Comprehensive Analysis of Gut Microbiota Alteration in the Patients and Animal Models with Polycystic Ovary Syndrome

Zhou Jing,Qiu Xuemei,Chen Xuejing,Ma Sihan,Chen Zhaoyang,Wang Ruzhe,Tian Ying,Jiang Yufan,Fan Li,Wang Jingjie 한국미생물학회 2023 The journal of microbiology Vol.61 No.9

Polycystic ovary syndrome (PCOS) is a common disease of endocrine–metabolic disorder, and its etiology remains largely unknown. The gut microbiota is possibly involved in PCOS, while the association remains unclear. The comprehensive analysis combining gut microbiota with PCOS typical symptoms was performed to analyze the role of gut microbiota in PCOS in this study. The clinical patients and letrozole-induced animal models were determined on PCOS indexes and gut microbiota, and fecal microbiota transplantation (FMT) was conducted. Results indicated that the animal models displayed typical PCOS symptoms, including disordered estrous cycles, elevated testosterone levels, and ovarian morphological change; meanwhile, the symptoms were improved after FMT. Furthermore, the microbial diversity exhibited disordered, and the abundance of the genus Ruminococcus and Lactobacillus showed a consistent trend in PCOS rats and patients. The microbiota diversity and several key genera were restored subjected to FMT, and correlation analysis also supported relevant conclusions. Moreover, LEfSe analysis showed that Gemmiger, Flexispira, and Eubacterium were overrepresented in PCOS groups. Overall, the results indicate the involvement of gut microbiota in PCOS and its possible alleviation of endocrinal and reproductive dysfunctions through several special bacteria taxa, which can function as the biomarker or potential target for diagnosis and treatment. These results can provide the new insights for treatment and prevention strategies of PCOS.

BF-30 effectively inhibits ciprofloxacin-resistant bacteria in vitro and in a rat model of vaginosis

Wang, Jing,Li, Bing,Li, Yang,Dou, Jie,Hao, Qingru,Tian, Yuwei,Wang, Hui,Zhou, Changlin 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.7

Bacterial infections are becoming increasingly difficult to treat due to the increasing number of multidrug-resistant strains. Cathelicidin-BF (BF-30) is a cathelicidin-like antimicrobial peptide and exhibits broad antimicrobial activity against bacteria. In the present study, the antibacterial activity of BF-30 against ciprofloxacin-resistant Escherichia coli and Staphylococcus aureus was examined, and the protective effects of this peptide against these bacteria in rats with bacterial vaginosis were identified for the first time. The data showed that BF-30 had effective antimicrobial activities against ciprofloxacin-resistant E. coli and S. aureus. The minimal inhibitory concentrations for both bacterial strains were $16{\mu}g/ml$, and the minimal bactericidal concentrations were 64 and $128{\mu}g/ml$, respectively. A time course experiment showed that the CFU counts rapidly decreased after BF-30 treatment, and the bacteria were nearly eliminated within 4 h. BF-30 could reduce the fold change (CFU/ml) in local colonization by drug-resistant E. coli and S. aureus to 0.01 at a dose of 0.8 mg/kg/day in the rats' vaginal secretions. In addition, BF-30 induced membrane permeabilization and bound to the genomic DNA, interrupting protein synthesis. Taken together, our data demonstrate that BF-30 has potential therapeutic value for the prevention and treatment of bacterial vaginosis.

Construction of a Protein-Protein Interaction Network for Chronic Myelocytic Leukemia and Pathway Prediction of Molecular Complexes

Zhou, Chao,Teng, Wen-Jing,Yang, Jing,Hu, Zhen-Bo,Wang, Cong-Cong,Qin, Bao-Ning,Lv, Qing-Liang,Liu, Ze-Wang,Sun, Chang-Gang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

Background: Chronic myelocytic leukemia is a disease that threatens both adults and children. Great progress has been achieved in treatment but protein-protein interaction networks underlining chronic myelocytic leukemia are less known. Objective: To develop a protein-protein interaction network for chronic myelocytic leukemia based on gene expression and to predict biological pathways underlying molecular complexes in the network. Materials and Methods: Genes involved in chronic myelocytic leukemia were selected from OMIM database. Literature mining was performed by Agilent Literature Search plugin and a protein-protein interaction network of chronic myelocytic leukemia was established by Cytoscape. The molecular complexes in the network were detected by Clusterviz plugin and pathway enrichment of molecular complexes were performed by DAVID online. Results and Discussion: There are seventy-nine chronic myelocytic leukemia genes in the Mendelian Inheritance In Man Database. The protein-protein interaction network of chronic myelocytic leukemia contained 638 nodes, 1830 edges and perhaps 5 molecular complexes. Among them, complex 1 is involved in pathways that are related to cytokine secretion, cytokine-receptor binding, cytokine receptor signaling, while complex 3 is related to biological behavior of tumors which can provide the bioinformatic foundation for further understanding the mechanisms of chronic myelocytic leukemia.

Gambogenic Acid Induction of Apoptosis in a Breast Cancer Cell Line

Zhou, Jing,Luo, Yan-Hong,Wang, Ji-Rong,Lu, Bin-Bin,Wang, Ke-Ming,Tian, Ye Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.12

Background: Gambogenic acid is a major active compound of gamboge which exudes from the Garcinia hanburyi tree. Gambogenic acid anti-cancer activity in vitro has been reported in several studies, including an A549 nude mouse model. However, the mechanisms of action remain unclear. Methods: We used nude mouse models to detect the effect of gambogenic acid on breast tumors, analyzing expression of apoptosis-related proteins in vivo by Western blotting. Effects on cell proliferation, apoptosis and apoptosis-related proteins in MDA-MB-231 cells were detected by MTT, flow cytometry and Western blotting. Inhibitors of caspase-3,-8,-9 were also used to detect effects on caspase family members. Results: We found that gambogenic acid suppressed breast tumor growth in vivo, in association with increased expression of Fas and cleaved caspase-3,-8,-9 and bax, as well as decrease in the anti-apoptotic protein bcl-2. Gambogenic acid inhibited cell proliferation and induced cell apoptosis in a concentration-dependent manner. Conclusion: Our observations suggested that Gambogenic acid suppressed breast cancer MDA-MB-231 cell growth by mediating apoptosis through death receptor and mitochondrial pathways in vivo and in vitro.

Lactate potentiates angiogenesis and neurogenesis in experimental intracerebral hemorrhage

Jing Zhou,Tao Liu,Hao Guo,Hanjin Cui,Pengfei Li,Dandan Feng,En Hu,Qing Huang,Ali Yang,Jun Zhou,Jiekun Luo,Tao Tang,Yang Wang 생화학분자생물학회 2018 Experimental and molecular medicine Vol.50 No.-

Lactate accumulation has been observed in the brain with intracerebral hemorrhage (ICH). However, the outcome of lactate accumulation has not been well characterized. Here, we report that lactate accumulation contributes to angiogenesis and neurogenesis in ICH. In the first set of the experiment, a rat model of ICH was induced by injecting collagenase into the brain. The effects of lactate accumulation on the neurological function, apoptosis, and numbers of newborn endothelial cells and neurons, as well as the proliferation-associated signaling pathway, were evaluated in the rat brain. In the second set, exogenous L-lactate was infused into intact rat brains so that its effects could be further assessed. Following ICH, lactate accumulated around the hematoma; the numbers of PCNA+/vWF+ nuclei and PCNA+/DCX+ cells were significantly increased compared with the numbers in the Sham group. Moreover, ICH induced translocation of nuclear factor-kappa B (NF-κB) p65 into the nucleus, resulting in a notable upregulation of VEGF and bFGF mRNAs and proteins compared with the levels in the Sham controls. Administration of a lactate dehydrogenase inhibitor dramatically inhibited these effects, decreased the vascular density, and aggravated neurological severity scores and apoptosis after ICH. After exogenous L-lactate infusion, the numbers of PCNA+/vWF+ nuclei and PCNA+/DCX+ cells were strikingly increased compared with the numbers in the Sham controls. In addition, lactate facilitated NF-κB translocation to induce increased transcription of VEGF and bFGF. Co-infusion with an NF-κB inhibitor significantly inhibited these effects. These data suggest that lactate potentiates angiogenesis and neurogenesis by activating the NF-κB signaling pathway following ICH.

Simultaneous treatment with sorafenib and glucose restriction inhibits hepatocellular carcinoma in vitro and in vivo by impairing SIAH1-mediated mitophagy

Zhou Jing,Feng Ji,Wu Yong,Dai Hui-Qi,Zhu Guang-Zhi,Chen Pan-Hong,Wang Li-Ming,Lu Guang,Liao Xi-Wen,Lu Pei-Zhi,Su Wen-Jing,Hooi Shing Chuan,Ye Xin-Pin,Shen Han-Ming,Peng Tao,Lu Guo-Dong 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Transarterial chemoembolization (TACE) is the first-line treatment for unresectable intermediate-stage hepatocellular carcinoma (HCC). It is of high clinical significance to explore the synergistic effect of TACE with antiangiogenic inhibitors and the molecular mechanisms involved. This study determined that glucose, but not other analyzed nutrients, offered significant protection against cell death induced by sorafenib, as indicated by glucose deprivation sensitizing cells to sorafenib-induced cell death. Next, this synergistic effect was found to be specific to sorafenib, not to lenvatinib or the chemotherapeutic drugs cisplatin and doxorubicin. Mechanistically, sorafenib-induced mitophagy, as indicated by PINK1 accumulation, increased the phospho-poly-ubiquitination modification, accelerated mitochondrial membrane protein and mitochondrial DNA degradation, and increased the amount of mitochondrion-localized mKeima-Red engulfed by lysosomes. Among several E3 ubiquitin ligases tested, SIAH1 was found to be essential for inducing mitophagy; that is, SIAH1 silencing markedly repressed mitophagy and sensitized cells to sorafenib-induced death. Notably, the combined treatment of glucose restriction and sorafenib abolished ATP generation and mitophagy, which led to a high cell death rate. Oligomycin and antimycin, inhibitors of electron transport chain complexes, mimicked the synergistic effect of sorafenib with glucose restriction to promote cell death mediated via mitophagy inhibition. Finally, inhibition of the glucose transporter by canagliflozin (a clinically available drug used for type-II diabetes) effectively synergized with sorafenib to induce HCC cell death in vitro and to inhibit xenograft tumor growth in vivo. This study demonstrates that simultaneous treatment with sorafenib and glucose restriction is an effective approach to treat HCC, suggesting a promising combination strategy such as transarterial sorafenib-embolization (TASE) for the treatment of unresectable HCC.

Activation of β2-Adrenergic Receptor Promotes Growth and Angiogenesis in Breast Cancer by Down-regulating PPARγ

Jing Zhou,Zhanzhao Liu,Lingjing Zhang,Xiao Hu,Zhihua Wang,Hong Ni,Yue Wang,Jun-fang Qin 대한암학회 2020 Cancer Research and Treatment Vol.52 No.3

Purpose Chronic stress and related hormones are key in cancer progression. Peroxisome proliferator- activated receptor ! (PPAR!) and its agonists was reported that inducing anti-tumor effect. However, the function of PPAR! in pro-tumorigenic effects induced by chronic stress in breast cancer remains unknown. Herein, we have characterized a novel role of PPAR! and vascular endothelial growth factor (VEGF)/fibroblast growth factor 2 (FGF2) signals in breast cancer promoted by chronic stress. Materials and Methods We performed experiments in vivo and in vitro and used bioinformatics data to evaluate the therapeutic potential of PPAR! in breast cancer promoted by stress. Results Chronic stress significantly inhibited the PPAR! expression and promoted breast cancer in vivo. VEGF/FGF2-mediated angiogenesis increased in the chronic stress group compared to the control group. PPAR! agonist pioglitazone (PioG) injection offset the pro-tumorigenic effect of chronic stress. Moreover, specific "2-adrenergic receptor ("2R) antagonist ICI11- 8551 inhibited the effect of chronic stress. In vitro, norepinephrine (NE) treatment had a similar tendency to chronic stress. The effect of NE was mediated by the "2R/adenylate cyclase signaling pathway and suppressed by PioG. PPAR! suppressed VEGF/FGF2 through reactive oxygen species inhibition. Bioinformatics data confirmed that there was a low PPAR! expression in breast invasive carcinoma. Lower PPAR! was associated with a significantly worse survival. Conclusion "2R activation induced by chronic stress and related hormones promotes growth and VEGF/ FGF2-mediated angiogenesis of breast cancer by down-regulating PPAR!. Our findings hint that " receptor and PPAR! as two target molecules and the novel role for their agonists or antagonists as clinical medicine in breast cancer therapy.

Transcriptome sequencing reveals non-coding RNAs respond to porcine reproductive and respiratory syndrome virus and Haemophilus parasuis co-infection in Kele piglets

( Jing Zhang ),( Chunping Zhao ),( Min Yao ),( Jing Qi ),( Ya Tan ),( Kaizhi Shi ),( Jing Wang ),( Sixuan Zhou ),( Zhixin Li ) 한국축산학회 2024 한국축산학회지 Vol.66 No.4

Co-infection with porcine reproductive and respiratory syndrome virus (PRRSV) and Haemophilus parasuis (HPS) has severely restricted the healthy development of pig breeding. Exploring disease resistance of non-coding RNAs in pigs co-infected with PRRSV and HPS is therefore critical to complement and elucidate the molecular mechanisms of disease resistance in Kele piglets and to innovate the use of local pig germplasm resources in China. RNA-seq of lungs from Kele piglets with single-infection of PRRSV or HPS and co-infection of both pathogens was performed. Two hundred and twenty-five differentially expressed long non-coding RNAs (DElncRNAs) and 30 DEmicroRNAs (DEmiRNAs) were identified and characterized in the PRRSV and HPS co-infection (PRRSV-HPS) group. Compared with the single-infection groups, 146 unique DElncRNAs, 17 unique DEmiRNAs, and 206 target differentially expressed genes (DEGs) were identified in the PRRSV-HPS group. The expression patterns of 20 DEmiRNAs and DElncRNAs confirmed by real-time quantitative polymerase chain reaction (RT-qPCR) were consistent with those determined by high-throughput sequencing. In the PRRSV-HPS group, the target DEGs were enriched in eight immune Gene Ontology terms relating to two unique DEmiRNAs and 16 DElncRNAs, and the unique target DEGs participated the host immune response to pathogens infection by affecting 15 immune-related Kyoto Encyclopedia of Genes and Genomes enrichment pathways. Notably, competitive endogenous RNA (ceRNA) networks of different groups were constructed, and the ssc-miR-671-5p miRNA was validated as a potential regulatory factor to regulate DTX4 and AEBP1 genes to achieve innate antiviral effects and inhibit pulmonary fibrosis by dual-luciferase reporter assays. These results provided insight into further study on the molecular mechanisms of resistance to PRRSV and HPS co-infection in Kele piglets.

NATURAL LANGUAGE SEMANTICS PROCESSING-CASE IDENTIFYING BASED ON MEANING RELATION

Wang Jian Bo,Wang Kai Zhu,Ma Yue,Zhou Jing Zhou 대한전자공학회 1992 대한전자공학회 Conference Vol.1992 No.2

BF-30 effectively inhibits ciprofloxacin-resistant bacteria in vitro and in a rat model of vaginosis

Jing Wang,Bing Li,Yang Li,Jie Dou,Qingru Hao,Yuwei Tian,Hui Wang,Changlin Zhou 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.7

Bacterial infections are becoming increasinglydifficult to treat due to the increasing number of multidrugresistantstrains. Cathelicidin-BF (BF-30) is a cathelicidinlikeantimicrobial peptide and exhibits broad antimicrobialactivity against bacteria. In the present study, the antibacterialactivity of BF-30 against ciprofloxacin-resistantEscherichia coli and Staphylococcus aureus was examined,and the protective effects of this peptide against these bacteriain rats with bacterial vaginosis were identified for thefirst time. The data showed that BF-30 had effective antimicrobialactivities against ciprofloxacin-resistant E. coliand S. aureus. The minimal inhibitory concentrations forboth bacterial strains were 16 lg/ml, and the minimal bactericidalconcentrations were 64 and 128 lg/ml, respectively. A time course experiment showed that the CFUcounts rapidly decreased after BF-30 treatment, and thebacteria were nearly eliminated within 4 h. BF-30 couldreduce the fold change (CFU/ml) in local colonization bydrug-resistant E. coli and S. aureus to 0.01 at a dose of0.8 mg/kg/day in the rats’ vaginal secretions. In addition,BF-30 induced membrane permeabilization and bound to thegenomic DNA, interrupting protein synthesis. Taken together,our data demonstrate that BF-30 has potential therapeuticvalue for the prevention and treatment of bacterialvaginosis.