The regulation of renal function by circadian gene BMAL1 has been recently recognized; however, the role and mechanism of BMAL1 in renal ischaemia‐reperfusion injury (IRI) are still unknown. The purpose of this study was to clarify the pathophysiological role of BMAL1 in renal IRI. We measured the levels of BMAL1 and mitochondrial biogenesis‐related proteins, including SIRT1, PGC‐1α, NRF1 and TFAM, in rats with renal IRI. In rats, the level of BMAL1 decreased significantly, resulting in inhibition of SIRT1 expression and mitochondrial biogenesis. In addition, under hypoxia and reoxygenation (H/R) stimulation, BMAL1 knockdown decreased the level of SIRT1 and exacerbated the degree of mitochondrial damage and apoptosis. Overexpression of BMAL1 alleviated H/R‐induced injury. Furthermore, application of the SIRT1 inhibitor EX527 not only reduced the activities of SIRT1 and PGC‐1α but also further aggravated mitochondrial dysfunction and partially reversed the protective effect of BMAL1 overexpression. Moreover, whether in vivo or in vitro, the application of SIRT1 agonist resveratrol rescued the mitochondrial dysfunction caused by H/R or IRI by activating mitochondrial biogenesis. These results indicate that BMAL1 is a key circadian gene that mediates mitochondrial homeostasis in renal IRI through the SIRT1/PGC‐1α axis, which provides a new direction for targeted therapy for renal IRI.

A novel and highly pathogenic coronavirus (2019-nCoV)-induced pneumonia spread worldwide in a short time. However, studies on the effects of 2019-nCoV on the male reproductive system are limited. The aim of this study is to describe the clinical characteristics of the male reproductive system of COVID-19 patients and to explore the presence of 2019-nCoV in semen. Retrospective, single-center case series of 112 male patients with confirmed COVID-19 who were admitted to Renmin Hospital of Wuhan University from January 2 to March 7, 2020. Demographic data, symptoms and signs related to the male reproductive system, throat swabs and semen samples were collected and analyzed. 2019-nCoV RNA measured in throat swab and semen samples. The organ distribution of ACE2 mRNA and protein in human tissue on The Human Protein Atlas portal and investigated immunohistochemistry (IHC) images of the testis. The HPA dataset revealed relatively high levels of ACE2 protein and RNA expression in the testis. A total of 3 severe COVID-19 patients (2.7%) presented with orchidoptosis, while no patients experienced other symptoms or signs related to the male reproductive system. The analysis of 2019-nCoV RNA in semen included 17 patients with fertility needs. Among these patients, 9 (52.9%) remained positive for 2019-nCoV according to throat swab analysis, and 8 (47.1%) became negative. In the semen 2019-nCoV analysis, all 17 patients were negative for the N gene and ORF1ab gene. In view of the potential impairment, long-term follow-up for male COVID-19 patients with fertility needs is of great significance.

Background: Prostate cancer (PCa) is a frequent malignant tumor worldwide with high morbidity along with mortality. MicroRNAs (miRNAs) have been identified as key posttranscriptional modulators in diverse cancers. Herein, we purposed to explore the impacts of miR‐363‐3p on PCa growth, migration, infiltration along with apoptosis.Methods: The expressions of miR‐363‐3p along with Dickkopf 3 (DKK3) were assessed in clinical PCa specimens. We adopted the PCa cell line PC3 and transfected it using miR‐363‐3p repressors or mimic. The relationship of miR‐363‐3p with DKK3 was verified by a luciferase enzyme reporter assay. Cell viability along with apoptosis were determined by MTT assay coupled with flow cytometry analysis. Cell migration along infiltration were detected via wound healing, as well as Transwell assays. The contents of DKK3, E‐cadherin, vimentin along with N‐cadherin were analyzed via Western blotting accompanied with qRT–PCR.Results: MiR‐363‐3p was found to be inversely associated with the content of DKK3 in clinical PCa specimens. Further investigations revealed that DKK3 was miR‐363‐3p's direct target. Besides, overexpression of miR‐363‐3p decreased the contents of DKK3, promoted cell viability, migration coupled with infiltration, and reduced cell apoptosis, while silencing of miR‐363‐3p resulted in opposite influence. Upregulation of miR‐363‐3p diminished E‐cadherin contents but increased vimentin along with N‐cadherin protein contents in PC3 cells; in contrast, miR‐363‐3p downregulation produced the opposite result.Conclusion: Our study indicates that miR‐363‐3p promotes PCa growth, migration coupled with invasion while dampening apoptosis by targeting DKK3.

Background: Tripartite motif-containing 26 (TRIM26), a member of the TRIM protein family, exerts dual function in several types of cancer. Nevertheless, the precise role of TRIM26 in clear cell renal cell carcinoma (ccRCC) has not been investigated. Methods: The expression of TRIM26 in ccRCC tissues and cell lines were examined through the use of public resources and experimental validation. The impacts of TRIM26 on cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) process were determined via CCK-8, colony formation, EdU incorporation, wound healing, Transwell invasion, Western blot, and Immunofluorescence assays. RNA-seq followed by bioinformatic analyses were used to identify the downstream pathway of TRIM26. The interaction between TRIM26 and ETK was assessed by co-immunoprecipitation, qRT-PCR, Western blot, cycloheximide (CHX) chase, and in vivo ubiquitination assays. Results: We have shown that TRIM26 exhibits a downregulation in both ccRCC tissues and cell lines. Furthermore, this decreased expression of TRIM26 is closely linked to unfavorable overall survival and diseases-free survival outcomes among ccRCC patients. Gain- and loss-of-function experiments demonstrated that increasing the expression of TRIM26 suppressed the proliferation, migration, invasion, and EMT process of ccRCC cells. Conversely, reducing the expression of TRIM26 had the opposite effects. RNA sequencing, coupled with bioinformatic analysis, revealed a significant enrichment of the mTOR signaling pathway in the control group compared to the group with TRIM26 overexpression. This finding was then confirmed by a western blot assay. Subsequent examination revealed that TRMI26 had a direct interaction with ETK, a non-receptor tyrosine kinase. This interaction facilitated the ubiquitination and degradation of ETK, resulting in the deactivation of the AKT/mTOR signaling pathway in ccRCC. ETK overexpression counteracted the inhibitory effects of TRIM26 overexpression on cell proliferation, migration, and invasion. Conclusion: Our results have shown a novel mechanism by which TRIM26 hinders the advancement of ccRCC by binding to and destabilizing ETK, thus leading to the deactivation of AKT/mTOR signaling. TRIM26 shows promise as both a therapeutic target and prognostic biomarker for ccRCC patients.

The homeobox (HOX) family genes have been linked to multiple types of tumors, while their effect on malignant behaviors of clear cell renal cell carcinoma (ccRCC) and clinical significance remains largely unknown. Here, we comprehensively analyzed the expression profiles and prognostic value of HOX genes in ccRCC using datasets from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. We developed a prognostic signature comprising eight HOX genes (HOXB1, HOXA7, HOXB5, HOXD8, HOXD9, HOXB9, HOXA9, and HOXA11) for overall survival prediction in ccRCC and it allowed patients to be subdivided into high- and low-risk groups. Kaplan-Meier survival analysis in all the internal and external cohorts revealed significant difference in clinical outcome of patients in different risk groups, indicating the satisfactory predictive power of the signature. Additionally, we constructed a prognostic nomogram by integrating signature-derived risk score and clinical factors such as gender, age, T and M status, which might be helpful for clinical decision-making and designing tailored management schedules. Immunological analysis revealed that the regulatory T cells (Tregs) infiltrated differently between the two subgroups in both TCGA and ICGC cohorts. ssGSEA method showed that the enrichment scores for mast cells were significantly lower in high-risk group compared with the low-risk group, which was consistent in both TCGA and ICGC cohorts. As for the related immune function, the enrichment scores of APC co-inhibition, para-inflammation, and type II IFN response were consistently lower in high-risk group in both cohorts. Of the eight HOX genes, the mRNA and protein levels of HOXD8 were downregulated in ccRCC than that in normal tissues, and decreased expression of HOXD8 was associated with increased tumor grade and stage, and lymph node metastasis. Survival analysis revealed that lower expression of HOXD8 predicted worse overall survival in ccRCC. In conclusion, our HOX gene-based signature was a favorable indicator to predict the prognosis of ccRCC cases and associated with immune cell infiltration. HOXD8 might be a tumor suppressor gene in ccRCC and a potential predictor of tumor progression.

A common urological disorder, calcium oxalate (CaOx) stones are the most common form of kidney stones. Deposition of CaOx crystals leads to tubular damage, interstitial fibrosis, and chronic kidney disease. Understanding the intrinsic mechanisms of kidney stone formation is essential for the prevention of kidney stones and the development of new therapeutic agents. The Golgi apparatus is a key organelle in the secretory pathway of eukaryotic cells, which plays an important role in the sorting, modification, and transport of proteins within the cell, and has been reported to be involved in several diseases, including prostate tumors, gastrointestinal tumors, sepsis, and so on. GOLPH3 is also known as GPP34, GMx33, or MIDAS. It is a glycoprotein that regulates traffic between the trans-Golgi network and the cell membrane. However, its role in renal injury caused by CaOx crystal deposition is still unclear. Results from immunohistochemistry, qRT-PCR, western blot, and public database single nucleotide RNA-seq showed that GOLPH3 was significantly upregulated in kidney stone patients and animal kidneys. Significant inhibition of Golgi stress, apoptosis, and renal fibrosis by GOLPH3 inhibition with siRNA in CaOx-stimulated HK-2 cells. The PI3K\AKT\mTOR signaling pathway was inhibited by GOLPH3 knockdown, which may be associated with reduced inflammatory response and apoptosis, as well as restoration of Golgi morphology and function. In conclusion, GOLPH3 plays a critical role in CaOx-induced kidney injury by promoting Golgi stress and increasing inflammatory responses, apoptosis, and renal fibrosis, suggesting that GOLPH3 is a potential therapeutic target for kidney stones.