Thymoquinone inhibits IL-7-induced tumor progression and metastatic invasion in prostate cancer cells by attenuating matrix metalloproteinase activity and Akt/NF-κB signaling.

Interleukin (IL)-7 acts via the IL-7 receptor in metastatic tumor progression in prostate cancer (PC). The current study aimed to evaluate thymoquinone (Tq), an active constituent from Nigella sativa against IL-7-driven tumor progression and metastatic invasion in PC cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to assess the proliferation of PC cells. Enzyme-linked immunosorbent assay was used to detect the expression of IL-7 and matrix metalloproteinases (MMPs). Tumor-cell transendothelial, scratch wound and cell scatter assays were performed to mimic metastasis. Western immunoblotting was used to measure the level of proteins. Tq effectively controlled the proliferation of DU-145, PC-3, and LNCaP cells with GI50 of 10.18, 12.40, and 16.78 µM, respectively. IL-7 and IL-7R were natively expressed in all PC types, while maximal expression was detected in DU-145. IL-7 promoted metastatic events, such as transendothelial migration, cell scatter, and cell invasion of DU-145 cells in a dose-dependent manner that was inhibited by Tq. Furthermore, Tq also downregulated p-Akt and NF-κB in DU-145 cells induced by IL-7 antibody and reduced the levels of MMP-3 and MMP-7 in these cells in a dose-dependent manner. Collectively, Tq has excellent efficacy in controlling tumor progression, migration, and invasion of DU-145 cells that were driven by the activation of MMPs through IL-7/Akt/NF-κB signaling.

Prevalence of nocturnal enuresis among children of Aseer region in Saudi Arabia.

Introduction: Nocturnal enuresis (NE) in children is a very common problem managed in pediatric urology. In this study, we present the prevalence of NE in children in Aseer region in Saudi Arabia. Methodology: This study was conducted as a descriptive cross-sectional survey to estimate the prevalence of NE among 555 Saudi children aged 5-15 years in Aseer region in Saudi Arabia. Data collection was done through a questionnaire, which included questions on sociodemographic data, personal knowledge, enuresis-related characteristics, risk factors, and management modalities. Results: This study identified a prevalence of enuresis of 24% of the study population, most of whom were boys. The majority of the parents had a high educational level. Clinical characteristics of the study population showed: 9% have a family history of NE, 2.2% have a history of neurological disorder, 10.0% have a history of urinary tract infections, 66.8% have associated daytime urgency, 67% have urine-holding behavior, and 19.5% have associated daytime enuresis of the study population. Conclusion: Our study found that 24% of children in the Aseer region in Saudi Arabia have NE. Our study finding helps us to understand the prevalence of NE in Aseer region in Saudi Arabia, and this can be applied to other regions in the kingdom. Furthermore, this finding helps us to understand the need to raise awareness in the community about NE and the need to educate the nonpediatric urologist health-care provider about the best management practice for NE.

Computational docking and in vitro analysis identifies novel arylidene analogue FPMXY-14 against renal cancer cells by attenuating Akt.

Targeted therapies are gaining global attention to tackle Renal Cancer (RC). This study aims to screen FPMXY-14 (novel arylidene analogue) for Akt inhibition by computational and in vitro methods. FPMXY-14 was subjected to proton NMR analysis and Mass spectrum analysis. Vero, HEK-293, Caki-1, and A498 cell lines were used. Akt enzyme inhibition was studied with the fluorescent-based kit assay. Modeller 9.19, Schrodinger 2018-1, LigPrep module, and Glide docking were used in computational analysis. The nuclear status was assessed by PI/Hoechst-333258 staining, cell cycle, and apoptosis assays were performed using flow cytometry. Scratch wound and migrations assays were performed. Western blotting was applied to study key signalling proteins. FPMXY-14 selectively inhibited kidney cancer cell proliferation with GI50 values of 77.5 nM and 101.40 nM in Caki-1 cells and A-498 cells, respectively. The compound dose-dependently inhibited Akt enzyme with an IC50 value of 148.5 nM and bound efficiently at the allosteric pocking of the Akt when computationally analyzed. FPMXY-14 caused nuclear condensation/fragmentation, increased the sub G0/G1, G2M populations, and induced early, late phase apoptosis in both cells when compared to controls. Treatment of the compound inhibited wound healing and migration of tumor cells, while proteins like Bcl-2, Bax, and caspase 3 were also altered. FPMXY-14 effectively inhibited the phosphorylation of Akt in these cancer cells, while total Akt was unaltered. FPMXY-14 exhibited anti-proliferative and anti-metastatic activities in kidney cancer cells by attenuating the Akt enzyme. Further pre-clinical research on animals with a detailed pathway elucidation is recommended.

Association of statins use and mortality outcomes in prostate cancer patients who received androgen deprivation therapy: a systematic review and meta-analysis.

INTRODUCTION: While several recent studies investigated the influence of statins on survival outcomes in prostate cancer (PCa) patients on androgen deprivation therapy (ADT), definitive conclusions are still missing. The present systematic review and meta-analysis aimed to develop an overarching framework for the association of statins use and survival outcomes in PCa patients who receive ADT. MATERIAL AND METHODS: We conducted a systematic review and meta-analysis of the literature assessing the survival outcomes for statin compared to non-statin users in PCa patients who received ADT. We searched PubMed and Web of Science for studies published before March 1, 2021. We used the random effect model in the presence of heterogeneity and the fixed-effects model in the absence of heterogeneity per the I 2 statistic. We did two meta-analyses; the primary meta-analysis was accomplished for articles reporting cancer-specific survival (CSS) as an outcome. A secondary meta-analysis was completed for articles reporting overall survival (OS) as an outcome. RESULTS: Ten studies were eligible for inclusion. Nine studies included in the first meta-analysis comprising 136,285 patients showed no statistically significant difference in CSS (HR 0.77; 95% CI 0.49-1.21) between statin users and non-users in PCa patients who received ADT. In four studies included in the second meta-analysis comprising 95,032 patients, statin users had a significantly better OS compared to non-users (HR 0.67; 95% CI 0.62-0.73). CONCLUSIONS: Although the combination of statins and ADT in PCa patients significantly improves OS, it seems not to be through an effect on cancer-specific factors.

Economic impacts of the Bacillus Calmette-Guérin (BCG) therapy shortage and the proposed solutions for patients with non-muscle invasive bladder Cancer in Aseer Province, Saudi Arabia.

OBJECTIVE: To report the magnitude, the financial and the economic impact of Bacillus Calmette-Guérin (BCG) shortage in our institute and transfer of non-muscle invasive bladder cancer (NMIBC) patients to higher centers to receive the treatment. METHODS: This is a retrospective study, between January 2015 and December 2017, the cases of NMIBC diagnosed at Aseer Central Hospital, Abha, Saudi Arabia were studied. Demographic features, clinical presentations, histopathological features, and the BCG therapy shortage and its economic impact were addressed. RESULTS: Over a three years study review of 62 urothelial bladder cancer, NMIBC was diagnosed in 55 (89%) patients. Forty-three (78%) patients were males and 12 (22%) patients were females. The mean age ± standard deviation (SD) (range) in this cohort was 59 ± 12 years (38-87). Gross hematuria was the main presentation in 51 (92%) patients of this cohort. Dysuria and other lower urinary tract symptoms were the presentations in 18 (32%) patients. Smoking history was positive in 33 (60%) patients and the rest 22 (40%) patients denied any form of tobacco consumptions. The BCG eligible were 46 (84%) patients of all NMIBC patients in this study. Twenty-seven (59%) patients of them received BCG in our institute. The rest 19 (41%) patients were opted to be transferred to a higher medical center to receive the BCG because of the BCG shortage in our center. The financial cost of traveling to receive the six-weeks induction BCG therapy was on average of 7200 Saudi riyals (1.745 €) for every patient. CONCLUSIONS: The BCG shortage in our institute is almost approaching half of eligible BCG cases. This has had an economic impact on the health budget. Such health catastrophe could be mitigated with proper health plans of a provision of the BCG to all tertiary care centers. Alternative therapies for such cases should be considered in cases of global BCG shortage.

Thymoquinone (Tq) protects necroptosis induced by autophagy/mitophagy-dependent oxidative stress in human bronchial epithelial cells exposed to cigarette smoke extract (CSE).

Chronic obstructive pulmonary disease (COPD) is characterized by cigarette smoke-induced emphysema. Herein, we demonstrate protective effects of Thymoquinone (Tq), an active constituent from Nigella sativa, against cigarette smoke extract (CSE)-induced abnormalities in bronchial epithelial cells. Dose-dependent reduction in cell viability was observed in BEAS-2B cells when exposed to different CSE concentrations, which was significantly reversed by Tq evident by LDH release. Levels of SOD, CAT, GR , GSH, and mitochondrial membrane ATPases were significantly reduced upon CSE exposure, an event, again, antagonized in presence of Tq. Similarly, Tq treatment significantly blocked CSE-induced 4HNE elevations. Further, Tq-improved mitochondrial dysfunction caused by CSE and significantly decreased autophagy/mitophagy markers like LC3II and p-Drp. Tq also reduced necroptosis markers such as p-MLKL, RIP-1, and RIP-3, by stabilizing PINK-1 levels. In summary, Tq possesses protective properties against human bronchial epithelial cell autophagy/mitophagy-dependent necroptosis caused by CSE, which warrants considerable attention for further preclinical evaluations. PRACTICAL APPLICATIONS: This study demonstrates Thymoquinone (Tq), a natural plant extract to possess protective properties against human bronchial epithelial cell autophagy/mitophagy-dependent necroptosis caused by cigarette smoke extract. The demonstrated efficacy of Tq will throw light for further preclinical evaluation of this molecule in CSE-mediated complications. A detailed in vivo research is recommended.

Thymoquinone and curcumin combination protects cisplatin-induced kidney injury, nephrotoxicity by attenuating NFκB, KIM-1 and ameliorating Nrf2/HO-1 signalling.

This study evaluates the protective effects of Thymoquinone (Tq) and Curcumin (Cur) in models of cisplatin-induced renal toxicity. Proliferation studies were carried out in HEK-293 cells. Cisplatin(ip) 5 mg/kg BW was used to induce renal injury in Sprague-Dawley rats. 50 mg/kg BW Tq + 100 mg/kg BW Cur, with or without cisplatin-treatment were administered for 5 days. Tq + Cur combination synergistically reduced the proliferation inhibition of HEK-293 cells resulted from cisplatin treatment and brought down cisplatin-induced apoptosis in these cells. In vitro studies revealed serum levels of BUN, creatinine, CK and pro-inflammatory cytokines like TNF-α, IL-6 and MRP-1 to be elevated in the cisplatin-treated group while reducing glomerular filtration rate. Tq + Cur treatment significantly improved these conditions. The antioxidant enzyme levels and mitochondrial ATPases were restored upon treatment, which were lessened in the cisplatin-treated group. Cisplatin induced the expression of KIM-1, which was brought down by the combination treatment. Tq + Cur treatment increased the expressions of phosphorylated Akt, Nrf2 and HO-1 proteins while decreasing the levels of cleaved caspase 3 and NFκB in kidney homogenates. In summary, Tq + Cur had protective effects on cisplatin-induced nephrotoxicity and renal injury, which could be mediated by up-regulation of survival signals like Akt, Nrf2/HO-1 and attenuation of KIM-1, NFκB.