Activating transcription factor 3 is an antitumor gene synergizing with growth differentiation factor 15 to modulate cell growth in human bladder cancer.

BACKGROUND: The functions of activating transcription factor 3 (ATF3) within the human bladder remain unexplored. This study delves into the expressions, functions, and regulatory mechanisms of ATF3 in human bladder cancer. MATERIAL AND METHODS: Gene expressions were determined by immunoblot, RT-qPCR, and reporter assays. Assays of Ki67, colony formation, Matrigel invasion, and the xenograft animal study were used to assess the cell proliferation, invasion, and tumorigenesis in vitro and in vivo. Silico analysis from TCGA database examined the correlations between GDF15 and ATF3 expressions, clinicopathologic features, and progression-free survival rates. RESULTS: Silico analysis confirmed that ATF3 is an antitumor gene, and the expression positively correlates with GDF15 in bladder cancer tissues. Multivariate analysis revealed that low ATF3/GDF15 but not a single low expression of ATF3 is an independent prognostic factor for progression-free survival of bladder cancer patients. Ectopic overexpression of ATF3 downregulated cell proliferation and invasion in bladder cancer cells in vitro, while ATF3-knockdown reversed these results. Knockdown of ATF3 upregulated EMT markers to enhance cell invasion in vitro and downregulated GDF15, NDRG1, and KAI-1 to elevate tumor growth in vivo. The activation of metformin on ATF3 and GDF15 in bladder cancer cells was blocked by SB431542, a TGFß receptor inhibitor. ATF3 positively regulated GDF15 expression in bladder cancer cells through a feedback loop. CONCLUSIONS: Our results identify that ATF3 is a metformin-upregulated antitumor gene. Results of Silico analysis align with cell-based studies suggesting that low ATF3/GDF15 could be a negative prognostic marker for bladder cancer.

Effects of Sapindus mukorossi Seed Oil on Bone Healing Efficiency: An Animal Study.

Natural products have attracted great interest in the development of tissue engineering. Recent studies have demonstrated that unsaturated fatty acids found in natural plant seed oil may exhibit positive osteogenic effects; however, few in vivo studies have focused on the use of plant seed oil for bone regeneration. The aim of this study is to investigate the effects of seed oil found in Sapindus mukorossi (S. mukorossi) on the osteogenic differentiation of mesenchymal stem cells and bone growth in artificial bone defects in vivo. In this study, Wharton-jelly-derived mesenchymal stem cells (WJMSCs) were co-cultured with S. mukorossi seed oil. Cellular osteogenic capacity was assessed using Alizarin Red S staining. Real-time PCR was carried out to evaluate ALP and OCN gene expression. The potential of S. mukorossi seed oil to enhance bone growth was assessed using an animal model. Four 6 mm circular defects were prepared at the parietal bone of New Zealand white rabbits. The defects were filled with hydrogel and hydrogel-S. mukorossi seed oil, respectively. Quantitative analysis of micro-computed tomography (Micro-CT) and histological images was conducted to compare differences in osteogenesis between oil-treated and untreated samples. Although our results showed no significant differences in viability between WJMSCs treated with and without S. mukorossi seed oil, under osteogenic conditions, S. mukorossi seed oil facilitated an increase in mineralized nodule secretion and upregulated the expression of ALP and OCN genes in the cells (p < 0.05). In the animal study, both micro-CT and histological evaluations revealed that new bone formation in artificial bone defects treated with S. mukorossi seed oil were nearly doubled compared to control defects (p < 0.05) after 4 weeks of healing. Based on these findings, it is reasonable to suggest that S. mukorossi seed oil holds promise as a potential candidate for enhancing bone healing efficiency in bone tissue engineering.

Analysis of urinary retention after endoscopic prostate enucleation and its subsequent impact on surgical outcomes.

PURPOSE: Postoperative urinary retention (PUR) is a common complication after prostate enucleation, which leads to an increased length of hospital stay and decreased postoperative satisfaction. This study determined the predictive factors of postoperative urine retention within 1 month after prostate enucleation and investigated whether PUR influences surgical outcomes at the 2-week, 3-month, and 6-month follow-up time points. METHODS: Data were collected from the electronic medical records of 191 patients with benign prostatic obstruction (BPO) during October 2018 to September 2021. Of them, 180 patients who underwent thulium laser or plasma kinetic enucleation of the prostate (ThuLEP, PKEP) were separated into the PUR group (n = 24) and the non-PUR (NPUR) group (n = 156). Uroflowmetry and the International Prostate Symptom Score (IPSS) questionnaire were followed up at 2 weeks, 3 months, and 6 months postoperatively. RESULTS: The PUR group had a significantly higher percentage of patients with type 2 diabetes mellitus (DM) than the NPUR group. Postoperatively, compared with the NPUR group, the PUR group had significantly less improvement in changes in the IPSS Quality of Life scores at 2 weeks, the total IPSS(International Prostate Symptom Score) at all follow-up times, the IPSS-S(IPSS storage subscores) at 2 weeks and 3 months, and the IPSS-V(IPSS voiding subscores) at all follow-up times. Predictive factors for PUR include lower preoperative maximum urinary flow (Qmax), lower preoperative total IPSS, and higher operation time. CONCLUSION: Lower preoperative Qmax, lower IPSS scores, and longer operation time were risk factors for PUR. Furthermore, PUR could be a prognostic factor for prostatic enucleation surgical outcomes.

Impact of age and anterior fibromuscular stroma preservation on post-enucleation voided volume.

PURPOSE: This study is centered on the critical role of anterior fibromuscular stroma (AFS) preservation in prostate enucleation, an emerging strategy aimed at minimizing postoperative urinary incontinence-a common concern in benign prostatic hyperplasia (BPH) surgeries. By focusing on postoperative voiding volumes (VV), our research investigates the efficacy of AFS preservation. This approach, distinct in its methodology, is hypothesized to improve urinary function post-surgery, thereby offering a potentially significant advancement in BPH surgical treatments. MATERIALS AND METHODS: A retrospective analysis was conducted, comparing patients who underwent prostate enucleation in 2017 without intentional AFS preservation to those in 2019 with this technique. We examined variables including age, BMI, diabetes, hypertension, and preoperative VV to assess their effect on post-catheter removal VV. The study's methodology includes a thorough review of the primary statistical analysis methods employed. RESULTS: Our analysis indicates that while the 2017 and 2019 cohorts were similar in most preoperative parameters, the 2019 group that underwent AFS-preserved surgery showed a significant improvement in postoperative VVs. This was less pronounced in the patient group aged over 70, underscoring the importance of this demographic in our study. CONCLUSIONS: The study concludes that intentional preservation of AFS during prostate enucleation positively impacts early postoperative VVs, with limited improvement in older patients. These findings highlight the potential of AFS preservation not only in enhancing urinary outcomes post-surgery but also in shaping future BPH surgical procedures and research directions.

Association between sodium-glucose cotransporter-2 (SGLT2) inhibitors and macular degeneration in patients with diabetes: a nationwide population-based study in Taiwan.

AIMS: Evidence showed that SGLT2 inhibitors have greater protective effects against retinal diseases compared to other hypoglycemic agents. Thus, we explore the association between SGLT2 inhibitor usage and macular degeneration (MD) in Taiwanese patients with diabetes. METHODS: The National Health Insurance (NHI) program's claim data are released as the National Health Insurance Research Database (NHIRD). This database covers more than 99% of the residents in Taiwan. We included data on patients who were newly diagnosed with type 2 diabetes mellitus (ICD-9-CM: 250, exclude 250.1x; ICD-10-CM: E11), with an age at diagnosis of over 20 years as our study population. Patients who received (sodium-glucose cotransporter 2 inhibitor) SGLT2i (ATC code: A10BK) over 90 days in 2016-2019 were defined as the SGLT2i cohort. Conversely, patients who did never received SGLT2i were defined as the non-SGLT2i cohort. The exclusion criteria were having MD before the index date, receiving SGLT2i within 1-89 days, and missing data on sex, age, or days of SGLT2i usage. Two cohorts were matched by 1:1 propensity score matching, which was based on age, sex, payroll bracket grade, urbanization, comorbidities, and medications. RESULTS: Compared to non-SGLT2i cohort, patients who received SGLT2i had a significantly lower risk of MD (adjusted hazard ratio = 0.70, 95%CI = 0.66-0.75). CONCLUSIONS: We found that SGLT2is has a strong protective effect against MD in patients with diabetes. SGLT2is may have benefits beyond glycemic control in patients with DR. However, additional clinical and experimental studies are required.

Surgical outcomes of endoscopic enucleation of the prostate in community aging males with or without preoperative urinary retention.

OBJECTIVES: This study aims to investigate the surgical outcomes of endoscopic enucleation of the prostate in older males with or without preoperative urinary retention (UR). MATERIAL AND METHODS: We conducted a study on selected patients with symptomatic benign prostatic hyperplasia (BPH) who underwent either thulium:YAG laser (vela XL) prostate enucleation (ThuLEP) or bipolar plasma enucleation of the prostate (B-TUEP) at the geriatric urology department of our institution. The studied patients were categorized into two groups, namely the UR group and the non-UR group, on the basis of whether they experienced UR in the 1 month preceding their surgery. Their clinical outcomes following prostate endoscopic surgery were evaluated and analyzed. RESULTS: Our results revealed comparable outcomes for operation time, length of hospital stay, percentage of tissue removed, re-catheterization rate, and urinary tract infection rate within the 1 month between the B-TUEP and ThuLEP surgery groups, regardless of UR history. However, the non-UR B-TUEP group experienced more blood loss relative to the non-UR ThuLEP group (P = .004). Notably, patients with UR exhibited significantly greater changes in IPSS total, IPSS voiding, and prostate-specific antigen values relative to those without UR. CONCLUSIONS: Both ThuLEP and B-TUEP were effective in treating BPH-related bladder outlet obstruction. Our study identified more pronounced changes in IPSS total, IPSS voiding, and prostate-specific antigens within the UR group. Moreover, the rate of postoperative UR in this group was not higher than that observed in the non-UR group. Our study also revealed that the presumed benefits of laser surgery in reducing blood loss were less pronounced for patients with UR.