Potential Therapeutic Targets for the Primary Gallbladder Carcinoma: Estrogen Receptors

Zhang, Ling-Qiang,Zhang, Xiu-De,Xu, Jia,Wan, Yong,Qu, Kai,Zhang, Jing-Yao,Wang, Zhi-Xin,Wei, Ji-Chao,Meng, Fan-Di,Tai, Ming-Hui,Zhou, Lei,Liu, Chang Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.4

Gallbladder carcinoma, the most frequent malignant neoplasm of the biliary tract system, has always been considered to feature late clinical presentation and diagnosis, limited treatment options and an extremely poor prognosis. In recent years, while the incidence of gallbladder cancer has appeared to be on the increase, the available treatment methods have not greatly improved survival of the affected patients. Thus, exploring new therapeutic targets for this devastating disease is an urgent matter at present. Epidemical studies have demonstrated that the incidence of gallbladder carcinoma exhibits a distinct gender bias, affecting females two to three times more than males, pointing to crucial roles of estrogen. It is well known that estrogen acts on target tissues by binding to estrogen receptors (ERs), which are mainly divided into three subtypes, $ER{\alpha}$, $ER{\beta}$ and $ER{\gamma}$. $ER{\alpha}$ and $ER{\beta}$ appear to have overlapping but also unique even opposite biological effects. As important pathogenic mediators, ERs have been considered to relate to several kinds of tumors. In gallbladder carcinoma tissue, ERs have been shown to be positively expressed, and ERs expression levels are associated with differentiation and prognosis of this cancer. Nevertheless, the exact mechanisms of estrogen inducing growth of gallbladder carcinoma remain poorly understood. On the base of the current investigations, we deduce that estrogen participates in promotion of gallbladder carcinoma by influencing the formation of gallstones, stimulating angiogenesis, and promoting abnormal proliferation. Since ERs mediate the carcinogenic actions of estrogen in gallbladder, and therapy targeting ERs may provide new directions for gallbladder carcinoma. Therefore, it should be stressed that ERs are potential therapeutic targets for gallbladder carcinoma.

MiR-126-3p inhibits apoptosis and promotes proliferation by targeting phosphatidylinositol 3-kinase regulatory subunit 2 in porcine ovarian granulosa cells

Zhou, Xiaofeng,He, Yingting,Jiang, Yao,He, Bo,Deng, Xi,Zhang, Zhe,Yuan, Xiaolong,Li, Jiaqi Asian Australasian Association of Animal Productio 2020 Animal Bioscience Vol.33 No.6

Objective: Numerous studies have indicated that the apoptosis and proliferation of granulosa cells (GCs) are closely related to the normal growth and development of follicles and ovaries. Previous evidence has suggested that miR-126-3p might get involved in the apoptosis and proliferation of GCs, and phosphatidylinositol 3-kinase regulatory subunit 2 (PIK3R2) gene has been predicted as one target of miR-126-3p. However, the molecular regulation of miR-126-3p on PIK3R2 and the effects of PIK3R2 on porcine GCs apoptosis and proliferation remain virtually unexplored. Methods: In this study, using porcine GCs as a cellular model, luciferase report assay, mutation and deletion were applied to verify the targeting relationship between miR-126-3p and PIK3R2. Annexin-V/PI staining and 5-ethynyl-2'-deoxyuridine assay were applied to explore the effect of PIK3R2 on GCs apoptosis and proliferation, respectively. Real-time quantitative polymerase chain reaction and Western Blot were applied to explore the regulation of miR-126-3p on PIK3R2 expression. Results: We found that miR-126-3p targeted at PIK3R2 and inhibited its mRNA and protein expression. Knockdown of PIK3R2 significantly inhibited the apoptosis and promoted the proliferation of porcine GCs, and significantly down-regulated the mRNA expression of several key genes of PI3K pathway such as insulin-like growth factor 1 receptor (IGF1R), insulin receptor (INSR), pyruvate dehydrogenase kinase 1 (PDK1), and serine/threonine kinase 1 (AKT1). Conclusion: MiR-126-3p might target and inhibit the mRNA and protein expressions of PIK3R2, thereby inhibiting GC apoptosis and promoting GC proliferation by down-regulating several key genes of the PI3K pathway, IGF1R, INSR, PDK1, and AKT1. These findings would provide great insight into further exploring the molecular regulation of miR-126-3p and PIK3R2 on the functions of GCs during the folliculogenesis in female mammals.

Effect of Ca²⁺ on the activity and structure of α-glucosidase: Inhibition kinetics and molecular dynamics simulations

Zhang, X.,Shi, L.,Li, X.,Sheng, Q.,Yao, L.,Shen, D.,Lu, Z.R.,Zhou, H.M.,Park, Y.D.,Lee, J.,Zhang, Q. Society for Bioscience and Bioengineering, Japan ; 2014 Journal of bioscience and bioengineering Vol.117 No.6

Understanding the mechanism of inhibition of α-glucosidase (EC 3.2.1.20) is clinically important because of the involvement of this enzyme in type 2 diabetes mellitus. In this study, we conducted inhibition kinetics of α-glucosidase with Ca<SUP>2+</SUP> and 10-ns molecular dynamics simulations. We found that direct binding of Ca<SUP>2+</SUP> to the enzyme induced structural changes and inhibited enzyme activity. Ca<SUP>2+</SUP> inhibited α-glucosidase in a mixed-type reaction (K<SUB>i</SUB> = 27.0 +/- 2.0 mM) and directly induced the unfolding of α-glucosidase, which resulted in the exposure of hydrophobic residues. The simulations suggest that thirteen Ca<SUP>2+</SUP> ions may interact with α-glucosidase residues and that the Ca<SUP>2+</SUP> binding sites are associated with the structural changes in α-glucosidase. Our study provides insight into the mechanism of the Ca<SUP>2+</SUP>-induced structural changes in α-glucosidase and the inhibition of ligand binding. These results suggest that Ca<SUP>2+</SUP> could act as a potent inhibitor of α-glucosidase for the treatment of type 2 diabetes mellitus.

Establishing a Nomogram for Stage IA-IIB Cervical Cancer Patients after Complete Resection

Zhou, Hang,Li, Xiong,Zhang, Yuan,Jia, Yao,Hu, Ting,Yang, Ru,Huang, Ke-Cheng,Chen, Zhi-Lan,Wang, Shao-Shuai,Tang, Fang-Xu,Zhou, Jin,Chen, Yi-Le,Wu, Li,Han, Xiao-Bing,Lin, Zhong-Qiu,Lu, Xiao-Mei,Xing, H Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.9

Background: This study aimed to establish a nomogram by combining clinicopathologic factors with overall survival of stage IA-IIB cervical cancer patients after complete resection with pelvic lymphadenectomy. Materials and Methods: This nomogram was based on a retrospective study on 1,563 stage IA-IIB cervical cancer patients who underwent complete resection and lymphadenectomy from 2002 to 2008. The nomogram was constructed based on multivariate analysis using Cox proportional hazard regression. The accuracy and discriminative ability of the nomogram were measured by concordance index (C-index) and calibration curve. Results: Multivariate analysis identified lymph node metastasis (LNM), lymph-vascular space invasion (LVSI), stromal invasion, parametrial invasion, tumor diameter and histology as independent prognostic factors associated with cervical cancer survival. These factors were selected for construction of the nomogram. The C-index of the nomogram was 0.71 (95% CI, 0.65 to 0.77), and calibration of the nomogram showed good agreement between the 5-year predicted survival and the actual observation. Conclusions: We developed a nomogram predicting 5-year overall survival of surgically treated stage IA-IIB cervical cancer patients. More comprehensive information that is provided by this nomogram could provide further insight into personalized therapy selection.

Analysis and Correction of Through-bolt End-region Overheating and Breakdown Failure in a Large Tubular Hydro-generator

Zhou, Zhi-ting,Fan, Zhen-nan,Li, Jian-fu,Wen, Kun,Zhang, Bide,Wang, Tao,Xia, Yan-kun,Sun, Zhang,Yao, Bing The Korean Institute of Electrical Engineers 2018 Journal of Electrical Engineering & Technology Vol.13 No.6

A field-circuit coupling model of a typical faulty generator is established to correct through-bolt end-region overheating and breakdown failure in a tubular hydro-generator. Using the model, eddy current loss and electromagnetic forces on through bolts under normal and failure conditions are analyzed and compared and the natural frequency of a through bolt is determined. Based on the analysis results, the causative mechanism of failure is revealed and targeted improvement design measures are proposed. The numerical results are found to be consistent with the actual fault characteristics, validating the design measure improvements. The results are useful in improving the design and manufacturing standards and enhancing the operational reliability of large tubular hydro-generators.

Cell-Free Massive MIMO: Zero Forcing and Conjugate Beamforming Receivers

Yao Zhang,Haotong Cao,Meng Zhou,Longxiang Yang 한국통신학회 2019 Journal of communications and networks Vol.21 No.6

In this paper, the uplink performance of cell-free massivemulti-input multi-output (mMIMO) system with the zero-forcing(ZF) and conjugate beamforming (CB) receivers is investigated. Anovel tight approximate rate expression for the ZF receiver is derived,which provides us with a tool for easily quantifying the impactsof the multi-antenna access point (AP), estimation error, pilotcontamination, and power control scheme. Then, leveraging on thetrackable ZF rate expression and the pre-studied CB rate expression,two power control algorithms are proposed. In particular, thefirst algorithm elaborates on maximizing the total rate, subjectingto the quality-of-service (QoS) constraint and each user power constraint. This algorithm utilizes the sequential convex approximationmethod to solve the non-convex issues. In addition, the secondaims at maximizing the rate of one user, in which the remainingusers can meet their QoS constraints. It can be characterized as ageometry programming. Simulation results are provided to showthat the ZF receiver is superior to the CB receiver in terms of sumrate and our proposed algorithms work well in many respects.

A reverse transcription loop-mediated isothermal amplification assay to rapidly diagnose foot-and-mouth disease virus C

Yao-zhong Ding,Jian-hua Zhou,Li-na Ma,Yan-ni Qi,Gang Wei,Jie Zhang,Yong-guang Zhang 대한수의학회 2014 JOURNAL OF VETERINARY SCIENCE Vol.15 No.3

A reverse transcription loop-mediated isothermalamplification (RT-LAMP) assay was developed to rapidlydetect foot-and-mouth disease virus serotype C (FMDV C). By testing 10-fold serial dilutions of FMDV C samples,sensitivity of the FMDV C RT-LAMP was found to be 10times higher than that of conventional reverse transcription-PCR (RT-PCR). No cross-reactivity with A, Asia 1, or OFMDV or swine vesicular disease virus (SVDV) indicatedthat FMDV C RT-LAMP may be an exciting novel method for detecting FMDV C.

Gut Microbiota Dysbiosis Correlates With Long COVID-19 at One-Year After Discharge

Zhang Dongmei,Zhou Yaya,Ma Yanling,Chen Ping,Tang Jian,Yang Bohan,Li Hui,Liang Mengyuan,Xue YuE,Liu Yao,Zhang Jianchu,Wang Xiaorong 대한의학회 2023 Journal of Korean medical science Vol.38 No.15

Background: Long coronavirus disease 2019 (COVID-19) in recovered patients (RPs) is gradually recognized by more people. However, how long it will last and the underlining mechanism remains unclear. Methods: We conducted a prospective follow-up study to evaluate the long-term symptoms and clinical indices of RPs at one-year after discharge from Union Hospital, Wuhan, China between December 2020 to May 2021. We also performed the 16S rRNA sequencing of stool samples from RPs and healthy controls (HCs) and analyzed the correlation between the gut microbiota and long COVID-19. Results: In total, 187 RPs were enrolled, among them, 84 (44.9%) RPs reported long COVID-19 symptoms at one-year after discharge. The most common long-term symptoms were cardiopulmonary symptoms, including chest tightness after activity (39/187, 20.9%), palpitations on exercise (27/187, 14.4%), sputum (21/187, 11.2%), cough (15/187, 8.0%) and chest pain (13/187, 7.0%), followed by systemic symptoms including fatigue (34/187, 18.2%) and myalgia (20/187, 10.7%), and digestive symptoms including constipation (14/187, 7.5%), anorexia (13/187, 7.0%), and diarrhea (8/187, 4.3%). Sixty-six (35.9%) RPs presented either anxiety or depression (42/187 [22.8%] and 53/187 [28.8%] respectively), and the proportion of anxiety or depression in the long symptomatic group was significantly higher than that in the asymptomatic group (41/187 [50.6%] vs. 25/187 [24.3%]). Compared with the asymptomatic group, scores of all nine 36-Item Short Form General Health Survey domains were lower in the symptomatic group (all P < 0.05). One hundred thirty RPs and 32 HCs (non-severe acute respiratory syndrome coronavirus 2 infected subjects) performed fecal sample sequencing. Compared with HCs, symptomatic RPs had obvious gut microbiota dysbiosis including significantly reduced bacterial diversities and lower relative abundance of short-chain fatty acids (SCFAs)-producing salutary symbionts such as Eubacterium_hallii_group, Subdoligranulum, Ruminococcus, Dorea, Coprococcus, and Eubacterium_ventriosum_group. Meanwhile, the relative abundance of Eubacterium_hallii_group, Subdoligranulum, and Ruminococcus showed decreasing tendencies between HCs, the asymptomatic group, and the symptomatic group. Conclusion: This study demonstrated the presence of long COVID-19 which correlates with gut microbiota dysbiosis in RPs at one-year after discharge, indicating gut microbiota may play an important role in long COVID-19.

Optimization for Scenedesmus obliquus Cultivation: the Effects of Temperature, Light Intensity and pH on Growth and Biochemical Composition

Zhang, Yonggang,Ren, Li,Chu, Huaqiang,Zhou, Xuefei,Yao, Tianming,Zhang, Yalei The Korean Society for Microbiology and Biotechnol 2019 한국미생물·생명공학회지 Vol.47 No.4

Microalgae have been explored as potential host species for biofuel production. Environmental factors affect algal growth and cellular composition. The effects of several key environmental factors, such as temperature, light, and pH of the medium on the growth and biochemical composition of Scenedesmus obliquus were investigated in this study. The highest growth rate of microalgae was observed at an optimal temperature of 25℃, 150 μmol/(m²·s) light intensity, and pH 10.0. The biochemical composition analysis revealed that the carbohydrate content decreased at lower (20℃) or higher temperature (35℃), whereas the protein and lipid contents increase at these temperatures. The fluctuation of light intensity significantly affected the contents of protein, carbohydrate, and lipid. The protein levels varied greatly when the pH of the medium was below 7.0. The carbohydrate and lipid contents significantly increased at pH above 7.0.

Detection of Listeria monocytogenes in CSF from Three Patients with Meningoencephalitis by Next-Generation Sequencing

Ming Yao,Jiali Zhou,Yicheng Zhu,Yinxin Zhang,Xia Lv,Ruixue Sun,Ao Shen,Haitao Ren,Liying Cui,Hongzhi Guan,Honglong Wu 대한신경과학회 2016 Journal of Clinical Neurology Vol.12 No.4

Background and Purpose Encephalitis caused by Listeria monocytogenes (L. monocyto¬genes) is rare but sometimes fatal. Early diagnosis is difficult using routine cerebrospinal flu¬id (CSF) tests, while next-generation sequencing (NGS) is increasingly being used for the detection and characterization of pathogens. Methods This study set up and applied unbiased NGS to detect L. monocytogenes in CSF collected from three cases of clinically suspected listeria meningoencephalitis. Results Three cases of patients with acute/subacute meningoencephalitis are reported. Magnetic resonance imaging and blood cultures led to a suspected diagnosis of L. monocy¬togenes, while the CSF cultures were negative. Unbiased NGS of CSF identified and se¬quenced reads corresponding to L. monocytogenes in all three cases. Conclusions This is the first report highlighting the feasibility of applying NGS of CSF as a diagnostic method for central nervous system (CNS) L. monocytogenes infection. Routine application of this technology in clinical microbiology will significantly improve diagnostic methods for CNS infectious diseases.