Meilian Liu

Empagliflozin (EMPA), a sodium-glucose cotransporter 2 inhibitor, has garnered attention for its cardiovascular benefits beyond glycemic control. Ferroptosis, a novel form of regulated cell death, contributes to the pathogenesis of diabetic cardiomyopathy (DCM). However, whether EMPA mitigates DCM by suppressing ferroptosis remains unclear. Here, Type 2 diabetic db/db mice were used to establish a DCM model and treated with EMPA (10 mg/kg/day) for 12 weeks. EMPA significantly improved cardiac function, reduced myocardial fibrosis, and attenuated ferroptosis, concomitant with upregulated silent information regulator 3 (SIRT3) expression. In the rat cardiomyocytes (H9c2 cells) exposed to high glucose and palmitic acid, EMPA treatment or SIRT3 overexpression alleviated oxidative stress, mitochondrial dysfunction, and ferroptosis. Mechanistically, molecular docking, molecular dynamics simulation, cellular thermal shift assay and drug affinity responsive target stability assay confirmed that SIRT3 is the drug target of EMPA, stabilizing its protein levels and reducing acetylated p53 expression. Notably, SIRT3 silencing abolished EMPA’s beneficial effects on oxidative stress and ferroptosis. Our findings demonstrate that EMPA exerts cardioprotective effects by inhibiting oxidative stress and ferroptosis in cardiomyocytes, which is mediated by SIRT3. This study provides novel insights into the mechanisms underlying EMPA’s therapeutic effects in DCM.

Background: Syndrome of inappropriate antidiuretic(SIAD) occurs secondary to various diseases, which is characterised by hypotonic hyponatremia and impaired urinary diluting capacity. Research on SIAD in both domestic and international contexts has a long history. This study objectively and comprehensively analyses the research trends, hotspots and development of SIAD research of the past 20 years using the method of bibliometric analysis.Methods: The 2003–2022 data in the Web of Science Core Collection database were searched. The Bibliometrix software package, VOSviewer and CiteSpace were used to mine, extract and visualise the retrieved literature, and the generated maps were used in analysing the main topics and trends in the field of SIAD research.Results: A total of 1215 articles published in 623 journals were included in the analysis, with a total of 18,886 citations. Results showed that the research output on SIAD has continuously increased in the past 20 years, and the United States had the highest number of publications and citations. Keywords with the highest burst strength in recent years were the most mentioned keywords, in addition to the search terms ‘hyponatremia’, ‘covid-19’, and ‘mortality’. Thus, the relationship among SIAD, covid-19 and mortality may become research frontiers and trends. Fifteen milestone articles were identified through co-citation analysis, which mainly focused on the pathophysiology and treatment of SIAD.Conclusion: Based on bibliometric analysis and knowledge mapping, this study summarises development trends in the field of SIAD research, providing references for current and future research into SIAD.

A Chinese family was identified to have two patients with rickets, an adult female and a male child (proband), both exhibiting signs related to X-linked hypophosphatemic rickets (XLH). Gene sequencing analysis revealed a deletion of adenine at position 1985 (c.1985delA) in the PHEX-encoding gene. To investigate the relationship between this mutation and the pathogenicity of XLH, as well as analyze the effects of different dosages of PHEX gene mutations on clinical phenotypes, we developed a rat model carrying the PHEX deletion mutation. The CRISPR/Cas9 gene editing technology was employed to construct the rat model with the PHEX gene mutation (c.1985delA). Through reproductive procedures, five genotypes of rats were obtained: female wild type (X/X), female heterozygous (-/X), female homozygous wild type (-/-), male wild type (X/Y), and male hemizygous (-/Y). The rats with different genotypes underwent analysis of growth, serum biochemical parameters, and bone microstructure. The results demonstrated the successful generation of a stable rat model inheriting the PHEX gene mutation. Compared to the wild-type rats, the mutant rats displayed delayed growth, shorter femurs, and significantly reduced bone mass. Among the female rats, the homozygous individuals exhibited the smallest body size, decreased bone mass, shortest femur length, and severe deformities. Moreover, the mutant rats showed significantly lower blood phosphorus concentration, elevated levels of FGF23 and alkaline phosphatase, and increased expression of phosphorus regulators. In conclusion, the XLH rat model with the PHEX gene mutation dosage demonstrated its impact on growth and development, serum biochemical parameters, and femoral morphology.

Doublesex and Mab-3 related Transcription Factor 3 (DMRT3) is associated with the prognosis of some tumors. It is possible to explore the role of DMRT3 in the cancer process using bioinformatic approaches and experimental validation. We comprehensively explored the clinical and immunological characteristics of DMRT3. The DMRT3 expression is abnormal in human cancers and correlates with clinical staging. A high DMRT3 expression is significantly associated with poor overall survival (OS) in KIRC, KIRP, LUAD, and UCEC. Amplification was the greatest frequency of the DMRT3 alterations in pan-cancer. The OS was significantly lower in the DMRT3 altered group than in the DMRT3 unaltered group (P = 0.0276). The DMRT3 expression was significantly associated with MSI in three cancer types and TMB in six cancer types. The DMRT3 expression was significantly correlated with the level of the immune cell infiltration and the immune checkpoint genes. The DMRT3 was involved in some pathways in pan-cancer. DMRT3 may play a role in chemotherapy and may be associated with chemoresistance. A ceRNA network of KCNQ1OT1/miR-335-5p/DMRT3 was constructed in LUAD. DMRT3 was significantly upregulated in the LUAD cell lines. DMRT3 was aberrantly expressed in pan-cancer and may promote tumorigenesis and progression via different mechanisms. DMRT3 can be used as a therapeutic target to treat cancer in humans.