Background: The coronavirus disease 2019 (COVID‐19) has been spreading all over the world since December 2019. However, medical information regarding the urogenital involvement in recovered COVID‐19 patients is limited or unknown.Objectives: To comprehensively evaluate urogenital involvement in recovered COVID‐19 patients.Materials and methods: Men aged between 20 years and 50 years who were diagnosed with SARS‐CoV‐2 infection and recovered when the study was conducted were enrolled in our study. Demographic and clinical characteristics, and history of hospitalization were collected and analyzed. Urine, expressed prostatic secretions (EPSs), and semen samples were collected for SARS‐CoV‐2 RNA detection. Semen quality and hormonal profiles were analyzed.Results: Among 74 male recovered COVID‐19 patients, 11 (14.9%) were asymptomatic, classified into mild type, and 31 (41.9%) were classified into moderate type. The remaining patients (32/74, 43.2%) had severe pneumonia. No critically ill recovered COVID‐19 patient was recruited in our cohort. The median interval between last positive pharyngeal swab RT‐PCR test and semen samples collection was 80 days (IQR, 64‐93). The median age was 31 years (IQR, 27‐36; range, 21‐49), and the median body mass index (BMI) was 24.40 (IQR, 22.55‐27.30). Forty‐five (61.6%) men were married, and 28 (38.4%) were unmarried. Fifty‐three (72.6%) patients denied cigarette smoking, 18 (24.7%) were active smokers, and 2 of them were past smokers. The majority of our participants (53/74, 72.6%) did not consume alcohol. Fever occurred in most of the patients (75.3%), and 63 of them had abnormal chest CT images. Only one patient complained of scrotal discomfort during the course of COVID‐19, which was ruled out orchitis by MRI (data not shown). A total of 205 samples were collected for SARS‐CoV‐2 detection (74 urine samples, 70 semen samples, and 61 EPS samples). However, viral nucleic acid was not detected in body fluids from the urogenital system. In terms of hormonal profiles, the levels of FSH, LH, testosterone, and estradiol were 5.20 [4.23] mIU/mL, 3.95 [1.63] mIU/mL, 3.65 [1.19] ng/mL, and 39.48 [12.51] pg/mL, respectively. And these values were within the normal limits. The overall semen quality of recovered COVID‐19 patients was above the lower reference limit released by the WHO. While compared with healthy control, sperm concentration, total sperm count, and total motility were significantly declined. In addition, different clinical types of COVID‐19 have no significant difference in semen parameters, but total sperm count showed a descending trend. Interestingly, subjects with a longer recovery time showed worse data for sperm quality. Small sample size and lacking semen parameters before the infection are the major limitations of our study.Discussion and conclusions: To the best of our knowledge, it is the largest cohort study with longest follow‐up for urogenital evaluation comprehensively so far. Direct urogenital involvement was not found in the recovered COVID‐19 male patients. SARS‐CoV‐2 RNA was undetectable in the urogenital secretions, and semen quality declined slightly, while hormonal profiles remained normal. Moreover, patients with a long time (≥90 days) since recovery had lower total sperm count. Great attention and further study should be conducted and follow‐up on the reproductive function in the following months.

Pharmacological therapy of diabetes mellitus-induced erectile dysfunction (DMED) is intractable owig to the poor response to phosphodiesterase type 5 inhibitors (PDE5i). The surge in the number of diabetic patients makes it extremely urgent to find a novel therapy for DMED. Ferroptosis is a recently discovered form of cell death evoked by lipid peroxidation and is related to several diabetic complications. GPX4, an important phospholipid hydroperoxidase, can alleviate ferroptosis and maintain redox balance via reducing lipid peroxides. However, whether GPX4 can be a prospective target of DMED needs to be determined. Fifty rats were randomly divided into control group, DMED group, DMED + negative control group (DMED + NC group), DMED + low-dose group (1 × 10⁶ infectious units), and DMED + high-dose group (2 × 10⁶ infectious units). Erectile function was assessed 4 weeks after intracavernous injection of GPX4 or negative control lentivirus. The penile shafts were collected for subsequent molecular biological and histological analysis. The results demonstrated that erectile function of the rats in DMED and DMED + NC groups was extremely impaired and was improved in a dose-dependent manner with GPX4 lentivirus (GPX4-LV) injection. Additionally, upregulation of the ACSL4-LPCAT3-LOX pathway, iron overload, oxidative stress, fibrosis, and decreased endothelial and smooth muscle cell numbers were observed in the corpus cavernosum of DMED group. Meanwhile, the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway was inhibited, and the Ras homolog gene family member A (RhoA)/Rho-associated protein kinase (ROCK) pathway was promoted in DMED rats. The above histologic alterations and related molecular changes were alleviated after GPX4-LV injection. The results revealed that GPX4 improved erectile function by modulating ferroptosis during DMED progression. This finding is of paramount significance in deciphering the molecular mechanism of hyperglycemia-induced ferroptosis, thereby providing a prospective target for preventing the development of DMED.

Background: Janus kinase 2 (JAK2) is activated in diabetic mellitus (DM) conditions and may enhance oxidative stress, apoptosis and fibrosis in many tissues. Whether JAK2 activation is involved in the occurrence of diabetic erectile dysfunction (ED) is unknown.Objectives: We performed this study to investigate the effect of JAK2 deficiency on diabetic ED.Materials and methods: Conditional JAK2 gene knockout mice (Cre^+/+‐JAK2^fl/fl) were used, in which JAK2 gene knockout could be induced by tamoxifen. Mice fell into four groups: control, JAK2 knockout (JAK2^−/−), DM, and DM with JAK2^−/−. DM was induced by intraperitoneal injection of streptozotocin. Two months later, JAK2 gene knockout was induced with tamoxifen in Cre^+/+‐JAK2^fl/fl mice. After another 2 months, erectile function was measured by electrical stimulation of the cavernous nerve, and penile tissues were harvested. Ratio of maximal intracavernosal pressure (MIP) to mean arterial blood pressure (MAP), expression and phosphorylation of JAK2, oxidative stress level, NO/Cyclic Guanosine Monophosphate (cGMP) pathway, apoptosis, fibrosis, and transforming growth factor beta 1 (TGF‐β1)/Smad/Collagen IV pathway in corpus cavernosum, were measured.Results: JAK2 expression was remarkably decreased after induction with tamoxifen. JAK2 was activated in penile tissues of diabetic mice, and JAK2 deficiency could improve the impaired erectile function caused by DM. However, in mice without DM, JAK2 deficiency had no apparent influence on erectile function. Levels of oxidative stress, apoptosis, fibrosis, and TGF‐β1/Smad/Collagen IV pathway were all elevated by DM, whereas JAK2 deficiency lessened these alterations in diabetic mice. Moreover, JAK2 deficiency improved the expression of the down‐regulated NO/cGMP pathway in diabetic mice. In non‐diabetic mice, no apparent changes were found in aforementioned parameters after JAK2 gene knockout.Discussion and conclusion: Our study showed that JAK2 deficiency could improve erectile function in diabetic mice, which might be mediated by reduction in oxidative stress, apoptosis, and fibrosis in corpus cavernosum.

Obesity has emerged as a significant public health crisis, closely linked to the pathogenesis and progression of chronic kidney disease (CKD). This review explores the intricate relationship between obesity-induced lipid metabolism disorders and renal health. We discuss how excessive free fatty acids (FFAs) lead to lipid accumulation in renal tissues, resulting in cellular lipotoxicity, oxidative stress, and inflammation, ultimately contributing to renal injury. Key molecular mechanisms, including the roles of transcriptional regulators like PPARs and SREBP-1, are examined for their implications in lipid metabolism dysregulation. The review also highlights the impact of glomerular and tubular lipid overload on kidney pathology, emphasizing the roles of podocytes and tubular cells in maintaining kidney function. Various therapeutic strategies targeting lipid metabolism, including pharmacological agents such as statins and SGLT2 inhibitors, as well as lifestyle modifications, are discussed for their potential to mitigate CKD progression in obese individuals. Future research directions are suggested to better understand the mechanisms linking lipid metabolism to kidney disease and to develop personalized therapeutic approaches. Ultimately, addressing obesity-related lipid metabolism disorders may enhance kidney health and improve outcomes for individuals suffering from CKD.

Backgrounds: Erectile dysfunction (ED) is a common andrological disorder that tends to afflict diabetic patients, among others. Pharmacological therapy of diabetes mellitus‐induced ED (DMED) is ineffective, as it is linked with smooth muscle cell loss in the corpus cavernosum. Ferroptosis is a recently identified kind of cell death evoked by lipid peroxidation, and it is connected with a number of diabetic complications.Objectives: To investigate the role of ferroptosis in DMED.Materials and methods: We established the rat model of DMED and conducted a combined analysis of RNA sequencing (RNA‐seq) and Gene Expression Omnibus (GEO) data to identify differentially expressed genes (DEGs). Next, DMED disease targets were determined by cross‐referencing DEGs and DMED‐related genes in the DisGeNET, GenCLiP3, and GeneCards databases. Additionally, these targets were analyzed using “clusterProfiler” in R utilizing Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations. Immunohistochemistry (IHC) staining of rat penile tissues was used to validate several targets. Notably, the Cell Counting Kit‐8 assay, Western blotting, oxidative stress (OS) level, and iron concentration were tested in corpus cavernosum smooth muscle cells (CCSMCs) stimulated with high glucose (HG), and treated with Ferrostatin‐1 (Fer‐1).Results: Sixty‐nine disease targets of DMED were identified. According to KEGG analysis, these targets were primarily enriched in the ferroptosis pathway. Additionally, IHC results revealed that the expression of GPX4, SLC7A11, and ACSL4 was deregulated in the DMED group compared to the control group. Significantly, HG decreased cell viability and increased OS and iron levels in CCSMCs, which could be reversed by Fer‐1 treatment.Discussion and conclusion: Our study revealed that ferroptosis may indeed exist in DMED. GPX4, SLC7A11, and ACSL4 all have a role in controlling the viability of CCSMCs, making them potential therapeutic targets.