Prevalence of urolithiasis in China: a systematic review and meta-analysis.

OBJECTIVE: To estimate the pooled prevalence, as well as the spatial and temporal distribution, of urolithiasis among subjects in China. MATERIALS AND METHODS: We conducted a comprehensive search of both Chinese and English databases to retrieve literature pertaining to the prevalence of urolithiasis in the indigenous Chinese population. A random-effects meta-analysis model was employed to calculate the pooled prevalence of urolithiasis. Subgroup analyses were conducted based on factors such as time, region, gender, and sample size. Prevalence and spatial distribution maps were created based on provinces and latitude/longitude coordinates. RESULTS: A total of 46 studies conducted in 22 provinces across China were included in this meta-analysis and the pooled prevalence of urolithiasis, kidney stones, ureteric calculi, urethral and bladder stones were 8.1% (95% confidence interval [CI] 5.6-11.1%), 7.8% (95% CI 5.8-10.0%), 3.2% (95% CI 0.6-5.7%), 0.5% (95% CI 0.1-0.9%). Most of the urolithiasis prevalence screening in China was concentrated between 100° E and 120° E, with higher rates observed in low latitude areas. Subgroup analysis of kidney stones revealed that Guangdong (12.7%) and Guangxi (10.3%) had the highest prevalence, with the eastern developed area exhibiting higher rates compared to the west. The prevalence in males was higher than in females (odds ratio 1.67, 95% CI 1.46-1.92), although the gender gap has significantly reduced since 2006. Moreover, a greater sample size is associated with a decreased prevalence of urolithiasis. CONCLUSIONS: The prevalence of urolithiasis is increasing in China, and there are noteworthy regional or provincial disparities in occurrence. It is worth noting that the current number of screening studies in some areas is insufficient. Additional investigations with appropriate sample sizes should be supplemented in time.

PGE2 binding to EP2 promotes ureteral stone expulsion by relaxing ureter via the cAMP-PKA pathway.

BACKGROUND: This study investigated the relaxation effect of PGE2 on the ureter and its role in promoting calculi expulsion following calculi development. METHODS: By using immunofluorescence and Western blot, we were able to locate EP receptors in the ureter. In vitro experiments assessed the impact of PGE2, receptor antagonists, and agonists on ureteral relaxation rate. We constructed a model of ureteral calculi with flowable resin and collected ureteral tissue from postoperative side of the ureter after obstruction surgery. Western blot analysis was used to determine the protein expression levels of EP receptors and the PGE2 terminal synthase mPGES-1. Additionally, PGE2 was added to smooth muscle cells to observe downstream cAMP and PKA changes. RESULTS: The expression of EP2 and EP4 proteins in ureteral smooth muscle was verified by Western blot analysis. According to immunofluorescence, EP2 was primarily found on the cell membrane, while EP4 was found in the nucleus. In vitro, PGE2 induced concentration-dependent ureteral relaxation. Maximum diastolic rate was 70.94 ± 4.57% at a concentration of 30µM. EP2 antagonists hindered this effect, while EP4 antagonists did not. Obstructed ureters exhibited elevated mPGES-1 and EP2 protein expression (P < 0.01). Smooth muscle cells treated with PGE2 displayed increased cAMP and phosphorylated PKA. CONCLUSIONS: PGE2 binding to EP2 induces ureteral relaxation through the cAMP-PKA pathway. This will provide a new theoretical basis for the development of new therapeutic approaches for the use of PGE2 in the treatment of ureteral stones.

Exposure to heavy metal elements may significantly increase serum prostate-specific antigen levels with overdosed dietary zinc.

BACKGROUND: Serum prostate-specific antigen (PSA) is a primary metric for diagnosis and prognosis of prostate cancer (PCa). Exposure to heavy metals, such as lead, cadmium, mercury, and zinc can impact PSA levels in PCa patients. However, it is unclear whether this effect also occurs in men without PCa, which may lead to the overdiagnosis of PCa. METHOD: Data on a total of 5089 American men who had never been diagnosed with PCa were obtained from the National Health and Nutrition Examination Survey performed from 2003-2010. The relationship between serum PSA levels (dependent variable) and concentrations of lead (µmol/L), cadmium (nmol/L), and mercury (µmol/L) were investigated with dietary zinc intake being used as a potential modifier or covariate in a weighted linear regression model and a generalized additive model. A series of bootstrapping analyses were performed to evaluate sensitivity and specificity using these models. RESULTS: Regression analyses suggested that, in general, lead, cadmium, or mercury did not show an association with PSA levels, which was consistent with the results of the bootstrapping analyses. However, in a subgroup of participants with a high level of dietary zinc intake (≥14.12 mg/day), a significant positive association between cadmium and serum PSA was identified (1.06, 95% CI, P = 0.0268, P for interaction=0.0249). CONCLUSIONS: With high-level zinc intake, serum PSA levels may rise in PCa-free men as the exposure to cadmium increases, leading to a potential risk of an overdiagnosis of PCa and unnecessary treatment. Therefore, environmental variables should be factored in the current diagnostic model for PCa that is solely based on PSA measurements. Different criteria for PSA screening are necessary based on geographical variables. Further investigations are needed to uncover the biological and biochemical relationship between zinc, cadmium, and serum PSA levels to more precisely diagnose PCa.

BSA modification of bacterial surface: a promising anti-cancer therapeutic strategy.

BACKGROUND: Attenuated live bacterial therapy and medical BSA materials have their own advantages in anti-cancer research, and their combination is expected to overcome some of the disadvantages of conventional anti-cancer therapeutics. METHODS AND OBJECTIVE: Utilizing the high affinity between biotin and streptavidin, BSA modification on the surface of Escherichia coli (E. coli) was achieved. Then, the adhesion and targeting abilities of BSA modified E. coli was explored on different bladder cancer cells, and the underlying mechanism was also investigated. RESULTS: BSA modification on the surface of E. coli enhances its ability to adhere and target cancer cells, and we speculate that these characteristics are related to the expression of SPARC in different bladder cancer cell lines. CONCLUSION: BSA and live bacteria have their own advantages in anti-cancer research. In this study, we found that E. coli surface-modified by BSA had stronger adhesion and targeting effects on bladder cancer cells with high expression of SPARC. These findings pave the way for the future studies exploring the combination of BSA combined with live bacteria for cancer therapy.

Construction of a novel rabbit model of ureteral calculi implanted with flowable resin.

BACKGROUND: The purpose of this study was to characterize the pathophysiological changes of hydronephrosis caused by ureteral calculi obstruction in a new rabbit ureteral calculi model by implanting flowable resin. METHODS: Forty New Zealand rabbits were randomly divided into two groups: the calculi group and the sham control group. In the calculi group (n = 20), rabbits were operated at left lower abdomen and the left ureter was exposed. Then flowable resin (flowable restorative dental materials) was injected into the left ureter using a 0.45 mm diameter intravenous infusion needle. Then light-cured for 40 s by means of a dental curing light to form calculi. In the sham control group, normal saline was injected into the ureter. Rabbits underwent X-ray and routine blood and urine tests preoperatively, as well as X-ray, CT, dissection, HE staining and routine blood and urine tests on 1, 3, 5 and 7 days postoperatively. Stone formation was assessed by X-ray and unenhanced CT scan after surgery. The pathophysiological changes were evaluated through dissection, HE staining and routine blood and urine tests. RESULTS: Ureteral calculi models were successfully constructed in 17 rabbits. In calculi group, high-density shadows were observed in the left lower abdomen on postoperative day 1st, 3rd, 5th and 7th by X-ray and CT scan. Dissection found obstruction formation of the left ureters, dilatation of the renal pelvis and upper ureter during 7 days after surgery. The renal long-diameters of the left ureters increased only on the 1st postoperative day. HE staining found ureteral and kidney damage after surgery. In calculi group and sham group,the serum creatinine, urea nitrogen, white blood cells and urine red blood cells were raised at day 1 after surgery. However, the indicators returned to normal at day 3, 5, and 7. CONCLUSIONS: This is a stable, less complicated operation and cost-effective ureteral calculi model by implanting flowable resin. And this novel model may allow us to further understand the pathophysiology changes caused by ureteral calculi obstruction.

Expression profiles, biological functions and clinical significance of circRNAs in bladder cancer.

Circular RNAs (circRNAs), which are single-stranded closed-loop RNA molecules lacking terminal 5' caps and 3' poly(A) tails, are attracting increasing scientific attention for their crucial regulatory roles in the occurrence and development of various diseases. With the rapid development of high-throughput sequencing technologies, increasing numbers of differentially expressed circRNAs have been identified in bladder cancer (BCa) via exploration of the expression profiles of BCa and normal tissues and cell lines. CircRNAs are critically involved in BCa biological behaviours, including cell proliferation, tumour growth suppression, cell cycle arrest, apoptosis, invasion, migration, metastasis, angiogenesis, and cisplatin chemoresistance. Most of the studied circRNAs in BCa regulate cancer biological behaviours via miRNA sponging regulatory mechanisms. CircRNAs have been reported to be significantly associated with many clinicopathologic characteristics of BCa, including tumour size, grade, differentiation, and stage; lymph node metastasis; tumour numbers; distant metastasis; invasion; and recurrence. Moreover, circRNA expression levels can be used to predict BCa patients' survival parameters, such as overall survival (OS), disease-free survival (DFS), and progression-free survival (PFS). The abundance, conservation, stability, specificity and detectability of circRNAs render them potential diagnostic and prognostic biomarkers for BCa. Additionally, circRNAs play crucial regulatory roles upstream of various signalling pathways related to BCa carcinogenesis and progression, reflecting their potential as therapeutic targets for BCa. Herein, we briefly summarize the expression profiles, biological functions and mechanisms of circRNAs and the potential clinical applications of these molecules for BCa diagnosis, prognosis, and targeted therapy.

Chronic exposure to di-n-butyl phthalate causes reproductive toxicity in zebrafish.

Di-n-butyl phthalate (DBP) is known to have adverse effects on reproduction in mammals and is pervasive in the aquatic environment. The objective of the present study was to investigate whether long-term exposure to low concentrations of DBP can affect fish reproduction. In this study, zebrafish (Danio rerio) embryos (F0 ) were exposed to low concentrations (4.9, 13.6 and 43.8 µg/L) of DBP from 2 hours post-fertilization until sexual maturation. The results demonstrate that chronic exposure to DBP (43.8 µg/L) impaired the reproductive function of zebrafish, as verified by reduced egg production and modifications to gonadal histology of the treated fish. Plasma 17ß-estradiol levels in female zebrafish decreased significantly in a concentration-dependent manner, while testosterone levels in males increased significantly when fish were exposed to 43.8 µg/L DBP. Real-time polymerase chain reaction was performed to examine selected genes in the hypothalamic-pituitary-gonadal (HPG) axis and liver. Hepatic vitellogenin gene transcription was downregulated in both males and females, suggesting that DBP possesses anti-estrogenic activity. The disturbed steroid hormones were accompanied by the significant alterations in gene expression along the HPG axis. Additionally, parental exposure to DBP caused reduced hatching and survival rate as well as decreased growth in the F1 generation. Taken together, these results demonstrate that long-term exposure to low concentrations of DBP in zebrafish could cause reproductive toxicity, implying that DBP could have significant adverse effects on fish populations, particularly in a highly DBP-contaminated aquatic environment.

Evaluation of three stone-scoring systems for predicting SFR and complications after percutaneous nephrolithotomy: a systematic review and meta-analysis.

BACKGROUND: Clinical studies assessing the feasibility and accuracy of three stone scoring systems's (SSSs: Guy's stone score, CROES nomogram and S.T.O.N.E nephrolithometry scoring system) have reported contradictory outcomes. This systematic evaluation was performed to obtain comprehensive evidence with regard to the feasibility and accuracy of three SSSs. METHODS: A systematic search of Embase, Pubmed, Medline, and the Cochrane Library was conducted to identify studies that compared three SSSs up to Mar 2018. Patients were categorized according to stone free (SF) and no-stone free (NSF), Outcomes of interest included perioperative variables, stone-free rate (SFR), and complications. RESULTS: Ten studies estimating three SSSs were included for meta-analysis. The results showed that SF patients had a significantly lower proportion of male (OR = 1.48, P = 0.0007), lower stone burden (WMD = -504.28, P < 0.0001), fewer No of involved calyces (OR = -1.23, P = 0.0007) and lower proportion of staghorn stone (OR = 0.33, P < 0.0001). Moreover, SF patients had significantly lower score of Guy score (WMD = -0.64, P < 0.0001), but, S.T.O.N.E. score (WMD = -1.23, P < 0.0001) and a higher score of CROES nomogram (WMD = 29.48, P = 0.003). However, the comparison of area under curves (AUC) of predicting SFR indicated that there was no remarkable difference between three SSSs. Nonetheless, Guy score was the only stone scoring system that predicted complications after PCNL (WMD = -0.29, 95% CI: - 0.57 to - 0.02, P = 0.03). CONCLUSIONS: Our meta-analysis indicated that the three SSSs were equally, feasible and accurate for predicting SFR after PCNL. However, Guy score was the only stone scoring system that predicted complications after PCNL.

Benign prostatic hyperplasia after prostatic arterial embolization in a canine model: A 3T multiparametric MRI and whole-mount step-section pathology correlated longitudinal study.

PURPOSE: To explore the morphological and functional characteristics of prostatic arterial embolization (PAE) in a canine model of benign prostatic hyperplasia (BPH) with 3T multiparametric magnetic resonance imaging (mp-MRI) and whole-mount step-section pathology correlation. MATERIALS AND METHODS: Eight adult male beagle dogs with hormone-induced BPH underwent 3T mp-MRI before and 1, 3, and 6 months after PAE, with subsequent whole-mount step-section pathologic assessment. Images were acquired using T1 -weighted images (T1 WI), T2 WI, 3D-SPACE, diffusion-weighted imaging (DWI), susceptibility-weighted imaging (SWI), T2 -mapping, and dynamic contrast-enhanced (DCE) sequences. Variance analysis was performed to assess statistical differences in prostatic volume (PV), apparent diffusion coefficient (ADC), and T2 values. Pearson correlation analysis was performed to correlate ADC, T2 , and PV. RESULTS: The PV decreased from baseline to 1, 3, and 6 months after PAE from (25.88 ± 7.09) cm3 to (6.48 ± 2.08) cm3 , (6.48 ± 3.39) cm3 , (6.20 ± 2.88) cm3 . The ADC values sequentially decreased from baseline to 1, 3, and 6 months after PAE from (1497.06 ± 222.72) × 10-6 mm2 /s to (1056.00 ± 189.46) × 10-6 mm2 /s, (950.48 ± 77.85) × 10-6 mm2 /s, (980.98 ± 107.78) × 10-6 mm2 /s. The T2 values decreased from baseline to 1, 3, and 6 months after PAE were (83.74 ± 5.29) msec, (68.72 ± 5.66) msec, (53.96 ± 15.04) msec, (49.81 ± 13.34) msec, respectively. ADC and T2 values were positively correlated with PV (r = 0.823 and 0.744, respectively). Microhemorrhages and hemosiderin were found on SWI after PAE. CONCLUSION: 3T mp-MRI may facilitate noninvasive assessment of morphological and functional changes of BPH after PAE. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017;46:1220-1229.

Significance of the detection of TIM-3 and FOXJ1 in prostate cancer.

PURPOSE: This study sought to identify and evaluate the diagnostic value of T-cell immunoglobulin domain and mucin-3 (TIM-3) and forkhead box protein J1 (FOXJ1) expression in prostate cancer. METHODS: Thirty prostate cancer patients and 30 individuals with benign prostatic hyperplasia diagnosed and treated at the Central Hospital of Enshi Autonomous Prefecture between March 2016 and October 2016 were selected for this study. The expression of TIM-3 and FOXJ1 in patient prostate tissue was detected by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). TIM-3 and FOXJ1 expression diagnostic value for prostate cancer was analyzed by using the receiver operating curve (ROC). RESULTS: Expression of TIM-3 and FOXJ1 in prostate cancer tissues was significantly higher than those in normal prostate tissues (p<0.05), and expression of TIM-3 and FOXJ1 in prostate cancer tissues were positively correlated with Gleason score and clinical stage (p<0.05). However, the expression of the two proteins were not correlated with age, PSA level, pathological type, or the maximum tumor diameter (p>0.05). ROC analysis indicated that TIM-3 mRNA could be used to diagnose prostate cancer with an accuracy of 0.824, a sensitivity of 85.9% and a specificity of 91.2%, while the diagnostic accuracy, sensitivity, and specificity of FOXJ1 were 0.843, 86.3%, and 82.7%, respectively. CONCLUSION: TIM-3 and FOXJ1 exhibited abnormally high expression levels in prostate cancer, and can therefore be important indicators for the diagnosis of this disease.

Retroperitoneoscopy Technique-Assisted Percutaneous Nephrolithotomy for Complexity Horseshoe Kidney with Renal Stones.

OBJECTIVE: To assess the safety and efficacy of retroperitoneoscopy technique-assisted percutaneous nephrolithotomy (PCNL) used in the treatment of complexity horseshoe kidney (HSK) with renal stones. METHODS: Between January 2012 and April 2015, 5 patients with renal stones in complexity HSK underwent retroperitoneoscopy technique-assisted PCNL. The perioperative data analyzed, included operation time, blood loss, incidence of complication rate, the stone-free rate (SFR), and so on. RESULTS: All the patients successfully completed the operation without need for an open surgery. The mean operative time in which this procedure was done was 77.5 ± 20.6 min, the mean hemoglobin that was reduced was 2.5 ± 0.8 g/dl, the mean time to remove nephrostomy tube and retroperitoneal tube were 3.0 ± 1.0, 3.5 ± 1.0 days, respectively. The mean hospital stay was 7.0 ± 1.5 days. The SFR of all the patients was 80% (4/5). One patient who had residual stones (6 × 5 mm) in the middle pole underwent additional shock wave lithotripsy after the operation and no serious perioperative complications were noticed. Study limitations include small sample size and short follow-up time. CONCLUSIONS: Retroperitoneoscopy technique-assisted PCNL is a feasible, safe, and an effective alternative to laparoscopic pyelolithotomy for treating complexity HSK with renal stones, especially in a situation where the HSK is tightly wrapped by the surrounding organs.

Baicalin attenuated oxidative stress and inflammation in ethylene glycol-induced urolithiasis in adult male SD rats.

AIMS: Baicalin is a flavonoid derived from the root of the medicinal plant Scutellaria baicalensis Georgi (S. baicalensis) and is known for its various pharmacological properties. This study aimed to investigate the impact of baicalin (BAI) on the occurrence of kidney calcium oxalate crystal formation induced by ethylene glycol in male SD rats. MAIN METHODS: A rat model of renal stones was created and various concentrations of baicalin were used for intervention. Samples of urine, blood, and kidney tissue were taken from the rats, and they were euthanized for biochemical and histopathological examinations. KEY FINDINGS: Our results show that baicalin treatment improved the weight loss induced by ethylene glycol (EG) and ammonium chloride (AC) in rats. Baicalin also reduced the formation of calcium oxalate crystals and protected kidney function in rats with urolithiasis. Furthermore, it lowered the level of malondialdehyde (MDA) and elevated the activity of antioxidant enzymes compared to the stone control group. Additionally, baicalin notably alleviated renal inflammation in rats with urolithiasis. SIGNIFICANCE: The present study attributed clinical evidence first time that claiming the significant antiurolithic effect of baicalin and could be a cost-effective candidate for the prevention and treatment of urolithiasis.

Chronic kidney disease with malignant peripheral nerve sheath tumor of the ureter: a case report.

Malignant peripheral nerve sheath tumors (MPNSTs) are a complex group of malignant tumors originating from nerve cells or benign peripheral nerve sheath tumors and are commonly found in major plexus/nerve root sites such as the limbs, head, and neck. Malignant peripheral nerve sheath tumors originating in the ureter are extremely rare. Herein, we report the case of a 63-year-old patient with a malignant peripheral nerve sheath tumor of the right ureter who underwent laparoscopic radical resection of the right kidney and ureter. The patient also had stage 5 chronic kidney disease (CKD). Therefore, chemotherapy and radiotherapy were not considered. No tumor recurrence was observed during the follow-up period.

Nanoparticles targeting the adenosine pathway for cancer immunotherapy.

Cancer immunotherapy, as an emerging approach to cancer treatment, has tremendous potential for application. Compared to traditional methods such as surgery, chemotherapy, and radiation therapy, it has the ability to restore the patient's immune system, leading to long-term immune memory with less damage to normal tissues. However, immunotherapy has its limitations, including limited therapeutic efficacy, restricted patient populations, and inconsistent treatment responses. Finding effective immunotherapeutic approaches has become a key focus of its clinical application. The adenosine pathway is a recently discovered tumor immune regulatory signaling pathway. It can influence the metabolism and growth of tumor cells by acting through key enzymes in the adenosine pathway, thereby affecting the development of tumors. Therefore, inhibiting the adenosine pathway is an effective cancer immunotherapy. Common adenosine pathway inhibitors include small molecules and antibody proteins, and extensive preclinical trials have demonstrated their effectiveness in inhibiting tumor growth. The short half-life, low bioavailability, and single administration route of adenosine pathway inhibitors limit their clinical application. With the advent of nanotechnology, nano-delivery of adenosine pathway inhibitors has addressed these issues. Compared to traditional drugs, nano-drugs extend the drug's circulation time and improve its distribution within the body. They also offer targeting capabilities and have low toxic side effects, making them very promising for future applications. In this review, we discuss the mechanism of the adenosine pathway in tumor immune suppression, the clinical applications of adenosine pathway inhibitors, and nano-delivery based on adenosine pathway inhibitors. In the final part of this article, we also briefly discuss the technical issues and challenges currently present in nano-delivery of adenosine pathway inhibitors, with the hope of advancing the progress of adenosine inhibitor nano-drugs in clinical treatment.

CENPW knockdown inhibits progression of bladder cancer through inducing cell cycle arrest and apoptosis.

Purpose: The objective of this study was to examine the expression and role of Centromere protein W (CENPW) in bladder cancer (BLCA), as well as its potential mechanistic impact on the progression of BLCA. Methods: In this study, we conducted a comparative analysis of the mRNA expression level of CENPW in BLCA tissues and adjacent normal tissues using data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Additionally, we investigated the association between CENPW expression and patient prognosis. Furthermore, we performed in vitro and in vivo experiments to assess the impact of CENPW knockdown on various tumor biological phenotypes in BLCA. Finally, we conducted an analysis to elucidate the underlying mechanisms responsible for the observed phenotypic alterations in BLCA. Results: The expression of CENPW was found to be upregulated in BLCA, and its higher expression was associated with a poorer disease-specific survival (DSS). CENPW was found to have close associations with the cell cycle, mitosis, and DNA replication. In vitro and in vivo experiments demonstrated that the inhibition of CENPW led to a suppression of BLCA progression. Specifically, the knockdown of CENPW resulted in cell cycle arrest phase and induced apoptosis in BLCA by potentially inactivating the signal transducer and activator of transcription3 (STAT3) signaling pathway. Conclusion: CENPW has the potential to function as a molecular marker indicating an unfavorable prognosis in BLCA. Additionally, CENPW exhibits promise as a novel therapeutic target for BLCA.

A review for the impacts of circadian disturbance on urological cancers.

Circadian rhythm is an internal timing system and harmonizes a variety of cellular, behavioral, and physiological processes to daily environment. Circadian disturbance caused by altered life style or disrupted sleep patterns inevitably contributes to various disorders. As the rapidly increased cancer occurrences and subsequent tremendous financial burdens, more researches focus on reducing the morbidity rather than treating it. Recently, many epidemiologic studies demonstrated that circadian disturbance was tightly related to the occurrence and development of cancers. For urinary system, numerous clinical researches observed the incidence and progress of prostate cancer were influenced by nightshift work, sleep duration, chronotypes, light exposure, and meal timing, this was also proved by many genetic and fundamental findings. Although the epidemiological studies regarding the relationship between circadian disturbance and kidney/bladder cancers were relative limited, some basic researches still claimed circadian disruption was closely correlated to these two cancers. The role of circadian chemotherapy on cancers of prostate, kidney, and bladder were also explored, however, it has not been regularly recommended considering the limited evidence and poor standard protocols. Finally, the researches for the impacts of circadian disturbance on cancers of adrenal gland, penis, testis were not found at present. In general, a better understanding the relationship between circadian disturbance and urological cancers might help to provide more scientific work schedules and rational lifestyles which finally saving health resource by reducing urological tumorigenesis, however, the underlying mechanisms are complex which need further exploration.

[Inhibitory effect of Akt inhibitor deguelin on the growth of PC-3 prostate cancer cells].

OBJECTIVE: To study the inhibitory effect of Akt inhibitor deguelin on PC-3 human prostate cancer cell lines and its possible mechanism. METHODS: PC-3 human prostate cancer cells were cultured in deguelin at the concentrations of 10, 100, 500 and 1 000 nmol/L for 24, 48 and 72 hours, respectively. Then the inhibitory effect of deguelin on the proliferation of the PC-3 cells was determined by MTT assay and that on the cell cycle was detected by flow cytometry. The expression levels of MDM2 and GSK3beta mRNA were measured by RT-PCR and those of MDM2 and GSK3beta proteins by Western blot. RESULTS: At 24, 48 and 72 hours, the inhibition rates of deguelin on the proliferation of the PC-3 prostate cancer cells were (91.10 +/- 3.75), (86.39 +/- 1.16) and (79.51 +/- 2.63)% at 10 nmol/L, (82.46 +/- 3.65), (76.84 +/- 0.97) and (69.69 +/- 2.30) % at 100 nmol/L, (81.46 +/- 0.41), (75.56 +/- 1.12) and (54.07 +/- 3.21)% at 500 nmol/L, and (66.77 +/- 2.82), (58.22 +/- 0.35) and (39.34 +/- 2.40)% at 1000 nmol/L, all with statistically significant differences from the control group (P < 0.01). Deguelin at 10, 100, 500 and 1 000 nmol/L increased the cell cycles blocked in the G0/G1 phase ([62.4 +/- 2.2], [63.6 +/- 1.1 ], [65.0 +/- 0.3] and [66.5 +/- 1.9]%, P < 0.01) and reduced the percentage of the S-phase cells ([14.7 +/- 2.4], [11.1 +/- 5.2], [5.8 +/- 1.1] and [7.0 +/- 0.6]%, P < 0.01). RT-PCR and Western blot showed markedly up-regulated expressions of GSK3 P3 a3beta down-regulated expressions of MDM2 mRNA and proteins in the PC-3 cells treated with deguelin. CONCLUSION: Akt inhibitor deguelin can inhibit the proliferation of PC-3 human prostate cancer cells by affecting the down-stream signal molecules GSK3P3 and betaDM2 in the Akt pathway.

Renal tubular epithelial cells treated with calcium oxalate up-regulate S100A8 and S100A9 expression in M1-polarized macrophages via interleukin 6.

Objectives: Calgranulins S100A8 and S100A9 are common in renal stones and they are up-regulated in both urinary exosomes and kidneys of stone patients. Renal sources and important regulators for S100A8 and S100A9 in nephrolithiasis were explored in this study. Materials and Methods: We identified S100A8 and S100A9 abundance in various renal cells by searching the Single Cell Type Atlas. Macrophages were polarized from human myeloid leukemia mononuclear cells. Human proximal renal tubular epithelial cells (HK-2) were stimulated with calcium oxalate monohydrate (COM). Coculture experiments involving HK-2 cells and macrophages were conducted. qPCR, Western blotting, ELISA, and immunofluorescence were used for detecting interleukin 6 (IL6), S100A8, and S100A9. Results: The Single Cell Type Atlas showed that S100A8 and S100A9 in human kidneys primarily originated from macrophages. M1 was the predominant macrophage type expressing S100A8 and S100A9. Direct culture with COM did not affect the expression of these two calgranulins in M1 macrophages but coculture with COM-treated HK-2 cells did. COM could promote HK-2 cells to secrete IL6. IL6 could up-regulate S100A8 and S100A9 expression in macrophages of M1 type. In addition, 0.5 µM SC144 (a kind of IL6 inhibitor) significantly prevented COM-treated HK-2 cells from up-regulating S100A8 and S100A9 expression in macrophages of M1 type. Conclusion: M1-polarized macrophages were the predominant cell type expressing S100A8 and S100A9 in the kidneys of nephrolithiasis patients. CaOx crystals can promote renal tubular epithelial cells to secrete IL6 to up-regulate S100A8 and S100A9 expression in macrophages of M1 type.

Metachronous urothelial carcinoma in the renal pelvis, bladder, and urethra: A case report.

BACKGROUND: Urothelial carcinoma (UC) is a common malignancy of the urinary system that can occur anywhere from the renal pelvis to the proximal urethra. Most UCs are in the bladder and have multifocal growth. Upper urinary tract UC (UTUC), which occurs in the renal pelvis or ureter, accounts for only 5% to 10% of UCs. CASE SUMMARY: In March 2015, a 70-year-old male who initially presented to a local hospital with a complaint of painless hematuria was diagnosed with UTUC of the right renal pelvis. The doctors administered radical nephroureterectomy and bladder cuff excision. Although the doctors recommended intravesical chemotherapy and regular follow-up, he rejected this advice. In December 2016, the patient presented at our hospital with dysuria. We identified UC in the residual bladder and administered radical cystectomy and left cutaneous ureterostomy. In November 2021, he presented again with urethral bleeding. We detected urethral UC as the cause of urethral orifice bleeding and administered radical urethrectomy. Since then, he has visited regularly for 6-mo follow-ups, and was in stable condition as of December 2022. CONCLUSION: UTUC is prone to seeding and recurrence. Adjuvant instillation therapy and intense surveillance are crucial for these patients.

Exploring the correlation of glycolysis-related chondroitin polymerizing factor (CHPF) with clinical characteristics, immune infiltration, and cuproptosis in bladder cancer.

Bladder cancer (BLCA) is a common malignant neoplasm of the urinary system. Glycolysis is an essential metabolic pathway regulated by various genes with implications for tumor progression and immune escape. Scoring the glycolysis for each sample in the TCGA-BLCA dataset was done using the ssGSEA algorithm for quantification. The results showed that the score in BLCA tissues was markedly greater than those in adjacent tissues. Additionally, the score was found to be correlated with metastasis and high pathological stage. Functional enrichment analyses of the glycolysis-related genes showed they were related to roles associated with tumor metastasis, glucose metabolism, cuproptosis, and tumor immunotherapy in BLCA. Using 3 different machine learning algorithms, we identified chondroitin polymerizing factor (CHPF) as a central glycolytic gene with high expression in BLCA. In addition, we showed CHPF is a valuable diagnostic marker of BLCA with an area under the ROC (AUC) of 0.81. Sequencing BLCA 5637 cells after siRNA-mediated CHPF silencing and bioinformatics revealed that CHPF positively correlated with the markers of epithelial-to-mesenchymal transformation (EMT), glycometabolism-related enzymes, and immune cell infiltration. In addition, CHPF silencing inhibited the infiltration of multiple immune cells in BLCA. Genes that promote cuproptosis negatively correlated with CHPF expression and were up-regulated after CHPF silencing. High CHPF expression was a risk factor for overall and progression-free survival of patients who received immunotherapy for BLCA. Finally, using immunohistochemistry, we demonstrated that the CHPF protein had high expression in BLCA, increasing in high-grade tumors and those with muscle invasion. The CHPF expression levels were also positively associated with 18F-fluorodeoxyglucose uptake in PET/CT images. We conclude that the glycolysis-related gene CHPF is an effective diagnostic and treatment target for BLCA.