RESUMO
BACKGROUND: Gastric cancer (GC) is one of the most common cancers worldwide. Tumor microenvironment plays an important role in tumor progression. This study aims to explore the role of cancer-associated fibroblasts (CAFs) in GC and the underlying mechanism. METHODS: Cell viability, proliferation, invasion and migration were assessed by MTT, EdU, transwell and wound healing assays, respectively. Sphere formation assay was used to evaluate cell stemness. Glucose consumption, lactate production and ATP consumption were measured to assess glycolysis. In addition, The RNA and protein expression were detected by qRT-PCR and western blot. The interaction between wingless Type MMTV Integration Site Family, Member 5 A (WNT5A) and hexokinase 2 (HK2) was verified by Co-immunoprecipitation. The xenograft model was established to explore the function of CAFs on GC tumor growth in vivo. RESULTS: CAFs promoted the proliferation, metastasis, stemness and glycolysis of GC cells. WNT5A was upregulated in CAFs, and CAFs enhanced WNT5A expression in GC cells. Knockdown of WNT5A in either GC cells or CAFs repressed the progression of GC cells. In addition, WNT5A promoted HK2 expression, and overexpression of HK2 reversed the effect of WNT5A knockdown in CAFs on GC cells. Besides, knockdown of WNT5A in CAFs inhibits tumor growth in vivo. CONCLUSION: CAF-derived WNT5A facilitates the progression of GC via regulating HK2 expression.
Assuntos
Fibroblastos Associados a Câncer , Movimento Celular , Proliferação de Células , Glicólise , Hexoquinase , Neoplasias Gástricas , Proteína Wnt-5a , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Humanos , Proteína Wnt-5a/metabolismo , Proteína Wnt-5a/genética , Animais , Camundongos , Hexoquinase/metabolismo , Hexoquinase/genética , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Regulação Neoplásica da Expressão Gênica , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Células Tumorais Cultivadas , Camundongos Nus , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto , Prognóstico , Camundongos Endogâmicos BALB C , Apoptose , Masculino , Linhagem Celular TumoralRESUMO
The association between specific genetic mutations and immunotherapy benefits has been widely known, while such studies in pan-cancer are still limited. SPEN, mainly involved in X chromosome inactivation (XCI), plays an essential in tumorigenesis and sex differences in cancer. Thus, we firstly analyzed the potential role of SPEN in the TCGA pan-cancer cohort and clinical samples. Bioinformatics analysis and immunohistochemistry (IHC) staining confirm that the expression of SPEN is significantly different in various cancers and may involve RNA splicing and processing via enrichment analysis. Then, our data further revealed that those patients with SPEN mutation could predict a better prognosis in pan-cancer and had distinct immune signatures, higher tumor mutation burden (TMB), and microsatellite instability (MSI) in common cancer types. Finally, the cancer patients from 9 studies treated with immune checkpoint inhibitors were included to investigate the efficacy of immunotherapy. The results further showed that SPEN mutation was associated with better clinical outcomes (HR, 0.74; 95%CI, 0.59-0.93, P = 0.01), and this association remained existed in female patients (HR, 0.60; 95%CI, 0.38-0.94 P = 0.024), but not in male patients (HR, 0.82; 95%CI, 0.62-1.08 P = 0.150). Our findings demonstrated that SPEN mutation might strongly predict immunotherapy efficacy in pan-cancer.
Assuntos
Neoplasias , Feminino , Humanos , Masculino , Neoplasias/genética , Neoplasias/terapia , Biomarcadores , Carcinogênese , Imunoterapia , Mutação , Proteínas de Ligação a DNA , Proteínas de Ligação a RNARESUMO
Although the beneficial effects of curcumin, extracted from rhizomes of the ginger family genus Curcuma, on the repair and regeneration of nerves have been evaluated in vitro, there are few studies concerning its effects on axon myelination. Here, we used pheochromocytoma cells as an in vitro model of peripheral nerves. Pheochromocytoma cells were cultured alone or cocultured with Schwann cells and treated with increasing concentrations of curcumin. Cell growth was observed, and the expression levels of growth-associated protein 43 (GAP-43), microtubule-associated protein 2 (MAP-2), myelin basic protein (MBP), myelin protein zero (MPZ), Krox-20, and octamer binding factor 6 (Oct-6) were quantified. We found a significant increase in expression of all six proteins following curcumin treatment, with a corresponding increase in the levels of MBP, MPZ, Krox-20, and Oct-6 mRNA. Upregulation was greater with increasing curcumin concentration, showing a concentration-dependent effect. The results suggested that curcumin can promote the growth of axons by upregulating the expression of GAP-43 and MAP-2, stimulate synthesis and secretion of myelin-related proteins, and facilitate formation of the myelin sheath in axons by upregulating the expression of Krox-20 and Oct-6. Therefore, curcumin could be widely applied in future strategies for the treatment of nerve injuries.
Assuntos
Neoplasias das Glândulas Suprarrenais , Curcumina , Feocromocitoma , Humanos , Bainha de Mielina/metabolismo , Curcumina/farmacologia , Proteína GAP-43/metabolismo , Feocromocitoma/metabolismo , Células de Schwann/metabolismo , Proteínas da Mielina/metabolismo , Axônios/metabolismo , Proteína P0 da Mielina/metabolismo , Neoplasias das Glândulas Suprarrenais/metabolismoRESUMO
INTRODUCTION: Cholelithiasis represents a known risk factor for digestive system neoplasm. Few studies reported the association between cholelithiasis and the risk of prostate cancer (PCa), and the results were controversial. METHODS: We reviewed the medical records of the Second Affiliated Hospital of Chongqing Medical University Hospital to perform a retrospective matched case-control study, which included newly diagnosed 221 PCa patients and 219 matched controls. Logistic regression was applied to compare cholelithiasis exposure and adjusted for confounding factors. Additionally, we conducted a meta-analysis pooling this and published studies further to evaluate the association between cholelithiasis and PCa risk. Related ratio (RR) and 95% confidence interval (95%CI) were used to assess the strength of associations. RESULTS: Our case-control study showed that cholelithiasis was associated with a higher incidence of PCa (OR = 1.87, 95% CI: 1.06-3.31) after multivariable adjustment for covariates. The incidence of PCa was increased in patients with gallstones but not cholecystectomy. 7 studies involving 80,403 individuals were included in the meta-analysis. Similarly, the results demonstrated that cholelithiasis was associated with an increased risk of PCa (RR = 1.35, 95%CI: 1.17-1.56) with moderate-quality evidence. Cholelithiasis patients with low BMI increased the PCa incidence. Moreover, Subgroup analysis based on region showed that cholelithiasis was associated with PCa in Europe (RR = 1.24, 95%CI 1.03-1.51) and Asia (RR = 1.32, 95%CI 1.24-1.41). CONCLUSIONS: The results suggested an association between cholelithiasis and the risk of PCa. There was no significant relationship between cholecystectomy therapy and PCa risk. Further cohort studies should be conducted to demonstrate the results better.
Assuntos
Colelitíase , Neoplasias da Próstata , Estudos de Casos e Controles , Colecistectomia/efeitos adversos , Colelitíase/complicações , Colelitíase/epidemiologia , Humanos , Masculino , Neoplasias da Próstata/complicações , Estudos Retrospectivos , Fatores de RiscoRESUMO
To explore the association between male infertility and hypertension risk, a meta-analysis and systematic review was conducted. Observational studies were sought in Medline, PubMed, EMBASE, Web of Science, and China National Knowledge Infrastructure up to April 30, 2021. Two independent reviewers selected available studies and extracted the data. The association between male infertility and hypertension risk was estimated by calculating the relative risk (RR) and 95% confidence interval (95% CI) using Stata12.0 statistical software. A total of seven studies were included in this meta-analysis, including 102,152 patients and 636,645 healthy individuals. The results demonstrated that male infertility was significantly associated with increased hypertension incidence (RR = 1.08; 95% CI 1.02-1.14; p = 0.004), with moderate-quality evidence. A subgroup analysis based on region showed that a positive association was observed in Europe but not the United States or Asia. This positive association was further confirmed in a cohort study, but not in a case-control study. After adjusting for potential confounders, male infertility was still significantly associated with hypertension risk (RR = 1.06, 95% CI 1.03-1.09). In conclusion, our findings suggest that male infertility increases the risk of hypertension incidence. However, further studies are needed to provide more conclusive evidence.
Assuntos
Hipertensão , Infertilidade Masculina , Estudos de Casos e Controles , Estudos de Coortes , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Incidência , Infertilidade Masculina/epidemiologia , MasculinoRESUMO
PURPOSE: To compare the efficacy and safety of bipolar and monopolar transurethral resection of bladder tumors (TURBT) in non-muscle invasive bladder cancer (NMIBC) treatment. METHODS: A systematic search of all Randomized Controlled Trials (RCTs), which compared bipolar TURBT (bTURBT) and monopolar TURBT (mTURBT) in NMIBC treatment, were performed in PubMed, Web of Science, Cochrane Library and Embase up to February 1, 2019. We evaluated their efficacy by operative time, hospitalization time, catheterization time, and recurrence rate. While obturator jerk, bladder perforation, thermal damage, and overall complications were used to evaluate their safety. RESULTS: A total of 13 RCTs, involving 2379 patients, were included. There were no statistically significant differences in efficacy between bTURBT and mTURBT in NMIBC treatment, such as operative time (p = 0.12), hospitalization time (p = 0.13), catheterization time (p = 0.50), and recurrence rate (p = 0.88). Compared to the safety in mTURBT in NMIBC treatment, no significant advantages were observed in that in bTURBT as well, such as obturator jerk (p = 0.12), bladder perforation (p = 0.11), thermal damage (p = 0.24), and overall complications (p = 0.65). CONCLUSIONS: Our analysis demonstrated that bTURBT has no significant advantages in efficacy and safety in NMIBC treatment compared to that in mTURBT. Thus, bTURBT could not completely replace mTURBT as a safer and more effective NMIBC treatment.
Assuntos
Cistectomia/métodos , Eletrocirurgia/métodos , Neoplasias da Bexiga Urinária/cirurgia , Humanos , Invasividade Neoplásica , Uretra , Neoplasias da Bexiga Urinária/patologiaRESUMO
BACKGROUND: Persistent or recurrent haemospermia often occurs in individuals with ejaculatory duct obstruction (EDO). This study aimed to evaluate the efficacy and safety of transurethral resection of the ejaculatory duct (TURED) combined with seminal vesiculoscopy in treating persistent or recurrent haemospermia in men with EDO. METHODS: From June 2014 to March 2018, 103 consecutive patients with EDO who underwent TURED combined with seminal vesiculoscopy for persistent or recurrent haemospermia at the Department of Urology of West China Hospital were enrolled into this retrospective study. The patients were evaluated mainly by detailed history-taking and performing semen analysis, transrectal ultrasonography, and magnetic resonance imaging. RESULTS: Among the 103 patients, 79 (76.70%) had cysts of the lower male genitourinary tract; 63 (61.17%) had blood clots; and 32 (31.07%) had calculi in the seminal vesicle and/or prostatic utricle. The duration of postoperative follow-up was 12 months, and the symptoms of haemospermia disappeared in 96 (93.20%) patients. There was no significant difference in the semen PH and sperm count before and after surgery; however, the ejaculate volume and sperm motility significantly improved postoperatively. Except for two cases of acute urinary retention and one case of watery ejaculate after surgery, no severe postoperative complications, including epididymitis, urethral stricture, urinary incontinence, retrograde ejaculation, or rectal injury, were observed. CONCLUSION: TURED combined with seminal vesiculoscopy is a suitable method for the diagnosis and treatment of persistent or recurrent haemospermia in men with EDO.
Assuntos
Ductos Ejaculatórios/cirurgia , Doenças dos Genitais Masculinos/cirurgia , Hemospermia/cirurgia , Glândulas Seminais/cirurgia , Adulto , Idoso , Endoscopia , Hemospermia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Uretra , Procedimentos Cirúrgicos Urológicos Masculinos/efeitos adversos , Procedimentos Cirúrgicos Urológicos Masculinos/métodosRESUMO
BACKGROUND: Controversy remains despite several studies have discussed the role of bariatric surgery in improving male's sexual function. This study aims to evaluate the efficacy of bariatric surgery in promoting male's erectile function. METHODS: PubMed, EMbase, The Cochrane Library, CNKI and Clinical Trails.gov were searched from database inception to May 2019. The language of publication was limited in English. The International Index of Erectile Function (IIEF) score and Brief Male Sexual Function Inventory (BSFI) score were set as the primary outcome. RESULTS: Eleven studies with a total of 370 patients were enrolled in this meta-analysis. The results showed significant improvement in the IIEF score (erectile function: MD = 5.33, 95% CI 4.12-6.54; intercourse satisfaction: MD = 2.57, 95% CI 1.19-3.94; orgasmic function: MD = 0.50, 95%CI 0.60-0.94; overall satisfaction: MD = 1.67, 95% CI 0.78-2.56; sexual desire: MD = 1.27, 95% CI 0.61-1.93; total erectile function: MD = 7.21, 95% CI 4.33-10.10) and the BSFI score (erection: MD =2.53, 95% CI 2.39-2.67; ejaculation: MD = 1.40, 95% CI 1.28-1.51; desire: MD =1.40, 95% CI 1.32-1.49; problem assessment: MD = 2.20, 95% CI 2.06-2.34; sexual satisfaction: MD = 0.70, 95% CI 0.60-0.76) in obese individuals after bariatric surgery. CONCLUSIONS: This systematic review and meta-analysis indicated that bariatric surgery could be effective in promoting males's sexual function for obese individuals.
Assuntos
Cirurgia Bariátrica , Disfunção Erétil/terapia , Obesidade Mórbida/cirurgia , Ereção Peniana/fisiologia , Disfunção Erétil/etiologia , Medicina Baseada em Evidências , Humanos , Masculino , Obesidade Mórbida/complicações , Resultado do TratamentoRESUMO
BACKGROUND: To compare the clinical efficiency between aspiration-sclerotherapy (AS) and laparoscopic de-roofing (LD) in the management of renal cysts through meta-analysis of comparative studies. METHOD: A comprehensive literature search was performed by PubMed, MEDLINE, Ovid and Web of Science for relevant studies published up to January 2020. The statistical analyses were conducted with Review Manager 5.3.0 and Stata 15.1. The sensitivity analysis was also carried out to confirm the reliability of this Meta-analysis. RESULTS: Our searches of literature generated 6 studies (1547 patients incorporated) comparing AS with LD in the impacts of renal cyst therapy. Of these, 6 studies contained 1106 and 441 patients who were treated with AS and LD, respectively. The outcome of this meta-analysis indicated that LD group was superior in symptomatic successful rate [Odds Ratio (OR): 0.28; 95%Confidence Interval (CI): 0.09 to 0.86; P = 0.03), radiological successful rate (OR: 0.06; 95%CI: 0.02 to 0.15; P < 0.01) and recurrence rate (OR: 6.08; 95%CI: 2.81 to 13.15; p < 0.01). Nevertheless, AS group had shorter treatment time [Mean Difference (MD):-51.10; 95% CI:-73.01 to - 29.20; p < 0.01]. No statistically significant difference was showed in the rate of complications (OR: 3.19; 95% CI: 0.39 to 25.88; P = 0.28). CONCLUSIONS: In our meta-analysis, LD had higher symptomatic successful rate, radiological successful rate as well as lower recurrence rate than AS, while the treatment time was longer.
Assuntos
Cistos/terapia , Nefropatias/terapia , Laparoscopia , Escleroterapia , Cistos/diagnóstico por imagem , Humanos , Nefropatias/diagnóstico por imagem , Laparoscopia/efeitos adversos , Duração da Cirurgia , Recidiva , Escleroterapia/efeitos adversos , Sucção/efeitos adversos , Resultado do TratamentoRESUMO
The association of genetic variants and congenital bilateral absence of the vas deferens (CBAVD) has been well acknowledged. By contrast, the link between nonobstructive azoospermia (NOA) or oligospermia and alterations in the cystic fibrosis transmembrane conductive regulator (CFTR) remains inconclusive. To clarify the problem, a meta-analysis was performed out after systematically searching Pubmed, Web of Science, Embase and the Chinese national knowledge infrastructure (CNKI) database. As we know, the ∆F508 and IVS8-5T gene mutations are the most studied genetic variants in CFTR gene. We reviewed the data from male patients who underwent the aforementioned genetic test. Our study revealed that the IVS8-5T mutation may be positively associated with the risk of nonobstructive male infertility (odds ratio (OR) 1.69; 95% CI: 1.12-2.55). This association strengthened when concerning NOA (OR: 2.62; 95% CI: 1.49-4.61). However, the ∆F508 mutation seemed to be a smaller contributing factor to this risk (OR: 1.63; 95% CI: 0.86-3.08). Our study aims to clarify the association between the ∆F508 and IVS8-5T gene mutations and nonobstructive male infertility. Therefore, screening for the IVS8-5T mutation in the CFTR gene may be recommended for men with NOA or severe oligozoospermia seeking assisted reproductive technology (ART).
Assuntos
Regulador de Condutância Transmembrana em Fibrose Cística/genética , Infertilidade Masculina/genética , Humanos , Masculino , MutaçãoRESUMO
BACKGROUND: The relationship between first-degree family history of female breast cancer and prostate cancer risk in the general population remains unclear. We performed a meta-analysis to determine the association between first-degree family history of female breast cancer and prostate cancer risk. METHODS: Databases, including MEDLINE, Embase, and Web of Science, were searched for all associated studies that evaluated associations between first-degree family history of female breast cancer and prostate cancer risk up to December 31, 2018. Information on study characteristics and outcomes were extracted based on the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement and Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines. The quality of evidence was assessed using the GRADE approach. RESULTS: Eighteen studies involving 17,004,892 individuals were included in the meta-analysis. Compared with no family history of female breast cancer, history of female breast cancer in first-degree relatives was associated with an increased risk of prostate cancer [relative risk (RR) 1.18, 95% confidence interval (CI) 1.12-1.25] with moderate-quality evidence. A history of breast cancer in mothers only (RR 1.19, 95% CI 1.10-1.28) and sisters only (RR 1.71, 95% CI 1.43-2.04) was associated with increased prostate cancer risk with moderate-quality evidence. However, a family history of breast cancer in daughters only was not associated with prostate cancer incidence (RR 1.74, 95% CI 0.74-4.12) with moderate-quality evidence. A family history of female breast cancer in first-degree relatives was associated with an 18% increased risk of lethal prostate cancer (95% CI 1.04-1.34) with low-quality evidence. CONCLUSIONS: This review demonstrates that men with a family history of female breast cancer in first-degree relatives had an increased risk of prostate cancer, including risk of lethal prostate cancer. These findings may guide screening, earlier detection, and treatment of men with a family history of female breast cancer in first-degree relatives.
Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Neoplasias da Próstata/genética , Neoplasias da Mama/epidemiologia , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Núcleo Familiar , Neoplasias da Próstata/epidemiologia , RiscoRESUMO
To evaluate the relationship between the aryl hydrocarbon receptor (AHR) rs2066853 gene polymorphism and the risk of male infertility. PubMed, Embase, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) were searched for relevant case-control studies up to 31 July 2019. Odds ratio (OR) and 95% confidence interval (95% CI) were used to assess the strength of associations. Finally, seven case-control studies involving 1247 cases and 1762 controls were included in this meta-analysis. The pooled results showed that there was no significant association between AHR rs2066853 gene polymorphism and male infertility risk (A vs. G: OR = 1.08, 95% CI = 0.83-1.39; AA vs. GG: OR = 1.16, 95% CI = 0.65-2.04; AA vs. GA + GG: OR = 1.17, 95% CI = 0.66-2.07; AA + GA vs. GG: OR = 0.99, 95% CI = 0.85-1.15). Subgroup analysis by ethnicity showed the same result. However, significant association was found between AHR rs2066853 gene polymorphism and male infertility risk in oligoasthenotspermia (A vs. G: OR = 2.52, 95% CI = 1.72-3.70). In conclusion, our meta-analysis indicated that AHR rs2066853 gene polymorphism might be associated with an increased susceptibility to oligoasthenotspermia.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Predisposição Genética para Doença , Oligospermia/genética , Receptores de Hidrocarboneto Arílico/genética , Alelos , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Domínios Proteicos/genéticaRESUMO
To evaluate the association between TP53 codon72 polymorphism and male infertility risk. We conducted a search on Medline, Embase, Web of Science and CNKI up to April 30, 2017. Odds ratio (OR) and 95% confidence interval (95% CI) were used to assess the strength of the association. Seven studies including 1,818 cases and 2,278 controls met the inclusion criteria. The pooled results indicated that no significant association was observed between TP53 codon72 polymorphism and male infertility risk (G versus C: OR = 1.11, 95%CI = 0.94-1.32; GG versus CC: OR = 1.26, 95%CI = 0.90-1.78; GG versus GC+CC: OR = 1.16, 95%CI = 0.90-1.49; GG+GC versus CC: OR = 1.15, 95%CI = 0.88-1.49). In the subgroup analysis by ethnicity, significant association was observed between TP53 codon72 polymorphism and male infertility risk in non-Chinese (G versus C: OR = 1.47, 95%CI = 1.14-1.89), but not in Chinese population (G versus C: OR = 1.03, 95%CI = 0.87-1.22). In conclusion, this study suggested that TP53 codon72 polymorphism might be associated with an increased susceptibility to male infertility in non-Chinese population, but not in Chinese population. Studies with larger sample sizes and representative population-based cases and well-matched controls are needed to validate our results.
Assuntos
Predisposição Genética para Doença , Infertilidade Masculina/genética , Proteína Supressora de Tumor p53/genética , Arginina/genética , Povo Asiático/genética , Humanos , Infertilidade Masculina/epidemiologia , Masculino , Polimorfismo de Nucleotídeo Único , Prolina/genéticaRESUMO
Varicocele (VC) is a most common risk factor of male infertility and its etiology, however, remains rarely explored. Some researchers reported the genetic predisposition of VC, showing that its prevalence was 3ï¼8 times higher in the first-degree relatives of the patients than in the controls. Studies on the genetic characteristics of VC are relatively rare, only a few relating its association with single nucleotide polymorphisms (SNP). The onset of VC is known to be related to venous varicosity (VV) in the lower extremity, and the two conditions have similar pathogenesis and clinical features. Several studies confirmed the association of the onset of VV with some SNPs, such as the essential transcription factor for the formation of venous valves and vascular development FOXC2, the gene of vascular endothelial growth factor A (VEGFA), and its receptor gene VEGFR2. The mechanisms of the SNPs affecting VV in the lower extremity are similar to the pathogenesis of VC, which may shed some light on the etiology of VC. The exploration of the genetic characteristics of VC is of much significance for the early prevention and precision therapy of diseases, and an insight into the correlation between VC and lower extremity VV may afford some valuable clues to studies on the genetic characteristics of VC.
Assuntos
Infertilidade Masculina , Polimorfismo de Nucleotídeo Único , Varicocele , Fatores de Transcrição Forkhead/genética , Predisposição Genética para Doença , Humanos , Infertilidade Masculina/genética , Masculino , Varicocele/genética , Fator A de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genéticaRESUMO
OBJECTIVE: To detect the expression and growth regulation effects of the factor inhibiting hypoxia-inducible factor (FIH-1) in renal carcinoma cells. METHODS: The expressions of FIH-1,hypoxia inducible factor (HIF) and vascular endothelial growth factor (VEGF) were examined in OS-RC-2 and 786-0 cell lines via real-time PCR (RT-PCR) and Western blot. Overexpression plasmid of FIH-1 were designed and constructed as EX-V1104-M45-FIH-1. After the transfection of the plasmid into OS-RC-2 and 786-0 cells,the expression levels of FIH-1,HIF and VEGF were measured by RT-PCR and Western blot,while cell proliferation was tested by MTT. RESULTS: The expressions of FIH-1,HIF-1α,HIF-2α and VEGF were detected in OS-RC-2 cells,and FIH-1,HIF-2α and VEGF were detected in 786-0 cells. After the transfection of EX-V1104-M45-FIH-1, the level of FIH-1 was increased in OS-RC-2,while the levels of HIF-2α,HIF-1α and VEGF were decreased. MTT showed that FIH-1 plasmid transfection decreased the cell proliferation of OS-RC-2,but did not show inhibition on 786-0 cells proliferation. CONCLUSION: FIH-1/HIF-1α/VEGF signaling pathway exists in renal carcinoma cell lines.
Assuntos
Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Oxigenases de Função Mista/metabolismo , Proteínas Repressoras/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Linhagem Celular Tumoral , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Transdução de Sinais , TransfecçãoRESUMO
BACKGROUND: Impaired function of endothelial nitric oxide synthase (eNOS) is involved in the pathologic processes of erectile dysfunction (ED), and three functional polymorphisms (G894T, T-786C, and a tandem repeat of 27 bp in intron 4) in the NOS3 gene, which encodes eNOS, are associated with the clinical characteristics of ED in several populations. AIM: To investigate the effect of these variations of NOS3 on ED phenotypes and the response to sildenafil in a Han Chinese population. METHODS: This case-control study enrolled 112 patients with ED and 156 age-matched healthy men. Their medical history and laboratory data were collected. ED severity and response to sildenafil were assessed using the five-item International Index of Erectile Function (IIEF-5) score. Routine polymerase chain reaction and Sanger sequencing were used to genotype the three polymorphisms of NOS3. OUTCOMES: The frequencies of alleles, genotypes, and haplotypes of the loci in patients and controls; the IIEF-5 scores of patients carrying the risk and non-risk genotype; and the frequencies of risk and non-risk genotypes in patients with different ages at onset and responses to sildenafil were assessed. RESULTS: The frequencies of drinkers and diabetic and hyperlipidemic patients in the ED group were higher than those in the age-matched control group (P < .05). The distributions of alleles (G894T, P < .005; T-786C, P < .015), genotypes (G894T, P < 0.015; T-786C, P < .010), and haplotypes (G894T/T-786C, P < .015) of the NOS3 polymorphisms were significantly different between patients with ED and controls. An increased risk for earlier onset of ED was observed in the G894T risk genotype carriers (odds ratio = 3.572; P < .020). Patients with the risk genotype of T-786C exhibited lower IIEF-5 scores than patients with the non-risk genotype (8.2 ± 4.5 vs 12.2 ± 5.0; P < .015). The influence of the T-786C or G894T genotype on the response to sildenafil was not observed. CLINICAL TRANSLATION: The detectable effect of NOS3 functional polymorphisms on ED suggests their application potential as a molecular biomarker in predicting ED susceptibility and severity in the Han Chinese population. STRENGTHS & LIMITATIONS: This study provides strong evidence that NOS3 functional variation is an independent risk factor for ED in the Han Chinese population, which should be confirmed in larger cohorts considering the limited number of subjects in this study. CONCLUSION: These results are the first to identify a clear association between NOS3 functional variation and ED susceptibility, age at onset, and severity in the Han Chinese population. Yang B, Liu L, Peng Z, et al. Functional Variations in the NOS3 Gene Are Associated With Erectile Dysfunction Susceptibility, Age of Onset and Severity in a Han Chinese Population. J Sex Med 2017;14:551-557.
Assuntos
Povo Asiático/genética , Disfunção Erétil/genética , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo Genético , Adulto , Alelos , Estudos de Casos e Controles , Suscetibilidade a Doenças , Genótipo , Heterozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fatores de RiscoRESUMO
To evaluate the association between the SPO11 gene C631T polymorphism and the risk of male infertility. We conducted a search on PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), China biology medical literature database (CBM), VIP, and Chinese literature database (Wan Fang) on 31 March 2016. Odds ratio (OR) and 95% confidence interval (95%CI) were used to assess the strength of associations. A total of five studies including 542 cases and 510 controls were involved in this meta-analysis. The pooled results indicated that the SPO11 gene C631T polymorphism was significantly associated with increased risk of male infertility (TT + CT vs. CC: OR = 4.14, 95%CI = 2.48-6.89; CT vs. CC: OR = 4.34, 95%CI = 2.56-7.34; T vs. C: OR = 4.35, 95%CI = 2.58-7.34). Subgroup analysis of different countries proved the relationship between SPO11 gene C631T polymorphism and male infertility risk in Chinese, but not in Iranian peoples. In conclusion, this study suggested that SPO11 gene C631T polymorphism may contribute as a genetic factor susceptible to cause male infertility. Furthermore, more large sample and representative population-based cases and well-matched controls are needed to validate our results.
Assuntos
Endodesoxirribonucleases/genética , Infertilidade Masculina , Adulto , China/epidemiologia , Predisposição Genética para Doença , Humanos , Infertilidade Masculina/epidemiologia , Infertilidade Masculina/genética , Masculino , Polimorfismo de Nucleotídeo Único , Medição de RiscoRESUMO
Ejaculatory duct obstruction(EDO) accounts for 1- 5% of the causes of male infertility and can be corrected by various surgical methods,among which transurethral resection of the ejaculatory ducts(TURED) is considered as the gold standard for its treatment and has been well established in clinical practice. Transutricular seminal vesiculoscopy has been gaining more and more attention for its cost-effectiveness and few complications in the treatment of EDO. The clinical evidence for treating EDO by balloon dilatation and seminal vesicle lavage is limited and its application value needs to be further investigated. This paper presents an overview on the treatment of EDO in infertile men by minimally invasive surgery.
Assuntos
Ductos Ejaculatórios/patologia , Ductos Ejaculatórios/cirurgia , Infertilidade Masculina/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Cateterismo , Endoscopia , Doenças dos Genitais Masculinos , Humanos , Masculino , Glândulas SeminaisRESUMO
BACKGROUND: Abnormal hematologic parameters before patients undergoing prostate biopsy play a pivotal role in guiding the surgical management of prostate cancer (PCa) incidence. This study aims to establish the first nomogram for predicting PCa risk for better surgical management. METHODS: We retrospectively reviewed and analyzed the data including basic information, preoperative hematologic parameters, and imaging examination of 540 consecutive patients who underwent transrectal ultrasound (TRUS)-guided prostate biopsy for elevated prostate-specific antigen (PSA) in our medical center between 2017 and 2021. Logistic regression analysis was used to determine the risk factors for PCa occurrence, and the nomogram was constructed to predict PCa occurrence. Finally, the data including 121 consecutive patients in 2022 were prospectively collected to further verify the results. RESULTS: In retrospective analyses, univariate and multivariate logistic analyses identified that three variables including age, diabetes, and De Ritis ratio (aspartate transaminase/alanine transaminase, AST/ALT) were determined to be significantly associated with PCa occurrence. A nomogram was constructed based on these variables for predicting the risk of PCa, and a satisfied predictive accuracy of the model was determined with a C-index of 0.765, supported by a prospective validation group with a C-index of 0.736. The Decision curve analysis showed promising clinical application. In addition, our results also showed that the De Ritis ratio was significantly correlated with the clinical stage of PCa patients, including T, N, and M stages, but insignificantly related to the Gleason score. CONCLUSIONS: The increased De Ritis ratio was significantly associated with the risk and clinical stage of PCa and this nomogram with good discrimination could effectively improve individualized surgical management for patient underdoing prostate biopsy.
Assuntos
Neoplasias da Próstata , Masculino , Humanos , Estudos Retrospectivos , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Próstata/diagnóstico por imagem , Próstata/patologia , Nomogramas , Antígeno Prostático Específico , Fatores de RiscoRESUMO
Male erectile dysfunction (ED) caused by cavernous nerve injury is a common complication of pelvic surgery, radiotherapy, transurethral surgery or other operations. However, clinical treatment for iatrogenic or traumatic male ED is difficult and not satisfactory. Many studies have shown that curcumin can promote the repair and regeneration of peripheral nerves; however, whether curcumin can rescue cavernous nerve injury is unknown, and the poor bioavailability of curcumin limits its application in vivo. Hence, the study was conducted. A curved slow-release membrane was produced, and the properties were examined. In addition, the effects of the curcumin slow-release membrane on cavernous nerve-injured SD rats were studied. We found that polylactic acid-glycolic acid-polyethylene glycol (PLGA-PEG) can be used as a good carrier material for curcumin, and curcumin-loaded PLGA-PEG membranes can effectively rescue the cavernous nerve in SD rats, restore the continuity of the cavernous nerve, and increase the expression of nNOS mRNA and proteins in penile tissue, which can improve the penile erectile function of injured SD rats, reduce the degree of penile tissue fibrosis, and effectively promote penis rehabilitation. The curcumin slow-release membrane is proposed to be a new therapeutic approach for penile rehabilitation of cavernous nerve injury.