkB) and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERKl/2) was determined by Western blot, and the expression BDNF mRNA in BLA was detected using reverse transcription fluorescence quantitative polymerase chain reaction assay. Results:Compared with group C, the percentage of time spent freezing was significantly decreased, and expression of BNDF protein and its mRNA in BLA and BDNF, p-TrkB and p-ERK1/2 in PL was down-regulated in group S ( P<0.05). Compared with group S, the percentage of time spent freezing was significantly increased, and expression of BNDF protein and its mRNA in BLA and BDNF, p-TrkB and p-ERK1/2 in PL was up-regulated in group B ( P<0.05). Compared with group B, the percentage of time spent freezing was significantly decreased, and expression of p-TrkB and p-ERK1/2 in PL was down-regulated in group A ( P<0.05). Conclusion:The mechanism of PND is probably related to reduction of BDNF secretion from BLA to PL caused by down-regulation of BDNF expression in BLA, and decreasing of post-synaptic phosphorylation of TrkB receptors in mice.

This paper investigated the effects of regular aerobic exercise on protein oxidative stress and apoptosis in aging rat striatum, and further analyzed its target proteins and mechanism based on differential carbonylation proteomics. Totally 24 specific pathogen-free (SPF) 23-month-old male Sprague-Dawley (SD) rats were randomly divided into aged sedentary control group (Con-SED, n = 12) and aged regular aerobic exercise runner group (Aero-EXE, n = 12). The medium intensity of regular aerobic exercise model: The intensity of maximum oxygen consumption (VO

Craniopharyngioma ; Humans ; Parapharyngeal Space ; Pharyngeal Neoplasms ; Pituitary Neoplasms

OBJECTIVE: To explore the influencing factors of low back pain and the relationship of the influence of bad working posture, weight load and frequency of load and the dose-response relationship among the occupational workers of key industries in China. METHODS: A total of 57 501 employees from 15 key industries in China were selected as research subjects using stratified cluster sampling method. The occurrence of low back pain in the past one year, as well as occupational factors such as job type, labor organization and work posture were investigated by using the Chinese version Musculoskeletal Disorders Questionnaire. RESULTS: The prevalence of low back pain in the occupational population of key industries in China was 16.4%(9 448/57 501). Multivariate Logistic regression analysis showed that the risk of low back pain in females was higher than that in males(P<0.01). Married, obese, occasional and frequent smokers, and a history of lower back disease were associated with increased risk of low back pain(all P<0.05). The risk of low back pain was associated with older age, higher education level, and lower frequency of physical exercise(all P<0.01). The risk of low back pain was higher with longer working time, greater back curvature, and the high frequency of long standing and sitting position work, uncomfortable working posture, repeated operation per minute, and lifting>5 kg weight(all P<0.01). CONCLUSION: The influencing factors of low back pain in the occupational population of key industries in China include bad working posture, high frequency load, weight load and other individual factors. There is a dose-response relationship with low back posture load and frequency of load.

Objective To analyze the changes of serum biochemical indexes with age and gender in Xinjiang Uygur and Kazak populations, and to compare the differences of serum biochemical indexes between Xinjiang Uygur and Kazak populations in gender and age. Methods Totally 511 Xinjiang Uygur and Kazak healthy adults were randomly selected from a hospital in Xinjiang Uygur autonomous region for normal physical examination, including 252 and 259 Xinjiang Uygur and Kazak healthy adults. Serum biochemical indexes were detected by CX-7 automatic biochemical analyzer produced by Beckman, USA, and statistical analysis was conducted by variance analysis, t test, correlation analysis and chi-square test. Results Xinjiang Uygur nationality and Kazak serum biochemical indexes for the male and the female, including glutamic-pyruvic transaminase (GPT), direct bilirubin (DBil), uric acid (UA), creatinine (Cre) and urea (Ure), glucose (Glu), total bilirubin(TBil), cystatin C(Cys-C) increased with the growth of the age, and sex between different age groups were statistically significant (P < 0. 05), the men than women with age (P < 0. 05); High-density lipoprotein (HDL) decreased gradually with age, and low-density lipoprotein (LDL), triglyceride and total cholesterol increased gradually with age, with statistical differences among different age groups (P<0. 05). Triglycerides(TG), total cholesterol (TC) and LDL were lower in females than in males in all age groups before the age of 50, and HDL was higher in females than in males (P<0. 05), and there was no difference after the age of 50 (P>0. 05). There were statistically significant differences in Glu, TG, TC, LDL and HDL between Xinjiang Uygur and Kazak people of the same gender and age group (P < 0. 05). Conclusion The serum biochemical indexes of Uygur and Kazak in Xinjiang are different in different ages and genders. The Glu and lipid levels of Uygur nationality in Xinjiang are different from those of Kazak nationality.

A chiral LC-MS/MS method for the simultaneous analysis of desvenlafaxine (DVS) enantiomers in human plasma was developed and applied to a pharmacokinetic study on 12 Chinese healthy volunteers. d6-Desvenlafaxine was used as internal standard (IS). Chromatographic separation was performed on the Astec Chirobiotic V chiral column (150 mm x 4.6 mm, 5 μm). The assay was linear over the concentration range of 0.500-150 ng x mL(-1) for both enantiomers (r2 > 0.99). The method was successfully applied to a stereoselective pharmacokinetic study of 100 mg desvenlafaxine sustained release tablets on 12 Chinese healthy volunteers under fasting conditions. The results showed that the pharmacokinetic parameters were similar to both enantiomers in Chinese healthy volunteers. The AUC(0-t), and C(max) of the two enantiomers were about 1.5 times higher than those of blacks and whites reported in the literature.
Administration, Oral ; Area Under Curve ; Asian Continental Ancestry Group ; Chromatography, Liquid ; Cyclohexanols ; blood ; pharmacokinetics ; Delayed-Action Preparations ; Desvenlafaxine Succinate ; Dose-Response Relationship, Drug ; Healthy Volunteers ; Humans ; Male ; Plasma ; chemistry ; Stereoisomerism ; Tablets ; Tandem Mass Spectrometry