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Fang Guo, Yong Zou, Yongjiang Zheng
Moracin M, a phenolic component obtained from Mori Cortex, has been reported to have anti-inflammatory activities. The present study was designed to investigate the effects and mechanisms of Moracin M on lipopolysaccharide (LPS)-treated nucleus pulposus cells (NPCs) in intervertebral disc. NPCs were treated with moracin M at different concentrations for 1 h and then stimulated with LPS (0.5 μg/mL) for 24 h. The result demonstrated that moracin M could significantly inhibit LPS-induced inflammation. The elevated levels of IL-1β, TNF-α and IL-6 induced by LPS could be reversed by moracin M in NPCs...
March 17, 2018: International Immunopharmacology
Quanwei Zhang, Qi Wang, Jishang Gong, Jiaxing Du, Yong Zhang, Xingxu Zhao
Insulin-like growth factor 2 (IGF2) recapitulates many of the activities of insulin and promotes differentiation of myoblasts and osteoblasts, which likely contribute to genetic variations of growth potential. However, little is known about the functions and signaling properties of IGF2 variants in yaks. The over-expression vector and knockdown sequence of yak IGF2 were transfected into yak fibroblasts, and the effects were detected by a series of assays. IGF2 expression in yak muscle tissues was significantly lower than that of other tissues...
March 20, 2018: Genes
Flora Pirozzi, Kai Ren, Alessandra Murabito, Alessandra Ghigo
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by irreversible chronic inflammation and airflow obstruction. It affects more than 64 million patients worldwide and it is predicted to become the third cause of death in the industrialized world by 2030. Current available therapies are not able to block disease progression and to reduce mortality, underlying the need of a better understanding of COPD pathophysiological mechanisms to identify new molecular therapeutic targets...
March 20, 2018: Current Medicinal Chemistry
Delia De Lisi, Ugo De Giorgi, Cristian Lolli, Giuseppe Schepisi, Vincenza Conteduca, Cecilia Menna, Giuseppe Tonini, Daniele Santini, Alberto Farolfi
To date, results of combination therapy studies have shown no meaningful clinical benefit over monotherapy and an unacceptably high degree of toxicity in the treatment of metastatic renal cell carcinoma (RCC), with the exception of a combination of immune-checkpoint inhibitors and the association of lenvatinib with everolimus. Lenvatinib is a potent multi-targeted tyrosine kinase inhibitor that targets VEGFR pathways. Everolimus inhibits primarily mTORC1 complex, a downstream effecter of the intracellular PI3K/AKT/mTOR pathway...
March 20, 2018: Expert Opinion on Drug Metabolism & Toxicology
Tinglei Huang, Meiling Wang, Bo Huang, Augustus Chang, Feng Liu, Yanjie Zhang, Bin Jiang
As an evolutionarily conserved serine/threonine kinase of the phosphoinositide 3-kinase (PI3K) related kinase family, the mechanistic/mammalian target of rapamycin (mTOR) plays vital roles in the PI3K/AKT/mTOR pathway, participating in different cellular processes including cell survival, metabolism and proliferation. Aberrant activity of this signaling pathway may lead to oncogenesis. Over the last two decades, great progress has been made in the understanding of mTOR activation and how its response is counteracted for maintaining tissue homeostasis...
March 19, 2018: Apoptosis: An International Journal on Programmed Cell Death
Hitendra S Solanki, Remya Raja, Alex Zhavoronkov, Ivan V Ozerov, Artem V Artemov, Jayshree Advani, Aneesha Radhakrishnan, Niraj Babu, Vinuth N Puttamallesh, Nazia Syed, Vishalakshi Nanjappa, Tejaswini Subbannayya, Nandini A Sahasrabuddhe, Arun H Patil, T S Keshava Prasad, Daria Gaykalova, Xiaofei Chang, Rachana Sathyendran, Premendu Prakash Mathur, Annapoorni Rangarajan, David Sidransky, Akhilesh Pandey, Evgeny Izumchenko, Harsha Gowda, Aditi Chatterjee
EGFR-based targeted therapies have shown limited success in smokers. Identification of alternate signaling mechanism(s) leading to TKI resistance in smokers is critically important. We observed increased resistance to erlotinib in H358 NSCLC (non-small cell lung carcinoma) cells chronically exposed to cigarette smoke (H358-S) compared to parental cells. SILAC-based mass-spectrometry approach was used to study altered signaling in H358-S cell line. Importantly, among the top phosphosites in H358-S cells we observed hyperphosphorylation of EGFR (Y1197) and non-receptor tyrosine kinase FAK (Y576/577)...
January 2018: Oncoscience
Kai Huang, Chuan Fang, Kaikai Yi, Xing Liu, Hongzhao Qi, Yanli Tan, Junhu Zhou, Ying Li, Mingyang Liu, Yuqing Zhang, Jingxuan Yang, Jianning Zhang, Min Li, Chunsheng Kang
Exosomes play critical roles in intercellular communication in both nearby and distant cells in individuals and organs. Polymerase I and transcript release factor (PTRF), also known as Cavin1, has previously been described as a critical factor in caveola formation, and aberrant PTRF expression has been reported in various malignancies. However, the function of PTRF in tumor progression remains controversial, and its role in glioma is poorly understood. In this study, we report that PTRF is associated with malignancy grade and poor prognosis in glioma patients...
2018: Theranostics
Wei Chen, Xiaoqun Liu, Sujuan Yuan, Tiankui Qiao
Although cisplatin (CDDP) is widely used for non-small-cell lung cancer (NSCLC) treatment, resistance remains a major problem that restricts its efficacy. Therefore, identification of drugs that reverse or prevent resistance to CDDP in NSCLC has been a focus of a number of studies. The results of the present study revealed the effect of heat shock protein family A member 12B (HSPA12B) overexpression on chemoresistance in A549 cells in vitro . The effect of HSPA12B overexpression on chemoresistance in mice bearing A549 xenografted tumors was then determined via stable HSPA12B transfection...
March 2018: Oncology Letters
Xiaoyu Wang, Libing Wang, Yan Xu, Guohua Zhang, Yunlin Wu, Ping Chen
Protein inhibitor of activated signal transducer and activator of transcription-1 (PIAS1) is an important regulator of the inflammatory signaling network, the expression of which was decreased in gastric cancer and implicated in the development of cancer. However, its mechanism has not been elucidated. The aim of the present study was to investigate the effect of PIAS1 on epithelial-mesenchymal transition (EMT) of gastric cancer cells within the inflammatory microenvironment. Recombinant adenovirus Ad5/F35-PIASl and Ad5/F35-null plasmids were constructed to transfect SGC7901 cells...
March 2018: Oncology Letters
Jun Zhang, Xiaohong Xiang, Shuangshuang Shu, Cuiling Zhang, Yuling Liang, Tingting Jiang, Wenying Zhang, Tingting Guo, Xiujie Liang, Xun Tang
It is well known that autophagy serves a crucial role in renal tubular epithelial cell (RTEC) injury in the pathogenesis of chronic kidney disease (CKD). The accumulation of advanced oxidation protein products (AOPPs) also participates in the progression of CKD. However, the effects of AOPPs on autophagy remain unknown. To clarify the underlying mechanism of RTEC injury in CKD, the effect of AOPPs on HK-2 cells, an RTEC cell line, was investigated. The results of the present study revealed that AOPP exposure downregulated the expression of B-cell lymphoma-2-interacting myosin-like coiled-coil protein 1, reduced the conversion of microtubule-associated proteins 1 light chain 3B (LC3)-I to LC3-II and the formation of autophagosomes, and lead to an accumulation of p62...
April 2018: Experimental and Therapeutic Medicine
Anna Kovalchuk, Yaroslav Ilnytskyy, Rocio Rodriguez-Juarez, Amanda Katz, David Sidransky, Bryan Kolb, Olga Kovalchuk
While the refinement of existing and the development of new chemotherapeutic regimens has significantly improved cancer treatment outcomes and patient survival, chemotherapy still causes many persistent side effects. Central nervous system (CNS) toxicity is of particular concern, as cancer patients experience significant deficits in memory, learning, cognition, and decision-making. These chemotherapy-induced cognitive changes are termed chemo brain, and manifest in more than half of cancer survivors. Moreover, recent studies have emerged suggesting that neurocognitive deficits manifest prior to cancer diagnosis and treatment, and thus may be associated with tumor presence, a phenomenon recently termed "tumor brain...
2018: Frontiers in Genetics
Alison M Condliffe, Anita Chandra
The activated phosphoinositide 3-kinase δ syndrome (APDS), also known as p110δ-activating mutation causing senescent T cells, lymphadenopathy, and immunodeficiency (PASLI), is a combined immunodeficiency syndrome caused by gain-of-function mutations in the phosphoinositide 3-kinase (PI3K) genes PIK3CD (encoding p110δ: APDS1 or PASLI-CD) and PIK3R1 (encoding p85α: APDS2 or PASLI-R1). While the disease is clinically heterogeneous, respiratory symptoms and complications are near universal and often severe...
2018: Frontiers in Immunology
Cheng Fu, Jie Luo, Shaotang Ye, Ziguo Yuan, Shoujun Li
Avian-like H5N1 canine influenza virus (CIV) causes severe respiratory infections in dogs. However, the mechanism underlying H5N1 CIV infection in dogs is unknown. The present study aimed to identify differentially expressed miRNAs and mRNAs in the lungs and trachea in H5N1 CIV-infected dogs through a next-generation sequencing-based method. Eighteen 40-day-old beagles were inoculated intranasally with CIV, A/canine/01/Guangdong/2013 (H5N1) at a tissue culture infectious dose 50 (TCID50 ) of 106 , and lung and tracheal tissues were harvested at 3 and 7 d post-inoculation...
2018: Frontiers in Microbiology
Akihiko Kimura, Yuko Ishida, Machi Furuta, Mizuho Nosaka, Yumi Kuninaka, Akira Taruya, Naofumi Mukaida, Toshikazu Kondo
BACKGROUND: A clear understanding of the molecular mechanisms underlying hemodynamic stress-initiated cardiac hypertrophy is important for preventing heart failure. Interferon-γ (IFN-γ) has been suggested to play crucial roles in various diseases other than immunological disorders by modulating the expression of myriad genes. However, the involvement of IFN-γ in the pathogenesis of cardiac hypertrophy still remains unclear. METHODS AND RESULTS: In order to elucidate the roles of IFN-γ in pressure overload-induced cardiac pathology, we subjected Balb/c wild-type (WT) or IFN-γ-deficient ( Ifng -/- ) mice to transverse aortic constriction (TAC)...
March 19, 2018: Journal of the American Heart Association
Ming Zhang, Xiaoming Chi, Na Qu, CongYing Wang
Non-alcoholic fatty liver disease and steatohepatitis (NAFLD and NASH) account for the majority of liver disease in industrialized countries. However, the pathogenesis still unclear. Long non-coding RNAs (lncRNAs) has been reported to be involved in various pathophysiological processes. Here, we reported a novel role of lncARSR in hepatic lipogenesis in NAFLD. The expression of lncARSR was induced both in NAFLD patients and mouse model, as well as in hepatocytes treated with fatty acid. Moreover, overexpression of lncARSR enhanced while knockdown of lncARSR ameliorated hepatic lipid accumulation in vivo and in vitro...
March 16, 2018: Biochemical and Biophysical Research Communications
Li Huang, Meijuan Wang, Yongdong Yan, Wenjing Gu, Xinxing Zhang, Jiahong Tan, Huiming Sun, Wei Ji, Zhengrong Chen
BACKGROUND: The aim of this study was to investigate the mechanisms of OX40L in regulating helper T (Th) cells differentiation through phosphoinositide 3-kinase (PI3K)/AKT and p38 mitogen-activated protein kinase signaling pathway in vitro and in vivo experiments. METHODS: Serum samples of patients with asthma and healthy controls were used to explore the association between OX40L and Th cells. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum concentrations of OX40L, IL-4, IFN-γ, IL-17 and TGF-β...
March 20, 2018: Journal of Translational Medicine
Tang Bufu, Xu Di, Zhao Yilin, Liang Gege, Chen Xi, Wang Ling
Colorectal cancer (CRC) is one of the most frequent malignant tumors. Signaling by the PI3K/AKT pathway is crucial for CRC development and progression, including proliferation and migration. Celastrol has an anticancer effect, but its mechanism needs to be determined. Here, we showed that celastrol suppressed CRC cell proliferation and migration. Celastrol treatment also decreased the PI3K/AKT pathway components, and MMP3 and MMP7 expression levels. In addition, knockdown of AKT, not mTOR, inhibited MMP3 and MMP7 expression levels and AKT silencing promoted the celastrol-induced effects on CRC cell proliferation and migration...
March 16, 2018: Anti-cancer Drugs
Qun Dai, Yu-Qing Ge
Platycodin D(PD) has a significantly inhibitory effect on multiple malignant tumors, and can inhibit the proliferation of leukemia cells K562 and induce apoptosis. However, its effect in improving the sensitivity of drug-resistant cells to imatinib and their molecular mechanism remained unclear. To investigate the effect and mechanism of PD alone or combined with imatinib (IM) in inhibiting CML imatinib resistant cell line K562/R, the cell proliferation was examined by CCK8 assay to reveal the effect of PD on the inhibitory function of imatinib...
January 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Wen-Wen Sun, Jin-Xia Dou, Lin Zhang, Li-Kui Qiao, Na Shen, Wen-Yuan Gao
To compare the therapeutic effects of different treatment methods on the nude mice bearing colon cancer HT29 cells. BalB/C nude mice colon cancer stem cell models were established and randomly divided into the following four groups, with 8 nude mice in each group: blank control group, DC-CIK group, Huaier group, and Huaier combined with DC-CIK group (combined treatment group). The mice in DC-CIK group and combined treatment group received 1×10⁶ DC-CIK cells treatment by tail vein injectionafter the tumor stem cells were inoculated for 4 days,2 times a week for three weeks...
January 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Ya-Ping Xiao, Jie Zeng, Lin-Na Jiao, Xiao-Yu Xu
The treatment effect and signaling pathway regulation effects of kidney-tonifying traditional Chinese medicine on osteoporosis have been widely studied, but there is no systematic summary currently. This review comprehensively collected and analyzed the traditional Chinese medicines on the treatment and signaling pathway regulation of osteoporosis in recent ten years, such as Epimedii Folium, Drynariae Rhizoma, Cnidii Fructus, Eucommiae Cortex, Psoraleae Fructus and Dipsaci Radix. Based on the existing findings, the following conclusions were obtained: ①kidney-tonifying traditional Chinese medicine treated osteoporosis mainly through BMP-Smads, Wnt/ β -catenin, MAPK, PI3K/AKT signaling pathway to promote osteoblast bone formation and through OPG/RANKL/ RANK, estrogen, CTSK signaling pathway to inhibit osteoclasts of bone resorption...
January 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
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