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

ObjectiveTo investigate the moderating effect of psychological resilience in relation to depressive symptoms and suicidal risk among adolescents. MethodsThe research is a descriptive survey. A total of 71 137 adolescents were selected from 163 schools in Deyang by stratified cluster sampling. Their psychological resilience， depressive symptoms and suicide risks were measured oneline by using 10-item Connor-davidson Resilience Scale （CD-RICS-10）， Patients’ Health Questionnaire Depression Scale-9 item （PHQ-9） and Suicidal Behaviors Questionnaire-Revised （SBQ-R）. The moderating effect of psychological resilience in relation to depressive symptoms and suicidal risk was examined by multivariate stratified regression analysis. Results① The score of CD-RISC-10 was negatively related to PHQ-9 score and SBQ-R score （r=-0.305， -0.268， P<0.01）. ② Psychological resilience significantly moderated the relationship between depressive symptoms and suicidal risk （β=-0.100， t=-31.716， P<0.01）. ③ In both male and female adolescents， resilience played a significant role in depressive symptoms and suicide risk （β=-0.086， -0.084， t=-17.502， -18.839， P<0.01）. ConclusionPsychological resilience could significantly alleviate the impact of high-level depressive symptoms on suicidal risk among adolescents， and this effects both male and female adolescents.

Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury, and its prognosis depends on the balance between hepatocyte death and regeneration. Sirtuin 6 (SIRT6) has been reported to protect against oxidative stress-associated DNA damage. But whether SIRT6 regulates APAP-induced hepatotoxicity remains unclear. In this study, the protein expression of nuclear and total SIRT6 was up-regulated in mice liver at 6 and 48 h following APAP treatment, respectively.

OBJECTIVETo investigate the transcriptional activity of P53 in gastric cancer.

METHODSThe activity of p53 in gastric cancer was investigated by dual-luciferase reporter assay. The coding sequence of the p53 was amplified by reverse transcription-polymerase chain reaction (RT-PCR) and sequenced. The expression of P21WAF1/Cip1, Gadd45alpha and Mdm2 was detected by immunohistochemistry in 76 samples of gastric carcinoma, and their adjacent tissues were analyzed as control.

RESULTSThe p53 activity was higher in human normal cell lines than that of gastric cancer. Furthermore, the transcriptional activity of P53 was lowest in MKN28 cells in which p53 was mutated. The expression level of P21WAF1/Cip1, Gadd45alpha and Mdm2 in the adjacent tissues was higher than that of cancer tissues (P<0.05), and there was a tendency of decline in the positive ratio with the poor differentiation of the carcinoma (P<0.05). In addition, a strong linear correlation was observed between P21WAF1/Cip1, Gadd45alpha and Mdm2 (P<0.05).

CONCLUSIONChanges of P53 transcriptional activity play an important role in the development of gastric cancer. p53 mutation could affect its transcriptional activity. P21WAF1/Cip1, Gadd45alpha and Mdm2 are a group of effecters that could reflect P53 transcriptional activity when detected together in cancer tissues.

Adult ; Aged ; Carcinoma ; genetics ; metabolism ; pathology ; Cell Cycle Proteins ; Cell Line ; Cyclin-Dependent Kinase Inhibitor p21 ; genetics ; metabolism ; Female ; Humans ; Male ; Middle Aged ; Nuclear Proteins ; Proto-Oncogene Proteins c-mdm2 ; genetics ; metabolism ; Stomach Neoplasms ; genetics ; metabolism ; pathology ; Transcriptional Activation ; Tumor Suppressor Protein p53 ; genetics ; metabolism ; Young Adult

BACKGROUNDTo evaluate and compare the effects and toxicity of the domestic product of recombinant mutant human tumor necrosis factor (rmhTNF) combined with chemotherapy and chemotherapy alone in the treatment of patients with non-small cell lung cancer (NSCLC).

METHODSTwo hundred patients with NSCLC in multicenter were randomly devided into trial group (150 cases) and control group (50 cases). Chemotherapy with CAP regimen was given to the patients. Meanwhile, rmhTNF injection of 4×10⁶U/m² was also given from the 1st to 7th days, the 11th to 17th days on the chemotherapy cycle in the trial group. The control patients received chemotherapy alone. Twenty-one days were as a cycle, 2 cycles were given to each patient. The chemotherapeutic effects and toxicity were observed and compared between the two groups after the therapy.

RESULTSof the 200 patients, 5 cases in the trial group and 3 cases in the control group were out of the trial because of economy. The other 192 cases (145 cases in the trial group and 47 cases in the control group) could be analyzed and evaluated the clinical effects and toxicity. The response rate of chemotherapy was 46.90% (68/145) in the trial group and 17.02% (8/47) in the control group respectively ( P =0.001). The KPS scores was 86.02±9.74 in the trial group, and 80.14±9.10 in the control group ( P =0.025). No significant difference of degree III+IV toxicity was observed between the two groups ( P > 0.05). The side effects related to rmhTNF included slight fever, cold-like symptoms, pain and red and swelling in the injection site. All of them were mild and didn't need any treatment and disappeared after the therapy. There were no severe abnormality of liver and kidney function and ECG in both groups.

CONCLUSIONSThe results demonstrate that the effects of domestic rmhTNF combined with chemotherapy are remarkably higher than that of chemotherapy alone in the treatment of NSCLC. rmhTNF can increase the sensitivity to chemotherapy and improve the quality of life of the patients with slight toxicity. Hence rmhTNF is worth expanding clinical use.