HO-1 attenuates testicular ischaemia/reperfusion injury by activating the phosphorylated C-jun-miR-221/222-TOX pathway.

Aims: Heme oxygenase (HO-1) affords protection against ischaemia/reperfusion (I/R) injury; however, its effects on testicular I/R injury remain poorly explored. Herein, we aimed to examine the effects of HO-1 on testicular I/R injury and elucidate the underlying mechanism. Methods: Using the TALEN technique, we knocked out the HO-1 gene from rats. In vivo: Thirty hmox+/+ and 30 hmox-/- rats were randomly assigned to six groups: sham-operated (sham), I/R (the left testicle torsion/detorsion) 0 d,I/R 1d, I/R 3d, I/R 7d and I/R 28d. In vitro: GC-1 were suffered from: control,H/R (oxygen-deprivation/reoxygenation),H/R + HO-1 siRNA,H/R + c-Jun siRNA or H/R + HO-1 siRNA + c-jun.We performed immunofluorescence and immunohistochemistry experiments to detect HO-1 nuclear translocation. Flow cytometry was used to detect cell apoptosis and analyse the cell cycle. High-resolution miRNA, mRNA sequencing, reverse transcription-quantitative PCR, and western blotting were performed to identify testicular I/R injury-related genes strongly conserved in HO-1 knockout rats. A double luciferase reporter assay was performed to verify the relationship between C-jun and miR-221/222. Main findings: In vivo, HO-1 improved the pathological damage induced by testicular I/R. In GC-1 cells, we confirmed the nuclear translocation of HO-1 and its protective effect against hypoxia/reoxygenation (H/R) damage. Accordingly, HO-1 protein itself, rather than heme metabolites, might play a key role in testicular I/R. Gene sequencing was performed to screen for miR221/222 and its downstream gene, thymocyte selection-associated high mobility group box (TOX). HO-1 increased c-Jun phosphorylation in the H/R group, knocked down c-Jun in GC-1 cells, and decreased miR-221/222 expression. Inhibition of HO-1 expression decreased the expression of c-Jun and miR-221/222, which was rescued by adding c-Jun. Dual-luciferase reporter assay confirmed the interaction between c-Jun and miR-221/222. Conclusions: HO-1 could exert a protective effect against testicular I/R via the phosphorylated c-Jun-miR-221/222-TOX pathway.

Bibliometric analysis of the 100 top-cited articles on immunotherapy of urological cancer.

PURPOSE: To highlight the scientific progress in immunotherapy of urological cancer by identifying and analyzing the 100 top-cited (T100) articles from the last 15 years. METHODS: Papers in immunotherapy of urological cancer were identified from Clarivate Web of Science Core Collection database. Data of the T100 articles and papers published in recent 2 years, including citations, topic, year of publication, country of origin, institution and authorship, were extracted and analyzed. RESULTS: Of the T100 articles, the citation number ranged from 7387 to 183 with a mean of 590.66. The USA led the field with 80 T100 articles and 53097 citations. Pro Sharma P from MD Anderson Cancer Center was at the top of list with 8 T100 articles (3 as first author and 6 as corresponding author). Memorial Sloan Kettering Cancer Center ranked first with 26 T100 articles and 22573 citations, followed by Johns Hopkins University with 21 T100 articles and 25095 citations. Forty-nine T100 articles were related to the renal cancer, followed by prostate cancer (29), bladder cancer (13) and urothelial cancer (13). According to the type of immunotherapy, most T100 articles were related to ICI (55 articles) and vaccine (19 articles). CONCLUSIONS: It is the first bibliometric analysis to identify the T100 articles on immunotherapy of urological cancer. The USA made great contribution in the field of immunotherapy related to urological cancer. Renal, bladder and prostate cancers were the major organs treated by immunotherapy especially by ICIs and vaccines. The multiple aspects of ICIs research in renal and bladder cancer and the neoantigen-based vaccine therapy will be hotspots for future research.

Identification of the Prognostic Value Among Suppressor Of Cytokine Signaling Family Members in Kidney Renal Clear Cell Carcinoma.

Background: Kidney renal clear cell carcinoma (KIRC) has become one of the most prevalent malignancies worldwide and remains a crucial cause of cancer-related morbidity and mortality. Aberrant activation of the JAK/STAT pathway acts as an important role in KIRC. The suppressor of cytokine signaling (SOCS) family members are the key negative regulators of the JAK/STAT pathway. SOCS family members have been verified to act as significant roles in regulating cellular responses to many cytokines and growth factors. However, whether the expression levels of SOCS affect the prognosis of patients with KIRC is still elusive. Methods: We first evaluated the expression of SOCS family genes in KIRC and determined the correlation between SOCS expression and different clinicopathological features. Then, we analyzed the genetic alterations, potential functions, transcription factor targets, and immune infiltration of SOCS family members based on the information available on public databases. Finally, we assessed the prognostic value of differentially expressed SOCS family members. Results: The expression levels of SOCS2, SOCS4, SOCS6, SOCS7, and CISH were downregulated in KIRC, and all SOCS genes were associated with clinicopathological features of patients with KIRC. SOCS family members have been predominantly related to protein binding, signaling adaptor activity, and JAK/STAT cascade. We found that STAT3, STAT6, and IRF1 are the key transcription factors that may be participated in the regulation of SOCS. We also found an association between the expression levels of SOCS and the immune infiltrates of KIRC. Finally, we have illuminated that SOCS1 and SOCS3 are risky genes, whereas SOCS2, SOCS4, SOCS6, SOCS7, and CISH are some of the protective genes for patients with KIRC; based on these, we have created a KIRC prognostic index for predicting the prognosis of patients of KIRC. Conclusion: Our study may contribute to further understanding the functions of SOCS genes in KIRC, which may help clinicians in selecting the appropriate drugs and predicting the outcomes for patients with KIRC.

Large calcified renal artery aneurysm in the renal sinus misdiagnosed as an intrapelvic calculus followed by mistakenly performed PCNL: a case report.

BACKGROUND: Renal artery aneurysms (RAAs) are rare and usually asymptomatic, and some RAAs can be associated with calcifications, which may lead to misdiagnoses as renal calculi, which are then mistakenly treated. CASE PRESENTATION: A 69-year-old female patient was admitted to the hospital with no discomfort and was diagnosed with a large right renal calculus. The ultrasound and computed tomography urography (CTU) scan suggested a large calculus in the right pelvis with hydrops of the kidney. Therefore, we chose percutaneous nephrolithotomy (PCNL) to treat the right renal calculus, but no calculi were found in the renal pelvis. When we removed the mucosa of the renal pelvis with a holmium laser, we observed a fluctuating unruptured aneurysm with calcification. Therefore, the previous diagnosis of a renal calculus was disregarded. The operation was stopped immediately, and then computed tomography (CT) angiography was performed, confirming the right renal aneurysm with calcification. Then, Renal artery aneurysm (RAA) coil embolization was performed. After a long-term follow-up, the patient recovered well. CONCLUSIONS: The RAA of this patient had calcific changes, which led us to errors in the diagnosis. Hence, it is very important for surgeons to effectively distinguish between renal calculi and aneurysms with ring-like calcifications. Our case report looks back at the thrilling situation during the operation and advises surgeons on how to deal with this situation properly.

The Biogenesis, Functions, and Roles of circRNAs in Bladder Cancer.

Bladder cancer (BCa) is the 10th most prevalent malignancy worldwide and remains a crucial cause of cancer-related morbidity and mortality. Circular RNAs (circRNAs), a large class of endogenous non-coding RNAs, contain unique covalent closed structures and their biogenesis and turnover are regulated by multiple factors. Recently, multiple circRNAs have been found to serve as important factors in several biological processes such as tumorigenesis. An increasing amount of research discovered that circRNAs are dysregulated in multiple cancer tissues compared with matched normal tissues, especially in BCa, indicating that circRNAs can act as biomarkers for the diagnosis and prognosis of BCa. In this review, we focus on the biogenesis, properties, turnover, and functions of circRNAs, summarizing their potential functions and clinical implications in BCa.

Metastatic castration-resistant prostate cancer: Academic insights and perspectives through bibliometric analysis.

BACKGROUND: In recent years, metastatic castration-resistant prostate cancer (MCRPC) and studies related to MCRPC have drawn global attention. The main objective of this bibliometric study was to provide an overview of MCRPC, explore clusters and trends in research and investigate the future direction of MCRPC research. METHODS: A total of 4089 publications published between 1979 and 2018 were retrieved from the Web of Science (WoS) Core Collection database. Different aspects of MCRPC research, including the countries/territories, institutions, journals, authors, research areas, funding agencies and author keywords, were analyzed. RESULTS: The number of annual MCRPC publications increased rapidly after 2010. American researchers played a vital role in this increase, as they published the most publications. The most productive institution was Memorial Sloan Kettering Cancer Center. De Bono, JS (the United Kingdom [UK]) and Scher, HI (the United States of America [USA]) were the two most productive authors. The National Institutes of Health (NIH) funded the largest number of published papers. Analyses of keywords suggested that therapies (abiraterone, enzalutamide, etc.) would attract global attention after US Food and Drug Administration (FDA) approval. CONCLUSIONS: Developed countries, especially the USA, were the leading nations for MCRPC research because of their abundant funding and frequent international collaborations. Therapy was one of the most vital aspects of MCRPC research. Therapies targeting DNA repair or the androgen receptor (AR) signing pathway and new therapies especially prostate-specific membrane antigen (PSMA)-based radioligand therapy (RLT) would be the next focus of MCRPC research.

The 100 most-cited articles in urological surgery: A bibliometric analysis.

BACKGROUND: The purpose of this bibliometric analysis was to identify and assess the 100 most-cited articles (T100 articles) on urological surgery. METHODS: The Web of Science (WoS) Core Collection database was used to investigate the T100 articles in the field of urological surgery. Different aspects of the T100 articles, including the countries, journals, authors, and topics, were analyzed. RESULTS: The number of citations of T100 articles published between 1989 and 2016 ranged from 334 to 2189. The T100 articles originated from 28 countries, with more than half originating from the USA (n = 80). Professor Bill-Axelson A from Uppsala University Hospital published the largest number of T100 articles as the first author (4) and as a coauthor (1). The Memorial Sloan Kettering Cancer Center from the USA is the top institution with the most T100 articles in the field of urological surgery. The special journal Journal of Urology published 41 of the T100 articles, which had a total of 19780 citations. CONCLUSIONS: Our study analyzed the 100 most-cited articles in the field of urological surgery. The USA is the dominant country in terms of the number of T100 articles, scientists and institutions. Surgery related to urological cancer has garnered the most academic attention, especially prostate cancer and renal cancer.