Publications by authors named "Haowen Jiang"

112 Publications

High-throughput sequencing identified circular RNA circUBE2K mediating RhoA associated bladder cancer phenotype via regulation of miR-516b-5p/ARHGAP5 axis.

Cell Death Dis 2021 Jul 20;12(8):719. Epub 2021 Jul 20.

Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.

Bladder cancer (BC) is known as a common and lethal urinary malignancy worldwide. Circular RNAs (circRNAs), an emerging non-coding RNA, participate in carcinogenesis process of several cancers including BC. In this study, high-throughput sequencing and RT-qPCR were applied to discover and validate abnormal high expression of circUBE2K in BC tissues. Fluorescence in situ hybridization (FISH) was used to detect hsa_circ_0009154 (circUBE2K) expression and subcellular localization in BC tissues. High circUBE2K predicted unfavorable prognoses in BCs, as well as correlated with clinical features. CCK8, transwell, EdU and wound healing assays demonstrated down-regulating circUBE2K decreased BC cell phenotype as proliferation, invasion, and migration, respectively. Further studies showed that circUBE2K promoted BC progression via sponging miR-516b-5p and enhancing ARHGAP5 expression through regulating RhoA activity. Dual-luciferase reporter, FISH and RNA pulldown assays were employed to verify the relationships among circUBE2K/miR-516b-5p/ARHGAP5/RhoA axis. Down-regulating miR-516b-5p or overexpressing ARHGAP5 restored RhoA activity mediated BC cell properties after silencing circUBE2K. Subcutaneous xenograft and metastasis model identified circUBE2K significantly increased BC cell metastasis and proliferation in-vivo. Taken together, we found that circUBE2K is a tumor-promoting circRNA in BC that functions as a ceRNA to regulate ARHGAP5 expression via sponging miR-516b-5p.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-021-03977-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292476PMC
July 2021

Gut Microbiota Dysbiosis Accelerates Prostate Cancer Progression Through Increased LPCAT1 Expression and Enhanced DNA Repair Pathways.

Front Oncol 2021 17;11:679712. Epub 2021 Jun 17.

Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.

Gut microbiota dysbiosis is related to cancer development and progression. Our previous study showed that was more abundant in CRPC (Castration-resistant prostate cancer) than HSPC (Hormone-sensitive prostate cancer) individuals. Here, we determined the potential mechanism of microbiota dysbiosis in prostate cancer (PCa) progression. Metagenomics was used to verify the gut microbial discrepancies between CRPC and HSPC individuals. Fecal microbiota transplantation (FMT) was performed by transferring the fecal suspension of CRPC or HSPC individuals to TRAMP mice. Afterwards, the mice's prostate histopathology and gut microbiota composition were determined. Since was demonstrated to correlate with phospholipid metabolism, we used lipidomics to examine the mice's fecal lipid profiles. The expression of LPCAT1 the key enzyme for phospholipid remodeling in mice prostate was also examined. Meanwhile, both microbial functions prediction and LPCAT1 GSEA analysis (Gene Set Enrichment Analysis) indicated DNA repair pathways, we further determined the expressions of RAD51 and DNA-PKcs in mice prostate. The results showed that gut was significantly more abundant in CRPC individuals. FMT using CRPC feces accelerated mice's PCa progression and increased their gut abundance. Majority of fecal lipids including lysophosphatidylcholine and phosphatidylcholine were upregulated in CRPC FMT treated mice, accompanied with enhanced expressions of LPCAT1, RAD51, and DNA-PKcs in mice prostate. We reported an abundant colonization of in the gut of CRPC individuals and mice receiving their fecal suspensions, and revealed the promotive capability of in PCa progression upregulating LPCAT1 and DNA repair protein expressions. The bacterium and its downstream pathways may become the targets of therapies for PCa in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.679712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8249243PMC
June 2021

[Application of non-stationary phase separation hyphenated with inductively coupled plasma mass spectrometry in the analysis of trace metal-containing nanoparticles in the environment].

Se Pu 2021 Aug;39(8):855-869

Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.

Engineered metal-containing nanoparticles (MCNs), which have unique physical and chemical properties, are widely used in various fields such as medicine, pharmaceuticals, and microelectronics as well as in daily supplies. These MCNs are inevitably released into the environment during production and use, thus posing a threat to bacterial communities, animals, plants, and human health. There are also abundant natural MCNs in the environment, which play an important role in the environmental cycle of metals. The shape, size, and surface properties of MCNs have a significant impact on their migration, chemical and physical transformation, and biological intake in the environment. Therefore, the analysis and detection of MCNs in the environment should be aimed not only at quantifying their concentration and chemical composition, but also at determining their shape, particle size, and surface charge. In addition, for the detection of MCNs in the environment, challenges due to their low concentrations and the interference from complex environmental matrices must be overcome. A single detection technique is often insufficient for the analysis and detection of MCNs in a complex environment matrix. Therefore, the development of an effective and reliable online hyphenated technique is urgently needed for the separation and detection of MCNs in the environment. Such online hyphenated techniques should be able to eliminate the interference by complex matrices, improve the particle size detection range, and reduce the element detection limit. The online hyphenation of stationary phase-based separation techniques such as liquid chromatography and gel electrophoresis with inductively coupled plasma-mass spectrometry (ICP-MS) can effectively separate MCNs according to their particle size, with low element detection limits. However, these stationary phase-based separation techniques have a shortcoming of the adsorption of nanoparticles on the stationary phase, which leads to blockage of separation channels and low recoveries of nanoparticles. The online hyphenation of a non-stationary phase separation technique with ICP-MS also shows strong nanoparticle separation ability and low element detection limits, so that the problem of colloid blockage in stationary phase-based separation can be resolved. This method is very promising for the rapid and accurate characterization of the particle size distribution and chemical composition of MCNs. However, it cannot provide information about the nanoparticle number concentration of MCNs and the elemental content of a single MCN. In complex environmental samples, pure MCNs cannot be effectively distinguished from MCNs with environmental corona having different thicknesses or pure MCNs adsorbed on/hetero-agglomerated with inorganic/organic colloids. Online coupling single-particle ICP-MS (SP-ICP-MS), an emerging particle detection technique with non-stationary phase separation, can effectively help overcome the above shortcomings. This method can provide information on the hydrodynamic diameter, metal mass-derived diameter, total number concentration, size-dependent number, and size-dependent mass concentration of MCNs. Therefore, it enables comprehensive characterization of MCNs based on a variety of three-dimensional contour plot chromatograms. This review summarizes the separation mechanisms and applicable detectors for three commonly used non-stationary phase separation techniques: hydrodynamic chromatography (HDC), capillary electrophoresis (CE), and field-flow fractionation (FFF). In addition, it focuses on the characteristics and applications of online-coupling non-stationary phase separation with ICP-MS and SP-ICP-MS. Regarding FFF, this review focuses on the separation techniques that are suitable for online coupling with ICP-MS, such as sedimentation FFF and flow FFF (symmetrical flow FFF, asymmetrical flow FFF, and hollow fiber flow FFF). In addition, the characteristics of the online hyphenation of three non-stationary phase separations, HDC, CE, and flow FFF, with ICP-MS are compared, including the separation mechanism, sample volume, analytical time, detection sensitivity, size range, size resolution, recovery, reproducibility, and capability for ion analysis. Finally, this review proposes the prospects for future development of the online hyphenation of non-stationary phase separation techniques with ICP-MS and SP-ICP-MS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3724/SP.J.1123.2020.12016DOI Listing
August 2021

Ureteroscopic Cryoablation for Patients with Upper Tract Urothelial Carcinoma of a Solitary Kidney: A Porcine Model and Our Pilot Clinical Experience.

Ann Surg Oncol 2021 Jun 15. Epub 2021 Jun 15.

Department of Urology, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.

Purpose: To investigate the safety and efficacy of ureteroscopic cryoablation by a liquid-nitrogen system in a porcine model and for patients with upper tract urothelial carcinoma (UTUC) of a solitary kidney.

Methods: In the animal experiment, the right-sided ureter was frozen in nine pigs. Eight were randomly assigned to two different groups according to the freezing duration of 60 or 90 s. The other one was designed to receive a 10-min freeze. The treated ureters were harvested at 30 min, 2 days, 4 weeks, and 3 months after cryoablation for histological evaluation. After the animal study, we conducted a pilot clinical trial that enrolled six patients who were diagnosed with UTUC of a solitary kidney and received therapeutic management with ureteroscopic cryoablation at our center. Perioperative adverse events and oncological outcomes were evaluated.

Results: In the porcine model, the liquid-nitrogen system was capable of forming a therapeutic ice ball which infiltrated the full-thickness ureter and induced apoptosis and necrosis from mucosa to lamina muscularis through histological examination. In the clinical trial, cryoablation was successfully performed under ureteroscopy in all the patients, without intraoperative ureteral perforation, avulsion, or active hemorrhage. No recurrence in situ was observed during a median follow-up period of 12.5 months. Hydronephrosis and ureteral stricture was observed in one patient and was managed with ureteroscopic balloon dilation.

Conclusions: Ureteroscopic cryoablation induced by liquid nitrogen is a promising technique for conservative management of UTUC with benefits of improving local tumor control and preservation of a solitary kidney.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1245/s10434-021-10233-5DOI Listing
June 2021

Virtual reality in medical students' education: a scoping review protocol.

BMJ Open 2021 05 26;11(5):e046986. Epub 2021 May 26.

Family Medicine and Primary Care, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore

Background: Virtual reality (VR) is a technology that produces a virtual manifestation of the real world. In recent years, VR has been increasingly used as a tool in medical education. The use of VR in medical education has large potential, as it allows for distance learning and training which may be challenging to deliver in real life. VR encompasses different tools and applications. There is a need to explore how VR has been employed in medical education to date.

Objective: The objective of this scoping review is to conceptualise the VR tools available and the applications of VR in undergraduate medical education as reported in the literature. This scoping review will identify any gaps in this field and provide suggestions for future research.

Methods And Analysis: The relevant studies will be examined using the Joanna Briggs Institute methodological framework for scoping studies. A comprehensive search from a total of six electronic databases and grey literature sources will be performed. The reference list of included studies will be screened for additional studies. The screening and data extraction will be done in parallel and independently by two review authors. Any discrepancies will be resolved through consensus or discussion with a third review author. A data extraction form has been developed using key themes from the research questions. The extracted data will be qualitatively analysed and presented in a diagrammatic or tabular form, alongside a narrative summary, in line with Preferred Reporting Items for Systematic Reviews and Meta-Analysis: extension for Scoping Reviews reporting guidelines.

Ethics And Dissemination: All data will be collected from published and grey literature. Ethics approval is therefore not a requirement. We will present our findings at relevant conferences and submit them for publications in peer-reviewed journals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2020-046986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160201PMC
May 2021

Cytotoxic tigliane diterpenoids from .

Nat Prod Res 2021 May 7:1-5. Epub 2021 May 7.

School of Pharmacy, Nantong University, Nantong, People's Republic of China.

Two new tigliane diterpenes, named eupneonoids A () and B (), together with four known analogues () were isolated from the whole plant of Bruyns. Their structures were deduced based on the detailed spectroscopic analysis. All the isolates displayed cytotoxic effects against A549 human tumor cell lines with IC values ranging from 1.318 to 7.042 μM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14786419.2021.1924712DOI Listing
May 2021

Rapid continuous photoflow synthesis of naturally occurring arylnaphthalene lignans and their analogs.

Nat Prod Res 2021 Apr 30:1-5. Epub 2021 Apr 30.

School of Pharmacy, Nantong University, Nantong, People's Republic of China.

Naturally occurring arylnaphthalene lignans (ANLs) are subclass of lignans in many dietary or medicinal plants. The progressing interest of ANLs is due to their diversified biological activities. Herein, we developed a convenient method for the preparation of naturally occurring ANLs and their analogs through the continuous photoflow intramolecular Diels-Alder reaction in several minutes under mild conditions with good yields and regioselectivities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14786419.2021.1920019DOI Listing
April 2021

Circular RNA RBPMS inhibits bladder cancer progression via miR-330-3p/RAI2 regulation.

Mol Ther Nucleic Acids 2021 Mar 16;23:872-886. Epub 2021 Jan 16.

Department of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.

Bladder cancer is a severe cancer with high mortality because of invasion and metastasis. Growing evidence has revealed that circular RNAs play critical roles in biological function, which is closely connected to proliferation and invasion of bladder cancer. In our study, we employed qRT-PCR, RNA fluorescence hybridization (FISH), 5-ethynyl-2'-deoxyuridine (EdU), CCK-8, Transwell assays, luciferase reporter assays, xenografts, and live imaging to detect the roles of circular RNA binding protein with multiple splicing (circRBPMS) in bladder cancer (BC). Bioinformatics analysis and WB were performed to investigate the regulatory mechanism. Expression profile analysis of circular RNAs (circRNAs) in BC revealed that circRBPMS was significantly downregulated. Low circRBPMS expression correlates with aggressive BC phenotypes, whereas upregulation of circRBPMS suppresses BC cell proliferation and metastasis by directly targeting the miR-330-3p/ retinoic acid induced 2 (RAI2) axis. miR-330-3p upregulation or silencing of RAI2 restored BC cell proliferation, invasion, and migration following overexpression of circRBPMS. RAI2 silencing reversed miR-330-3p-induced cell invasion and migration as well as growth inhibition . Moreover, through bioinformatic analysis of the downstream target of RAI2 in the TCGA database, we identified and validated the biological role of circRBPMS through the RAI2-mediated ERK and epithelial-mesenchymal transition (EMT) pathways. We summarize the circRBPMS/miR-330-3p/RAI2 axis, where circRBPMS acts as a tumor suppressor, and provide a potential biomarker and therapeutic target for BC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.omtn.2021.01.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868720PMC
March 2021

Transcriptomic Analysis of Glycolysis-Related Genes Reveals an Independent Signature of Bladder Carcinoma.

Front Genet 2020 23;11:566918. Epub 2020 Dec 23.

Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.

Background: Bladder carcinoma (BC) is one of the most prevalent and malignant tumors. Multiple gene signatures based on BC metabolism, especially regarding glycolysis, remain unclear. Thus, we developed a glycolysis-related gene signature to be used for BC prognosis prediction.

Methods: Transcriptomic and clinical data were divided into a training set and a validation set after they were downloaded and analyzed from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Gene-set enrichment analysis (GSEA) and differential analysis were used to screen differentially expressed genes (DEGs), while univariate Cox regression and lasso-penalized Cox regression were employed for signature establishment. To evaluate the prognostic power of the signature, receiver operating characteristic (ROC) curve and Kaplan-Meier (KM) survival analysis were also used. Additionally, we developed a nomogram to predict patients' survival chances using the identified prognostic gene signature. Further, gene mutation and protein expression, as well as the independence of signature genes, were also analyzed. Finally, we also performed qPCR and western blot to detect the expression and potential pathways of signature genes in BC samples.

Results: Ten genes were selected for signature construction among 71 DEGs, including nine risk genes and one protection gene. KM survival analysis revealed that the high-risk group had poor survival and the low-risk group had increased survival. ROC curve analysis and the nomogram validated the accurate prediction of survival using a gene signature composed of 10 glycolysis-related genes. Western blot and qPCR analysis demonstrated that the expression trend of signature genes was basically consistent with previous results. These 10 glycolysis-related genes were independent and suitable for a signature.

Conclusion: Our current study indicated that we successfully built and validated a novel 10-gene glycolysis-related signature for BC prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2020.566918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786194PMC
December 2020

Compositional differences of gut microbiome in matched hormone-sensitive and castration-resistant prostate cancer.

Transl Androl Urol 2020 Oct;9(5):1937-1944

Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.

Background: It is known that gut microbiota can regulate cancer therapies. We hypothesized that gut microbiota may interact with androgen deprivation therapy (ADT) in the process of castration-resistant prostate cancer (CRPC). Here, the differences in gut microbiota between matched hormone-sensitive prostate cancer (HSPC) and CRPC were determined before and after ADT.

Methods: We profiled the fecal microbiota in matched HSPC and CRPC from 21 patients who received ADT at our urological center using 16S rRNA gene amplicon sequencing. Differences in microbiota were determined with α/β-diversity and LefSe analysis. Functional inference of microbiota was performed with PICRUSt.

Results: The results showed that the gut microbial community in CRPC was significantly altered with increased abundance of several bacterial flora including genus and . For functional analyses, bacterial gene pathways involved in terpenoids/polyketides metabolism and ether lipid metabolism were significantly activated in CRPC.

Conclusions: Measurable differences in the gut microbiota were identified between HSPC and CRPC. Functional validations are further needed to ascertain the underlying mechanism of these differential microbiota in the process of CRPC, and their potential as new targets to enhance ADT responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/tau-20-566DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7658119PMC
October 2020

FGF18 Inhibits Clear Cell Renal Cell Carcinoma Proliferation and Invasion via Regulating Epithelial-Mesenchymal Transition.

Front Oncol 2020 29;10:1685. Epub 2020 Sep 29.

Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.

Fibroblast growth factor 18 (FGF18) is a member of the FGF family and contributes to a broad range of biological events. The important role of the overexpression of FGF18 has been identified in the progression of several types of cancers. However, there is still little information on the biological role of FGF18 on clear cell renal cell carcinoma (ccRCC), which is of interest in investigating the biological functions of FGF18 in ccRCC. Our results showed that FGF18 was lowly expressed in ccRCC tissues compared to paired normal renal tissue from the TCGA database and clinical cohort of Huashan Hospital and that high expression of FGF18 correlated with a good prognosis in ccRCC patients. In addition, overexpression of FGF18 significantly inhibited the proliferation ability of ccRCC cell lines and . Gene set enrichment analysis (GSEA) identified epithelial-mesenchymal transition (EMT) involved in a high FGF18 expression group of ccRCC patients in the TCGA cohort, which was further validated with EMT related markers in FGF18 overexpressed ccRCC cell lines. Furthermore, FGF18 overexpression significantly inhibited the PI3K/Akt pathway in ccRCC cells. Taken together, this study concludes that FGF18 is of potential value as a target for ccRCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2020.01685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552945PMC
September 2020

Mayer-Rokitansky-Küster-Hauser syndrome with rare findings of inferior crossed-fused renal ectopia and Gartner's duct cyst: a video case report.

Fertil Steril 2021 Feb 14;115(2):525-527. Epub 2020 Oct 14.

Department of Urology, Huashan Hospital, Fudan University, Shanghai, People's Republic of China.

Objective: To describe the treatments of a patient using the laparoscopic Davydov's method for Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome and ureteral reimplantation for hydronephrosis and hydroureter.

Design: Surgical video article. A consent form from the patient was obtained as appropriate; the nature of the study did not necessitate ethics committee approval. There were no conflicts of interest.

Setting: University hospital.

Patient(s): A 28-year-old woman who presented at our gynecology department with the symptoms of primary amenorrhea and difficult intercourse. She had repaired congenital rectovestibular fistula and imperforate anus at the age of 8. At physical examination, she had a phenotypically normal vulva with a vaginal small pouch (0.5 cm). Magnetic resonance imaging of the pelvis revealed normal ovaries, a primordial uterus, absence of vaginal canal, and a 4.0 × 4.2 × 4.0 cm cystic structure posterior to the bladder. Magnetic resonance urography showed right to left renal crossed-ectopia with inferior fusion, and hydronephrosis and hydroureter from the superior kidney with Grade Ⅳ vesicoureteral reflux. Karyotype was 46, XX.

Intervention(s): Saline solution 300 mL was injected into the rectovesical space with an infusion of diluted adrenaline (1:200,000). The goal of this injection was to aid in the identification of tissue planes and reduce blood loss. The space between urethra/bladder and rectum progressively was dissected. Blunt dissection was performed initially with digital separation of tissues. Then, an 8-cm-long neovaginal vault of about 3 cm in diameter was created. The mobilized peritoneum was pulled downward with eight Vicryl sutures and connected to the vaginal epithelium. By cystoscope, we found the left orifice but could not find the right orifice of the hydroureter. Then we ligated the hydroureter by 2-0 absorbable suture near the cyst and cut off the hydroureter, and then incised of all the layers at the top of the bladder to make a bladder flap. We placed the 5 Fr double J stent in the hydroureter and the bladder and anastomozed with the ureteral stump (3-0 Vicryl). Then we removed the cyst laparoscopically. We performed a purse-string stitch to create the apex of the neovagina by taking posterior serosa of the bladder, the pelvic peritoneum between the ovary and rectum, primordial uterus, and anterior rectal serosa.

Main Outcome Measure(s): Measurement of the final canal length, sexual function (Female Sexual Function Index), and degree of hydronephrosis.

Result(s): Three days later, we started to change the vaginal mold and the patient was advised to wear it day and night for the first postoperative month. The vaginal mold had to be worn each night until normal sexual intercourse was possible. Findings confirmed the cyst was Gartner's duct cyst. One year after the surgery, the final canal length was 9 cm and Female Sexual Function Index score was 28. The ultrasound showed that the degree of hydronephrosis of upper moiety was mild.

Conclusion(s): The distal Wolffian ducts in the female are absorbed but may persist as vestigial remnants (Gartner's duct cysts). A few cases of the combined urogenital-Wolffian anomalies are reported; most of them are associated with the anomalies of müllerian duct fusion, such as Herlyn-Werner-Wunderlich syndrome (uterus didelphys, obstructed hemivagina, and mesonephric duct anomalies). The embryogenesis of the combined anomalies is not completely understood. With comprehensive preoperative assessments, laparoscopic surgery could be a safe and effective treatment to these cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fertnstert.2020.08.1433DOI Listing
February 2021

Icaritin reduces prostate cancer progression via inhibiting high-fat diet-induced serum adipokine in TRAMP mice model.

J Cancer 2020 21;11(22):6556-6564. Epub 2020 Sep 21.

Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.

Obesity resulting from high-fat diets has a close relationship with the morbidity and mortality associated with Prostate cancer (PCa) in males. The anti-cancer role of Icaritin (ICT, a traditional Chinese herbal medicine) has been reported in several types of cancer including PCa. Adipokines are novel adipocyte-specific secretory protein, which plays a key role in the development of various diseases including obesity, diabetes, atherosclerosis, and cancer. However, the function of ICT and the molecular mechanisms underlying its role in PCa regression through modulation of adipokines have not been studied. Here, we assessed the anti-cancer properties of ICT under the influence of human epidermal growth factor receptor type 2 (HER2) pathway modulating adipokines in obese PCa models. In this study, we used transgenic adenocarcinoma of mouse prostate (TRAMP), a well-established animal model for the study of PCa pathogenesis. All the animals were fed on a high-fat diet (HFD with 40% fat) and divided into two groups, one received ICT solution of 30 mg/kg body bwt (i.p) while the other group served as control without any ICT treatment. The mortality rate, tumor formation and fat ratio were assessed by histopathological and magnetic resonance analysis at different time points of 20, 24 and 28 weeks. The protein expression of HER2 and serum levels of adipokines were measured using western blotting, IHC and multiplex immunoassays. The PCa grade in 12 TRAMP mice were longitudinally evaluated to visualize PCa development and progression upon post-surgery using PET/CT scanning. We observed that ICT treatment significantly reduces the total mortality rate of TRAMP mice ( = 0.045) and the percentage of prostate intraepithelial neoplasia (PIN) or PCa ( = 0.029). Interestingly, significantly decreased levels of leptin ( = 0.006 @20 wk) and the elevated levels of adiponectin ( = 0.030 @20 wk) were observed in different subgroups upon ICT treatment in a time-dependent manner. In addition, a decrease level of HER2 ( = 0.032 @28 wk) and an elevated level of PEA3 ( = 0.014 @28 wk) were also detected in ICT treated group. The PET/CT-based imaging showed that ICT vs non-ICT treated mice had different standard uptake value and metastasis. Our results showed potent anti-cancer properties of ICT through the modulation of adipokine secretion may alter the expression and activation of HER2 pathway as an alternative mechanism to prevent PCa progression. Altogether, our findings indicate that ICT could be a promising cancer preventive agent with the potential to target and eradicate tumor cells in obese PCa patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/jca.48413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545683PMC
September 2020

The triterpenoid sapogenin (2α-OH-Protopanoxadiol) ameliorates metabolic syndrome via the intestinal FXR/GLP-1 axis through gut microbiota remodelling.

Cell Death Dis 2020 09 17;11(9):770. Epub 2020 Sep 17.

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, P.R. China.

Gypenosides, extracts of Gynostemma yixingense, have been traditionally prescribed to improve metabolic syndrome in Asian folk and local traditional medicine hospitals. However, the mechanism of its action remains unclarified. In this work, our results indicated that chronic administration of 2α-OH-protopanoxadiol (GP2), a metabolite of gypenosides in vivo, protected mice from high-fat diet-induced obesity and improved glucose tolerance by improving intestinal L-cell function. Mechanistically, GP2 treatment inhibited the enzymatic activity of bile salt hydrolase and modulated the proportions of the gut microbiota, which led to an increase in the accumulation of tauro-β-muricholic acid (TβMCA) in the intestine. TβMCA induced GLP-1 production and secretion by reducing the transcriptional activity of nuclear receptor farnesoid X receptor (FXR). Transplantation of GP2-remodelled fecal microbiota into antibiotic-treated mice also increased the intestinal TβMCA content and improved intestinal L-cell function. These findings demonstrate that GP2 ameliorates metabolic syndrome at least partly through the intestinal FXR/GLP-1 axis via gut microbiota remodelling and also suggest that GP2 may serve as a promising oral therapeutic agent for metabolic syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-020-02974-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7499306PMC
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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.taap.2020.115169DOI Listing
October 2020

Recent Advances in DNA Repair Pathway and Its Application in Personalized Care of Metastatic Castration-Resistant Prostate Cancer (mCRPC).

Methods Mol Biol 2020 ;2204:75-89

Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.

Prostate cancer (PCa) is one of the common malignancies in male adults. In the era of precision medicine, many other novel agents targeting advanced prostate cancer, especially metastatic castration-resistant prostate cancer (mCRPC), are currently being evaluated. Among all these candidate therapies, poly-ADP ribose polymerase (PARP) inhibitors targeting DNA damage response (DDR) pathway has proven improving survival outcomes in clinical trials. In this review, we focus on recent advances in biology and clinical implication of DDR pathway and aim to discuss the latest results in advanced prostate cancer, especially mCRPC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-0716-0904-0_7DOI Listing
March 2021

Hsa_circ_0068307 mediates bladder cancer stem cell-like properties via miR-147/c-Myc axis regulation.

Cancer Cell Int 2020 6;20:151. Epub 2020 May 6.

1Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.

Background: Circular RNAs (circRNAs) play an essential role in the regulation of gene expression. However, the underlying mechanisms remain unknown. This study aimed to evaluate the role of hsa_circ_0068307 in bladder cancer (BCa).

Methods: Rt-qPCR was used to detect hsa_circ_0068307 expression in BCa cell lines. The CCK8, colony formation, and Transwell assays were used to evaluate the effect of hsa_circ_0068307 on BCa cell migration and proliferation. Bioinformatics and luciferase reporter experiments were used to study the regulatory mechanism. Nude mouse xenografts were generated to examine the effect of hsa_circ_0068307 on tumor growth.

Results: The results showed that hsa_circ_0068307 was upregulated in BCa cell lines. Downregulation of hsa_circ_0068307 suppressed cell migration and proliferation in T24 and UMUC3 cells. Hsa_circ_0068307 silencing suppressed cancer stem cell differentiation by upregulating miR-147 expression. Upregulation of miR-147 suppressed c-Myc expression, which is involved in cancer stem cell differentiation. Luciferase reporter assays confirmed that hsa_circ_0068307 upregulated c-Myc expression by targeting miR-147. In vivo studies showed that hsa_circ_0068307 knockdown suppressed T24 tumor growth.

Conclusions: These data indicate that downregulation of hsa_circ_0068307 reversed the stem cell-like properties of human bladder cancer through the regulation of the miR-147/c-Myc axis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12935-020-01235-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7204228PMC
May 2020

Genetic risk scores based on risk-associated single nucleotide polymorphisms can reveal inherited risk of bladder cancer in Chinese population.

Medicine (Baltimore) 2020 May;99(19):e19980

Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, PR China.

Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with bladder cancer (BCa) risk in Caucasian and East Asian population. The objective of this study was to validate these SNPs in Chinese population and evaluate whether these SNPs could differentiate the individual inherited risk for BCa.A case-control study including 581 BCa cases and 1561 healthy controls was performed. Germline DNA samples from all individuals were genotyped for eight SNPs. Genetic risk score (GRS) was calculated for each individual based on the odds ratios and risk allele frequencies of five risk-associated SNPs.Among eight SNPs evaluated in this study, rs798766 at 4p16.3 [OR = 1.39 (1.15-1.67), P < .001], rs9642880 [OR = 1.17 (1.06-1.30), P < .001] and rs4813953 at 20p12.2 [OR = 1.09 (1.02-1.17), P = .016] were found associated with BCa risk in Chinese population. A genetic risk score was established based on five SNPs (including the above three SNPs and two other SNPs which have the consistent direction with previous reported genome-wide association study). The mean GRS was significantly higher in BCa cases than controls (1.22 vs. 1.01, P < .001). When subjects were categorized into low- (<0.8), average- (0.8-1.2), and high-risk (>1.2) groups, the likelihoods of BCa were 25.2%, 33.7% and 55.0%, respectively (P-trend < 2.2 × 10). In subgroup analyses, no significant difference was observed in mean GRS among BCa patients with different stages or grades.In conclusion, two SNPs derived from East Asian and one SNP from Caucasian were associated with BCa risk in Chinese population. These results provided additional information of genetic risks for BCa in Chinese population. Genetic risk score based on these SNPs can reveal inherited risk of BCa, and may have potential for modifying personalized cancer screening strategy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000019980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7220229PMC
May 2020

Circular RNA circRGNEF promotes bladder cancer progression via miR-548/KIF2C axis regulation.

Aging (Albany NY) 2020 04 19;12(8):6865-6879. Epub 2020 Apr 19.

Department of Urology, Huashan Hospital, Fudan University, Shanghai 200040, China.

Circular RNAs (circRNAs) play an important role in bladder cancer (BC). Though circRNA involvement in BC has been reported, the underlying regulatory mechanisms are unknown. In this study, we performed EdU, CCK8, colony formation and Transwell assays to establish the role of circRGNEF in BC cell migration, proliferation, and invasion. We used bioinformatics and luciferase reporter experiments to investigate the regulatory mechanism. Nude mice xenografts and live imaging were used to explore the role of circRGNEF in tumor metastasis and growth. Expression profile analysis of human circRNAs in BC revealed that circRGNEF was upregulated significantly. High circRGNEF expression was correlated with aggressive BC phenotypes. The downregulation of circRGNEF suppressed BC cell metastasis and proliferation by targeting the miR-548/KIF2C axis and ; these results were verified with luciferase reporter assays. Our results show that miR-548 downregulation or KIF2C overexpression restored BC cell proliferation, migration, and invasion following silencing of circRGNEF. KIF2C overexpression reversed miR-548-induced cell invasion and migration as well as growth inhibition . In summary, the data illustrate that circRGNEF suppresses BC progression by functioning as a miR-548 sponge to enhance KIF2C expression. Therefore, circRGNEF might be a candidate BC treatment target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.103047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202505PMC
April 2020

Identification and structural insight of an effective PPARγ modulator with improved therapeutic index for anti-diabetic drug discovery.

Chem Sci 2020 Feb 21;11(8):2260-2268. Epub 2020 Jan 21.

Guangzhou Municipal and Guangdong Provincial Key Laboratory of Protein Modification and Degradation & Molecular Target and Clinical Pharmacology , State Key Laboratory of Respiratory Disease , School of Pharmaceutical Sciences & the Fifth Affiliated Hospital , Guangzhou Medical University , Guangzhou , Guangdong 511436 , China . Email:

Peroxisome proliferator-activated receptor γ (PPARγ) is a key regulator of glucose homeostasis and lipid metabolism, and an important target for the development of modern anti-diabetic drugs. However, current PPARγ-targeting anti-diabetic drugs such as classical thiazolidinediones (TZDs) are associated with undesirable side effects. To address this concern, we here describe the structure-based design, synthesis, identification and detailed and characterization of a novel, decanoic acid (DA)-based and selective PPARγ modulator (SPPARγM), VSP-77, especially (S)-VSP-77, as the potential "hit" for the development of improved and safer anti-diabetic therapeutics. We have also determined the co-crystal structure of the PPARγ ligand-binding domain (LBD) in complex with two molecules of (S)-VSP-77, which reveal a previously undisclosed allosteric binding mode. Overall, these findings not only demonstrate the therapeutic advantage of (S)-VSP-77 over current TZD drugs and representative partial agonist INT131, but also provide a rational basis for the development of future SPPARγMs as safe and highly efficacious anti-diabetic drugs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/c9sc05487aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7059199PMC
February 2020

First-time versus recurrent penoscrotal extramammary Paget's disease: Clinicopathological characteristics and risk factors in 164 Chinese male patients.

Indian J Dermatol Venereol Leprol 2020 Mar-Apr;86(2):134-140

Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.

Background: Penoscrotal extramammary Paget's disease is a rare, slow-growing neoplasm with high frequency of local recurrence.

Aims: The aim of this study was to investigate the difference in clinicopathological characteristics between first-time and recurrent penoscrotal Paget's disease, and to discover the potential risk factors of recurrence.

Methods: Between January 2007 and February 2014, a total of 164 Chinese patients with biopsy-proven tramammary Paget's diseaseex in penis and scrotum underwent wide local resection in our institution. Among them, 142 patients with first-time disease and other 22 patients with recurrent disease were enrolled in this retrospective analysis.

Results: The median duration of symptoms was much shorter in recurrent disease than in first-timers (3 vs. 24 months, P < 0.001). Patients with recurrent disease tended to have lower lesion exudation rates (27.3% vs. 51.8%, P= 0.032). In addition, patients with distant stage were more likely to obtain recurrent disease compared with first-time disease (P = 0.005). Through immunohistochemical detection of extramammary Paget's specimen, we found that HER2/neu protein expression in the recurrent group was significantly higher than first-timers (P = 0.036).

Limitations: In this study, the information on familial history of most patients was insufficient. Moreover, due to the lack of follow-up data of our included cases, we were unable to evaluate the prognosis after diagnosis of extramammary Paget's disease.

Conclusion: Patients with penoscrotal Paget's disease, especially those with shorter duration of symptoms, exudation of lesions, distant-stage, Paget cells infiltrating into adnexa, and HER2/neu expression, should be followed up more carefully after surgery, as they were more likely to suffer recurrence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/ijdvl.IJDVL_382_18DOI Listing
November 2020

Anticancer effect of icaritin on prostate cancer via regulating miR-381-3p and its target gene UBE2C.

Cancer Med 2019 12 24;8(18):7833-7845. Epub 2019 Oct 24.

Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.

Prostate cancer (PCa) is one of the most common health-related issues in the male individuals of western countries. Icaritin (ICT) is a traditional Chinese herbal medicine that exhibits antitumor efficacy in variety of cancers including PCa. However, the precise function and detailed molecular mechanism of ICT in the regression of PCa remain unclear. Ubiquitin-conjugating enzyme E2C (UBE2C) is an anaphase-promoting complex/cyclosome (APC/C)-specific ubiquitin conjugating enzyme, which acts as an oncogene in PCa progression. The function of ICT in PCa was investigated in transgenic adenocarcinoma mouse prostate (TRAMP) mice using survival analysis, hematoxylin and eosin (HE) staining, TUNEL assay, and immunohistochemistry and in human PCa cell lines using various molecular techniques and functional assays including plasmid construction and transfection. Bioinformatic analyses were performed to identify the interaction between miRNA and UBE2C via the TargetScan algorithm. We demonstrated that ICT inhibited the development and progression of PCa in TRAMP mice by improving the survival rate and tumor differentiation. Furthermore, we found that ICT could significantly inhibit cell proliferation and invasion and induce apoptosis in PCa cells. Consistently, downregulation of UBE2C suppressed the proliferation and invasion of PCa cells. Moreover, a luciferase reporter assay confirmed that UBE2C was a direct target of miR-381-3p. Meanwhile, ICT simultaneously downregulated UBE2C expression and upregulated miR-381-3p levels in human PCa cells. Altogether, our findings provide a strong rationale for the clinical application of ICT as a potential oncotherapeutic agent against PCa via a novel molecular mechanism of regulating the miR-381-3p/UBE2C pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cam4.2630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912031PMC
December 2019

Mitochondrial Uncoupling Coordinated With PDH Activation Safely Ameliorates Hyperglycemia via Promoting Glucose Oxidation.

Diabetes 2019 12 30;68(12):2197-2209. Epub 2019 Aug 30.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China

Uncoupling of mitochondrial respiration by chemical uncouplers has proven effective in ameliorating obesity, insulin resistance, and hyperglycemia. However, development of uncoupler-based therapy remains challenging due to its potentially lethal adverse effects. Here, we identify pyruvate dehydrogenase (PDH) as a key modifier of the toxicity profile of 2, 4-dinitrophenol (DNP), a prototypical mitochondrial uncoupler. PDH activation by dichloroacetic acid (DCA) protects mice from DNP-induced hyperlactacidemia, hyperthermia, and death while preserving the ability of DNP to promote fuel oxidation and improve insulin sensitivity in mice. Mechanistically, PDH activation switches on mitochondrial glucose oxidation to accommodate increased glycolytic flux, leading to reduced lactate secretion during uncoupler treatments. We devised a chemical screening strategy and discovered compound 6j as a dual-action compound that simultaneously activates PDH and uncouples mitochondrial respiration. Compound 6j exhibits an excellent efficacy and safety profile in restoring glucose homeostasis in diabetic mice. This work establishes a new principle to safely harness the power of chemical uncouplers for the treatment of metabolic disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2337/db19-0589DOI Listing
December 2019

The comparison between force volume and peakforce quantitative nanomechanical mode of atomic force microscope in detecting cell's mechanical properties.

Microsc Res Tech 2019 Nov 30;82(11):1843-1851. Epub 2019 Jul 30.

Huashan Hospital, Fudan University, Shanghai, China.

Atomic force microscope (AFM) has been widely used in the biological field owing to its high sensitivity (subnanonewton), high spatial resolution (nanometer), and adaptability to physiological environments. Nowadays, force volume (FV) and peakforce quantitative nanomechanical (QNM) are two distinct modes of AFM used in biomechanical research. However, numerous studies have revealed an extremely confusing phenomenon that FV mode has a significant difference with QNM in determining the mechanical properties of the same samples. In this article, for the case of human benign prostatic hyperplasia cells (BPH) and two cancerous prostate cells with different grades of malignancy (PC3 and DU145), the differences were compared between FV and QNM modes in detecting mechanical properties. The results show measured Young's modulus of the same cells in FV mode was much lower than that obtained by QNM mode. Combining experimental results with working principles of two modes, it is indicated that surface adhesion is highly suspected to be a critical factor resulting in the measurement difference between two modes. To further confirm this conjecture, various weight ratios of polydimethylsiloxane (PDMS) were assessed by two modes, respectively. The results show that the difference of Young's modulus measured by two modes increases with the surface adhesion of PDMS, confirming that adhesion is one of the significant elements that lead to the measurement difference between FV and QNM modes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jemt.23351DOI Listing
November 2019

Berberine promotes the recruitment and activation of brown adipose tissue in mice and humans.

Cell Death Dis 2019 06 13;10(6):468. Epub 2019 Jun 13.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, P. R. China.

Brown adipose tissue (BAT) dissipates metabolic energy and mediates non-shivering thermogenesis, thereby boosting energy expenditure. Increasing BAT mass and activity is expected to be a promising strategy for combating obesity; however, few medications effectively and safely recruit and activate BAT in humans. Berberine (BBR), a natural compound, is commonly used as a nonprescription drug to treat diarrhea. Here, we reported that 1-month BBR intervention increased BAT mass and activity, reduced body weight, and improved insulin sensitivity in mildly overweight patients with non-alcoholic fatty liver disease. Chronic BBR treatment promoted BAT development by stimulating the expression of brown adipogenic genes, enhanced BAT thermogenesis, and global energy expenditure in diet-induced obese mice and chow-fed lean mice, Consistently, BBR facilitated brown adipocyte differentiation in both mouse and human primary brown preadipocytes. We further found that BBR increased the transcription of PRDM16, a master regulator of brown/beige adipogenesis, by inducing the active DNA demethylation of PRDM16 promoter, which might be driven by the activation of AMPK and production of its downstream tricarboxylic acid cycle intermediate α-Ketoglutarate. Moreover, chronic BBR administration had no impact on the BAT thermogenesis in adipose-specific AMPKa1 and AMPKa2 knockout mice. In summary, we found that BBR intervention promoted recruitment and activation of BAT and AMPK-PRDM16 axis was indispensable for the pro-BAT and pro-energy expenditure properties of BBR. Our findings suggest that BBR may be a promising drug for obesity and related metabolic disorders in humans partially through activating BAT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-019-1706-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565685PMC
June 2019

High dietary fat intake lowers serum equol concentration and promotes prostate carcinogenesis in a transgenic mouse prostate model.

Nutr Metab (Lond) 2019 11;16:24. Epub 2019 Apr 11.

Department of Urology, Huashan Hospital, Fudan University, No. 12 Middle Wulumuqi Road, Shanghai, 200040 China.

Background: Consumption of diet high in soy products is suggested to contribute to lower prostate cancer incidence in Asian men. But little has been known about the influences of dietary patterns on gut microbiota and microbiota-mediated isoflavone metabolism. Here, we determined the influences of western pattern diet on prostate carcinogenesis, gut microbiota and microbiota-mediated equol metabolism using a transgenic adenocarcinoma of mouse prostate (TRAMP) model.

Methods: We mimicked the western pattern diet using a high fat diet (HFD). TRAMP mice were fed with either control diet (CD) or HFD. At the age of 24 weeks, mice were orally administered daidzein over a 4-day period, and then sacrificed. The serum daidzein and equol were analyzed by ultra high performance liquid chromatography. Fecal microbiome was analyzed with fecal 16S rRNA pyrosequencing, and prostate was dissected and performed with histopathology.

Results: HFD could promote prostate carcinogenesis in TRAMP mice ( = 0.045). The daidzein showed no significant differences between CD and HFD groups, while equol was significantly decreased in HFD group ( = 0.019). Fecal microbiotas differed between the two groups, 21 microbial phylotypes were increased and 11 phylotypes were decreased in abundance in HFD group, including decreased abundance of equol-producing bacterium (0.08% vs. 0.27%)

Conclusions: HFD may promote prostate carcinogenesis through adversely affecting equol-producing bacterium. Further functional validations are required to ascertain the mechanism of those HFD-responsive bacteria in carcinogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12986-019-0351-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6460650PMC
April 2019

Clinicopathological and prognostic significance of preoperative plasma fibrinogen level in patients with upper urinary tract urothelial carcinoma: A retrospective tumor marker prognostic study.

Int J Surg 2019 May 2;65:88-93. Epub 2019 Apr 2.

Department of Urology, Huashan Hospital, Fudan University, Shanghai, China; Fudan Institute of Urology, Huashan Hospital, Fudan University, Shanghai, China. Electronic address:

Purpose: To retrospectively evaluate the prognostic value of preoperative plasma fibrinogen to predict oncological outcome and intravesical recurrence in upper urinary tract urothelial carcinoma.

Methods: This retrospective study comprised 130 patients with non-metastatic upper urinary tract urothelial carcinoma who underwent surgery between June 2009 and June 2017 at a single center. Patients were categorized base on an optimal value of preoperative plasma fibrinogen. Progression-free and cancer-specific survival were assessed using Kaplan-Meier method. The associations between plasma fibrinogen and clinical outcomes were assessed with univariate and Multivariate analysis.

Results: Elevated plasma fibrinogen was associated with advance tumor stage, high tumor grade and tumor size. No significant association was found between plasma fibrinogen and intravesical recurrence. Multivariate analysis revealed that plasma fibrinogen ≥3.602 g/L was an independent prognostic indicator for progression-free survival (HR = 2.18; 95% CI: 1.17-4.06; p = 0.01) and cancer-specific survival (HR = 2.2; 95% CI: 1.13-4.28; p = 0.02), as well as pathological T stage and tumor grade.

Conclusions: Elevated preoperative plasma fibrinogen is an independent unfavorable prognostic factor for oncological outcomes in patients with upper urinary tract urothelial carcinoma. However, there is no association between preoperative plasma fibrinogen and intravesical recurrence. As an effective and easily accessible biomarker, this parameter can be applied in pre-intervention risk stratification of upper urinary tract urothelial carcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijsu.2019.03.022DOI Listing
May 2019

Genistein treatment duration effects biomarkers of cell motility in human prostate.

PLoS One 2019 27;14(3):e0214078. Epub 2019 Mar 27.

Division of Hematology/Oncology, Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon, United States of America.

Background: Long term dietary consumption of genistein by Chinese men is associated with decreased PCa metastasis and mortality. Short term treatment of US men with prostate cancer (PCa) with genistein decreases MMP-2 in prostate tissue. MEK4 regulates MMP-2 expression, drives PCa metastasis, and genistein inhibits MEK4, decreases MMP-2 expression and dietary dosing inhibits human PCa metastasis in mice. This study examines short- versus long-term treatment effects of genistein in humans and in vitro.

Methods And Findings: US men with localized PCa were treated on a phase II trial with genistein (N = 14) versus not (N = 14) for one month prior to radical prostatectomy. Prostate epithelial cells were removed from fresh frozen tissue by laser capture microdissection, and the expression of 12,000 genes profiled. Genistein significantly altered the expression of four genes, three had established links to cancer cell motility and metastasis. Of these three, one was a non-coding transcript, and the other two were BASP1 and HCF2. Genistein increased BASP1 expression in humans, and its engineered over expression and knockdown demonstrated that it suppressed cell invasion in all six human prostate cell lines examined. Genistein decreased HCF2 expression in humans, and it was shown to increase cell invasion in all cell lines examined. The expression of MMP-2, MEK4 and BASP1 was then measured in formalin fixed prostate tissue from N = 38 Chinese men living in China and N = 41 US men living in the US, both cohorts with localized PCa. MMP-2 was 52% higher in Chinese compared to US tissue (P < 0.0001), MEK4 was 48% lower (P < 0.0001), and BASP1 was unaltered. Treatment of PC3 human PCa cells in vitro for up to 8 weeks demonstrated that short term genistein treatment decreased MMP-2, while long term treatment increased it, both changes being significant (P<0.05) compared to untreated control cells. Long term genistein-treated cells retained their responsiveness to genistein's anti-motility effect.

Conclusions: Genistein inhibits pathways in human prostate that drive transformation to a lethal high motility phenotype. Long term treatment induces compensatory changes in biomarkers of efficacy. The current strategy of using such biomarkers after short term intervention as go/no-go determinants in early phase chemoprevention trials should be carefully examined.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0214078PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436751PMC
December 2019

Establishment and characterization of a fibroblast-like cell line from the muscle of turbot (Scophthalmus maximus L.).

Fish Physiol Biochem 2019 Jun 19;45(3):1129-1139. Epub 2019 Mar 19.

Key Laboratory of Aquaculture Nutrition (Ministry of Agriculture), Ocean University of China, No. 5 Yushan Rd, Qingdao, 266003, People's Republic of China.

A continuous fibroblast-like cell line, TMF (turbot muscle fibroblasts), was established from juvenile turbot Scophthalmus maximus muscle with the method of trypsin digestion. It has been subcultured more than 60 passages for over 150 days. The TMF cells were cultured in L-15 medium supplemented with HEPES, fetal bovine serum (FBS), GlutaMAX, and basic fibroblast growth factor (bFGF). The optimal temperature for TMF culture was 24 °C. TMF cells were predominantly composed of fibroblastic-like cells, and the transcription factor 4 (TCF-4) was highly expressed in TMF cells. Chromosome analysis revealed that it had a diploid chromosome number of 2n = 44. The transfection efficiency achieved 54.95 ± 6.59%, and the cell mortality rate was about 8.70% when transfected with the nucleofection method. Meanwhile, the TMF cells showed a sensitive response to amino acid levels and activation target of rapamycin (TOR) signaling pathway. These results indicate that TMF was a potential tool to explore the signal transduction of teleost in vitro.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10695-019-00628-3DOI Listing
June 2019