The role of the methyltransferase METTL3 in prostate cancer: a potential therapeutic target.

The incidence of prostate cancer (PCa), the most prevalent malignancy, is currently at the forefront. RNA modification is a subfield of the booming field of epigenetics. To date, more than 170 types of RNA modifications have been described, and N6-methyladenosine (m6A) is the most abundant and well-characterized internal modification of mRNAs involved in various aspects of cancer progression. METTL3, the first identified key methyltransferase, regulates human mRNA and non-coding RNA expression in an m6A-dependent manner. This review elucidates the biological function and role of METTL3 in PCa and discusses the implications of METTL3 as a potential therapeutic target for future research directions and clinical applications.

The Efficacy and Safety of Hyperthermia Intravesical Chemotherapy in the Treatment of Non-Muscle-Invasive Bladder Cancer: A Meta-Analysis.

INTRODUCTION: The current treatment of non-muscle-invasive bladder cancer is suboptimal. However, in recent years, hyperthermia intravesical chemotherapy (HIVEC) has emerged as a more effective alternative to conventional bladder perfusion. This novel treatment approach appears to have a similar therapeutic effect as Bacillus Calmette-Guérin (BCG) perfusion. This study aims to evaluate the safety and effectiveness of HIVEC compared to conventional bladder perfusion chemotherapy for non-muscle-invasive bladder cancer. Additionally, it aims to evaluate the safety and effectiveness of HIVEC in comparison to BCG perfusion therapy for non-muscle-invasive bladder cancer. METHODS: We conducted a comprehensive search of PubMed, Embase, Cochrane Library, and Web of Science databases to gather relevant studies on HIVEC for non-muscle-invasive bladder cancer. The analysis of the collected data was carried out using RevMan 5.3 software. RESULTS: A total of 8 randomized controlled trials were included in this meta-analysis, involving 1,203 patients. Among them, 629 cases received HIVEC, 419 cases received conventional bladder perfusion chemotherapy with mitomycin C, and 155 cases received BCG. The combined analysis revealed that the recurrence rate of bladder hyperthermic perfusion was significantly lower than that of conventional perfusion chemotherapy (RR = 0.65, 95% CI: 0.52, 0.82, p = 0.0003). However, there was no significant difference in recurrence rate between HIVEC and BCG perfusion (RR = 0.78, 95% CI: 0.56, 1.09, p = 0.14). Furthermore, no significant difference was found in the progression rate between the HIVEC group and either the conventional bladder chemotherapy group (RR = 1.08, 95% CI: 0.52, 2.26, p = 0.83) and the BCG perfusion group (RR = 0.48, 95% CI: 0.19, 1.25, p = 0.13). However, compared with the conventional bladder perfusion chemotherapy group, there was no significant statistical difference in adverse events between the bladder hyperthermia chemotherapy group and the conventional bladder perfusion chemotherapy group (RR 1.08, 95% CI: 0.80, 1.45, p = 0.63). No significant difference in the incidence of adverse events was observed between HIVEC and BCG perfusion (RR 1.03, 95% CI: 0.83, 1.29, p = 0.79). CONCLUSION: The existing results indicate that HIVEC, when compared to conventional bladder perfusion chemotherapy, can lower the recurrence rate of non-muscle-invasive bladder cancer. However, it does not significantly affect the progression rate. There was no statistically significant difference observed in the incidence of adverse events between the use of HIVEC and conventional chemotherapy. Additionally, there was no significant difference in the recurrence rate, progression rate, and incidence of adverse events when compared to BCG.

Lower SLC7A2 expression is associated with enhanced multidrug resistance, less immune infiltrates and worse prognosis of NSCLC.

BACKGROUND: Solute carrier family 7 member 2 (SLC7A2), a cationic amino acid transporter, is lowly expressed in ovarian and hepatocellular cancers, which is associated with their worse prognosis. However, its roles in the prognosis, drug resistance and immune infiltration in non-small-cell lung cancer (NSCLC) are unclear. METHODS: We chose SLC7A2 from RNA-Seq of paclitaxel/cisplatin-resistant A549 cells, then bioinformatics, cell lines construction, RT-qPCR, and CCK8 were performed to investigate SLC7A2 role. RESULT: We analyzed the 223 differentially expressed genes (DEGs) from RNA-Seq of paclitaxel/cisplatin-resistant A549 cells and found that SLC7A2 expression was down-regulated in NSCLC. Lower SLC7A2 expression was associated with worse recurrence-free survival (RFS) in NSCLC. SLC7A2 silencing enhanced the proliferation of NSCLC cells and their insensitivity to paclitaxel, cisplatin, and gemcitabine in vitro. Activation of AMPK has up-regulated SLC7A2 expression and enhanced the sensitivity of NSCLC cells to anti-tumor drugs, which could be attributed to E2F1's regulation. In addition, the levels of SLC7A2 expression were correlated to the numbers of infiltrated neutrophils, macrophages, dendritic cells and their marker genes, like CD86, HLA-DPA1 and ITGAM. CONCLUSIONS: SLC7A2 may act as a tumor suppressor to modulate drug sensitivity, immune infiltration and survival in NSCLC. Video abstract.

Protective Effects and Mechanisms of Flavonoids in Renal Ischemia-Reperfusion Injury.

BACKGROUND: Acute kidney injury (AKI) is a common and potentially fatal complication encountered during a variety of kidney surgeries. Renal ischemia/reperfusion (I/R) injury is the predominant mechanism of AKI in this setting. Hence, controlling I/R injury is a key research imperative as it is directly related to the prognosis of patients. SUMMARY: In the last decade, studies in vitro and in animal models have demonstrated that flavonoids can significantly alleviate I/R-induced AKI through a variety of pathways, including anti-oxidative stress, anti-inflammation, anti-cell death, inhibition of endoplasmic reticulum stress, and alleviation of mitochondrial dysfunction. Based on the extensive role of flavonoids in ischemia-reperfusion injury, the lack of drugs entering the clinic so far is a question worthy of consideration. KEY MESSAGES: This review summarizes the available evidence pertaining to the protective effect of flavonoids against renal I/R injury and discusses their potential clinical application in renal I/R injury.

Overexpression of SATB1 correlates with epithelial-mesenchymal transition and lymphatic metastasis in gastric cancer.

BACKGROUND: Gastric cancer (GC) is a malignant tumor with a high mortality rate, and lymphatic metastasis is the main mode of GC metastasis. The nuclear transcriptional regulatory protein SATB1 has been confirmed to be closely related to GC metastasis, but the mechanism has not been elucidated. METHODS: Epithelial-mesenchymal transition (EMT) is known as the pivotal process of GC metastasis. To evaluate the relationship between SATB1 and EMT in GC metastasis, the immunohistochemical method was used to detect the expression of SATB1, E-cadherin, N-cadherin, Vimentin protein in 52 paraffin-embedded specimens of gastric cancer, and analyze the relationship between their expression and pathological parameters. RESULTS: Abnormal positive expression of SATB1 protein in paraffin-embedded tumor tissues was positively correlated with local invasion, lymph node metastasis, and TNM staging in gastric cancer. There was a statistically significant difference in the expression of SATB1 between the early stage of gastric cancer (stage I) and the advanced stage (stageII, III, IV). Moreover, SATB1 expression was positively correlated to N-cadherin and Vimentin but negatively to E-cadherin from Stages I to IV. CONCLUSION: The GC patients with overexpression of SATB1 tended to have advanced stage and lymph node metastasis. SATB1 was positively correlated with EMT in Gastric Cancer.

Chronic Intermittent Hypoxia Exposure Alternative to Exercise Alleviates High-Fat-Diet-Induced Obesity and Fatty Liver.

Obesity often concurs with nonalcoholic fatty liver disease (NAFLD), both of which are detrimental to human health. Thus far, exercise appears to be an effective treatment approach. However, its effects cannot last long and, moreover, it is difficult to achieve for many obese people. Thus, it is necessary to look into alternative remedies. The present study explored a noninvasive, easy, tolerable physical alternative. In our experiment, C57BL/6 mice were fed with a high-fat diet (HFD) to induce overweight/obesity and were exposed to 10% oxygen for one hour every day. We found that hypoxia exerted protective effects. First, it offset HFD-induced bodyweight gain and insulin resistance. Secondly, hypoxia reversed the HFD-induced enlargement of white and brown adipocytes and fatty liver, and protected liver function. Thirdly, HFD downregulated the expression of genes required for lipolysis and thermogenesis, such as UCP1, ADR3(beta3-adrenergic receptor), CPT1A, ATGL, PPARα, and PGC1α, M2 macrophage markers arginase and CD206 in the liver, and UCP1 and PPARγ in brown fat, while these molecules were upregulated by hypoxia. Furthermore, hypoxia induced the activation of AMPK, an energy sensing enzyme. Fourthly, our results showed that hypoxia increased serum levels of epinephrine. Indeed, the effects of hypoxia on bodyweight, fatty liver, and associated changes in gene expression ever tested were reproduced by injection of epinephrine and prevented by propranolol at varying degrees. Altogether, our data suggest that hypoxia triggers stress responses where epinephrine plays important roles. Therefore, our study sheds light on the hope to use hypoxia to treat the daunting disorders, obesity and NAFLD.

AMPK inhibits Smad3-mediated autoinduction of TGF-ß1 in gastric cancer cells.

We have previously shown that adenine monophosphate-activated protein kinase (AMPK) regulates transforming growth factor ß (TGF-ß)-triggered Smad3 phosphorylation. Here we report that AMPK inhibits TGF-ß1 production. First, metformin reduced mRNA levels of TGF-ß1 in gastric cancer cells, in parallel to the decrease of its protein abundance. The effects were more prominent in the cells containing LKB1, an upstream kinase of AMPK. Second, knockdown of Smad3 by siRNA abrogated the expression of TGF-ß1. Third, metformin suppressed firefly luciferase activity whose transcription was driven by TGF-ß1 promoter. In accordance, deletion of the putative binding site of Smad3 in the TGF-ß1 promoter region severely impaired the promoter activity and response to metformin. Fourth, in support of our in vitro study, clinical treatment of type 2 diabetes with metformin significantly reduced the plasma level of TGF-ß1. Finally, immunohistochemical studies revealed that TGF-ß1 was highly expressed in human gastric cancer tissues as compared with adjacent normal tissues. In contrast, p-AMPK exhibited opposite changes. Furthermore, the survival rate of gastric cancer patients was positively correlated with p-AMPK and negative with TGF-ß1. Therefore, our present studies depict a mechanism underlying AMPK suppression of TGF-ß1 autoinduction, which is mediated through inhibition of Smad3 phosphorylation and activation. Collectively, our study sheds a light on the potential usage of AMPK activators in the treatment of TGF-ß1-mediated gastric cancer progression.

A Review of Recent Research on the Role of MicroRNAs in Renal Cancer.

Renal cell carcinoma (RCC) is a most common type of urologic neoplasms; it accounts for 3% of malignant tumors, with high rates of relapse and mortality. The most common types of renal cancer are clear cell carcinoma (ccRCC), papillary renal cell carcinoma (pRCC), and chromophobe renal carcinoma (chRCC), which account for 90%, 6-15%, and 2-5%, respectively, of all renal malignancies. Although surgical resection, chemotherapy, and radiotherapy are the most common treatment method for those diseases, their effects remain dissatisfactory. Furthermore, recent research shows that the treatment efficacy of checkpoint inhibitors in advanced RCC patients is widely variable. Hence, patients urgently need a new molecular biomarker for early diagnosis and evaluating the prognosis of RCC. MicroRNAs (miRNAs) belong to a family of short, non-coding RNAs that are highly conserved, have long half-life evolution, and post-transcriptionally regulate gene expression; they have been predicted to play crucial roles in tumor metastasis, invasion, angiogenesis, proliferation, apoptosis, epithelial-mesenchymal transition, differentiation, metabolism, cancer occurrence, and treatment resistance. Although some previous papers demonstrated that miRNAs play vital roles in renal cancer, such as pathogenesis, diagnosis, and prognosis, the roles of miRNAs in kidney cancer are still unclear. Therefore, we reviewed studies indexed in PubMed from 2017 to 2020, and found several studies suggesting that there are more than 82 miRNAs involved in renal cancers. The present review describes the current status of miRNAs in RCC and their roles in progression, diagnosis, therapy targeting, and prognosis of RCC.

Metformin attenuates trauma-induced heterotopic ossification via inhibition of Bone Morphogenetic Protein signalling.

AMP-activated protein kinase (AMPK) is an intracellular sensor of energy homoeostasis that is activated under energy stress and suppressed in energy surplus. AMPK activation leads to inhibition of anabolic processes that consume ATP. Osteogenic differentiation is a process that highly demands ATP during which AMPK is inhibited. The bone morphogenetic proteins (BMPs) signalling pathway plays an essential role in osteogenic differentiation. The present study examines the inhibitory effect of metformin on BMP signalling, osteogenic differentiation and trauma-induced heterotopic ossification. Our results showed that metformin inhibited Smad1/5 phosphorylation induced by BMP6 in osteoblast MC3T3-E1 cells, concurrent with up-regulation of Smad6, and this effect was attenuated by knockdown of Smad6. Furthermore, we found that metformin suppressed ALP activity and mineralization of the cells, an event that was attenuated by the dominant negative mutant of AMPK and mimicked by its constitutively active mutant. Finally, administration of metformin prevented the trauma-induced heterotopic ossification in mice. In conjuncture, AMPK activity and Smad6 and Smurf1 expression were enhanced by metformin treatment in the muscle of injured area, concurrently with the reduction of ALK2. Collectively, our study suggests that metformin prevents heterotopic ossification via activation of AMPK and subsequent up-regulation of Smad6. Therefore, metformin could be a potential therapeutic drug for heterotopic ossification induced by traumatic injury.

AMP-activated protein kinase regulates cancer cell growth and metabolism via nuclear and mitochondria events.

Adenine monophosphate-activated protein kinase (AMPK) is a fuel sensing enzyme that is activated in shortage of energy and inhibited in its surplus. Cancer is a metabolic disease characteristic of aerobic glycolysis, namely Warburg effect, and possesses heterogeneity featured by spatiotemporal hypoxia and normoxia, where AMPK is deeply implicated. The present study delineates the regulation of mitochondrial functions by AMPK in cancer cells. On the one hand, AMPKα subunit binds to mitochondria independently of ß subunit and targeting AMPK to mitochondria facilitates oxidative phosphorylation and fatty acid oxidation, and inhibits glycolysis. As such, mitochondrial AMPK inhibits the growth of cancer cells and tumorigenesis. On the other hand, ablation of the ß subunits completely abolishes AMPK activity and simultaneously leads to decreases in mitochondria DNA and protein contents. The effect of the ß deletion is rescued by overexpression of the active mutant of bulky AMPKα1 subunit. In conjunction, the transcriptional factors PGC1α and Nrf-1 are up-regulated by LKB1/AMPK, an event that is abolished in the absence of the ß subunits. Intriguingly, the stimulation of mitochondria biogenesis is not achieved by mitochondria-targeted AMPK. Therefore, our study suggests that AMPK inhibits cancer cell growth and tumorigenesis via regulation of mitochondria-mediated metabolism.

LKB1/AMPK inhibits TGF-ß1 production and the TGF-ß signaling pathway in breast cancer cells.

Adenosine monophosphate-activated protein kinase (AMPK) acts as a fuel gauge that maintains energy homeostasis in both normal and cancerous cells, and has emerged as a tumor suppressor. The present study aims to delineate the functional relationship between AMPK and transforming growth factor beta (TGF-ß). Our results showed that expression of liver kinase B1 (LKB1), an upstream kinase of AMPK, impeded TGF-ß-induced Smad phosphorylation and their transcriptional activity in breast cancer cells, whereas knockdown of LKB1 or AMPKα1 subunit by short hairpin RNA (shRNA) enhanced the effect of TGF-ß. Furthermore, AMPK activation reduced the promoter activity of TGF-ß1. In accordance, type 2 diabetic patients taking metformin displayed a trend of reduction of serum TGF-ß1, as compared with those without metformin. A significant reduction of serum TGF-ß1 was found in mice after treatment with metformin. These results suggest that AMPK inhibits the transcription of TGF-ß1, leading to reduction of its concentration in serum. Finally, metformin suppressed epithelial-to-mesenchymal transition of mammary epithelial cells. Taken together, our study demonstrates that AMPK exerts multiple actions on TGF-ß signaling and supports that AMPK can serve as a therapeutic drug target for breast cancer.

Autonomic Nervous System Dysfunction Is Related to Chronic Prostatitis/Chronic Pelvic Pain Syndrome.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common and non-lethal urological condition with painful symptoms. The complexity of CP/CPPS's pathogenesis and lack of efficient etiological diagnosis results in incomplete treatment and recurrent episodes, causing long-term mental and psychological suffering in patients. Recent findings indicate that the autonomic nervous system involves in CP/CPPS, including sensory, sympathetic, parasympathetic, and central nervous systems. Neuro-inflammation and sensitization of sensory nerves lead to persistent inflammation and pain. Sympathetic and parasympathetic alterations affect the cardiovascular and reproductive systems and the development of prostatitis. Central sensitization lowers pain thresholds and increases pelvic pain perception in chronic prostatitis. Therefore, this review summarized the detailed processes and mechanisms of the critical role of the autonomic nervous system in developing CP/CPPS. Furthermore, it describes the neurologically relevant substances and channels or receptors involved in this process, which provides new perspectives for new therapeutic approaches to CP/CPPS.

Crosstalk between m6A modification and autophagy in cancer.

Autophagy is a cellular self-degradation process that plays a crucial role in maintaining metabolic functions in cells and organisms. Dysfunctional autophagy has been linked to various diseases, including cancer. In cancer, dysregulated autophagy is closely associated with the development of cancer and drug resistance, and it can have both oncogenic and oncostatic effects. Research evidence supports the connection between m6A modification and human diseases, particularly cancer. Abnormalities in m6A modification are involved in the initiation and progression of cancer by regulating the expression of oncogenes and oncostatic genes. There is an interaction between m6A modification and autophagy, both of which play significant roles in cancer. However, the molecular mechanisms underlying this relationship are still unclear. m6A modification can either directly inhibit autophagy or promote its initiation, but the complex relationship between m6A modification, autophagy, and cancer remains poorly understood. Therefore, this paper aims to review the dual role of m6A and autophagy in cancer, explore the impact of m6A modification on autophagy regulation, and discuss the crucial role of the m6A modification-autophagy axis in cancer progression and treatment resistance.

Prognostic significance and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer: A clinicopathological study.

BACKGROUND: The TGF-ß/SMAD3 and VEGFR-1 signaling pathways play important roles in gastric cancer metastasis. SMAD3 phosphorylation is a crucial prognostic marker in gastric cancer. AIM: To determine the prognostic value and relationship of SMAD3 phospho-isoforms and VEGFR-1 in gastric cancer. METHODS: This was a single-center observational study which enrolled 98 gastric cancer patients and 82 adjacent normal gastric tissues from patients aged 32-84 years (median age 65) between July 2006 and April 2007. Patients were followed up until death or the study ended (median follow-up duration of 28.5 mo). The samples were used to generate tissue microarrays (TMAs) for immunohistochemical (IHC) staining. The expressions of TGF-ß1, pSMAD3C(S423/425), pSMAD3L(S204), and VEGFR-1 in gastric cancer (GC) tumor tissue and normal tissue were measured by IHC staining using TMAs obtained from 98 GC patients. Prognosis and survival information of the patients was recorded by Outdo Biotech from May 2007 to July 2015. The relationship between TGF-ß1, pSMAD3C(S423/425), pSMAD3L(S204), and VEGFR-1 protein expression levels was analyzed using Pearson's correlation coefficient. The relationship between protein expression levels and clinicopathological parameters was analyzed using the Chi-squared test. A survival curve was generated using the Kaplan-Meier survival analysis. RESULTS: TGFß-1 and VEGFR-1 expression was significantly upregulated in gastric cancer tissue compared to adjacent non-cancerous tissue. The positive expression of phosphorylated isoforms of Smad3 varied depending on the phosphorylation site [pSMAD3C(S423/425): 51.0% and pSMAD3L(S204): 31.6%]. High expression of pSMAD3L(S204) was significantly correlated with larger tumors (P = 0.038) and later N stages (P = 0.035). Additionally, high expression of VEGFR-1 was closely correlated with tumor size (P = 0.015) and pathological grading (P = 0.013). High expression of both pSMAD3L(S204) and VEGFR-1 was associated with unfavorable outcomes in terms of overall survival (OS). Multivariate analysis indicated that high expression of pSMAD3L(S204) and VEGFR-1 were independent risk factors for prognosis in GC patients. VEGFR-1 protein expression was correlated with TGF-ß1 (r = 0.220, P = 0.029), pSMAD3C(S423/425) (r = 0.302, P = 0.002), and pSMAD3L(S204) (r = 0.201, P = 0.047), respectively. Simultaneous overexpression of pSMAD3L(S204) and VEGFR-1 was associated with poor OS in gastric cancer patients. CONCLUSION: Co-upregulation of pSMAD3L(S204) and VEGFR-1 can serve as a predictive marker for poor gastric cancer prognosis, and pSMAD3L(204) may be involved in enhanced gastric cancer metastasis in a VEGFR-1-dependent manner.

Knockout of phosphatidylethanolamine binding protein4 (PEBP4) promotes chronic non-bacterial prostatitis by mediating the activation of NF-κB signaling.

BACKGROUND: The etiology of chronic prostatitis remains unclear; consequently, this disease is associated with recurrence and ineffective clinical therapy. Therefore, there is an urgent need to investigate the underlying pathogenesis of chronic prostatitis in order to develop more efficacious treatments. OBJECTIVE: The previous study found that knocking out of PEBP4 leads to chronic prostatitis in the male mice. This research aimed to identify the role of PEBP4 in prostatitis, determine the molecular pathogenic mechanisms associated with chronic prostatitis, and provide guidelines for the development of new treatment strategies for chronic prostatitis. MATERIALS AND METHODS: A PEBP4 exon knockout strain (PEBP4-/-) was established in C57BL/6 mice via the Cre-loxP system. Hematoxylin-eosin (H&E) staining was used to investigate histological changes. RNA-sequencing was used to investigate the gene expression signature of the prostate and the levels of inflammatory cytokines were determined by real-time polymerase chain reaction (RT-PCR). The expression of PEBP4 protein in prostate tissue was determined by immunohistochemistry in specimens from patients with BPH and BPH combined with chronic prostatitis. Finally, we used a CRISPR-Cas9 plasmid to knockout PEBP4 in RWPE-1 cells; western blotting was subsequently used to measure the level of activation in the NF-κB signaling pathway after activating with TNF-α. RESULTS: Hemorrhage and inflammatory cell infiltration were incidentally observed in the seminal vesicles and prostate glands of PEBP4-/- mice after being fed with a normal diet for 1 year. In addition, we found significantly lower (p < 0.001) expression levels of PEBP4 protein in prostate tissues from patients with benign prostate hyperplasia (BPH) and chronic and non-bacterial prostatitis (CNP) when compared to those with BPH only. The reduced expression of PEBP4 led to a higher risk of prostatitis recurrence in patients after 2 years of follow-up. Increased levels of NF-κB and IκB phosphorylation were observed in PEBP4-knockout RWPE-1 cells and prostate glands from PEBP4-/- mice. CONCLUSION: The knockout of PEBP4 in experimental mice led to chronic prostatitis and the reduced expression of PEBP4 in patients with higher risk of chronic and non-bacterial prostatitis suggested that PEBP4 might act as a protective factor against chronic prostatitis. The knockout of PEBP4 in RWPE-1 cells led to the increased activation of NF-κB and IκB, thus indicating that inhibition of PEBP4 faciliated the NF-κB signaling cascade. Our findings provide a new etiology and therapeutic target for chronic prostatitis.

MicroRNA-21 in urologic cancers: from molecular mechanisms to clinical implications.

The three most common kinds of urologic malignancies are prostate, bladder, and kidney cancer, which typically cause substantial morbidity and mortality. Early detection and effective treatment are essential due to their high fatality rates. As a result, there is an urgent need for innovative research to improve the clinical management of patients with urologic cancers. A type of small noncoding RNAs of 22 nucleotides, microRNAs (miRNAs) are well-known for their important roles in a variety of developmental processes. Among these, microRNA-21 (miR-21) stands out as a commonly studied miRNA with implications in tumorigenesis and cancer development, particularly in urological tumors. Recent research has shed light on the dysregulation of miR-21 in urological tumors, offering insights into its potential as a prognostic, diagnostic, and therapeutic tool. This review delves into the pathogenesis of miR-21 in prostate, bladder, and renal cancers, its utility as a cancer biomarker, and the therapeutic possibilities of targeting miR-21.

Pretreatment of the urethral mucosa at the tip of the prostate: a retrospective review in preventing stress urinary incontinence after thulium laser enucleation of the prostate.

Objective: Explore the clinical application value of urethral mucosal pretreatment at the tip of the prostate in preventing stress urinary incontinence (SUI) after thulium laser enucleation of the prostate (ThuLEP). Methods: Eighty-seven patients with benign prostatic hyperplasia (BPH) treated with ThuLEP from June 2021 to December 2022 were divided into two groups. Of these, 42 patients (group A) underwent conventional ThuLEP and 45 patients (group B) were enucleated after pretreatment of the urethral mucosa. At the tip of the prostate, pretreatment of the urethral mucosa consisted of pushing the gland separately on both sides at the level of the verumontanum and cutting off the mucosa near the external urethral sphincter clockwise and counterclockwise. The perioperative and postoperative follow-up indicators [operation time, hemoglobin reduction, complications, Qmax, International Prostate Symptom Score (IPSS), quality of life (QoL), and post-void residual (PVR) volume] of the two groups of patients were collected and compared. All patients were followed up 1 month after surgery. Results: All 87 procedures were successfully completed. There was no significant difference in age and gland size between the two groups (P > 0.05). There was no significant difference between operating time and hemoglobin reduction in the two groups (P > 0.05). The Qmax, IPSS, QOL, and PVR volume were significantly improved postoperatively in both groups (P < 0.05). Temporary SUI occurred in both groups [12 cases (28.5%) in group A and 3 cases (6.7%) in group B (P < 0.05)]. There was no significant difference in the incidence of infection and urethral stricture between the two groups (P > 0.05). Conclusion: Pretreatment of the urethral mucosa before ThuLEP for BPH significantly reduces the incidence of SUI after surgery. This technique, which preconditions the apical urethral mucosa of the prostate, is safe and effective, has few complications, and is worthy of clinical application.

Critical roles of lncRNA-mediated autophagy in urologic malignancies.

Urologic oncology is a significant public health concern on a global scale. Recent research indicates that long chain non-coding RNAs (lncRNAs) and autophagy play crucial roles in various cancers, including urologic malignancies. This article provides a summary of the latest research findings, suggesting that lncRNA-mediated autophagy could either suppress or promote tumors in prostate, kidney, and bladder cancers. The intricate network involving different lncRNAs, target genes, and mediated signaling pathways plays a crucial role in urological malignancies by modulating the autophagic process. Dysregulated expression of lncRNAs can disrupt autophagy, leading to tumorigenesis, progression, and enhanced resistance to therapy. Consequently, targeting particular lncRNAs that control autophagy could serve as a dependable diagnostic tool and a promising prognostic biomarker in urologic oncology, while also holding potential as an effective therapeutic approach.

Autophagy in erectile dysfunction: focusing on apoptosis and fibrosis.

In most types of erectile dysfunction, particularly in advanced stages, typical pathological features observed are reduced parenchymal cells coupled with increased tissue fibrosis. However, the current treatment methods have shown limited success in reversing these pathologic changes. Recent research has revealed that changes in autophagy levels, along with alterations in apoptosis and fibrosis-related proteins, are linked to the progression of erectile dysfunction, suggesting a significant association. Autophagy, known to significantly affect cell fate and tissue fibrosis, is currently being explored as a potential treatment modality for erectile dysfunction. However, these present studies are still in their nascent stage, and there are limited experimental data available. This review analyzes erectile dysfunction from a pathological perspective. It provides an in-depth overview of how autophagy is involved in the apoptotic processes of smooth muscle and endothelial cells and its role in the fibrotic processes occurring in the cavernosum. This study aimed to develop a theoretical framework for the potential effectiveness of autophagy in preventing and treating erectile dysfunction, thus encouraging further investigation among researchers in this area.

Therapeutic potential of vasculogenic mimicry in urological tumors.

Angiogenesis is an essential process in the growth and metastasis of cancer cells, which can be hampered by an anti-angiogenesis mechanism, thereby delaying the progression of tumors. However, the benefit of this treatment modality could be restricted, as most patients tend to develop acquired resistance during treatment. Vasculogenic mimicry (VM) is regarded as a critical alternative mechanism of tumor angiogenesis, where studies have demonstrated that patients with tumors supplemented with VM generally have a shorter survival period and a poorer prognosis. Inhibiting VM may be an effective therapeutic strategy to prevent cancer progression, which could prove helpful in impeding the limitations of lone use of anti-angiogenic therapy when performed concurrently with other anti-tumor therapies. This review summarizes the mechanism of VM signaling pathways in urological tumors, i.e., prostate cancer, clear cell renal cell carcinoma, and bladder cancer. Furthermore, it also summarizes the potential of VM as a therapeutic strategy for urological tumors.