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https://www.readbyqxmd.com/read/28938737/complex-catsper-dependent-and-independent-ca2-i-signalling-in-human-spermatozoa-induced-by-follicular-fluid
#1
Sean G Brown, Sarah Costello, Mark C Kelly, Mythili Ramalingam, Ellen Drew, Stephen J Publicover, Christopher L R Barratt, Sarah Martins Da Silva
STUDY QUESTION: Does progesterone in human follicular fluid (hFF) activate CatSper and do other components of hFF modulate this effect and/or contribute separately to hFF-induced Ca2+ signaling? SUMMARY ANSWER: hFF potently stimulates CatSper and increases [Ca2+]i, primarily due to high concentrations of progesterone, however, other components of hFF also contribute to [Ca2+]i signaling, including modulation of CatSper channel activity and inhibition of [Ca2+]i oscillations...
October 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28938694/preclinical-evidence-of-ghrelin-as-a-therapeutic-target-in-epilepsy
#2
REVIEW
Tongtong Ge, Wei Yang, Jie Fan, Bingjin Li
Ghrelin, an orexigenic peptide synthesized by endocrine cells of the gastric mucosa, plays a major role in inhibiting seizures. However, the underlying mechanism of ghrelin's anticonvulsant action is still unclear. Nowadays, there are considerable evidences showing that ghrelin is implicated in various neurophysiological processes, including learning and memory, neuroprotection, neurogenesis, and inflammatory effects. In this review, we will summarize the effects of ghrelin on epilepsy. It may provide a comprehensive picture of the role of ghrelin in epilepsy...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938693/the-regulation-of-immune-cells-by-lactobacilli-a-potential-therapeutic-target-for-anti-atherosclerosis-therapy
#3
REVIEW
Ya-Hui Ding, Lin-Yan Qian, Jie Pang, Jing-Yang Lin, Qiang Xu, Li-Hong Wang, Dong-Sheng Huang, Hai Zou
Atherosclerosis is an inflammatory disease regulated by several immune cells including lymphocytes, macrophages and dendritic cells. Gut probiotic bacteria like Lactobacilli have been shown immunomodificatory effects in the progression of atherogenesis. Some Lactobacillus stains can upregulate the activity of regulatory T-lymphocytes, suppress T-lymphocyte helper (Th) cells Th1, Th17, alter the Th1/Th2 ratio, influence the subsets ratio of M1/M2 macrophages, inhibit foam cell formation by suppressing macrophage phagocytosis of oxidized low-density lipoprotein, block the activation of the immune system with dendritic cells, which are expected to suppress the atherosclerosis-related inflammation...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938651/positive-transcription-elongation-factor-b-p-tefb-is-a-therapeutic-target-in-human-multiple-myeloma
#4
Yu Zhang, Liang Zhou, Yun Leng, Yun Dai, Robert Z Orlowski, Steven Grant
The role of the positive RNA Pol II regulator, P-TEFb (positive transcription elongation factor b), in maintenance of the anti-apoptotic protein Mcl-1 and bortezomib (btz) resistance was investigated in human multiple myeloma (MM) cells. Mcl-1 was up-regulated in all MM lines tested, including bortezomib-resistant lines, human MM xenograft mouse models, and primary CD138(+) MM cells. Mcl-1 over-expression significantly reduced bortezomib lethality, indicating a functional role for Mcl-1 in bortezomib resistance...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938648/a-novel-lncrna-ll22nc03-n64e9-1-represses-klf2-transcription-through-binding-with-ezh2-in-colorectal-cancer
#5
Yifan Lian, Changsheng Yan, Jie Ding, Rui Xia, Zhonghua Ma, Bingqing Hui, Hao Ji, Jing Zhou, Keming Wang
Long noncoding RNAs (lncRNA) have been implicated in variety human cancer but their mechanisms of function are mainly undocumented. In the present study, we investigated lncRNAs alteration that contributed to colorectal cancer (CRC) by utilizing TCGA RNA sequencing data and other publicly available lncRNAs expression profiling data. Here, We screened out the CRC-associated lncRNA LL22NC03-N64E9.1, a key regulator of CRC development and progression. We also revealed that knockdown of LL22NC03-N64E9.1 inhibited cell proliferation, colony formation, tumorigenicity and apoptosis promotion, both in vitro and in vivo...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938647/long-non-coding-rna-malat1-for-promoting-metastasis-and-proliferation-by-acting-as-a-cerna-of-mir-144-3p-in-osteosarcoma-cells
#6
Yong Wang, Yueyang Zhang, Tao Yang, Wei Zhao, Ningning Wang, Pengcheng Li, Xiandong Zeng, Weiguo Zhang
Long non-coding RNAs (lncRNAs) are involved in various biological processes and diseases including osteosarcoma. Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is overly expressed in osteosarcoma. But the function and mechanism it works on in osteosarcoma proliferation and metastasis mediated by Rho associated coiled-coil containing protein kinase 1 (ROCK1) and Rho associated coiled-coil containing protein kinase 2 (ROCK2) remain unclear. In the present study, an elevated MALAT1 was found in osteosarcoma tissues and cell lines, and the elevated MALAT1 was correlated with a poor prognosis in osteosarcoma patients...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938642/facile-total-synthesis-of-lysicamine-and-the-anticancer-activities-of-the-ru-ii-rh-iii-mn-ii-and-zn-ii-complexes-of-lysicamine
#7
Jiao-Lan Qin, Ting Meng, Zhen-Feng Chen, Xiao-Li Xie, Qi-Pin Qin, Xiao-Ju He, Ke-Bin Huang, Hong Liang
Lysicamine is a natural oxoaporphine alkaloid, which isolated from traditional Chinese medicine (TCM) herbs and has been shown to possess cytotoxicity to hepatocarcinoma cell lines. Reports on its antitumor activity are scarce because lysicamine occurs in plants at a low content. In this work, we demonstrate a facile concise total synthesis of lysicamine from simple raw materials under mild reaction conditions, and the preparation of the Ru(II), Rh(III), Mn(II) and Zn(II) complexes 1-4 of lysicamine (LY). All the compounds were fully characterized by elemental analysis, IR, ESI-MS, (1)H and (13)C NMR, as well as single-crystal X-ray diffraction analysis...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938641/potential-independent-action-of-sigma-receptor-ligands-through-inhibition-of-the-kv2-1-channel
#8
Xinying Liu, Yingmei Fu, Huan Yang, Timur Mavlyutov, Jun Li, Christopher R McCurdy, Lian-Wang Guo, Bikash R Pattnaik
The sigma-1 receptor (σ1-R) and sigma-2 receptor (σ2-R) are potential drug targets for treatment of cancer, pain, depression, retinal degeneration and other neuronal diseases. Previous reports show that sigma-1 receptor modulates the activities of multiple channels. We are interested in possible sigma receptor modulation of Kv2.1, a K(+) channel abundant in retinal photoreceptors. We tested the effect of established sigma receptor ligands on Kv2.1 channels which were stably expressed in HEK293 cells. Surprisingly, σ1-R antagonists inhibited Kv2...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938639/spondin2-is-a-new-prognostic-biomarker-for-lung-adenocarcinoma
#9
Xiaopeng Yuan, Tingting Bian, Jian Liu, Honggang Ke, Jia Feng, Qing Zhang, Li Qian, Xiaoli Li, Yifei Liu, Jianguo Zhang
Spondin 2 (SPON2) is a member of the F-spondin superfamily of genes that encode an extracellular matrix protein. SPON2 has been identified by mRNA differential display screening of cancerous and noncancerous lung cell lines in vitro [1], however, its role in pulmonary adenocarcinoma (ADC) patients remains unclear. In our study, we evaluated whether SPON2 can be used as a biomarker for the diagnosis of pulmonary ADC and any association between SPON2 protein levels and clinicopathological characteristics. Firstly, the mRNA levels of SPON2 in pulmonary ADCs and normal adjacent tissue samples were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR) (n = 60) assay and the expression of SPON2 protein were detected by tissue microarray immunohistochemistry analysis (TMA-IHC) (n = 280)...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938637/the-loss-of-function-of-dna-methyltransferase-1-by-sirna-impairs-the-growth-of-non-small-cell-lung-cancer-with-alleviated-side-effects-via-reactivation-of-rassf1a-and-apc-in-vitro-and-vivo
#10
Qi Lai, Yin-Hui Xu, Qiang Chen, Liang Tang, An-Gui Li, Li-Fei Zhang, Chun-Fang Zhang, Jian-Fei Song, Zhen-Zong Du
Hypermethylation of tumor suppressor genes (TSGs) promoters by DNA methyltransferase (DNMT) can be observed in almost all cancers which represent a hallmark of carcinogenesis, including lung cancer. DNMT inhibitors (e.g.5-Aza-CR/CdR) reactivate TSGs to exert anti-cancer activity and have been applied into the clinical. However, it is cytotoxic even at low concentrations, which might be not directly related to DNA methylation. We here investigated an alternative strategy in the lung cancer therapy and aimed to estimate and compare its efficiency and side effects of knockdown of DNMT1 in vitro and in vivo...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938629/role-of-caspase-3-e-cadherin-in-helicobacter-pylori-induced-apoptosis-of-gastric-epithelial-cells
#11
Yongmei Yang, Jie Du, Fen Liu, Xiaoyan Wang, Xiaohui Li, Yuanjian Li
This study was designed to investigate the role of caspase-3/E-cadherin in Helicobacter pylori (H. pylori) -induced gastric epithelial apoptosis in cells, animal models and clinical gastritis patients. In cultured gastric mucosal epithelial cells, gastric glandular epithelial cells and C57BL/6 mice, H. pylori infection significantly induced apoptosis of gastric epithelial cells, down-regulated full-length E-cadherin and Bcl-2 expression, and up-regulated cleaved-caspase-3, E-cadherin/carboxy-terminal fragment 3 and Bax expression...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938628/mir-144-promotes-%C3%AE-amyloid-accumulation-induced-cognitive-impairments-by-targeting-adam10-following-traumatic-brain-injury
#12
Liqian Sun, Manman Zhao, Jingbo Zhang, Aihua Liu, Wenjun Ji, Youxiang Li, Xinjian Yang, Zhongxue Wu
The dysregulation expression of microRNAs (miRNAs) including miR-144, has been widely documented in TBI. However, little is known about the potential roles of miR-144 in the pathogenesis of TBI. In this study, we investigated the potential effects of miR-144 on cognitive function in vivo and in vitro. The results indicated that inhibition of miR-144 conferred a better neurological outcome after TBI in vivo, as evidenced by reduced lesion volume, alleviated brain edema and increased mNSS, of particular importance, improved cognitive deficits...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938624/addition-of-2-ethylamino-acetonitrile-group-to-nitroxoline-results-in-significantly-improved-anti-tumor-activity-in-vitro-and-in-vivo
#13
Ana Mitrović, Izidor Sosič, Špela Kos, Urša Lampreht Tratar, Barbara Breznik, Simona Kranjc, Bojana Mirković, Stanislav Gobec, Tamara Lah, Gregor Serša, Janko Kos
Lysosomal cysteine peptidase cathepsin B, involved in multiple processes associated with tumor progression, is validated as a target for anti-cancer therapy. Nitroxoline, a known antimicrobial agent, is a potent and selective inhibitor of cathepsin B, hence reducing tumor progression in vitro and in vivo. In order to further improve its anti-cancer properties we developed a number of derivatives using structure-based chemical synthesis. Of these, the 7-aminomethylated derivative (compound 17) exhibited significantly improved kinetic properties over nitroxoline, inhibiting cathepsin B endopeptidase activity selectively...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938623/mifepristone-inhibits-ovarian-cancer-metastasis-by-intervening-in-sdf-1-cxcr4-chemokine-axis
#14
Ning Zheng, Jiahang Chen, Weiqun Liu, Jian Liu, Tao Li, Hongning Chen, Jichuang Wang, Lee Jia
SDF-1/CXCR4 signaling axis determines the proliferative potential and site-specific cancer metastasis. Recent studies suggest involvement of the axis and steroidal hormone in ovarian cancer metastasis. Here we hypothesize that mifepristone (RU486), a well-known progesterone-based abortifacient, might interfere this axis and inhibit ovarian cancer metastasis. Mifepristone at concentrations < IC50 inhibited expression of CXCR4 on cell surface of ovarian cancer SKOV-3 and IGROV-1, and reduced expression of the intracellular CXCR4 protein and its related mRNA activated by SDF-1...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938620/pathological-expression-of-tissue-factor-confers-promising-antitumor-response-to-a-novel-therapeutic-antibody-sc1-in-triple-negative-breast-cancer-and-pancreatic-adenocarcinoma
#15
Xuesai Zhang, Qingrou Li, Hui Zhao, Lanping Ma, Tao Meng, Jianchang Qian, Rui Jin, Jingkang Shen, Ker Yu
The pathological presence of tissue factor (TF) in cancer cells promotes tumor-initiated thrombosis and cancer metastasis. We found that TF is aberrantly present in large percentage of aggressive triple negative breast cancer (TNBC) and pancreatic adenocarcinoma (PaC), two most lethal forms of malignancy that urgently need effective treatment. TF expression in TNBC clustered with higher levels of vimentin, basal-type keratins KRT5/14 and caveolin-1 but lower levels of luminal-type biomarkers. We developed a novel and specific anti-TF therapeutic antibody SC1, which displayed an exceedingly high potency against TF extracellular domain (EC50: 0...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938619/anti-cancer-efficacy-of-biotinylated-chitosan-nanoparticles-in-liver-cancer
#16
Mingrong Cheng, Weiping Zhu, Qing Li, Dejian Dai, Yiming Hou
The present study investigated the synthesis of biotinylated chitosan (Bio-CS) from chitosan using a nanomaterial skeleton with biotin and the successful targeting of the formulation in liver cancer cells. Bio-CS was validated by fourier transformed infrared spectroscopy and hydrogen(-1) nuclear magnetic resonance spectroscopy. Bio-CS and plasmid DNA were used to construct Bio-CS/plasmid DNA nanoparticles according to the optimal molar ratio of 1:1 and the optimal pH-value of 5.5. Under these conditions, the parameters mean particle size, potential, encapsulation rate and drug loading, were 82...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938614/phenformin-enhances-the-therapeutic-effect-of-selumetinib-in-kras-mutant-non-small-cell-lung-cancer-irrespective-of-lkb1-status
#17
Jun Zhang, Sreenivas Nannapaneni, Dongsheng Wang, Fakeng Liu, Xu Wang, Rui Jin, Xiuju Liu, Mohammad Aminur Rahman, Xianghong Peng, Guoqing Qian, Zhuo G Chen, Kwok-Kin Wong, Fadlo R Khuri, Wei Zhou, Dong M Shin
MEK inhibition is potentially valuable in targeting KRAS-mutant non-small cell lung cancer (NSCLC). Here, we analyzed whether concomitant LKB1 mutation alters sensitivity to the MEK inhibitor selumetinib, and whether the metabolism drug phenformin can enhance the therapeutic effect of selumetinib in isogenic cell lines with different LKB1 status. Isogenic pairs of KRAS-mutant NSCLC cell lines A549, H460 and H157, each with wild-type and null LKB1, as well as genetically engineered mouse-derived cell lines 634 (kras(G12D/wt)/p53(-/-)/lkb1(wt/wt)) and t2 (kras(G12D/wt)/p53(-/-)/lkb1(-/-)) were used in vitro to analyze the activities of selumetinib, phenformin and their combination...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938609/pegylated-arginine-deiminase-can-modulate-tumor-immune-microenvironment-by-affecting-immune-checkpoint-expression-decreasing-regulatory-t-cell-accumulation-and-inducing-tumor-t-cell-infiltration
#18
Elena Brin, Katherine Wu, Hsin-Tze Lu, Yudou He, Zhaoming Dai, Wei He
PEGylated arginine deiminase (ADI-PEG 20) is being investigated in clinical studies in arginine auxotrophic cancers and is well-tolerated. The anti-tumor properties of ADI-PEG 20 have been extensively investigated - ADI-PEG 20 inhibits the growth of auxotrophic cancers in vitro and in vivo - however, its impact on immune cells is largely unknown. Here we report the potential impact of ADI-PEG 20 on the tumor immune microenvironment. ADI-PEG 20 induced immunosuppressive programmed death-ligand 1 expression on some cancer cells in vitro, but the magnitude of the increase was cell line dependent and in most relatively small...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938606/oroxylin-a-inhibits-colitis-by-inactivating-nlrp3-inflammasome
#19
Wei Zhou, Xiuting Liu, Xin Zhang, Jingjing Tang, Zhiyu Li, Qing Wang, Rong Hu
NLRP3 inflammasome is a novel therapeutic target for inflammatory bowel disease (IBD). The aim of this study was to investigate the anti-inflammatory effect of a bioactive flavonoid-oroxylin A on the treatment of dextran sulfate sodium (DSS)-induced murine colitis via targeting NLRP3 inflammasome. In this study, we found that oroxylin A attenuated experimental colitis in mice, including loss of body weights, shortening of the colon lengths and infiltration of inflammatory cells. The production of IL-1β, IL-6 and TNF-α in colon was also markedly reduced by oroxylin A...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938603/inhibition-of-avian-tumor-virus-replication-by-ccch-type-zinc-finger-antiviral-protein
#20
Mingjun Zhu, Xiaoqian Ma, Xiyao Cui, Jing Zhou, Chengui Li, Libo Huang, Yingli Shang, Ziqiang Cheng
CCCH type zinc finger antiviral protein (ZAP) is a host restriction factor that inhibits the replication of a variety of viruses in mammals. However, little is known about its antiviral activity on avian tumor virus. Avian leukosis virus subgroup J (ALV-J), an oncogenic retrovirus, induces myelocytomas and various other tumors in meat and egg type chickens. Here, we identified a chicken ZAP (chZAP) that increased at early stage, and subsequently decreased after infection of ALV-J in DF-1 cells, indicating the inducible feature of the endogenous chZAP...
August 29, 2017: Oncotarget
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