Publications by authors named "Yao Zhu"

326 Publications

Effect of Guanxin V in animal model of acute myocardial infarction.

BMC Complement Med Ther 2021 Feb 22;21(1):72. Epub 2021 Feb 22.

Department of Cardiology, Nanjing Hospital of Chinese Medicine, Affiliated to Nanjing University of Chinese Medicine, Daming Road 157#, Nanjing, 210000, Jiangsu, People's Republic of China.

Background: Acute myocardial infarction (AMI) is the most serious and lethal manifestation of coronary heart disease worldwide, presenting extremely high disability and mortality. Our previous studies have shown that Guanxin V (GXV) could significantly improve the cardiac function and the blood flow dynamics, and reduce serum levels of inflammatory factors in AMI rats, thus triggering ventricular remodeling (VR) at post-AMI.

Methods: An in vivo AMI model was established in Syrian hamsters by performing the ligation of the left anterior descending coronary artery. Syrian hamsters were randomly divided into four groups, namely Sham operation group (n = 12), AMI group (n = 12), GXV group (GXV 6 g/Kg/d, n = 12), and Tranilast group (Tra 105 mg/Kg/d, n = 12). Drug intervention was conducted for consecutive 8 weeks. Relative biological indicators were measured in the 4th and 8th week, respectively.

Results: Cardiac functions were improved, and the infarcted size and heart weight index were limited in Syrian hamsters of GXV and Tra groups compared with those in AMI group. Furthermore, GXV was able to decrease the number of mast cells and chymase level in Syrian hamsters with AMI. Administration of GXV remarkably inactivated the renin-angiotension-aldosterone system, and alleviated myocardial fibrosis and cardiomyocyte apoptosis, thus slowing down VR at post-AMI.

Conclusion: GXV slows down the process of VR at post-AMI by reducing chymase level and mast cells number, as well as inactivating the reninangiotension-aldosterone system..
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http://dx.doi.org/10.1186/s12906-021-03211-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898759PMC
February 2021

Ultrasound molecular imaging-guided tumor gene therapy through dual-targeted cationic microbubbles.

Biomater Sci 2021 Feb 17. Epub 2021 Feb 17.

Paul C. Lauterbur Research Center for Biomedical Imaging, Institute of Biomedical and Health Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.

The success of gene therapy depends largely on the development of gene vectors and effective gene delivery systems. It has been demonstrated that cationic microbubbles can be loaded with negatively charged plasmid DNA and thus improve gene transfection efficiency. In this study, we developed dual-targeting cationic microbubbles conjugated with iRGD peptides(Cyclo(Cys-Arg-Gly-Asp-Lys-Gly-Pro-Asp-Cys)) and CCR2 (chemokine (C-C motif) receptor 2) antibodies (MBiRGD/CCR2) for ultrasound molecular imaging and targeted tumor gene therapy. The ultrasound molecular imaging experiments showed that there were significantly enhanced ultrasound molecular imaging signals in the tumor that received MBiRGD/CCR2, compared with those that received MBiRGD, MBCCR2, or MBcontrol. As a therapy plasmid, pGPU6/GFP/Neo-shAKT2, carrying an expression cassette for the human AKT2 RNA interference sequence, was used. Our results demonstrated that MBiRGD/CCR2 had a significantly higher gene transfection efficiency than MBiRGD, MBCCR2, or MBcontrol under ultrasound irradiation, resulting in much lower AKT2 protein expression and stronger tumor growth inhibition effects in vivo and in vitro. In conclusion, our study demonstrated a novel gene delivery system via MBiRGD/CCR2 for ultrasound molecular-imaging-guided gene therapy of breast cancer.
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http://dx.doi.org/10.1039/d0bm01857kDOI Listing
February 2021

Pentacyclic Triterpenes from the resin of Liquidambar formosana have anti-angiogenic properties.

Phytochemistry 2021 Feb 5;184:112676. Epub 2021 Feb 5.

School of Pharmacy, Wenzhou Medical University, Wenzhou, 325035, People's Republic of China. Electronic address:

Phytochemical investigation of the resin of Liquidambar formosana Hanc led to the separation and identification of five undescribed pentacyclic triterpenoids, including two lupane type, one taraxerane type, and two oleanane type triterpenoids, in addition to ten known analogues. Structures and relative or absolute configurations were elucidated by intensive spectroscopic methods, and single-crystal X-ray diffraction analysis. All isolated compounds were evaluated for their anti-angiogenic effects in vitro against VEGF-induced endothelial cell proliferation and migration in HUVECs. Among them, (5R, 8R, 9R, 10R, 13S, 14R, 17R, 18R, 19S)-17,18-epoxy-17,18-seco-28-norlupa-17- hydroxy-20 (29) -ene-3-one, (5R, 8R, 9R, 10R, 13S, 14R, 17S, 18S, 19S, 20S)-17, 20-peroxy-28- norlupa -29 -hydroxy- 3-one, 11α,12α:13β,28-diepoxyoleanane- 3-one, 28-norlup-20 (29)-ene- 3β,17β-diol, liquidambaric lactone and 13,28-epoxy-11- oleanene- 3-one significantly inhibited VEGF-induced HUVECs proliferation with IC values ranging from 1.64 ± 0.36 to 7.06 ± 0.28 μM. In addition, they also effectively decreased VEGF-induced cell migration with IC values ranging from 1.57 ± 0.60 to 4.77 ± 0.62 μM. The structure-activity relationship of these compounds is discussed. The anti-angiogenic property of (5R, 8R, 9R, 10R, 13S, 14R, 17R, 18R, 19S)-17,18-epoxy-17,18-seco-28-norlupa-17- hydroxy-20 (29) -ene-3-one is mediated by the VEGFR2 - AKT signaling pathway.
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http://dx.doi.org/10.1016/j.phytochem.2021.112676DOI Listing
February 2021

[Safety of two ventilator weaning strategies after high-frequency oscillatory ventilation in preterm infants with respiratory distress syndrome: a prospective randomized controlled trial].

Zhongguo Dang Dai Er Ke Za Zhi 2021 Jan;23(1):18-24

Department of Neonatology, Women and Children's Hospital, School of Medicine, Xiamen University, Xiamen Key Laboratory of Perinatal-Neonatal Infection, Xiamen, Fujian 361001, China.

Objective: To study the safety of two ventilator weaning strategies after high-frequency oscillatory ventilation (HFOV) for the treatment of neonatal respiratory distress syndrome (NRDS) in preterm infants.

Methods: A prospective randomized controlled trial was conducted for 101 preterm infants with NRDS, with a gestational age of ≤32 weeks or a birth weight of ≤1 500 g, who were admitted to the neonatal intensive care unit of Xiamen Maternal and Child Health Hospital from January 1, 2019 to June 30, 2020. The infants underwent HFOV as the preferred treatment. The infants were randomly divided into an observation group (50 infants with direct weaning from HFOV) and a control group (51 infants with weaning after HFOV was switched to conventional mechanical ventilation). The two groups were compared in terms of failure rate of ventilator weaning within 72 hours, changes in blood gas parameters at 2 hours before weaning and at 2 and 24 hours after weaning, respiratory support therapy, incidence rates of complications, and outcome at discharge.

Results: There was no significant difference in the failure rate of ventilator weaning within 72 hours (8% vs 14%, > 0.05). The observation group had a significantly shorter duration of mechanical ventilation than the control group [(64±39) hours vs (88±69) hours, < 0.05]. There were no significant differences between the two groups in the duration of mechanical ventilation, total oxygen supply time, blood gas parameters before and after ventilator weaning, incidence rates of complications, and outcome at discharge ( > 0.05).

Conclusions: For preterm infants with NRDS, the strategy of weaning directly from HFOV is safe and reliable and can reduce the duration of invasive mechanical ventilation, and therefore, it holds promise for clinical application.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818152PMC
January 2021

YQWY Decoction Improves Myocardial Remodeling via Activating the IL-10/Stat3 Signaling Pathway.

Evid Based Complement Alternat Med 2020 14;2020:7532892. Epub 2020 Dec 14.

Department of Cardiology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China.

Heart failure (HF) has been known as a global health problem, and cardiac remodeling plays an essential role in the development of HF. We hypothesized that YQWY decoction might exert a cardioprotective effect against myocardium inflammation, fibrosis, and apoptosis via activating the interleukin-10 (IL-10)/Stat3 signaling pathway. To test this hypothesis, the HF model in rats was established by pressure overload through the minimally invasive transverse aortic constriction (MTAC). Echocardiography was performed to assess the left ventricular function of rats. Myocardial fibrosis in rats was observed by Masson and Picrosirius red staining, and the degree of myocardial apoptosis was detected via TUNEL staining. In addition, expression levels of IL-10, tumor necrosis factor- (TNF-), Stat3 (P-Stat3), P65 (P-P65), CD68, collagen I, TGF-, CTGF, Bax, Bcl-2, cleaved caspase-3, and PARP in rat serum and myocardium samples were examined by ELISA, western blot, and immunohistochemistry, respectively. YQWY decoction treatment significantly improved left ventricular function in HF rats, especially in those of the high-dose group (LVEF%: 51.29 ± 5.876 vs. 66.02 ± 1.264, < 0.01;, LVFS%: 27.75 ± 3.757 vs. 37.76 ± 1.137, < 0.01). Furthermore, YQWY decoction markedly inhibited MTAC-induced myocardial fibrosis as evidenced by downregulated collagen I, TGF-, and CTGF in myocardium and alleviated apoptosis (downregulated caspase-3 and PARP and increased Bcl-2/Bax ratio in cardiomyocytes). In addition, YQWY decoction decreased the level of the proinflammatory cytokine TNF- in both circulating blood and myocardium and attenuated infiltration of inflammatory cells in heart tissue from HF rats. Most importantly, YQWY decoction suppressed MTAC-induced NF-B activation and phosphorylated Stat3 by upregulating IL-10 in rat heart tissues. Our study showed that YQWY decoction could attenuate MTAC-induced myocardial inflammation, fibrosis, apoptosis, and reverse the impairment of cardiac function in rats by activating the IL-10/Stat3 signaling pathway and improving myocardium remodeling. Our findings suggested a therapeutic potential of YQWY decoction in HF.
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http://dx.doi.org/10.1155/2020/7532892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787750PMC
December 2020

Outcomes of treatment with genioplasty and temporomandibular joint anchorage surgery.

J Craniomaxillofac Surg 2021 Mar 5;49(3):177-183. Epub 2021 Jan 5.

Department of Stomatology,Shenzhen University General Hospital and Shenzhen University Clinical Medical Academy,Shenzhen University, 1098# XueYuan Road, NanShan District, Shenzhen City, 518055, GuangDong Province, China. Electronic address:

Background: Anterior Disc Displacement without Reduction (ADDwoR) in adolescence can result in condylar resorption which produces mandibular retrusion/deviation (MR/D) in adulthood. This study aims to analyze the therapeutic effect of simultaneous genioplasty and temporomandibular joint (TMJ) anchorage surgery on ADDwoR with MR/D patients.

Methods: During 2016-2018, ADDwoR with MR/D cases were included and underwent TMJ anchorage surgery and genioplasty guided by digital design. Pre-/Post-surgical clinical manifestations, facial photography, radiographic data, facial shape satisfaction of clinicians/patients/third-party were recorded and analyzed.

Results: A total of 32 cases (52 joints) were included. The average age was 24.09. Ratio of male/female was 4/28. Visual analog pain scale (VAS) score pre-/post-surgical ranged from 3 to 9 and 0-3, with an average of 6.03 and 1.18 (p < 0.01). Maximal mouth opening pre-/post-surgical ranged from 16 to 33 mm and 33-40 mm, with an average of 22.43 mm and 36.46 mm (p < 0.01). MRI was completed and showed stable disc reduction without recurrence 1 year postoperatively. MR/D was corrected and a better face shape was obtained. The satisfaction rate of clinicians, patients and third-parties was 92.375%, 94.156% and 94.218%, with an average of 93.583%.

Conclusion: For ADDwoR with MR/D patients, simultaneous TMJ anchorage surgery and genioplasty can improve TMJ symptoms/functions, correct facial appearance, and enhance the degree of satisfaction. The postoperative effect is stable, safe and reliable, which is worthy of clinical promotion.
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http://dx.doi.org/10.1016/j.jcms.2021.01.001DOI Listing
March 2021

Identification of an IS431-derived translocatable unit containing the erm(C) gene in Staphylococcus aureus.

J Antimicrob Chemother 2021 Jan 11. Epub 2021 Jan 11.

Institute of Microbiology and Epizootics, Centre for Infection Medicine, Department of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.

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http://dx.doi.org/10.1093/jac/dkaa555DOI Listing
January 2021

Prognostic Value of Local Treatment in Prostate Cancer Patients With Different Metastatic Sites: A Population Based Retrospective Study.

Front Oncol 2020 8;10:527952. Epub 2020 Dec 8.

Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.

Purpose: Our study aims to examine the impact of definitive local therapy in prostate cancer patients with different metastatic sites.

Methods: Totally, 5,849 patients diagnosed with metastatic prostate carcinoma from 2010 to 2014 were selected from Surveillance, Epidemiology, and End Results (SEER). Log-rank analyses, multivariable regression analysis, and Kaplan-Meier methods were used to assess prognostic impact of local treatment in patients with different metastatic sites. Survival curves and forest plots were also plotted to describe the prognostic value of definitive local therapy.

Results: In our study, 159 patients received radical prostatectomy, and 62 received brachytherapy, while 5,628 did not receive local definitive local therapy. Survival analysis revealed that patients who received definitive local therapy had a better 5-year overall survival (OS) (P = 0.011) and cancer-specific survival (CSS) (P = 0.012). Multivariate regression analyses demonstrated that type of treatment was an independent prognostic indicator for OS (P = 0.011) and CSS (P = 0.012), along with age at diagnosis, chemotherapy, PSA level, and Gleason score. According to subgroup analysis, patients with bone metastasis or distant lymph node (LN) metastasis were significantly more likely to benefit from definitive local therapy. In addition, forest plots demonstrated that RP group had significant favorable OS and CSS in subgroups of younger age at diagnosis, T2-3 stage, N0-1 stage, Gleason score =7 or ≥8, bone metastasis, and distant LN metastasis.

Conclusions: Our study suggested that local therapy improved survival in prostate cancer patients with bone or distant LN metastasis. Furthermore, patients who were at T2-3 stage or Gleason score ≥7 also significantly benefit from definitive local therapy.
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http://dx.doi.org/10.3389/fonc.2020.527952DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753115PMC
December 2020

Silent Counterattack: The Impact of Workplace Bullying on Employee Silence.

Front Psychol 2020 23;11:572236. Epub 2020 Nov 23.

School of Economics and Management, Tongji University, Shanghai, China.

The purpose of this paper is to explore the relationship between workplace bullying (WB) and employee silence (ES) as well as its mechanism. This paper collects data from 322 employees of three Chinese enterprises in two waves, with a 2 months interval between the two waves. Moreover, this paper uses confirmatory factor analysis, a bootstrapping mediation test, a simple slope test, and other methods to verify the hypothesis. We find that: (1) WB is positively correlated with ES; (2) psychological safety (PS) and affective commitment mediated the relationship between WB and ES, respectively, and these two variables have a chain mediating effect in the above relationship; and (3) a forgiveness climate moderates this chain mediating effect by weakening the negative impact of WB on PS. Our findings can effectively guide organizations to ultimately adjust their management style, pay attention to employees' cognitive and emotional resources, and formulate some measures to curb WB in organizations.
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http://dx.doi.org/10.3389/fpsyg.2020.572236DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719624PMC
November 2020

Kalopanaxsaponin A induces reactive oxygen species mediated mitochondrial dysfunction and cell membrane destruction in Candida albicans.

PLoS One 2020 30;15(11):e0243066. Epub 2020 Nov 30.

Department of Genetics, Xuzhou Medical University, Xuzhou, China.

Candidiasis causes high morbidity and mortality among immunocompromised patients. Antifungal drug resistance and cytotoxicity highlight the need of effective antifungal therapeutics. In this study, we found that kalopanaxsaponin A (KPA), a triterpenoid saponin natural product, could inhibit the proliferation of various Candida species, and exerted a fungicidal effect against C. albicans. To further explore its antifungal action mode, spectrofluorophotometer, fluorescence microscopy and transmission electron microscopy were performed, showing that KPA treatment induced the accumulation of intracellular reactive oxygen species (ROS), resulting in mitochondrial dysfunction. Meanwhile, KPA treatment also broke down the membrane barrier of C. albicans causing the leakage of intracellular trehalose, the entrance of extracellular impermeable substance and the decrease of ergosterol content. Both ROS accumulation and membrane destruction contributed to the death of C. albicans cells. Our work preliminarily elucidated the potential mechanisms of KPA against C. albicans on a cellular level, and might provide a potential option for the treatment of clinical candidiasis.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243066PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703927PMC
January 2021

Identification of a novel tetracycline resistance gene, tet(63), located on a multiresistance plasmid from Staphylococcus aureus.

J Antimicrob Chemother 2021 Feb;76(3):576-581

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.

Objectives: To identify and characterize a novel tetracycline resistance gene on a multiresistance plasmid from Staphylococcus aureus SA01 of chicken origin.

Methods: MICs were determined by broth microdilution according to CLSI recommendations. The whole genome sequence of S. aureus SA01 was determined via Illumina HiSeq and Oxford Nanopore platforms followed by a hybrid assembly. The new tet gene was cloned and expressed in S. aureus. The functionality of the corresponding protein as an efflux pump was tested by efflux pump inhibition assays.

Results: A novel tetracycline resistance gene, tet(63), was identified on a plasmid in S. aureus SA01. The cloned tet(63) gene was functionally expressed in S. aureus and shown to confer resistance to tetracycline and doxycycline, and a slightly elevated MIC of minocycline. The tet(63) gene encodes a 459 amino acid efflux protein of the major facilitator superfamily that consists of 14 predicted transmembrane helices. The results of efflux pump inhibitor assays confirmed the function of Tet(63) as an efflux protein. The deduced amino acid sequence of the Tet(63) protein exhibited 73.0% identity to the tetracycline efflux protein Tet(K). The plasmid pSA01-tet, on which tet(63) was located, had a size of 25664 bp and also carried the resistance genes aadD, aacA-aphD and erm(C).

Conclusions: A novel tetracycline resistance gene, tet(63), was identified in S. aureus. Its location on a multiresistance plasmid might support the co-selection of tet(63) under the selective pressure imposed by the use of macrolides, lincosamides and aminoglycosides.
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http://dx.doi.org/10.1093/jac/dkaa485DOI Listing
February 2021

Association Between Human Papillomavirus Infection and Outcome of Perioperative Nodal Radiotherapy for Penile Carcinoma.

Eur Urol Oncol 2020 Nov 13. Epub 2020 Nov 13.

San Raffaele Hospital and Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy; Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address:

Background: Data on the impact of human papillomavirus (HPV) infection status and outcomes for perioperative treatments for patients with lymph node-involved penile squamous-cell carcinoma (PSCC) are lacking.

Objective: To analyze the benefit from perioperative radiotherapy (RT) for PSCC according to HPV infection status.

Design, Setting, And Participants: In an international multicenter database of 1254 patients with PSCC who received inguinal lymph node dissection (ILND), 507 had suitable clinical information.

Intervention: ILND, with or without chemotherapy or RT for involved lymph nodes.

Outcome Measurements And Statistical Analysis: Kaplan-Meier and restricted mean survival time (RMST) analyses for overall survival (OS) were performed for all patients and after propensity score-matching (PSM; n = 136), for which patient age, histology, type of penile surgical procedure, pathological tumor and nodal stage, ILND laterality, pelvic LND, and perioperative treatment were taken into account when assessing differences between HPV and HPV- patients. Finally, we looked at genomic alterations in PSCC using data from the Foundation Medicine database (n = 199) to characterize HPV PSCC.

Results And Limitations: Patients with HPV PSCC (n = 86; 17%) had lower clinical N stage (p < 0.001) and inguinal lymph node metastasis density (p < 0.001). Perioperative RT was delivered in 49 patients (9.7%), with the vast majority receiving adjuvant RT (n = 40). HPV patients had similar median OS (p = 0.1) but longer RMST than HPV- patients at different time points. Nevertheless, HPV patients treated with perioperative RT exhibited longer median OS (p = 0.015) and longer RMST compared to HPV- patients. In the PSM cohorts, HPV status remained significantly associated with longer OS after RT. The HPV- PSCC group had a higher frequency of TP53 mutations compared to HPV PSCC (75% vs 15%; p < 0.001). The results are limited by the retrospective nature of the data.

Conclusions: Perioperative RT was more effective in the HPV PSCC subgroup. Reasons for the enhanced radiosensitivity may be related to the lack of TP53 mutations.

Patient Summary: We analyzed data from a large multicenter database for patients with penile cancer who had received inguinal lymph node dissection, with or without chemotherapy or radiotherapy. We found that for tumors positive for human papillomavirus (HPV), use of radiotherapy resulted in prolonged survival compared to HPV-negative tumors. On the basis of these results we are inspired to design studies on the use of radiotherapy in HPV-selected patients.
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http://dx.doi.org/10.1016/j.euo.2020.10.011DOI Listing
November 2020

Identification of a methylation panel aid in risk stratification in node-positive penile squamous cell carcinoma.

Int J Cancer 2021 Mar 5;148(5):1289-1298. Epub 2020 Nov 5.

Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.

Molecular prognostic factors for individualized treatment of squamous cell carcinoma (SCC) are poorly defined. Our study developed and validated a novel molecular tools aid in preinguinal and postinguinal lymphadenectomy risk stratification in node-positive penile SCC. Patients with node-positive penile SCC who underwent inguinal or ilioinguinal lymphadenectomy were divided into three cohorts: a discovery set, a development set and a validation set. The local ethics committee approved the study. The primary endpoint was cancer-specific survival (CSS). At the discovery stage, 17 CpG sites were significantly associated with CSS. In the development set, we constructed a 3-CpG-based prognostic score for survival prediction. The hazard ratio (HR) of the panel (dichotomized using the optimal cutoff) was 5.8 in the multivariate analyses (P < .001). The addition of the methylation score significantly improved the pN-stage C-index from 0.70 to 0.79 (incremental C = 0.09, P < .001). In the validation set, the methylation panel showed a HR of 9.9 in the multivariate analyses. The addition of the molecular marker improved the pN-stage C-index from 0.69 to 0.78 (incremental C = 0.09, P < .001). The methylation score remarkably separated survival curves in different pN stages, which indicate that the tool can be applied to tailor the treatment in both preinguinal and postinguinal lymphadenectomy settings. We developed and validated a prognostic methylation panel for node-positive penile SCC. The tool may aid in the risk stratification of the population with heterogeneous outcomes and needs prospective validation. Patients in high-risk group may benefit from more aggressive therapy or clinical trials.
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http://dx.doi.org/10.1002/ijc.33355DOI Listing
March 2021

Importance of HPV in Chinese Penile Cancer: A Contemporary Multicenter Study.

Front Oncol 2020 4;10:1521. Epub 2020 Sep 4.

Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.

To investigate the HPV DNA prevalence and genotype distribution among penile cancer in China. To identify association between HPV prevalence, different histological subtypes, tumor stage, tumor grade, demographics, comorbidity, and phimosis incidence trend. Standardized HPV DNA detection and p16 expression were used in a multi-center series of 340 penile squamous cell carcinomas diagnosed from 2006 to 2017. HPV DNA detection and genotyping were examined by a validated kit for 23 different HPV subtypes (PCR-RDB HPV test). The cases with positive HPV DNA were additional tested for p16 expression to confirm the HPV infection. Using the PCR-RDB HPV test, overall HPV prevalence was 48.8% (166/340) and that of p16 expression was 45.6%. In this studied population, HPV16 was the most frequent HPV type detected in HPV-positive cancers (76.5%). HPV18 was the second most common type in penile cancers (15.1%). After pathology review, 307 cases were confirmed as invasive penile cancer, and the other 33 were non-invasive caners. The histologic subtypes of warty, basaloid, clear cell papillary, adenosquamaous and pseudohyperplastic were showed high HPV DNA prevalence. Among invasive cancers, no statistically significant differences in prevalence were observed by tumor grade, tumor stage or lymphnode stage at diagnosis. HPV positive penile cancer incidence significantly increase and the phimosis incidence significantly decrease from 2006 to 2017. About a half of penile cancers were related to HPV infection. Our findings highlight the phimosis related penile cancers have been declining, the HPV related in the development of penile cancer and a fully aware of regional differences in HPV genotype distribution are tasks for penile cancer control and prevention.
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http://dx.doi.org/10.3389/fonc.2020.01521DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498546PMC
September 2020

Prevalence of comprehensive DNA damage repair gene germline mutations in Chinese prostate cancer patients.

Int J Cancer 2021 Feb 16;148(3):673-681. Epub 2020 Oct 16.

Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.

Germline DNA damage repair (DDR) deficiency has been associated with increased cancer risk, poor prognosis and therapeutic opportunity for prostate cancer (PCa) patients. However, the landscape of germline mutations in PCa covering comprehensive DDR genes has not been reported. We performed whole-exome sequencing in 246 patients who meet the National Cancer Center Network guidelines for genetic testing and analyzed variants in 276 DDR genes, which was from the Cancer Genome Atlas. A total of 79 deleterious germline alterations in 60 DDR genes were identified in 31% (76/246) patients. Mutations were found in nine DDR pathways, including 11.8% men in homologous recombination repair (HR) pathways, 2.4% men in mismatch repair (MMR) pathway and 16.7% (41/246) patients in non-HR/MMR pathways. In HRR and MMR pathways, mutations were mostly identified in BRCA2 (5.3%), HFM1 (0.8%), ZSWIM7 (0.8%), MSH2 (0.8%) and MSH3 (0.8%). When compared with the cancer-free cohort, POLN and POLG conferred high risk to PCa with odds ratio 6.9 and 20.5, respectively. We provided a comprehensive view of germline DDR gene mutations in PCa patients. We also identified two potential PCa predisposition genes: POLN and POLG, which have not been reported in the Western population, confirming the necessity of customizing a multigene panel for Chinese PCa patients.
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http://dx.doi.org/10.1002/ijc.33324DOI Listing
February 2021

A novel gene signature to predict immune infiltration and outcome in patients with prostate cancer.

Oncoimmunology 2020 06 1;9(1):1762473. Epub 2020 Jun 1.

Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.

Prostate cancer (PCa) is one of the most common malignancies in male. We aim to establish a novel gene signature for immune infiltration and outcome (biochemical recurrence (BCR) and overall survival (OS)) of patients with prostate cancer (PCa) to augment Gleason patterns for evaluating prognosis and managing patients undergoing radical prostatectomy (RP). Combined with our microarray data and the Cancer Genome Atlas Project (TCGA) database (discovery set), we identified a six-gene signature. The Gene Expression Omnibus (GEO) database served as the test set. The databases of Fudan University Shanghai Cancer Center (FUSCC) and Third Affiliated Hospital of Nantong University (TAHNU) served as an external validation set. Immunohistochemistry was used to investigate the relationship between risk groups and the immune infiltrate. We identified a six-gene signature to predict immune cell infiltration and outcome of PCa patients. The AUC values used to predict early BCR in the discovery, test, FUSCC, and TAHNU sets were 0.73, 0.76, 0.72, and 0.81, respectively. Low-risk score patients in each dataset experienced significantly longer OS ( = .01, 0.04, 0.02, respectively). The signature also predicted high regulatory T cells (Tregs) and M2-polarized macrophages infiltration in high-risk score patients with PCa. Additionally, high mutation load, related signal pathways, and sensitivity to anticancer drugs that correlated with high-risk score of cancer progression and death were also identified. The six-gene signature may improve prognostic information, serve as a prognostic tool to manage patients after RP, and advance basic studies of PCa.
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http://dx.doi.org/10.1080/2162402X.2020.1762473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7458664PMC
June 2020

Characterization of a Novel Hybrid Plasmid Coharboring and in a Clinical Citrobacter freundii Strain.

Antimicrob Agents Chemother 2020 10 20;64(11). Epub 2020 Oct 20.

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, China

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http://dx.doi.org/10.1128/AAC.01379-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577163PMC
October 2020

A nanostructured anti-biofilm surface widens the efficacy against spindle-shaped and chain-forming rod-like bacteria.

Nanoscale 2020 Sep 8;12(36):18864-18874. Epub 2020 Sep 8.

Division of Restorative Dental Sciences, Faculty of Dentistry, PPDH 34 Hospital Road, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

Current control of pathogenic bacteria at all biomaterial interfaces is poorly attuned to a broad range of disease-causing pathogens. Leading antimicrobial surface functionalization strategies with antimicrobial peptides (AMPs), defensins, have not shown their promised efficacy. One of the main problems is the lack of stability and swift clearance from the surface. Surface nanotopography bearing sharp protrusions is a non-chemical solution that is intrinsically stable and long-lasting. Previously, the geometrically ordered arrays of nanotipped spines repelled or rapidly ruptured bacteria that come into contact. The killing properties so far work on cocci and rod-like bacteria, but there is no validation of the efficacy of protrusional surfaces on pathogenic bacteria with different sizes and morphologies, thus broadening the utility of such surfaces to cover increasingly more disease entities. Here, we report a synthetic analogue of nanotipped spines with a pyramidal shape that show great effectiveness on species of bacteria with strongly contrasting shapes and sizes. To highlight this phenomenon in the field of dental applications where selective bacterial control is vital to the clinical success of biomaterial functions, we modified the poly(methyl)-methacrylate (PMMA) texture and tested it against Streptococcus mutans, Enterococcus faecalis, Porphyromonas gingivalis, and Fusobacterium nucleatum. These nanopyramids performed effectively at levels well above those of normal and roughened PMMA biomaterials for dentistry and a model material for general use in medicine and disease transmission in hospital environments.
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http://dx.doi.org/10.1039/d0nr03809aDOI Listing
September 2020

Liquid-phase exfoliation of black sesame to create a nanoplatform for photoluminescence and photothermal therapy.

Nanomedicine (Lond) 2020 09 1;15(21):2041-2052. Epub 2020 Sep 1.

Department of Anatomy, Hebei Medical University, Shijiazhuang, PR China.

The present study aims to apply the facile liquid-phase exfoliation (LPE) strategy to fabricate 2D organic materials and thus to broaden the family of biocompatible and multifunctional 2D materials. 2D material-organic melanin and cellulose nanosheets were synthesized from black sesame hull using LPE. Photoluminescence and photothermal properties of the nanosheets were assessed, as well as stability and cell killing ability. The prepared 2D nanoplatform exhibited broad and multiple photoluminescent emission bands. It also demonstrated efficient photothermal cancer therapy with excellent biocompatibility. The present study could open an avenue in exfoliating organic materials using the LPE strategy. This could make the fabrication of multifunctional 2D organic materials more efficient and broaden the family of biocompatible 2D nanomaterials.
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http://dx.doi.org/10.2217/nnm-2020-0151DOI Listing
September 2020

Disrupted rich-club network organization and individualized identification of patients with major depressive disorder.

Prog Neuropsychopharmacol Biol Psychiatry 2020 Aug 18:110074. Epub 2020 Aug 18.

Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, China; Neuropsychiatric Institute, Affiliated ZhongDa Hospital, Southeast University, Nanjing, Jiangsu 210009, China. Electronic address:

Background: Altered structural and functional brain networks have been extensively studied in major depressive disorder (MDD) patients. However, whether the differential connectivity patterns in the rich-club organization, assessed from structural brain network analyses, and the associated connections of these regions are particularly susceptible to depression remain unclear.

Methods: We acquired resting-state functional magnetic resonance imaging (R-fMRI) and diffusion tensor imaging (DTI) from 31 unmedicated MDD patients and 32 cognitively normal (CN) subjects and completed a series of neuropsychological tests. Rich-club organization, network properties, and coupling between structural and functional connectivity (SC-FC) were explored. Furthermore, whether these indices could potentially deliver effective clinical predictive value for MDD patients were examined.

Results: The MDD patients showed disrupted structural rich-club organization and modularity, as well as a distinct correlation pattern between global efficiency and rich-club organization. Importantly, reduced SC-FC coupling, reflecting a decreased agreement in the integrity of the networks, was significantly associated with the strength of structural rich-club connections in the MDD patients. Furthermore, the disrupted structural rich-club organization, which was primarily located in the default mode network (DMN) and executive control network (ECN), emerged as a valuable indicator to distinguish between MDD and CN.

Conclusions: Findings of this study identified that the disrupted rich-club structural organization significantly influenced brain structural network modularity and integrity and could serve as a promising biological marker for the identification of MDD patients.
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http://dx.doi.org/10.1016/j.pnpbp.2020.110074DOI Listing
August 2020

Single-cell transcriptomics identifies a distinct luminal progenitor cell type in distal prostate invagination tips.

Nat Genet 2020 09 17;52(9):908-918. Epub 2020 Aug 17.

State Key Laboratory of Cell Biology, Shanghai Key Laboratory of Molecular Andrology, Shanghai Institute of Biochemistry and Cell Biology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Shanghai, China.

The identification of prostate stem/progenitor cells and characterization of the prostate epithelial cell lineage hierarchy are critical for understanding prostate cancer initiation. Here, we characterized 35,129 cells from mouse prostates, and identified a unique luminal cell type (termed type C luminal cell (Luminal-C)) marked by Tacstd2, Ck4 and Psca expression. Luminal-C cells located at the distal prostate invagination tips (termed Dist-Luminal-C) exhibited greater capacity for organoid formation in vitro and prostate epithelial duct regeneration in vivo. Lineage tracing of Luminal-C cells indicated that Dist-Luminal-C cells reconstituted distal prostate luminal lineages through self-renewal and differentiation. Deletion of Pten in Dist-Luminal-C cells resulted in prostatic intraepithelial neoplasia. We further characterized 11,374 human prostate cells and confirmed the existence of h-Luminal-C cells. Our study provides insights into the prostate lineage hierarchy, identifies Dist-Luminal-C cells as the luminal progenitor cell population in invagination tips and suggests one of the potential cellular origins of prostate cancer.
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http://dx.doi.org/10.1038/s41588-020-0642-1DOI Listing
September 2020

Endocytosis-pathway polygenic scores affects the hippocampal network connectivity and individualized identification across the high-risk of Alzheimer's disease.

Brain Imaging Behav 2020 Aug 16. Epub 2020 Aug 16.

Department of Neurology, School of Medicine, Affiliated ZhongDa Hospital, Southeast University, Nanjing, 210000, Jiangsu, China.

The neural mechanisms underlying the polygenic effects of the endocytosis pathway on the brain function of Alzheimer's Disease (AD) remain unclear, especially in the prodromal stages of AD from early mild cognitive impairment (EMCI) to late mild cognitive impairment (LMCI). We used an imaging genetic approach to investigate the polygenic effects of the endocytosis pathway on the hippocampal network across the prodromal stages of AD. The subjects' data were selected from the Alzheimer's Disease Neuroimaging Initiative. Hippocampal volumes were examined in subjects of cognitive normal (CN), EMCI and LMCI groups. Multivariate linear regression analysis was employed to measure the effects of disease and endocytosis-based multilocus genetic risk scores (MGRS) on the hippocampal network which was constructed using the bilateral hippocampal regions. We identified hippocampal volumes in LMCI group were smaller than those in CN and EMCI groups. Endocytosis-based MGRS was widely influenced the neural structures within the hippocampal network, especially in the prefrontal-occipital regions and striatum. Compared to low endocytosis-based MGRS carriers, high MGRS carriers showed the opposite trajectory of hippocampal network functional connectivity (FC) across the prodromal stages of AD. Further, a model composed of selected hippocampal FCs and hippocampal volume yielded strong classification powers of EMCI and LMCI. These findings expand our understanding of the pathophysiology of polygenic effects underlying brain network in the prodromal stages of AD.
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http://dx.doi.org/10.1007/s11682-020-00316-4DOI Listing
August 2020

E3 ubiquitin ligase HRD1 modulates the circadian clock through regulation of BMAL1 stability.

Exp Ther Med 2020 Sep 10;20(3):2639-2648. Epub 2020 Jul 10.

Laboratory of Clinical Pharmacy, Department of Pharmacy, The Affiliated Suzhou Science and Technology Town Hospital of Nanjing Medical University, Suzhou, Jiangsu 215153, P.R. China.

Circadian rhythm serves an essential role in numerous physiological functions. Circadian oscillations are organized by circadian clock components at the molecular level. The precision of the circadian clock is controlled by transcriptional-translational negative feedback loops, as well as post-translational modifications of clock proteins, including ubiquitination; however, the influence of E3 ligases on clock protein ubiquitination requires further investigation. The results of co-immunoprecipitation and immunofluorescent localization, indicated that the endoplasmic reticulum transmembrane E3 ubiquitin ligase HRD1, encoded by the synoviolin 1 gene, interacted with brain and muscle ARNT-like 1 (BMAL1) and enhanced BMAL1 protein ubiquitination. In addition, the results of western blotting and reverse transcription-quantitative PCR suggested that HRD1 promoted K48-associated polyubiquitination of BMAL1 and thus mediated its degradation via the ubiquitin-proteasome system. Furthermore, gene knockdown and gene overexpression assays revealed that HRD1-dependent degradation of BMAL1 protein regulated the expression of BMAL1 target genes and the amplitude of circadian oscillations in mammalian cells. The findings of the current study indicate that HRD1 may influence the regulation of circadian rhythm via modulation of BMAL1 stability.
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http://dx.doi.org/10.3892/etm.2020.8988DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401958PMC
September 2020

A novel bile acid analog, A17, ameliorated non-alcoholic steatohepatitis in high-fat diet-fed hamsters.

Toxicol Appl Pharmacol 2020 10 30;404:115169. Epub 2020 Jul 30.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address:

Being endocrine signaling molecules that regulate lipid metabolism and affect energy balance, bile acids are potential drug candidates for non-alcoholic steatohepatitis (NASH). Obeticholic acid (OCA) could improve NASH accompanied by significant side effects. Therefore, it is worthwhile to develop safer and more effective bile acid analogs. In this study, a new bile acid analog A17 was synthesized and its potential anti-NASH effects were assessed in vitro and in vivo. The impact of A17 on steatosis was investigated in the rat primary hepatocytes challenged with oleic acid. It was found that A17 alleviated lipid accumulation by reducing fatty acid (FA) uptake and promoting FA oxidation. The reduction of FA uptake came from inhibiting fatty acid translocase (Cd36) expression. The promotion of FA oxidation came from stimulating the phosphorylation of adenosine monophosphate (AMP)-activated protein kinase alpha (AMPKα). In addition, A17 reduced lipopolysaccharide-induced inflammation in Raw264.7 cells by activating Takeda G protein-coupled receptor 5 (TGR5). In in vivo study, male Golden Syrian hamsters were fed with high fat (HF) diet and then treated with 50 mg/kg/d A17 for 6 weeks. A17 lowered the lipid profiles and liver enzyme levels in serum and improved liver pathological conditions with less side effects compared with OCA. Further studies confirmed that the molecular mechanisms of A17 in vivo were similar to those in vitro. In conclusion, a novel bile acid analog A17 was identified to ameliorate NASH in HF-fed hamsters. The potential mechanisms could be contributed to reducing FA uptake, stimulating FA oxidation and relieving inflammation.
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http://dx.doi.org/10.1016/j.taap.2020.115169DOI Listing
October 2020

Identification of a novel optrA-harbouring transposon, Tn6823, in Staphylococcus aureus.

J Antimicrob Chemother 2020 Nov;75(11):3395-3397

State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150069, China.

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http://dx.doi.org/10.1093/jac/dkaa323DOI Listing
November 2020

Cortical atrophy mediates the accumulating effects of vascular risk factors on cognitive decline in the Alzheimer's disease spectrum.

Aging (Albany NY) 2020 07 29;12(14):15058-15076. Epub 2020 Jul 29.

Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing 210009, Jiangsu, China.

There are increasing concerns regarding the association of vascular risk factors (VRFs) and cognitive decline in the Alzheimer's disease (AD) spectrum. Currently, we investigated whether the accumulating effects of VRFs influenced gray matter volumes and subsequently led to cognitive decline in the AD spectrum. Mediation analysis was used to explore the association among VRFs, cortical atrophy, and cognition in the AD spectrum. 123 AD spectrum were recruited and VRF scores were constructed. Multivariate linear regression analysis revealed that higher VRF scores were correlated with lower Mini-Mental State Examination scores and higher Alzheimer's Disease Assessment Scale-Cognitive Subscale scores, indicating higher VRF scores lead to severer cognitive decline in the AD spectrum. In addition, subjects with higher VRF scores suffered severe cortical atrophy, especially in medial prefrontal cortex and medial temporal lobe. More importantly, common circuits of VRFs- and cognitive decline associated with gray matter atrophy were identified. Further, using mediation analysis, we demonstrated that cortical atrophy regions significantly mediated the relationship between VRF scores and cognitive decline in the AD spectrum. These findings highlight the importance of accumulating risk in the vascular contribution to AD spectrum, and targeting VRFs may provide new strategies for the therapeutic and prevention of AD.
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http://dx.doi.org/10.18632/aging.103573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7425455PMC
July 2020

Locoregional surgical treatment improves the prognosis in patients with primary metastatic testicular cancer with a single bone or brain metastasis.

Mol Clin Oncol 2020 Aug 3;13(2):146-154. Epub 2020 Jun 3.

Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China.

The present study investigated the clinical significance afforded by locoregional surgery in improving the prognosis of primary metastatic testicular cancer (pMTC). The population-based Surveillance, Epidemiology and End Results database was used as the primary source of data in the present study. Stratification analysis was employed to identify the effects of testicular surgery on testicular cancer-specific survival and overall survival. Propensity score matching and Cox regression models were then employed to find and evaluate the extent of improvements to the survival of patients with pMTC by testicular surgery. The median testicular cancer-specific survival and overall survival in the surgery group were 10% higher than those in the group without surgery. Testicular surgery was demonstrated to have provided a survival advantage for patients with a single metastasis in the bone or brain, but not in the liver or lung. When combined with radiotherapy and chemotherapy, surgery significantly improved the survival of patients. However, according to the surgical outcome based on molecular subtypes, when deciding on the surgery for patients with metastatic testicular cancer, only human chorionic gonadotropin and lactate dehydrogenase, and not α-fetoprotein should be considered. Surgery serves a significant role in the management of non-seminoma, whereas its role in the management of seminoma is far more limited. The effects of locoregional surgery have been neglected when treating patients with pMTC. Surgical procedures should be considered more seriously when planning combination treatments for patients with pMTC with a single bone or brain metastasis.
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http://dx.doi.org/10.3892/mco.2020.2057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366240PMC
August 2020

A risk calculator predicting recurrence in lymph node metastatic penile cancer.

BJU Int 2020 11 7;126(5):577-585. Epub 2020 Aug 7.

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.

Objectives: To develop and externally validate a risk calculator for prediction of any cancer recurrence in patients with penile squamous cell carcinoma (pSCC) and inguinal lymph node metastases (ILNM), as to date no validated prognostic tool is available for patients with pSCC and ILNM.

Patients And Methods: The development cohort included 234 patients from seven referral centres. The external validation cohort included 273 patients from two additional referral centres. Cox regression identified predictors of any recurrence, which were used to develop a risk calculator. The risk-calculator grouped the development and the validation cohorts according to the individual risk of any recurrence at 24 months (24m-R). Adjuvant treatment effects were tested on overall survival (OS) according to the derived tertiles, within the development and validation cohorts.

Results: Positive surgical margins, pN , and ILNM ratio were associated with higher recurrence rate. The 2-year OS rates were lower for patients with high (>37%) and intermediate (19-37%) compared to low (<19%) 24m-R risk of recurrence, for both the development (43% and 58% vs 83%, P < 0.001) and validation cohort (44% and 50% vs 85%, P < 0.001). Results were confirmed in the subgroup of patients who did not receive adjuvant treatment (P < 0.001), but not in patients who did receive adjuvant treatments in both the development and validation cohorts (P > 0.1).

Conclusion: Adjuvant treatment planning is crucial in patients with pSCC with ILNM, where only weak evidence is available. The current tool proved to successfully stratify patients according to their individual risk, potentially allowing better tailoring of adjuvant treatments.
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http://dx.doi.org/10.1111/bju.15177DOI Listing
November 2020

Targeting CPT1B as a potential therapeutic strategy in castration-resistant and enzalutamide-resistant prostate cancer.

Prostate 2020 09 10;80(12):950-961. Epub 2020 Jul 10.

Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, China.

Background: Prostate cancer is characterized by aberrant lipid metabolism, including elevated fatty acid oxidation. Carnitine palmitoyltransferase 1B (CPT1B) catalyzes the rate-limiting step of fatty acid oxidation. This study aimed to determine if CPT1B has a critical role in prostate cancer progression and to identify its regulatory mechanism.

Methods: CPT1B expression data from The Cancer Genome Atlas and Gene Expression Omnibus databases was compared with patient survival data. A tissue microarray was constructed with 60 samples of prostate cancer and immunohistochemically stained for CPT1B. Castration-resistant prostate cancer (CRPC) cell lines 22RV1 and C4-2 in which CPT1B expression had been stably knocked down were established; and cell proliferation, cell cycle distribution, and invasion were investigated by Cell Counting Kit-8 (CCK-8) and colony formation assays, flow cytometry, and Transwell assays, respectively. To examine the impact of androgen receptor (AR) inhibition on CPT1B expression, JASPAR CORE was searched to identify AR-binding sites in CPT1B. Dual luciferase and ChIP assays were performed to confirm CPT1B activity and AR binding, respectively. Differentially expressed genes (DEGs) in prostate cancer underwent gene set enrichment analysis (GSEA). Enzalutamide-resistant C4-2 cells were generated and the mechanism of enzalutamide resistance and downstream signaling pathway changes of CPT1B to C4-2 was explored through CCK-8 test.

Results: CPT1B expression was upregulated in human prostate cancer compared with normal prostate tissue and was associated with poor disease-free survival and overall survival. Silencing of CPT1B resulted in downregulated cell proliferation, reduced S-phase distribution, and lower invasive ability, whereas the opposite was observed in CRPC cells overexpressing CPTB1. DEGS in prostate cancer were correlated with G-protein-coupled receptor signaling, molecular transducer activity, and calcium ion binding. AR may regulate CPT1B expression and activity via specific binding sites, as confirmed by dual luciferase and ChIP assays. The CCK-8 experiment demonstrated that CPT1B overexpression in C4-2 cells did not significantly increase the ability of enzalutamide resistance. However, overexpression of CPT1B in C4-2R cells significantly increased the enzalutamide resistance. Upregulation of CPT1B expression increased AKT expression and phosphorylation.

Conclusions: CPT1B is upregulated in prostate cancer and is correlated with poor prognosis, indicating its potential as a biomarker. AR inhibits the transcription of CPT1B. In the CRPC cell line, overexpression of CPT1B alone cannot promote enzalutamide resistance, but in the drug-resistant line C4-2R, overexpression of CPT1B can promote the resistance of C4-2R to enzalutamide.
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http://dx.doi.org/10.1002/pros.24027DOI Listing
September 2020