Publications by authors named "Zhiping Wang"

356 Publications

Atorvastatin Enhances Inhibitory Effects of Irradiation on Tumor Growth by Reducing MSH2 Expression both in Prostate Cancer Cells and Xenograft Tumor Models.

Anticancer Agents Med Chem 2021 Jun 2. Epub 2021 Jun 2.

Institute of Urology, Lanzhou University Second Hospital, Lanzhou, Gansu Province 730030, China.

Background: Prostate cancer (PCa) is the fourth most common tumor in males.

Objective: To investigate effects of atorvastatin (AS) on PCa cells proliferation and clarify the associated mechanisms.

Methods: PCa cell lines were cultured and treated with irradiation (IR) (4 Gy), AS (6 μg/ml), transfected with Bcl-2 siRNA, and then divided into different groups. Xenograft tumor mouse model was established. Bcl-2 and MSH2 gene transcription and protein expression were evaluated using RT-PCR assay and western blot assay. Plate clone formation assay was employed to examine colony formation. MTT assay was used to detect cell viabilities. Flow cytometry analysis was utilized to verify apoptosis. Co-immunoprecipitation and immuno-fluorescence assay were used to identify interaction between Bcl-2 and MSH2.

Results: IR significantly reduced colony formation, enhanced Bcl-2 and reduced MSH2 gene transcription in PCa cells compared to un-treated cells (p<0.05). AS significantly strengthened radio-therapeutic effects of IR on colony formation, decreased cell apoptosis and increased Bcl-2 gene transcription/protein expression in PCa cells compared to single IR treatment cells (p<0.05). AS combining IR down-regulated MSH2 gene transcription/protein expression in PCa cells compared to single IR treatment cells (p<0.05). Bcl-2 interacted with MSH2 both in PCa cells and tumor tissues administrating with AS. AS enhanced reductive effects of IR on tumor size of Xenograft tumor mice.

Conclusion: Atorvastatin administration enhanced inhibitory effects of IR either on PCa cells or on tumor size of Xenograft tumor mice. The inhibitory effects of atorvastatin were mediated by reducing MSH2 expression and triggering interaction between Bcl-2 and MSH2, both in vitro and in vivo levels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1871520621666210602133005DOI Listing
June 2021

Prognostic value of preoperative inflammation-based predictors in patients with bladder carcinoma after radical cystectomy.

Open Med (Wars) 2021 21;16(1):816-825. Epub 2021 May 21.

Institute of Urology, Lanzhou University Second Hospital, Chengguan District, 82 Cuiying Gate, Lanzhou University, Lanzhou 730000, P. R. China.

Aims: Emerging evidence has related inflammation-based biomarkers to numerous carcinomas, including bladder carcinoma (BC). However, the role of inflammatory biomarkers in the prognosis of BC remains inconclusive. This study aimed to compare preoperative plasma fibrinogen (PF) and other inflammatory biomarkers such as the platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), C-reactive protein (CRP) level, and serum albumin level to predict the prognosis of patients with BC.

Methods: This article focused on a retrospective analysis of 175 patients with newly diagnosed BC who were admitted to our hospital from March 2005 to March 2016. Of these BC patients, 136 had undergone radical cystectomy (RC).

Results: According to multivariate analysis, high PF level was an independent predictor of overall survival (OS) in 136 BC patients receiving RC (HR = 3.759; = 0.011), but not for all 175 BC patients. Combining the NLR and PF values showed higher predictive accuracy for OS than NLR or PF alone ( < 0.05). Additionally, for 136 BC patients who had undergone RC, a close relationship was found between high PF levels (≥3.39 g/L) and lymph node metastasis ( = 0.011) and clinical T stage ( = 0.015). Furthermore, PF was a superior prognostic factor compared with the LMR, PLR, CRP, and albumin values in 136 BC patients who had undergone RC ( < 0.001).

Conclusions: The preoperative PF level may be a prognostic biomarker; and when combined with the NLR, it can improve the predictive ability of the survival of BC patients, particularly of BC patients who underwent RC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/med-2021-0277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8142381PMC
May 2021

Endarterectomy for Pulmonary Embolism in a Woman with Unilateral Absence of Pulmonary Artery.

Ann Thorac Surg 2021 May 25. Epub 2021 May 25.

Department of Cardiac Surgery, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China. Electronic address:

Unilateral absence of pulmonary artery (UAPA) is a very rare congenital cardiovascular malformation. To the best of our knowledge, chronic thromboembolic pulmonary hypertension has never been reported in adults with UAPA. In this report, we present the case of a 31-year-old woman with UAPA who developed chronic thromboembolic pulmonary hypertension following multiple episodes of pulmonary embolism due to thrombophilia. Pulmonary thromboendarterectomy was performed, and the short-term outcome was satisfactory.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.athoracsur.2021.05.002DOI Listing
May 2021

Myrtenol improves brain damage and promotes angiogenesis in rats with cerebral infarction by activating the ERK1/2 signalling pathway.

Pharm Biol 2021 Dec;59(1):584-593

Department of Neurology, Luohe Central Hospital, Luohe City, China.

Context: Cerebral ischaemia/reperfusion (I/R) injury has a high disability and fatality worldwide. Myrtenol has protective effects on myocardial I/R injury through antioxidant and anti-apoptotic effects.

Objective: This study investigated the effect of myrtenol on cerebral ischaemia/reperfusion (I/R) injury and the underlying mechanism.

Materials And Methods: Cerebral I/R injury was induced in adult Sprague-Dawley rats by middle cerebral artery occlusion (MCAO) for 90 min. MCAO rats were treated with or without myrtenol (10, 30, or 50 mg/kg/day) or/and U0126 (10 μL) intraperitoneally for 7 days.

Results: In the present study, myrtenol had no toxicity at concentrations up to 1.3 g/kg. Myrtenol treatment improved neurological function of MCAO rats, with significantly ( < 0.05) improved neurological deficits (4.31 ± 1.29 vs. 0.00) and reduced brain edoema (78.95 ± 2.27% vs. 85.48 ± 1.24%). Myrtenol extenuated brain tissue injury and neuronal apoptosis, with increased Bcl-2 expression (0.48-fold) and decreased Bax expression (2.02-fold) and caspase-3 activity (1.36-fold). Myrtenol promoted angiogenesis in the brain tissues of MCAO rats, which was reflected by increased VEGF (0.86-fold) and FGF2 (0.51-fold). Myrtenol promoted the phosphorylation of MEK1/2 (0.80-fold) and ERK1/2 (0.97-fold) in MCAO rats. U0126, the inhibitor of ERK1/2 pathway, reversed the protective effects of myrtenol on brain tissue damage and angiogenesis in MCAO rats.

Discussion And Conclusions: Myrtenol reduced brain damage and angiogenesis through activating the ERK1/2 signalling pathway, which may provide a novel alternative strategy for preventing cerebral I/R injury. Further work detailing its mechanism-of-action for improving ischaemic cerebral infarction is needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13880209.2021.1917626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143630PMC
December 2021

Circulating Tumor DNA Analyses Predict Disease Recurrence in Non-Muscle-Invasive Bladder Cancer.

Front Oncol 2021 28;11:657483. Epub 2021 Apr 28.

Health Science Center, The First Affiliated Hospital of Shenzhen University, and Guangdong Key Laboratory of Systems Biology and Synthetic Biology for Urogenital Tumors, Shenzhen Second People's Hospital, Shenzhen, China.

Circulating tumor DNA (ctDNA) can be a prognostic biomarker for non-muscle-invasive bladder cancer (NMIBC); however, targeted sequencing has not been performed to detect ctDNA in NMIBC. We applied targeted sequencing based on an 861-gene panel to determine mutations in tumor tissue DNA and plasma ctDNA in 82 NMIBC patients receiving transurethral resection (TUR) of bladder followed by immunotherapy. We detected 476 and 165 somatic variants in tumor DNA from 82 NMIBC patients (100%) and ctDNA from 54 patients (65.85%), respectively. Patients with high heterogeneity in tumor DNA had a significantly shorter disease-free survival than those with low heterogeneity. Tumor-derived alterations were detectable in plasma of 43 patients (52.44%). The concordance of somatic variants between tumor DNA and plasma ctDNA were higher in patients with T1 stage (p < 0.0001) and tumor size ≥3 cm (p = 0.0002). Molecular tumor burden index (mTBI) in ctDNA positively correlated with larger tumor size (p = 0.0020). A higher mTBI was an independent predictor of recurrence after TUR of bladder followed by immunotherapy. Analysis of ctDNA based on targeted sequencing is a promising approach to predict disease recurrence for NMIBC patients receiving TUR of bladder followed by immunotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.657483DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114939PMC
April 2021

GALNT2/14 overexpression correlate with prognosis and methylation: potential therapeutic targets for lung adenocarcinoma.

Gene 2021 Jul 5;790:145689. Epub 2021 May 5.

Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian, China. Electronic address:

Objective: GALNT2/14 are members of the glycosyltransferase protein family, which initiate mucin-type O-glycosylation of peptides in the Golgi apparatus. However, the correlation between GALNT2/14 and disease prognosis and methylation in lung adenocarcinoma (LUAD) remains unclear. Thus, we sought to identify their potential values in LUAD.

Methods: GALNT2/14 expressions were analyzed using publicly-available datasets. The association between GALNT2/14 and disease prognosis was evaluated. In addition, gene set enrichment analysis (GSEA) and single sample GSEA (ssGSEA) were used to explore the potential biological functions of GALNT2/14. The correlation between the copy number variations and methylation level of GALNT2/14 and their mRNA expressions was analyzed via cBioPortal. Finally, we explored the prognostic value of the GALNT2/14 methylation levels by MethSurv in LUAD.

Results: GALNT2/14 were highly expressed in LUAD tumor tissue than normal tissue (P < 0.001). Multivariate analysis showed that high GALNT2/14 expressions were both an independent prognostic factor. GSEA found that GALNT2/14 expressions were associated with the methylation, gene silencing, and cell division, whereas immune analysis showed that GALNT2/14 expressions positively correlated with the expression level of PD-L1. Finally, the methylation levels of GALNT2/14 negatively correlated with the GALNT2/14 expressions (R = -0.26 and -0.36, P < 0.001, respectively), and patients with GALNT2/14 hypomethylation had worse overall survival than patients with high methylation (P < 0.05).

Conclusions: This study demonstrated that the overexpression of GALNT2/14 in LUAD can serve as biomarkers for poor prognosis. The biological functions of GALNT2/14 are potentially related to methylation, gene silencing, tumorigenesis, and cell division. These findings help elucidate the role of GALNT2/14 in tumorigenesis and provide additional insight for therapy and prognosis of LUAD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gene.2021.145689DOI Listing
July 2021

Li-ESWT treatment reduces inflammation, oxidative stress, and pain via the PI3K/AKT/FOXO1 pathway in autoimmune prostatitis rat models.

Andrology 2021 May 7. Epub 2021 May 7.

Institute of Urology, Lanzhou University Second Hospital, Key Laboratory of Urological Diseases, Gansu Province (Lanzhou University), Gansu Nephro-Urological Clinical Center, Lanzhou, China.

Background: Due to limited data on the pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and the suboptimal therapeutic effect, the development of new and effective treatment modalities was needed urgently. Low-intensity extracorporeal shock wave therapy (Li-ESWT) has been reported for the treatment of CP/CPPS. However, the underlying mechanism remains to be elucidated.

Objective: To interrogated the efficacy and the mechanism of Li-ESWT in the treatment of CP/CPPS.

Materials And Methods: According to different treatments, RWPE-1 cells (human prostate epithelial cells) were randomly divided into three groups: control group, LPS(lipopolysaccharide) group, or Li-ESWT group (LPS induced RWPE-1 managed by Li-ESWT). Following the Li-ESWT treatment, the levels of oxidative stress was assayed. We then established a rat model of experimental autoimmune prostatitis (EAP) by injecting prostatic protein homogenate mixed with complete Freund's adjuvant. The Sprague-Dawley rats were randomly divided into the control group, EAP group, or Li-ESWT group. Von Frey Filament was used to quantify pelvic hyperalgesia in the rats. Prostates tissues from each group were collected for immunohistochemistry, oxidation stress, and western blot analysis.

Results: Histological analysis showed reduced inflammation and expression of cytokines (TNF-α, IL-1β, IL-6, COX-2, SP) in prostate tissues from the Li-ESWT group compared with those from the EAP group (all P < 0.05). Similarly, there was reduced pelvic pain and allergic symptoms in the Li-ESWT group compared with the EAP group (all P < 0.05). Besides, Li-ESWT treatment could decrease oxidative stress in the prostate and in RWPE-1 cells, respectively (both P < 0.05). Moreover, the Li-ESWT up-regulated the expression of CAT through the inhibition of phosphorylation of AKT/FOXO1 signaling pathway.

Discussion And Conclusions: Li-ESWT may reduce inflammation, oxidative stress and pain in rats with autoimmunity-induced prostatitis via the PI3K/AKT/FOXO1 pathway. It implies that Li-ESWT can present a potential therapeutic option for the treatment of CP/CPPS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/andr.13027DOI Listing
May 2021

Relationship among lymphocytes, free/total prostate specific antigen, lower urinary tract symptoms and prostatic inflammation in benign prostatic hyperplasia patients.

Asian J Surg 2021 Jun 18;44(6):921-922. Epub 2021 Apr 18.

Department of Urology, Lanzhou University Second Hospital, Lanzhou, 730000, China. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.asjsur.2021.04.006DOI Listing
June 2021

Inhibition of CXCR4 ameliorates hypoxia-induced pulmonary arterial hypertension in rats.

Am J Transl Res 2021 15;13(3):1458-1470. Epub 2021 Mar 15.

Department of Anesthesiology, The Affiliated Wuxi People's Hospital of Nanjing Medical University Wuxi, Jiangsu Province, China.

Pulmonary vascular remodeling due to aberrant proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) is the main characteristic of pulmonary arterial hypertension (PAH). CXCR4 is a specific stem cell surface receptor of cytokine CXCL12 which could regulate homing of hematopoietic progenitor cells and their mobilization. There is evidence that bone marrow-derived CXCR4 proangiogenic cell accumulation take an important part in the development of pulmonary arterial hypertension; however, the underlying mechanisms still remain unknown. Here, we explored the expression profile of CXCR4 both in hypoxia rats and PAH patients by measuring proliferation and migration of PASMCs. We performed western blot analysis to detect downstream molecules. We demonstrated that CXCR4 expression level was increased in both rats exposed to chronic hypoxia and PAH patients in reconstructed pulmonary arterioles. The inhibition of CXCR4 expression slowed down the process of hypoxic-PAH by reducing the mean right ventricular systolic pressure, right ventricular hypertrophy, and pulmonary vascular remodeling in vivo experimental mode. CXCR4 overexpression and inhibition regulated the cell growth of PASMCs in hypoxia condition, which are the critical cellular events in vascular disease. Furthermore, activation of β-catenin signaling and upregulation of CXCR4 could be blocked by AMD3100 both in vivo and vitro. Taken together, inhibition of CXCR4 expression could downregulate β-catenin, reduced pulmonary artery smooth muscle cell proliferation, and ameliorated pulmonary vascular remodeling in hypoxia rats. These findings suggest that CXCL12/CXCR4 is critical in driving PAH and uncover a correlation between β-catenin dependent signaling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014346PMC
March 2021

Spatially dependent hyper-Raman scattering in five-level cold atoms.

Opt Express 2021 Mar;29(7):10914-10922

We demonstrate a scheme to control the spatially dependent hyper-Raman scattering based on electromagnetically induced transparency in a cold atomic system. By adjusting the different system parameters, one can effectively modulate the phase and intensity of the generated Raman field. Specifically, we show that electromagnetically induced transparency creates quantum interference, which results in greatly enhanced efficiency for the generated Raman field. Such improvement in Raman efficiency makes our scheme suitable for generation of short-wavelength coherent radiation, conversion of frequency, and nonlinear spectroscopy based on orbital angular momentum light.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OE.420015DOI Listing
March 2021

Disturbance-level-dependent post-disturbance succession in a Eurasian steppe.

Sci China Life Sci 2021 Mar 19. Epub 2021 Mar 19.

Key Laboratory of Dryland Agriculture, Ministry of Agriculture, Institute of Environment and Sustainable Development in Agriculture, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.

Anthropogenic disturbances may decrease as we take measures to control them. However, the patterns and mechanisms of post-disturbance ecosystem succession have rarely been studied. Here we reported that disturbance level determined the importance of stochastic relative to deterministic changes in ecosystem components (plant community composition, soil microbial community composition, and soil physicochemical indices), and thus predefined the pattern of post-disturbance ecosystem succession. We proposed a theoretical framework with five disturbance levels corresponding to distinct succession patterns. We conducted a nitrogen addition experiment in a temperate steppe, monitored these ecosystem components during "disturbance" treatment (2010-2014) and post-treatment "succession" (2014-2018). The disturbance level experienced by each component in each treatment was inferred by fitting the observed succession patterns into the theoretical framework. The mean disturbance level of these components was found to increase quadratically with nitrogen addition rate. This was because increasing nitrogen addition reduced the importance of stochastic relative to deterministic changes in these components, and these changes had a quadratic relationship with disturbance level. Overall, our results suggested that by monitoring the importance of stochastic relative to deterministic changes in an ecosystem, we can estimate disturbance levels and predict succession patterns, as well as propose disturbance-level-dependent strategies for post-disturbance restoration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11427-020-1894-8DOI Listing
March 2021

Association of TERT gene polymorphisms with clinical benign prostatic hyperplasia in a Chinese Han population of the Northwest region.

Transl Androl Urol 2021 Feb;10(2):692-702

Institute of Urology, Lanzhou University Second Hospital, Key Laboratory of Urological Diseases in Gansu Province, Gansu Nephron-Urological Clinical Center, Lanzhou, China.

Background: To investigate the association between single nucleotide polymorphisms (rs10078761, rs12696304, rs2853669, rs16847897, rs2736100, rs10069690) of telomerase gene (TERT) and the risk clinical benign prostatic hyperplasia (BPH) in a Chinese Han population of the Northwest region.

Methods: A total of 150 BPH patients and 150 healthy older males from the northwest Chinese Han population were included in this study. The sample size for this unmatched case-control study was estimated by the look-up table method. Meanwhile, the general information and disease data of patients were collected. Age was only collected in healthy control subjects for statistical correction. Genotypes were detected using a multiplex PCR + ligase detection reaction (LDR). Typing results and clinical data were statistically analyzed using multiple linear regression and logistic regression. Pearson correlation was used for Hardy-Weinberg equilibrium.

Results: The included population is in Hardy-Weinberg equilibrium. There was no significant association between SNP and the risk of BPH by correlation analysis. However, 4 haplotypes (TCTGGT, TCTGTC, TGCCTC, and TGTGTC) were identified as risk factors of BPH by haplotype analysis. The SNP rs2853669 is an independent risk factor for smooth muscle type of hyperplasia. Besides, rs2736100, rs10078761, and rs10069690 which are in linkage disequilibrium are associated with the severity of BPH.

Conclusions: Polymorphism of the TERT gene determines the different disease development and pathological manifestations of BPH in the Chinese Han population the Northwest region.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/tau-20-1032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947465PMC
February 2021

Endoscopic transpapillary gallbladder drainage for management of acute cholecystitis with coagulopathy.

J Int Med Res 2021 Mar;49(3):300060521996912

Department of Urology, Lanzhou University Second Hospital, Lanzhou, Gansu, China.

Acute cholecystitis is a common and frequently occurring disease, and laparoscopic cholecystectomy is the preferred treatment method. Percutaneous transhepatic gallbladder drainage is regarded as the first-line palliative procedure for elderly patients with poor cardiopulmonary function who cannot tolerate general anesthesia. However, for patients with acute cholecystitis who are undergoing treatment with oral antithrombotics or who have abnormal coagulation mechanisms, endoscopic transpapillary gallbladder drainage may be a good choice. Endoscopic transpapillary gallbladder drainage is an endoscopic retrograde cholangiopancreatography-based technique that drains the gallbladder by placing a tube into the cavity of the gallbladder though the cystic gall duct. It is the application of the concept of natural orifice transluminal endoscopic surgery in the biliary system. This technique can not only achieve gallbladder drainage but can also minimize the risk of procedure-induced bleeding. In this paper, we describe a representative case to introduce the key points of this procedure and the associated clinical care, hoping to provide useful information for clinicians and nurses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/0300060521996912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168036PMC
March 2021

FAM72 serves as a biomarker of poor prognosis in human lung adenocarcinoma.

Aging (Albany NY) 2021 03 3;13(6):8155-8176. Epub 2021 Mar 3.

Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, Fujian, China.

FAM72A-D promote the self-renewal of neural progenitor cells. There is accumulating evidence that FAM72 promotes tumorigenicity. However, its effects in lung adenocarcinoma (LUAD) have not been determined. Thus, we evaluated the prognostic value of in LUAD using bioinformatics approaches. In particular, we evaluated the relationship between FAM72 and LUAD using a wide range of databases and analysis tools, including TCGA, GEO, GEPIA, Metascape, cBioPortal, and MethSurv. Compared with its expression in normal lung tissues, FAM72 expression was significantly increased in LUAD tissues. A univariate Cox analysis showed that high FAM72 expression levels were correlated with a poor OS in LUAD. Additionally, FAM72 expression was independently associated with OS through a multivariate Cox analysis. GO and GSEA revealed enrichment in mitotic nuclear division and cell cycle. Moreover, high FAM72 expression was associated with poor survival. An analysis of immune infiltration showed that FAM72 is correlated with immune cell infiltration. Finally, we found that the methylation level was associated with prognosis in patients with LUAD. In summary, these results indicate that FAM72 is a potential molecular marker for poor prognosis in LUAD and provide additional insight for the development of therapies and prognostic markers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.202625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034972PMC
March 2021

Comparison of open and intracorporeal modified ureterosigmoidostomy (Mainz II) after laparoscopic radical cystectomy with bladder cancer.

World J Surg Oncol 2021 Feb 20;19(1):57. Epub 2021 Feb 20.

Department of Urology, Institute of Urology, Key Laboratory of Urological Diseases of Gansu Province, Lanzhou University Second Hospital, No.82 Cui Ying Gate, Cheng guan District, Lanzhou, 730030, Gansu, China.

Objective: To compare perioperative and oncologic outcomes of open modified ureterosigmoidostomy urinary diversion (OMUUD) and intracorporeal modified ureterosigmoidostomy urinary diversion (IMUUD) following laparoscopic radical cystectomy (LRC).

Patients And Methods: We retrospectively reviewed our single institutional collected database patients undergoing LRC from October 2011 to October 2019. The perioperative characteristics were compared between OMUUD and IMUUD, and overall survival (OS) and progression-free survival (PFS) were evaluated by the Kaplan-Meier method.

Results: Overall, 84 patients were included. OMUUD and IMUUD were performed in 63 (75%) and 21 (25%) patients, respectively. IMUUD patients demonstrated shorter postoperative length of stay (16.24 ± 3.91 days vs. 18.98 ± 7.41 days, P = 0.033), similar operation time (498.57 ± 121.44 vs. 462.24 ± 99.71, P = 0.175), similar estimated blood loss [400 (200-475) ml vs. 400 (200-700) ml, P = 0.095], and similar overall complication rate within 30 days (19.05% vs. 25.40%, P = 0.848) and 90 days (23.81% vs. 17.46%, P = 0.748). Complete urinary control rate was 87.3% (55/63) in the OMUUD group. In IMUUD, the complete urinary control rate was 90.5% (19/21). There was no significant difference in OS (χ = 0.015, P = 0.901) and PFS (χ = 0.107, P = 0.743) between the two groups.

Conclusion: IMUUD postoperative recovery is faster; other perioperative outcomes and oncology results are not significantly different with OMUUD. It is indicated that IMUUD can be utilized safely and effectively in the urinary diversion after LRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12957-021-02148-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897376PMC
February 2021

Proteasome regulation by reversible tyrosine phosphorylation at the membrane.

Oncogene 2021 Mar 18;40(11):1942-1956. Epub 2021 Feb 18.

Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, China.

Reversible phosphorylation has emerged as an important mechanism for regulating 26S proteasome function in health and disease. Over 100 phospho-tyrosine sites of the human proteasome have been detected, and yet their function and regulation remain poorly understood. Here we show that the 19S subunit Rpt2 is phosphorylated at Tyr439, a strictly conserved residue within the C-terminal HbYX motif of Rpt2 that is essential for 26S proteasome assembly. Unexpectedly, we found that Y439 phosphorylation depends on Rpt2 membrane localization mediated by its N-myristoylation. Multiple receptors tyrosine kinases can trigger Rpt2-Y439 phosphorylation by activating Src, a N-myristoylated tyrosine kinase. Src directly phosphorylates Rpt2-Y439 in vitro and negatively regulates 26S proteasome activity at cellular membranes, which can be reversed by the membrane-associated isoform of protein tyrosine phosphatase nonreceptor type 2 (PTPN2). In H1975 lung cancer cells with activated Src, blocking Rpt2-Y439 phosphorylation by the Y439F mutation conferred partial resistance to the Src inhibitor saracatinib both in vitro and in a mouse xenograft tumor model, and caused significant changes of cellular responses to saracatinib at the proteome level. Our study has defined a novel mechanism involved in the spatial regulation of proteasome function and provided new insights into tyrosine kinase inhibitor-based anticancer therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41388-021-01674-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990385PMC
March 2021

Liq_ccRCC: Identification of Clear Cell Renal Cell Carcinoma Based on the Integration of Clinical Liquid Indices.

Front Oncol 2020 6;10:605769. Epub 2021 Jan 6.

Institute of Urology, Lanzhou University Second Hospital, Key Laboratory of Gansu Province for Urological Diseases, Clinical Center of Gansu Province for Nephrourology, Lanzhou, China.

Currently, preoperative diagnosis and differentiation of renal clear cell carcinoma and other subtypes remain a serious challenge for doctors. The liquid biopsy technique and artificial intelligence have inspired the pursuit of distinguishing clear cell renal cell carcinoma using clinically available test data. In this work, a method called liq_ccRCC based on the integration of clinical blood and urine indices through machine learning approaches was successfully designed to achieve this goal. Clinically available biochemical blood data and urine indices were collected from 306 patients with renal cell carcinoma. Finally, the integration of 18 top-ranked clinical liquid indices (13 blood samples and 5 urine samples) was proven to be able to distinguish renal clear cell carcinoma from other subtypes of renal carcinoma by cross-valuation with an AUC of 0.9372. The successful introduction of this identification method suggests that subtype differentiation of renal cell carcinoma can be accomplished based on clinical liquid test data, which is noninvasive and easy to perform. It has huge potential to be developed as a promising innovation strategy for preoperative subtype differentiation of renal cell carcinoma with the advantages of convenience and real-time testing. liq_ccRCC is available online for the free test of readers at http://lishuyan.lzu.edu.cn/liq_ccRCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.605769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873977PMC
January 2021

Bioinformatics analysis combined with experiments predicts CENPK as a potential prognostic factor for lung adenocarcinoma.

Cancer Cell Int 2021 Jan 21;21(1):65. Epub 2021 Jan 21.

Department of Radiation Oncology, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, No.420, Fuma Road, Fuzhou, 350014, China.

Background: Lung cancer is the most common malignant tumor. Identification of novel diagnostic and prognostic biomarkers for lung cancer is a key research imperative. The role of centromere protein K (CENPK) in cancer is an emerging research hotspot. However, the role of CENPK in the progression of lung adenocarcinoma (LAC) is not well characterized.

Methods: In this study, we identified CENPK as a potential new gene for lung cancer based on bioinformatics analysis. In addition, in vitro experiments were performed to verify the function of this gene. We investigated the expression of CENPK in LAC by analyses of datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Differential expression analyses, gene ontology (GO) enrichment, Kyoto encyclopedia of genes and genomes (KEGG) analysis, and gene set enrichment analysis (GSEA) were conducted to evaluate the diagnostic and prognostic relevance of CENPK. Then, for evaluating the biological behavior and role of CENPK in lung cancer cells, we did a series of vitro experiments, such as immunohistochemistry analysis, Western blot analysis, CCK8 assay, transwell assay, flow cytometry, and wound healing assay.

Results: We demonstrated overexpression of CENPK in LAC; in addition, increased expression of CENPK was associated with clinical progression. Moreover, CENPK was found to be an independent risk factor in patients with LAC. Furthermore, we observed activation of CENPK-related signaling pathways in patients with LAC.

Conclusions: Our findings indicate a potential role of CENPK in promoting tumor proliferation, invasion, and metastasis. It may serve as a novel diagnostic and prognostic biomarker in patients with LAC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12935-021-01760-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818917PMC
January 2021

Structural basis for the shared neutralization mechanism of three classes of human papillomavirus type 58 antibodies with disparate modes of binding.

J Virol 2021 Jan 20. Epub 2021 Jan 20.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, School of Life Sciences, Xiamen University, Xiamen, China 361102.

Human papillomavirus type 58 (HPV58) is associated with cervical cancer and poses a significant health burden worldwide. Although the commercial 9-valent HPV vaccine covers HPV58, the structural and molecular-level neutralization sites of the HPV58 complete virion are not fully understood. Here, we report the high-resolution (∼3.5 Å) structure of the complete HPV58 pseudovirus (PsV58) using cryo-electron microscopy (cryo-EM). Three representative neutralizing monoclonal antibodies (nAbs 5G9, 2H3 and A4B4) were selected through clustering from a nAb panel against HPV58. Bypassing the steric hindrance and symmetry-mismatch in the HPV Fab-capsid immune-complex, we present three different neutralizing epitopes in the PsV58, and show that, despite differences in binding, these nAbs share a common neutralization mechanism. These results offer insight into HPV58 genotype specificity and broaden our understanding of HPV58 neutralization sites for antiviral research. Cervical cancer primarily results from persistent infection with high-risk types of human papillomavirus (HPV). HPV type 58 (HPV58) is an important causative agent, especially within Asia. Despite this, we still have limited data pertaining to the structural and neutralizing epitopes of HPV58, and this encumbers our in-depth understanding of the virus mode of infection. Here, we show that representative nAbs (5G9, 10B11, 2H3, 5H2 and A4B4) from three different groups share a common neutralization mechanism that appears to prohibit the virus from associating with the extracellular matrix and cell surface. Furthermore, we identify that the nAbs engage via three different binding patterns: top-center binding (5G9 and 10B11), top-fringe binding (2H3 and 5H2), and fringe binding (A4B4). Our work shows that, despite differences in the pattern in binding, nAbs against HPV58 share a common neutralization mechanism. These results provide new insight into the understanding of HPV58 infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/JVI.01587-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092703PMC
January 2021

miR-541-3p enhances the radiosensitivity of prostate cancer cells by inhibiting HSP27 expression and downregulating β-catenin.

Cell Death Discov 2021 Jan 18;7(1):18. Epub 2021 Jan 18.

Institute of Urology, Lanzhou University Second Hospital, Lanzhou, 730030, China.

Heat shock protein 27 (HSP27), a regulator of cell survival, can enhance the resistance of cancer cells to radiotherapy. As microRNA-541-3p (miR-541-3p) was recently predicted to be a putative upstream modulator of HSP27, the present study was designed to investigate the function and mechanism underlying how miR-541-3p modulates the radiosensitivity of prostate cancer (PCa) cells by regulating HSP27. Through quantitative PCR, miR-541-3p was determined to be poorly expressed in PCa tissues relative to normal controls, whereas its expression was enhanced after radiotherapy. Consistently, miR-541-3p expression levels in PCa cells were elevated after radiation. Cell viability and proliferation and apoptosis under radiation were subsequently evaluated in response to loss-of-function of miR-541-3p. It was found that inhibition of miR-541-3p facilitated the viability and proliferation of PCa cells and promoted their apoptosis post radiation, hence reducing the radiosensitivity of LNCaP cells. Dual-luciferase reporter assay identified that miR-541-3p negatively regulated the HSP27 mRNA expression by targeting its 3'-UTR. Meanwhile, miR-541-3p overexpression inhibited the β-catenin expression by targeting HSP27. Furthermore, HSP27 or β-catenin overexpression was noted to significantly reverse the miR-541-3p-mediated changes in the biological functions of PCa cells post radiation, suggesting that HSP27-dependent activation of β-catenin might be the mechanism responsible for the promotive effect of miR-541-3p on radiosensitivity. Collectively, this study suggests that miR-541-3p specifically inhibits the HSP27 expression and downregulates β-catenin, thereby enhancing the radiosensitivity of PCa cells. Our findings highlight the underlying mechanism of the miR-541-3p/HSP27/Wnt/β-catenin axis regarding radiotherapy for PCa.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41420-020-00387-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813831PMC
January 2021

The prognostic value of peak arterial lactate levels within 72 h of lung transplantation in identifying patient outcome.

J Thorac Dis 2020 Dec;12(12):7365-7373

Department of Anesthesiology, the Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.

Background: Lactic acidosis is often seen in lung transplantation (LTx). Postoperative lactate is frequently associated with poor outcome in postoperative and critically ill patients. Our aim was to evaluate the predictive value of postoperative peak lactate levels within 72 h of LTx for 30-day and late mortality.

Methods: We evaluated patients who underwent LTx from January 2015 to September 2017. All admitted patients were classified according to the peak lactate level (PL) within 72 h of surgery: PL <5 mmol/L (Group 1); PL =5-10 mmol/L (Group 2), and PL >10 mmol/L (Group 3). We performed logistic regression analysis and used Cox regression models to identify the peak lactate level as a predictive factor for 30-day and late mortality, respectively.

Results: Of 255 eligible patients, mean age 55.61±12.16, mean lactate 4.99±2.93 and 80% male, and 40% had hyperlactatemia (PL >5 mmol/L) after LTx. The 30-day mortality rate was 17.9%, 28.9% and 68.8% in the three groups, respectively (P<0.05). Multivariate regression analyses revealed postoperative PL as a notable predictor of 30-day mortality [odds ratio =2.62 (1.42-4.84), P=0.002] as well as for late mortality [hazard ratio =2.70 (1.13-6.42), P=0.025].

Conclusions: The postoperative peak lactate level within 72 h of surgery was an independent predictor for 30-day and late mortality in LTx patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/jtd-20-3445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797848PMC
December 2020

Regulation of glial size by eicosapentaenoic acid through a novel Golgi apparatus mechanism.

PLoS Biol 2020 12 28;18(12):e3001051. Epub 2020 Dec 28.

Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.

Coordination of cell growth is essential for the development of the brain, but the molecular mechanisms underlying the regulation of glial and neuronal size are poorly understood. To investigate the mechanisms involved in glial size regulation, we used Caenorhabditis elegans amphid sheath (AMsh) glia as a model and show that a conserved cis-Golgi membrane protein eas-1/GOLT1B negatively regulates glial growth. We found that eas-1 inhibits a conserved E3 ubiquitin ligase rnf-145/RNF145, which, in turn, promotes nuclear activation of sbp-1/ SREBP, a key regulator of sterol and fatty acid synthesis, to restrict cell growth. At early developmental stages, rnf-145 in the cis-Golgi network inhibits sbp-1 activation to promote the growth of glia, and when animals reach the adult stage, this inhibition is released through an eas-1-dependent shuttling of rnf-145 from the cis-Golgi to the trans-Golgi network to stop glial growth. Furthermore, we identified long-chain polyunsaturated fatty acids (LC-PUFAs), especially eicosapentaenoic acid (EPA), as downstream products of the eas-1-rnf-145-sbp-1 pathway that functions to prevent the overgrowth of glia. Together, our findings reveal a novel and potentially conserved mechanism underlying glial size control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1371/journal.pbio.3001051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7793280PMC
December 2020

Stress-responses of microbial population and activity in activated sludge under long-term ciprofloxacin exposure.

J Environ Manage 2021 Mar 25;281:111896. Epub 2020 Dec 25.

China-UK Low Carbon College, Shanghai Jiao Tong University, Shanghai, 200240, China.

In this study, the effects of ciprofloxacin on activated sludge were evaluated based on the microbial community and metabolic characteristics. The results indicated that the metabolism of chemical oxygen demand (COD) and nitrogen were inhibited with ciprofloxacin at mg/L level compared to the control experiment, and the concentration of ciprofloxacin was slightly decreased. High-throughput sequencing (HTS) results showed that ciprofloxacin greatly shaped the microbial communities in activated sludge, especially for the Nitrospirae phylum and Nitrospira genus. High concentrations of ciprofloxacin stimulated the enrichment of Zoogloea, thus reducing the stability of the activated sludge. Moreover, quinolone resistance proteins in Aeromonas were enriched, which demonstrates their competitive advantage in these enrichment incubations. Finally, the functional profiles were predicted through Tax4Fun, which revealed the adaption to microbes in activated sludge to the ciprofloxacin selective pressure. This work demonstrates the influence of ciprofloxacin on the activated sludge process, and can provide a useful reference for the assessment of the ecological security of ciprofloxacin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jenvman.2020.111896DOI Listing
March 2021

Exposure to O during pregnancy and offspring asthma induced by OVA: Sensitive window identification.

Environ Pollut 2021 Feb 13;270:116297. Epub 2020 Dec 13.

Department of Occupational and Environmental Health, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, China. Electronic address:

Background: Evidence proved that gestational ozone (O) exposure can increase the risk of neonatal adverse respiratory outcomes, but offspring asthma is unclear.

Objective: This study aimed to investigate whether gestational O exposure could exacerbate offspring asthma, and to research the differences in effects of O exposure at different gestational periods on offspring asthma.

Methods: The pregnant ICR mice were randomly grouped and were administered O (air as control) at gestational day (GD) 1-6, 7-12, and 13-18, respectively. The pups aged 2-4 weeks were treated with ovalbumin (OVA) to establish a model of early life asthma. Asthma characteristics such as pulmonary inflammation, goblet cell proliferation, airway remodeling, OVA-specific immunoglobulin (Ig) E secretion and cytokines were examined.

Results: OVA sensitization and challenge successfully induced asthma in offspring. Compared with the air control, pulmonary inflammation infiltration, mucous secretion, the concentration of OVA-specific IgE, the level of tumor necrosis factor (TNF)-α, and T helper (Th) 2-skewed response were significantly exacerbated when O exposure at GD13-18 following inhaling OVA, while pulmonary inflammatory infiltration, mucus secretion, and Th2-skewed response were not significantly changed when O exposure at both GD1-6 and GD7-12. What's more, the above indicators in asthmatic offspring due to O exposure at GD13-18 were more severe than at GD1-6 and GD7-12. Interestingly, the signs of asthma only appeared in the offspring after OVA inhalation. When offspring were not treated with OVA, the prenatal O exposure alone did not lead to asthmatic reactions in offspring. In addition, O exposure at GD13-18 markedly increased the number of neutrophils and macrophages in Bronchoalveolar Lavage Fluid (BALF) of asthmatic offspring, and significantly exacerbated Th2 immune imbalance in asthmatic offspring, but had no effect on Th17 immune imbalance.

Conclusion: Exposure to O during pregnancy aggravated asthma in offspring, in which the third trimester is the most sensitive window.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2020.116297DOI Listing
February 2021

Teratogenic Toxicity Evaluation of Bladder Cancer-Specific Oncolytic Adenovirus on Mice.

Curr Gene Ther 2021 ;21(2):160-166

Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases, Gansu Province (Lanzhou University), Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou730000, China.

Background: In our previous studies, we had demonstrated the efficiency and specificity of constructed bladder tissue-specific adenovirus Ad-PSCAE-UPII-E1A-AR (APU-EIA-AR) on bladder cancer. The virus biodistribution and body toxicity in nude mice have also been investigated. However, the safety of the bladder cancer-specific oncolytic adenovirus on fetal mice and F1 mice should be under intense investigation.

Objective: In order to evaluate the teratogenic toxicity of bladder cancer-specific oncolytic adenovirus APU-EIA-AR on mice, in this study, we investigated the fetal mice weight, fetal body length and tail length, fetal skeleton development, as well as the F1 mice weight, growth curve, and major organ pathology. These teratogenic toxicity data of bladder tissue-specific adenovirus Ad-PSCAE- UPII-E1A-AR (AD) would provide safe information prior to embarking on clinical trials.

Methods: On the sixth day of being fertilized, the pregnant mice began to be intramuscularly administrated with AD (1×10VP, 1×10VP, 1×10VP) every other day for ten days. The pregnant mice were then divided into two groups. One group was euthanized on the seventeenth day; the fetal mice were taken out, and the bone structure of the infants was observed. The other group was observed until natural childbirth. The Filial Generation (F1) is fed for 30 days; the variations in the growth progress and development were assessed. The mice were then euthanized; The tissues from major organs were harvested and observed under the microscope.

Results: In the process of teratogenic toxicity test, the Placenta weight, fetal mice weight, body length, and a tail length of mice fetal in adenovirus treated group did not reveal any alteration. Meanwhile, comparing with the PBS group, there is no obvious change in the skeleton of fetal mice treated with adenovirus. During the development process of F1 mice treated with adenovirus, the changes in mice weight show statistical significance. However, in the progress of the growth curve, this difference is not very obvious. Furthermore, the pathological section showed no obvious alteration in major organs.

Conclusion: Our study demonstrated that bladder cancer-specific adenovirus Ad-PSCAE-UPII- E1A-AR appears safe in pregnant mice without any discernable effects on fetal mice and F1 development. Hence, it is relatively safe for tumor gene therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1566523220999201217161258DOI Listing
January 2021

Teratogenic Toxicity Evaluation of Bladder Cancer-Specific Oncolytic Adenovirus on Mice.

Curr Gene Ther 2021 ;21(2):160-166

Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases, Gansu Province (Lanzhou University), Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou730000, China.

Background: In our previous studies, we had demonstrated the efficiency and specificity of constructed bladder tissue-specific adenovirus Ad-PSCAE-UPII-E1A-AR (APU-EIA-AR) on bladder cancer. The virus biodistribution and body toxicity in nude mice have also been investigated. However, the safety of the bladder cancer-specific oncolytic adenovirus on fetal mice and F1 mice should be under intense investigation.

Objective: In order to evaluate the teratogenic toxicity of bladder cancer-specific oncolytic adenovirus APU-EIA-AR on mice, in this study, we investigated the fetal mice weight, fetal body length and tail length, fetal skeleton development, as well as the F1 mice weight, growth curve, and major organ pathology. These teratogenic toxicity data of bladder tissue-specific adenovirus Ad-PSCAE- UPII-E1A-AR (AD) would provide safe information prior to embarking on clinical trials.

Methods: On the sixth day of being fertilized, the pregnant mice began to be intramuscularly administrated with AD (1×10VP, 1×10VP, 1×10VP) every other day for ten days. The pregnant mice were then divided into two groups. One group was euthanized on the seventeenth day; the fetal mice were taken out, and the bone structure of the infants was observed. The other group was observed until natural childbirth. The Filial Generation (F1) is fed for 30 days; the variations in the growth progress and development were assessed. The mice were then euthanized; The tissues from major organs were harvested and observed under the microscope.

Results: In the process of teratogenic toxicity test, the Placenta weight, fetal mice weight, body length, and a tail length of mice fetal in adenovirus treated group did not reveal any alteration. Meanwhile, comparing with the PBS group, there is no obvious change in the skeleton of fetal mice treated with adenovirus. During the development process of F1 mice treated with adenovirus, the changes in mice weight show statistical significance. However, in the progress of the growth curve, this difference is not very obvious. Furthermore, the pathological section showed no obvious alteration in major organs.

Conclusion: Our study demonstrated that bladder cancer-specific adenovirus Ad-PSCAE-UPII- E1A-AR appears safe in pregnant mice without any discernable effects on fetal mice and F1 development. Hence, it is relatively safe for tumor gene therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1566523220999201217161258DOI Listing
January 2021

Comparative Efficacy of Combined Radiotherapy, Systemic Therapy, and Androgen Deprivation Therapy for Metastatic Hormone-Sensitive Prostate Cancer: A Network Meta-Analysis and Systematic Review.

Front Oncol 2020 20;10:567616. Epub 2020 Oct 20.

Key Laboratory of Urological Diseases in Gansu Province, Department of Urology, Gansu Nephro-Urological Clinical Center, Lanzhou University Second Hospital, Lanzhou, China.

Recent randomized clinical trials have examined the efficacy of different combinations of systemic and local treatment approaches for metastatic hormone-sensitive prostate cancer (mHSPC). We compared the efficacy of these combined regimens in order to identify the optimal therapy for specific patient subgroups. The treatments were abiraterone (ABI), apalutamide (APA), docetaxel (DOC), enzalutamide (ENZ), and radiotherapy (RT) combined with androgen-deprivation therapy (ADT). Five electronic databases were searched up to May 7, 2020 for relevant trials. The risk of bias in the included trials was evaluated with the Cochrane tool. The hazard ratio (HR) with 95% confidence interval (CI) was determined for the included trials and indirect comparisons were performed using the R software. In total, 10 randomized, controlled trials with 11,194 patients were included in the meta-analysis. ADT + RT was superior to ADT monotherapy in terms of overall survival (HR = 0.96, 95% CI: 0.85-1.1) and conferred a survival benefit in a subgroup of low-volume patients (HR = 0.68, 95% CI: 0.54-0.87). Combined systemic treatments were significantly superior to ADT monotherapy in comparisons of survival and prostate-specific antigen response, including in the high-volume subgroup; meanwhile, in the low-volume subgroup only ADT + ENZ (HR = 0.38, 95% CI 0.21-0.69) showed a significant clinical benefit. In the Gleason score <8 subgroup, all combined systemic treatments were superior to ADT monotherapy, but the results were only significant for ADT + APA (HR = 0.56, 95% CI: 0.33-0.95) and ADT + DOC (HR = 0.71, 95% CI: 0.54-0.92). In the Gleason score ≥8 subgroup, ADT monotherapy was inferior (albeit not significantly) to combined treatments. In a ranking of performed comparisons, ADT + ENZ was the optimal regimen, although this was non-significant. Combined therapies also demonstrated superiority in quality-of-life indicators such as time to skeletal events and pain progression. ADT + radiotherapy led to superior outcomes in mHSPC patients with low-volume disease. While all combined systemic regimens confer a survival advantage over ADT monotherapy, the optimal treatment approach for certain mHSPC patient subgroups remains to be determined.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.567616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606969PMC
October 2020

Compositional changes of sedimentary microbes in the Yangtze River Estuary and their roles in the biochemical cycle.

Sci Total Environ 2021 Mar 6;760:143383. Epub 2020 Nov 6.

School of Environment Science and Technology, Shanghai Jiao Tong University, Shanghai 200240, China.

Due to the geographical circumstances, the Yangtze River Estuary (YRE) and the adjacent East China Sea are extensively influenced by both anthropogenic activities and environmental factors. To reveal the responses of microbes in surface sediment to environmental factors and their contributions to the biogeochemical cycle in this area, surface sediment and overlying water samples were collected at 21 stations from the estuary to the coastal region. Water and sediment parameters were determined, and 16S rRNA genes of microbes in sediment samples were sequenced using high throughput sequencing technology. The results indicated that ocean currents, sediment density (SD), nutrients, sulfate (SO), and salinity were the key factors shaping the microbial communities. Coastal microbes were affected mainly by SD, whereas anthropogenic discharge might have been responsible for a decrease in indigenous microbial diversity in the ocean. Due to the anthropogenic discharge, the most representative bacteria in the nearshore were aerobic and chemoheterotrophic bacteria, including ammonia-oxidizing bacteria, nitrite-oxidizing bacteria, denitrifying bacteria, and polyphosphate accumulating organisms. In the offshore, anaerobic bacteria, thermophilic bacteria, halophilic bacteria, sulfate-reducing bacteria, and sulfide oxidizing bacteria were the dominant bacteria, and these were characterized by strong solidarity and cooperative properties within the malnourished environment. In summary, these results provide a new perspective for revealing the biogeochemical significance of the bacterial lineages in the YRE, as well as constructive guidance for the management of the marginal sea ecosystems in distinct regions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.143383DOI Listing
March 2021

Synergistic induction of IL-23 by TNFα, IL-17A, and EGF in keratinocytes.

Cytokine 2021 Feb 2;138:155357. Epub 2020 Nov 2.

Department of Dermatology, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address:

IL-23 is an inflammatory cytokine that plays an essential role in Th17 immunity by enhancing Th17 cell proliferation and survival, and Th17 cytokine production. IL-23 has pathogenic roles in the development of Th17-mediated inflammatory diseases including psoriasis. Despite successful treatment of psoriasis by blocking IL-23, the regulation of IL-23 expression in psoriasis patients is largely unknown. Dendritic cells are generally considered to be the primary source of IL-23 in psoriasis. While high levels of IL-23 are found in psoriatic epidermis, IL-23 expression in psoriatic keratinoctyes remains a controversial issue. In this study, we demonstrated that IL-23 production is induced by a combination of TNFα and IL-17A in human keratinocytes. Additionally, this IL-23 induction by TNFα and IL-17A is further increased in psoriatic keratinocytes and is enhanced by EGFR signaling. Although IL-23 is also robustly induced by toll-like receptor agonists in dendritic cells and macrophages, IL-23 expression in these cell types is not regulated by TNFα, IL-17A, and EGFR signaling. Given that IL-23 is essential for maintaining Th17 activation, IL-23 induction by TNFα, IL-17A, and EGF in keratinocytes could play an important pathological role in psoriasis pathogenesis as well as the cutaneous rash associated with EGFR inhibition therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cyto.2020.155357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856048PMC
February 2021

Chinese Medicine Huzhen Tongfeng Formula Effectively Attenuates Gouty Arthritis by Inhibiting Arachidonic Acid Metabolism and Inflammatory Mediators.

Mediators Inflamm 2020 9;2020:6950206. Epub 2020 Oct 9.

Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Department of Pharmaceutics, Guangdong Engineering Research Center of Natural Products and New Drugs, Guangdong Provincial University Engineering Technology Research Center of Natural Products and Drugs, Guangdong Pharmaceutical University, Guangzhou, China.

The Chinese herbal medicine, Huzhen Tongfeng Formula (HZTF), derived from traditional Chinese medicine (TCM) practice, has recognized therapeutic benefits for gouty arthritis (GA). HZTF is currently in the late stage of approval process as a new anti-GA drug application. However, the underlying mechanism of HZTF as an antigout medication is unclear. In this study, we combined network pharmacology and experimental validation approaches to elucidate the mechanism of action of HZTF. First, the relative drug-disease target networks were constructed and analyzed for pathway enrichment. Potential pathways were then validated by and experiments. We found that 34 compounds from HZTF matched 181 potential drug targets. Topology analysis revealed 77 core targets of HZTF, which were highly related to gout, following screening of KEGG pathway enrichment. Further analysis demonstrated that the arachidonic acid metabolic pathway was the most relevant pathway involved in the mechanism of HZTF. Validation experiments showed that HZTF significantly inhibited the inflammatory cell infiltration into gouty joints, improved the swelling of affected joints, and increased the pain threshold. HZTF significantly reduced the transcription and production of various cytokines and inflammatory mediators . In particular, cyclooxygenase (COX)-1, COX-2, and 5-lipoxygenase were simultaneously downregulated. In conclusion, our study suggests that the antigout mechanism of HZTF is associated with the inhibition of the arachidonic acid pathway, resulting in the suppression of inflammatory cytokines and mediators. These findings extend our understanding of the pharmacological action of HZTF, rationalizing the application HZTF as an effective herbal therapy for GA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/6950206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568794PMC
October 2020