RESUMO
HnRNPA2/B1 is highly expressed in many tumors. However, the role of hnRNPA2/B1 in breast cancer is not clear. In this study, we found the proliferation rate was decreased after knockout of hnRNPA2/B1 by CRISPR-CAS9 in MCF-7 cells, as demonstrated by the reduced expression of CDK4 and p-AKT, and the increased expression of P27. Besides this, the western blot results showed that knockout of hnRNPA2/B1 increased the rate of apoptosis and declined autophagy. By in vivo assay, we found that knockout of hnRNPA2/B1 suppressed tumor growth in a xenograft mouse model. Immunohistochemical staining results confirmed knockout of hnRNPA2/B1 impaired tumor angiogenesis, as illustrated by downregulated expression of VEGF-A. Besides this, interacting proteins with hnRNPA2/B1 were identified by mass spectrometry and the PPI network was constructed. GO analysis suggests that the Interacting proteins are mainly enriched in the Wnt signaling pathway, tumor necrosis factor-mediated signaling pathway, translation, and so on. We then identified hnRNPA2/B1 interacted with signal transducer and activator of transcription 3 (STAT3), as supported by the colocalization of hnRNPA2/B1 and STAT3. Meanwhile, knockout of hnRNPA2/B1 inhibited the phosphorylation of STAT3. Collectively, our results demonstrate that hnRNPA2/B1 promotes tumor cell growth in vitro and in vivo by activating the STAT3 pathway, regulating apoptosis and autophagy.
Assuntos
Neoplasias da Mama/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/metabolismo , Animais , Apoptose/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Humanos , Imuno-Histoquímica , Células MCF-7 , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/fisiologiaRESUMO
OBJECTIVE: To evaluate the effects of different treatments of unilateral testicular torsion on the long-term fertility of the patient. METHODS: We reviewed the clinical and fertility-related follow-up data on 92 cases of unilateral testicular torsion treated by orchiectomy (the OE group, n = 49) or orchiopexy (the OP group, n = 43) between January 2000 and December 2014. We compared the testis volume, semen parameters, reproductive hormone indexes, natural pregnancy rate (NPR) and time to pregnancy (TTP) between the two groups, and analyzed the influence of orchiectomy and orchiopexy on the fertility of the patients. RESULTS: Totally, 77 of the men met the inclusion criteria and included in this study, 40 in the OE and 37 in the OP group. Follow-up data exhibited no statistically significant difference between the two groups of patients in the age of marriage, mean frequency of intercourse or sexual function. The men in the OE group, compared with those in the OP group, showed a larger volume of the opposite testis (ï¼»17.62 ± 2.15ï¼½ vs ï¼»16.86 ± 2.05ï¼½ ml, P > 0.05), but lower semen volume (ï¼»4.09 ± 0.89ï¼½ vs ï¼»4.11 ± 0.76ï¼½ ml, P > 0.05), sperm concentration (ï¼»27.60 ± 7.58ï¼½ vs ï¼»27.74 ± 6.80ï¼½ ×106/ml, P > 0.05), sperm motility (ï¼»60.14 ± 14.50ï¼½% vs ï¼»60.29 ± 16.36ï¼½%, P > 0.05), and percentages of progressively motile sperm (PMS) (ï¼»38.37 ± 10.88ï¼½% vs ï¼»38.82 ± 9.73ï¼½%, P > 0.05) and morphologically abnormal sperm (MAS) (ï¼»29.80 ± 7.29ï¼½% vs ï¼»29.55 ± 7.03ï¼½%, P > 0.05), lower levels of FSH (ï¼»8.01 ± 2.31ï¼½ vs ï¼»8.12 ± 2.63ï¼½ IU/L, P > 0.05), LH (ï¼»15.05 ± 4.20ï¼½ vs ï¼»15.46 ± 4.76ï¼½ IU/L,P > 0.05) and T (ï¼»19.06 ± 3.60ï¼½ vs ï¼»19.46 ± 4.02ï¼½ nmol/L, P > 0.05), lower NPR (75.0% ï¼»30/40ï¼½ vs 83.8% ï¼»31/37ï¼½, P > 0.05) and longer TTP (ï¼»18.0 ± 5.7ï¼½ vs ï¼»14.6 ± 3.8ï¼½ mo, P > 0.05). CONCLUSIONS: For patients with unilateral testicular torsion, orchiectomy achieved a lower semen quality and NPR and a longer TTP than orchiopexy, but induced no significant fertility decrease. Detorsion of the torsioned testis little affects the fertility of the patient.
Assuntos
Torção do Cordão Espermático , Fertilidade , Humanos , Masculino , Análise do Sêmen , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Torção do Cordão Espermático/cirurgiaRESUMO
OBJECTIVE: To assess the rates of atypical small acinar proliferation (ASAP) and high-grade prostatic intraepithelial neoplasia (HGPIN) detected in prostate biopsy in China and the risk of PCa found in subsequent repeat biopsy. METHODS: A total of 2,456 patients underwent TRUS-guided prostate biopsy with the samples of ASAP and/or HGPIN tissues in our hospital at least twice between July 2014 and June 2019. We analyzed the findings of digital rectal examination, prostate volumes, PSA levels, and the results of prostate biopsies. RESULTS: Initial prostate biopsies revealed 737 cases of PCa (30.0%), 215 cases of ASAP (8.8%), 98 cases of HGPIN (4.0%), and 18 cases of ASAP+HGPIN (0.7%). Totally, 313 of the patients met the inclusion criteria and included in this study. Of the 215 cases of ASAP confirmed in the first biopsy, 72 and 25 were diagnosed with PCa in the second and third biopsies, respectively, 83 with Gleason score (GS) 6, 14 with GS7, 57 with T1c and 40 with T2a tumors. Of the 98 cases of HGPIN confirmed in the first biopsy, 1 was diagnosed with PCa in the second and another 1 in the third biopsy, both with GS6 and T1c tumors. Of the 18 cases of ASAP+HGPIN confirmed in the first biopsy, 7 and 3 were diagnosed with PCa in the second and third biopsies, respectively, 7 with GS6, 3 with GS7, 6 with T1c and 4 with T2a tumors. CONCLUSIONS: ASAP is a significant risk factor for PCa and repeat prostate biopsy should be performed for patients diagnosed with ASAP in the first biopsy. Whether repeat biopsy is necessary for those diagnosed with HGPIN depends on other related clinical parameters./.
Assuntos
Neoplasia Prostática Intraepitelial , Neoplasias da Próstata , Biópsia , Proliferação de Células , China/epidemiologia , Humanos , Masculino , PróstataRESUMO
Objective: To investigate the impact of macrophage-induced immune inflammation on the proliferation and apoptosis of BPH cells and its possible mechanism. METHODS: Macrophages were stimulated with phorbol myristate acetate, co-cultured with BPH-1 cells, and then treated with the androgen receptor (AR) inhibitor or anti-CD40L antibody. The immunohistochemical biomarkers of the T lymphocytes (CD4 and CD8), B lymphocyte (CD20) and macrophages (CD68), AR, CD40/CD40L, and inflammatory factors IL-1, IL-6 and TNF-α were measured before and after treatment. The proliferation and apoptosis of the cells were observed by MTT assay, colony-forming assay and flow cytometry, and the expressions of cell apoptosis- and MAPK signaling pathway-related proteins were determined by qRT-PCR and Western blot. RESULTS: Significantly increased proliferation and decreased apoptosis of the cells, up-regulated expressions of Bcl-2, IL-1, IL-6, TNF-α, AR, CD40 and CD40L, and down-regulated expression of Bax were observed in the BPH-1 cells co-cultured with macrophages (the M-BPH-1 group) compared with those in the blank control (B-BPH-1) group (P < 0.01). In comparison with the BPH-1 cells treated with normal saline, those treated with either low-dose CD40L (L-CD40L) or high-dose CD40L (H-CD40L) showed markedly inhibited proliferation, increased apoptosis, up-regulated expression of Bax, and down-regulated expressions of Bcl-2, IL-1, IL-6 and TNF-α (P < 0.01), and those in the low- and high-dose AR (L-AR and H-AR) inhibitor groups exhibited remarkably reduced proliferation, increased apoptosis, down-regulated expressions of Bcl-2, IL-1, IL-6 and TNF-α, and up-regulated expression of Bax (P < 0.01). The phosphorylation levels of JNK, ERK and P38 were significantly elevated in the M-BPH-1 group, but declined in the H-CD40L and the H-AR inhibitor groups compared with those in the B-BPH-1 group, all in a concentration-dependent manner (P < 0.01). CONCLUSIONS: Macrophage-induced immune inflammation regulates AR and CD40/CD40L expressions and promotes the proliferation and inhibits the apoptosis of BPH-1 cells by activating the MAPK signaling pathway. /.
Assuntos
Hiperplasia Prostática , Apoptose , Proliferação de Células , Humanos , InflamaçãoRESUMO
Emerging studies have shown that circular RNAs could be ideal biomarkers and even potential therapeutic targets for some tumors, including bladder cancer. However, only a few studies have investigated the circular RNAs in human bladder cancer. The key circular RNA molecules are closely related to bladder cancer and their roles remain largely unknown. Here, we investigated a novel circular RNA molecule, hsa-circ-0003221(circPTK2), which is differentially expressed in bladder carcinoma. Significant differential expression levels of circPTK2 were confirmed with quantitative PCR in 40 pairs of tissue and blood samples from patients with bladder carcinoma. Moreover, circPTK2 levels both in tissue and blood were significantly correlated with several clinicopathologic characteristics, including poor differentiation (P = 0.0103 in tissue, P = 0.024 in blood), N2-N3 lymph node metastasis (P = 0.0065 in tissue, P = 0.016 in blood), and T(II-III-IV) stage (P = 0.008 in tissue, P = 0.0003 in blood). Quantitative PCR results confirmed that circPTK2 is highly expressed in migrated cells separated by Transwell assay and in metastatic lymph nodes of tumors transplanted in nude mice. In vitro silence of circPTK2 by small interfering RNA inhibited the proliferation and migration of bladder cancer cells. On the contrary, circPTK2 overexpression promoted proliferation and migration. This study showed that circPTK2 promotes proliferation and migration of cells and may be a novel potential biomarker and therapeutic target for bladder cancer diagnosis and therapy.
Assuntos
RNA/genética , Regulação para Cima , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Estadiamento de Neoplasias , RNA CircularRESUMO
OBJECTIVE: To observe the therapeutic effect of Qilin Pills combined with clomiphene on idiopathic oligoasthenospermia. METHODS: We randomly assigned 300 patients with idiopathic oligoasthenospermia to a trial (n = 156) and a control group (n = 144) to be treated with Qilin Pills (6 g, tid) combined with clomiphene (50 mg, qd) and clomiphene alone (50 mg, qd), respectively, both for a course of 12 weeks. Before and after 4, 8, and 12 weeks of medication, we determined sperm concentration, the percentages of grade a and grade a + b sperm, sperm motility, and the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T), followed by evaluation of the clinical efficacy of Qilin Pills with the pregnancy rate in the patients' spouses as the secondaty therapeutic indexes. RESULTS: Compared with the baseline, both groups of patients showed remarkably improved semen parameters and hormone levels after treatment (all P < 0.01). After 4, 8, and 12 weeks of medication, statistically significant differences were observed between the trial and control groups in sperm concentration ([17.06 ± 2.24] vs [15.07 ± 2.48], [22.10 ± 2.65] vs [18.11 ± 2.97], and [28.13 ± 3.59] vs [21.21 ± 3.60] x 10(6)/mL, P < 0.01), the percentage of grade a sperm ([15.03 ± 2.39] vs [13.08 ± 2.51], [21.08 ± 3.16] vs [16.04 ± 3.05], and [28.08 ± 4.70] vs [20.14 ± 4.74]%, P < 0.01), the percentage of grade a + b sperm ([30.10 ± 5.07] vs [26.21 ± 3.96], [38.08 ± 5.64] vs [30.07 ± 4.80], and [48.04 ± 6.49] vs [35.28 ± 4.77]%, P < 0.01), sperm motility ([42.04 ± 4.86] vs [40.29 ± 4.19], [52.05 ± 5.58] vs [48.03 ± 4.40], and [65.03 ± 5.13] vs [56.67 ± 4.99]%), the FSH level ([7.75 ± 1.38] vs [7.20 ± 1.17], [10.83 ± 1.23] vs [9.10 ± 1.32], and [14.22 ± 0.84] vs [12.06 ± 1.45] IU/L, P < 0.01), the LH level ([10.05 ± 1.68] vs [9.18 ± 1.54], [13.96 ± 1.68] vs [11.99 ± 1.71], and [19.01 ± 2.42] vs [15.86 ± 2.08] IU/L, P < 0.01) and the T level ([19.19 ± 192] vs [18.34 ± 1.79] [21.06 ± 1.63] vs [20.06 ± 1.56], and [24.63 ± 1.06] vs [22.03 ± 1.49] nmol/L, P < 0.01). The pregnancy rate in the patients' spouses was significantly higher in the trial than in the control group at 4, 8, and 12 weeks (1.92 vs 0.69, 4.81 vs 3.47, and 11.54 vs 8.33%, P < 0.01). There were no statistically significant differences in drug tolerance between the two groups (P > 0.05). No obvious adverse reactions were observed. CONCLUSION: Qilin Pills combined with clomiphene can evidently improve the seminal quality and hormone level of oligoasthenospermia patients with no obvious adverse events. However, its long-term efficacy and tolerance deserve further clinical investigation.
Assuntos
Astenozoospermia/tratamento farmacológico , Clomifeno/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Fármacos para a Fertilidade/uso terapêutico , Taxa de Gravidez , Astenozoospermia/sangue , Quimioterapia Combinada , Feminino , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Masculino , Gravidez , Sêmen , Contagem de Espermatozoides , Motilidade dos Espermatozoides , Espermatozoides , Testosterona/sangueRESUMO
OBJECTIVE: To determine whether antibiotic prophylaxis can reduce the risk of postoperative infective complications in patients undergoing percutaneous nephrolithotomy (PCNL) who have sterile preoperative urine. METHODS: MEDLINE, EMBASE, Cochrane Collaboration Reviews, CMCC and CNKI were searched for RCTs comparing antibiotic prophylaxis with placebo (or blank controls) for patients undergoing PCNL with preoperative sterile urine. The search strategy was made according to the Collaborative Review Group search strategy. Data were extracted by 2 reviewers using the designed extraction form. The software RevMan 4.2 was used to review management and data analysis. RESULTS: A total of 9 trails, 1 placebo controlled, 3 non treatment controlled, and 5 active controlled, involving 1018 patients, met the inclusion criteria. Prophylactic antibiotic use in patients at low risk undergoing PCNL significantly decreased fever (RR = 0.71, 95% CI: 0.54-0.92, P = 0.009), bacteriuria (RR = 0.39, 95%CI: 0.23-0.67, P = 0.0006) and bacteremia incidence (RR = 0.43, 95%CI: 0.25-0.73, P = 0.002). Effective antibiotic classes included quinolone which significantly decreased bacteriuria incidence (RR = 0.31, 95%CI: 0.12-0.82, P = 0.010) and nitrofurantoin which significantly decreased fever incidence (RR = 0.38, 95%CI: 0.24-0.61, P = 0.005). Extended course significantly decreased fever incidence (RR = 0.64, 95%CI: 0.47-0.87, P = 0.004) and bacteriuria incidence (RR = 0.35, 95%CI: 0.18-0.71, P = 0.003). CONCLUSIONS: Prophylactic antibiotics can significantly decrease the incidence of postoperative infective complications. A significant decrease in bacteriuria incidence can be achieved with quinolones. Extended course is effective in decreasing fever, and bacteriuria incidence.
Assuntos
Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Bacteriúria/prevenção & controle , Nefrostomia Percutânea , Complicações Pós-Operatórias/prevenção & controle , HumanosRESUMO
BACKGROUND: Atrial natriuretic peptide (ANP) and its natriuretic peptide receptors A (NPR-A) and C (NPR-C) are involved in the regulation of physiological and pathophysiological process of blood pressure. The present study aimed to determine the role of NPR-C in the development of salt-sensitive hypertension. METHODS: The Dahl salt-sensitive (DS) and salt-resistant (DR) rats were used in this study. Animals were matched according to their age and weight, and then placed on either a high-salt (HS, 8%) or a normal-salt (NS, 0.4%) diet for 6 weeks randomly using random number table. The systolic blood pressure (SBP), plasmatic sodium concentration (PLNa), urinary sodium excretion (UVNa), and serum creatinine concentration (Scr) were measured. The concentration of ANP in blood and tissues (heart and kidney) was detected by enzyme-linked immunosorbent assay. The expression of ANP, NPR-A, and NPR-C in kidney was evaluated with western blot analysis. Regarding renal redox state, the concentration changes in malondialdehyde (MDA), lipofuscin, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), and nitric oxide synthase (NOS) in kidney were detected by a spectrophotometric method. The kidney damage was evaluated using pathological techniques and the succinodehydrogenase (SDHase) examination. Furthermore, after an intra-peritoneal injection of C-atrial natriuretic peptide (ANP)4-23 (C-ANP4-23), an NPR-C receptor agonist, the SBP, biochemical values in blood and urine, and renal redox state were evaluated. The paired Student's t test and analysis of variance followed by the Bonferroni test were performed for statistical analyses of the comparisons between two groups and multiple groups, respectively. RESULTS: The baseline SBP in all groups was within the normal range. At the end of the 6-week experiment, HS diet significantly increased the SBP in DS rats from 116.63â±â2.90 mmHg to 162.25â±â2.15 mmHg (tâ=â-10.213, Pâ<â0.001). The changes of SBP were not significant in DS rats on an NS diet and DR rats on an NS diet or on an HS diet (all Pâ>â0.05). The significant increase of PLNa, UVNa, and Scr related to an HS diet was found in both DS and DR rats (all Pâ<â0.05). However, significant changes in the concentration (tâ=â-21.915, Pâ<â0.001) and expression of renal ANP (tâ=â-3.566, Pâ=â0.016) and the expression of renal NPR-C (tâ=â5.864, Pâ=â0.002) were only observed in DS hypertensive rats. The significantly higher desmin immunochemical staining score (tâ=â-5.715, Pâ=â0.005) and mitochondrial injury score (tâ=â-6.325, Pâ=â0.003) accompanied by the lower SDHase concentration (tâ=â3.972, Pâ=â0.017) revealed mitochondrial pathologic abnormalities in podocytes in DS rats with an HS diet. The distinct increases of MDA (tâ=â-4.685, Pâ=â0.009), lipofuscin (tâ=â-8.195, Pâ=â0.001), and Nox (tâ=â-12.733, Pâ<â0.001) but not NOS (tâ=â-0.328, Pâ=â0.764) in kidneys were also found in DS hypertensive rats. C-ANP4-23 treatment significantly decreased the SBP induced by HS in DS rats (Pâ<â0.05), which was still higher than NS groups with the vehicle or C-ANP4-23 treatment (Pâ<â0.05). Moreover, the HS-induced increase of MDA, lipofuscin, Nox concentrations, and Nox4 expression in DS rats was significantly attenuated by C-ANP4-23 treatment as compared with those with HS diet and vehicle injection (all Pâ<â0.05). CONCLUSIONS: The results indicated that the renal NPR-C might be involved in the salt-sensitive hypertension through the damage of mitochondria in podocytes and the reduction of the anti-oxidative function. Hence, C-ANP4-23 might serve as a therapeutic agent in treating salt-sensitive hypertension.