The role of glutamine metabolism in castration-resistant prostate cancer

Reprogramming of metabolism is a hallmark of tumors,which has been explored for therapeutic purposes.Prostate cancer(PCa),particularly advanced and therapy-resistant PCa,displays unique metabolic properties.Targeting metabolic vulnerabilities in PCa may benefit patients who have exhausted currently available treatment options and improve clinical outcomes.Among the many nutrients,glutamine has been shown to play a central role in the metabolic reprogramming of advanced PCa.In addition to amino acid metabolism,glutamine is also widely involved in the synthesis of other macromolecules and biomasses.Targeting glutamine metabolic network by maximally inhibiting glutamine utilization in tumor cells may significantly add to treatment options for many patients.This review summarizes the metabolic landscape of PCa,with a particular focus on recent studies of how glutamine metabolism alterations affect therapeutic resistance and disease progression of PCa,and suggests novel therapeutic strategies.

MicroRNA expression profile in chronic nonbacterial prostatitis revealed by next-generation small RNA sequencing

MicroRNAs (miRNAs) are con sidered to be involved in the pathogenic in itiatio n and progress! on of chronic non bacterial prostatitis (CNP);however, the comprehensive expression profile of dysregulated miRNAs, relevant signaling pathways, and core machineries in CNP have not been fully elucidated. In the current research, CNP rat models were established through the intraprostatic injection of carrageenan into the prostate. Then, next?generation sequencing was performed to explore the miRNA expression profile in CNP. Gene Ontology (GO) and Kyoto En cyclopedia of Genes and Geno mes (KEGG) bioinformatical an a lyses were conducted to reveal the enriched biological processes, molecular functions, and cellular components and signaling pathways. As a result, 1224, 1039, and 1029 known miRNAs were annotated in prostate tissues from the blank control (BC), normal saline injection (NS), and carrageenan injection (CAR) groups (n = 3 for each group), respectively. Among them, 84 miRNAs (CAR vs BC) and 70 miRNAs (CAR vs NS) with significantly different expression levels were identified. Compared with previously reported miRNAs with altered expression in various inflammatory diseases, the majority of deregulated miRNAs in CNP, such as miR-146b-5p, miR?155-5p, miR-150-5p, and miR-139-5p, showed similar expression patter ns. Moreover, bioinformatics analyses have en riched mitoge reactivated protei n kinase (MAPK), cyclic adenosine monophosphate (cAMP), endocytosis, mammalian target of rapamycin (mTOR), and forkhead box 0 (FoxO) signaling pathways. These pathways were all invoIved in immune response, which indicates the critical regulatory role of the immune system in CNP initiati on and progression. Our inv estigatio n has presented a global view of the d iff ere ntially expressed miRNAs and potential regulatory networks containing their target genes, which may be helpful for identifying the novel mechanisms of miRNAs in immune regulation and effective target-specific theragnosis for CNP.

Clinical efficacy of low-dose emetine for patients with COVID-19:a real-world study

Objective:Emetine,an isoquinoline alkaloid that is enriched at high concentrations in the lung,has shown potent in vitro activity against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).The aim of this study was to better understand the effectiveness of low-dose emetine for patients with coronavirus disease 2019(COVID-19).Methods:In this real-world study,63 patients with mild or common COVID-19 were recruited from Wuhan Fangcang Shelter Hospital and five COVID-19-designated hospitals in Anhui Province,China from February to March 2020.Thirty-nine patients from Wuhan Fangcang Shelter Hospital were assigned to a pragmatic randomized controlled clinical trial,and 24 patients from the 5 COVID-19-designated hospitals in Anhui Province underwent a real-world study.The medication course of emetine was less than 10 days.The main symptoms and adverse reactions of all patients were observed and recorded.The primary outcome measure was the time required for a negative SARS-CoV-2 RNA result or the negative result rate on day 10.Secondary outcomes included axillary temperature,transcutaneous oxygen saturation,and respiratory frequency recovery.The study was approved by the Ethics Committee of The First Affiliated Hospital of Anhui Medical University on February 20,2019(approval No.PJ2020-03-19)and was registered with the Chinese Clinical Trial Registry on February 20,2019(registration number:ChiCTR2000030022).Results:The oxygen saturation values were higher in the treatment group than in the control group on the first day after enrollment for patients treated at Fangcang Shelter Hospital.The axillary body temperature,respiratory rate,and oxygen saturation among patients in Fangcang Shelter Hospital were related to the time effect but not to the intervention measures.The respiratory rate and oxygen saturation of patients in the Anhui designated hospitals were related to the intervention measures but not to the time effect.The axillary body temperature of patients in Anhui designated hospitals was related to the time effect but not to the intervention measures.Conclusion:Our preliminary study shows that low-dose emetine combined with basic conventional antiviral drugs improves clinical symptoms in patients with mild and common COVID-19 without apparent adverse effects,suggesting that moderately increased doses of emetine may have good potential for treatment and prevention of COVID-19.