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https://www.readbyqxmd.com/read/30535458/role-of-the-mtor%C3%A2-foxo1-pathway-in-obesity%C3%A2-associated-renal-tubulointerstitial-inflammation
#1
Hong Sun, Xinyu Shao, Jiajia He, Michal Golos, Bimin Shi
Since obesity is largely responsible for the growing incidence of renal tubulointerstitial inflammation, exploration into the mechanisms of obesity‑associated tubulointerstitial inflammation is essential. Studies have demonstrated that mammalian target of rapamycin (mTOR) is a crucial molecule in the pathogenesis of renal inflammation, including regulating the expression of inflammatory factors. The purpose of the present study was to further elucidate the role of mTOR in obesity‑associated tubulointerstitial inflammation...
December 5, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/30510689/an-in-vitro-method-for-nephrotoxicity-evaluation-using-hk-2-human-kidney-epithelial-cells-combined-with-biomarkers-of-nephrotoxicity
#2
Xuan Qiu, Xiaobing Zhou, Yufa Miao, Bo Li
The kidney is one of the major target organs for drug-induced toxicity. During drug development, the traditional markers of nephrotoxicity indicate only severe and late damage, which leads to high costs. The new biomarkers are needed for a more sensitive and reliable evaluation of nephrotoxicity, especially for the regulatory accepted and validated in vitro model. We developed an in vitro model based on the HK-2 cell using the biomarkers of nephrotoxicity as endpoints for the evaluation of nephrotoxicity. The predictive performance of the biomarkers including LDH, GGT, KIM-1, clusterin, CysC, NGAL, TIMP-1, GSTπ and osteopontin was evaluated with 22 well characterized compounds...
November 1, 2018: Toxicology Research
https://www.readbyqxmd.com/read/30507306/in-vitro-cytotoxicity-evaluation-of-thiourea-derivatives-bearing-salix-sp-constituent-against-hk-1-cell-lines
#3
Norsyafikah Asyilla Nordin, Vannessa Lawai, Zainab Ngaini, Ainaa Nadiah Abd Halim, Siaw San Hwang, Reagan Entigu Linton, Boon Kiat Lee, Paul Matthew Neilsen
In searching for drugs from natural product scaffolds has gained interest among researchers. In this study, a series of twelve halogenated thiourea (ATX 1-12) via chemical modification of aspirin (a natural product derivative) and evaluated for cytotoxic activity against nasopharyngeal carcinoma (NPC) cell lines, HK-1 via MTS-based colorimetric assay. The cytotoxicity studies demonstrated that halogens at meta position of ATX showed promising activity against HK-1 cells (IC50 value ≤15 µM) in comparison to cisplatin, a positive cytotoxic drug (IC50 value =8...
December 3, 2018: Natural Product Research
https://www.readbyqxmd.com/read/30502093/pyrroloquinoline-quinine-protects-hk-2-cells-against-high-glucose-induced-oxidative-stress-and-apoptosis-through-sirt3-and-pi3k-akt-foxo3a-signaling-pathway
#4
Ziqiang Wang, Ying Li, Ying Wang, Kunxiao Zhao, Yanqing Chi, Baoxing Wang
High glucose(HG)-induced oxidative stress and apoptosis in renal tubular epithelial cells play an important role in the pathogenesis of diabetic nephropathy. Pyrroloquinoline quinine (PQQ), a new B vitamin, has been demonstrated to be important in antioxidant and anti-apoptotic effects. However, its effect on HK-2 cells and the potential mechanism are rarely investigated. In this study, we investigated that PPQ had protective effects against HG-induced oxidative stress damage and apoptosis in vitro model of diabetic nephropathy...
November 28, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/30501438/the-risk-of-dermatological-toxicities-of-combined-braf-and-mek-inhibition-versus-braf-inhibition-alone-in-melanoma-patients-a-systematic-review-and-meta-analysis
#5
Chen Peng, Chen Fuchao, Zhou Benhong
BACKGROUND: This meta-analysis was conducted to assess the risk of dermatological toxicities of combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma patients. METHODS: We considered relevant prospective randomized Phase I, II and III trials of melanoma patients on the combined BRAF and MEK inhibition versus BRAF inhibition, describing events of rash, photosensitivity reaction (PR), hyperkeratosis (HK), alopecia, cutaneous squamous-cell carcinom(cSCC), skin papilloma(SP), pruritus and hand-foot syndrome(HFS), as eligible for inclusion...
December 2, 2018: Cutaneous and Ocular Toxicology
https://www.readbyqxmd.com/read/30496037/hypermethylated-in-cancer-1-hic1-mediates-high-glucose-induced-ros-accumulation-in-renal-tubular-epithelial-cells-by-epigenetically-repressing-sirt1-transcription
#6
Sheng Zeng, Xiaoyan Wu, Xuyang Chen, Huihui Xu, Tao Zhang, Yong Xu
Reactive oxygen species (ROS) is a key regulator of an array of physiological and pathological processes. While essential for the host defense mechanism, excessive ROS generation and/or deficient clearance is blamed for the pathogenesis of human diseases. In the present study, we investigated the regulatory role of hypermethylated in cancer 1 (HIC1), a transcription factor, in high glucose-induced ROS accumulation in renal tubular epithelial cells (HK-2). Treatment with high glucose (HG) not only markedly up-regulated HIC1 expression but prompted its translocation into the nucleus...
October 2018: Biochimica et biophysica acta. Gene regulatory mechanisms
https://www.readbyqxmd.com/read/30485514/microrna-194-overexpression-protects-against-hypoxia-reperfusion-induced-hk-2-cell-injury-through-direct-targeting-rheb
#7
Yan Shen, Yan Zhao, Lijun Wang, Wenjing Zhang, Chao Liu, Aiping Yin
Renal ischemia-reperfusion injury, a major cause of renal failure, always leads to acute kidney injury and kidney fibrosis. MicroRNAs (miRs) have been reported to be associated with renal ischemia-reperfusion injury. miR-194 was downregulated following renal ischemia-reperfusion injury; however, the function and mechanism of miR-194 in renal ischemia-reperfusion injury have not yet been fully understood. In the present study, we constructed renal ischemia-reperfusion injury model in vitro through treatment of human kidney proximal tubular epithelial cells HK-2 by hypoxia/reperfusion (H/R)...
November 28, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/30483732/astragaloside-iv-ameliorates-high-glucose%C3%A2-induced-renal-tubular-epithelial%C3%A2-mesenchymal-transition-by-blocking-mtorc1-p70s6k-signaling-in-hk%C3%A2-2-cells
#8
Xiao Chen, Yang Yang, Chenxu Liu, Zhigao Chen, Dongdong Wang
Astragaloside IV (AST) is the major active saponin in Astragalus membranaceus and, reportedly, has a variety of pharmacological activities. However, the potential of AST to ameliorate high glucose‑mediated renal tubular epithelial‑mesenchymal transition (EMT) remains undetermined. The aim of the present research was to explore the effect and mechanism of AST in EMT of renal tubular epithelial cells, as an underlying mechanism of renal fibrosis and a vital feature involved in diabetic nephropathy. The effect of AST on the EMT of renal tubular epithelial cells (HK‑2) stimulated by high glucose was investigated and it was attempted to elucidate the potential underlying mechanism...
November 26, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/30474301/microrna-34a-inhibit-hepatocellular-carcinoma-progression-by-repressing-hexokinase-1
#9
Yitong Zhou, Kai Liu, Yahui Liu, Ludong Tan
Hepatocellular carcinoma (HCC) is known as a frequent type of primary cancer in the liver, and it is the third-most common cause of cancer-related death all over the world. However, the molecular mechanism in the progression of HCC is still unclear. The current study was designed to investigate the expression and function of microRNA-34a (miR-34a) in HCC. In HCC tissues and cells, the expression levels of miR-34a were analyzed by quantitative real-time polymerase chain reaction. The association between the level of miR-34a and hexokinase (HK)-1 was also investigated via luciferase reporter assay...
November 26, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/30472374/folate-dactolisib-conjugates-for-targeting-tubular-cells-in-polycystic-kidneys
#10
Haili Shi, Wouter N Leonhard, Niels J Sijbrandi, Mies J van Steenbergen, Marcel H A M Fens, Joep B van de Dikkenberg, Javier Sastre Toraño, Dorien J M Peters, Wim E Hennink, Robbert Jan Kok
The aim of the present study was to develop folic acid (FA) conjugates which can deliver the kinase inhibitor dactolisib to the kidneys via folate receptor-mediated uptake in tubular epithelial cells. Dactolisib is a dual inhibitor of phosphatidylinositol 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) and is considered an attractive agent for treatment of polycystic kidney disease. The ethylenediamine platinum(II) linker, herein called Lx, was employed to couple dactolisib via coordination chemistry to thiol-containing FA-spacer adducts to yield FA-Lx-dactolisib conjugates...
November 23, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/30465787/clozapine-induced-reduction-of-l-carnitine-reabsorption-via-inhibition-down-regulation-of-renal-carnitine-organic-cation-transporter-2-contributes-to-liver-lipid-metabolic-disorder-in-mice
#11
Wei Wang, Mengru Bai, Ting Jiang, Cui Li, Ping Li, Hui Zhou, Zemin Wang, Liping Li, Huidi Jiang
Clozapine, an atypical antipsychotic drug, is widely utilized for the treatment of schizophrenia; however, clozapine-induced metabolic disorders, such as fatty liver and weight gain, warrant increased attention. Considering the crucial role of l-carnitine (L-Car) in fatty acid oxidation and carnitine/organic cation transporter (OCTN) 2 in renal reabsorption of L-Car, we aimed to study whether clozapine-induced liver lipid metabolic disorder is associated with L-Car dysregulation via inhibition/down-regulation of renal OCTN2...
November 19, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/30456273/proteomic-profiling-data-of-hek293-proteins-bound-to-human-recombinant-renalases-1-and-2
#12
Valerii I Fedchenko, Arthur T Kopylov, Olga A Buneeva, Alexei A Kaloshin, Victor G Zgoda, Alexei E Medvedev
Renalase (RNLS) is a recently discovered protein involved in blood pressure regulation. It exists both as an intracellular catalytically active flavoprotein (EC 1.6.3.5 dihydro-NAD(P):oxygen oxidoreductase) and an extracellular protein that demonstrates various cell protecting effects. Using a twenty-membered peptide corresponding to the residues 220-239 of the renalase sequence (RP-220) and the HK-2 cell line Wang et al. identified a renalase-binding protein, which was considered as a receptor for extracellular renalase crucial for MAPK signaling (Wang et al...
December 2018: Data in Brief
https://www.readbyqxmd.com/read/30452898/omeprazole-protects-against-cisplatin-induced-nephrotoxicity-by-alleviating-oxidative-stress-inflammation-and-transporter-mediated-cisplatin-accumulation-in-rats-and-hk-2-cells
#13
Huan Gao, Sixi Zhang, Tingting Hu, Xiaoyu Qu, Jinghui Zhai, Yueming Zhang, Lina Tao, Jianyuan Yin, Yanqing Song
The present study assessed the therapeutic potential of omeprazole (OME), the most commonly prescribed proton pump inhibitor (PPI) used to treat gastroesophageal hyperacidity, against cisplatin (CP)-induced toxicity in human renal tubular HK-2 cells and rat kidneys. Herein, we observed that exposure of HK-2 cells to OME reversed the injury caused by CP, including enhancing cell viability and alleviating intracellular reactive oxygen species (ROS) generation and membrane damage. Concomitantly, acute exposure of male SD rats to CP induced histopathological changes, which were prevented by co-administration with OME...
November 16, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/30450602/igfbp7-regulates-sepsis-induced-acute-kidney-injury-through-erk1-2-signaling
#14
Xiaolin Wang, Teng Ma, Xiaojian Wan, Yan Meng, Zhenzhen Zhao, Jinjun Bian, Rui Bao, Xiaoming Deng, Tao Yang
IGFBP7 as an early biomarker has been used to identify patients at risk of developing acute kidney injury (AKI). Nevertheless, its role in AKI remains obscure. The aim of our study is to determine the role and mechanism of IGFBP7 in lipopolysaccharide (LPS)-induced HK-2 cells in vitro and on sepsis-induced AKI by cecal ligation and puncture (CLP) in vivo. Here, we identified that IGFBP7 expression was increased in patients with AKI and HK-2 cells with LPS (1, 2, and 5 μg/mL) induction. HK-2 cells with LPS induction showed cell cycle arrest at G1-G0 phases and cell apoptosis and activated ERK1/2 parallel with the changes in the proteins belonging to the ERK1/2 pathway, including Cyclin D1, P21, Bax, and Bcl-2, which were inhibited by the IGFBP7 knockdown...
November 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/30445987/sirtuin-3-deficiency-aggravates-contrast-induced-acute-kidney-injury
#15
Qinghai Zhang, Xun Liu, Na Li, Jihong Zhang, Jianmin Yang, Peili Bu
BACKGROUND: Sirtuin 3 (Sirt3) is a key regulator of energy metabolism and oxidative stress. To investigate the role of Sirt3 in contrast-induced acute kidney injury (CIAKI), we established the model both in vivo and in vitro to explore the potential mechanisms. METHODS: In vivo, we established CIAKI models in wild-type (WT) and Sirt3-knockout (Sirt3-KO) mice. Blood urea nitrogen (BUN) and serum creatinine (Scr) were detected by enzyme-linked immunosorbent assay, Glomerular Filtration Rate (GFR) and creatinine clearance were also investigated...
November 16, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/30425061/targeting-the-cda1-cda1bp1-axis-retards-renal-fibrosis-in-experimental-diabetic-nephropathy
#16
Zhonglin Chai, Tieqiao Wu, Aozhi Dai, Pacific Huynh, Frank Koentgen, Guy Krippner, Shuting Ren, Mark E Cooper
Targeting Cell Division Autoantigen 1 (CDA1) is postulated to attenuate the profibrotic actions of transforming growth factor-β in diabetic nephropathy. This study has identified a regulatory protein for CDA1 and has then used genetic and pharmacological approaches to test in vivo if strategies to target this pathway would lead to reduced renal injury. A novel protein, named CDA1BP1, was identified as critical in regulating the profibrotic activity of CDA1. Genetic deletion of CDA1BP1 attenuated key parameters of renal fibrosis in diabetic mice...
November 13, 2018: Diabetes
https://www.readbyqxmd.com/read/30417389/the-pkc%C3%AE-p66shc-nadph-oxidase-pathway-plays-a-crucial-role-in-diabetic-nephropathy
#17
Yu-Si Cheng, Jie Chao, Chen Chen, Lin-Li Lv, Yu-Chen Han, Bi-Cheng Liu
OBJECTIVES: Oxidative stress plays a critical role in the pathogenesis of diabetic nephropathy (DN). p66shc is closely related to oxidative stress. However, the exact mechanism of its involvement in diabetic nephropathy is poorly understood. This study aimed to investigate the role of the p66shc-related pathway in diabetic nephropathy. METHODS: In an in-vivo experiment, rats were injected with streptozotocin to induce early diabetic nephropathy. The treatment groups were an aminoguanidine group and an enzastaurin group...
November 12, 2018: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/30410608/cip2a-promotes-proliferation-invasion-and-chemoresistance-to-cisplatin-in-renal-cell-carcinoma
#18
Yongzhen Zhang, Liang Fang, Yuanwei Zang, Juchao Ren, Zhonghua Xu
CIP2A is a well-known oncoprotein whose expression is elevated in multiple human solid tumor types. However, its role in renal cell carcinoma (RCC) development is poorly understood. Thus, in our present study, we used the renal cancer cell lines 786-O, A498 and CAKI-1 and the renal epithelial cell line HK-2 to clarify the function of CIP2A in RCC. We found that CIP2A expression is much higher in the RCC cells than in the normal renal epithelial cell. Lentivirus covered coding region CIP2A cDNA sequence and CIP2A siRNA were used to up and down regulate CIP2A expression in vitro ...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/30408549/withdrawn-spleen-tyrosine-kinase-syk-protects-renal-tubular-epithelial-cell-against-hypoxia-injury-in-children-with-acute-kidney-injury
#19
Zhiyong Zhang, Ya Gao, Ximin Qiao
This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
November 5, 2018: Gene
https://www.readbyqxmd.com/read/30407728/%C3%AE-secretase-inhibitor-dapt-mitigates-cisplatin-induced-acute-kidney-injury-by-suppressing-notch1-signaling
#20
Hitesh Soni, Anberitha T Matthews, Sandeep Pallikkuth, Rajashekhar Gangaraju, Adebowale Adebiyi
Organ toxicity, including kidney injury, limits the use of cisplatin for the treatment of multiple human cancers. Hence, interventions to alleviate cisplatin-induced nephropathy are of benefit to cancer patients. Recent studies have demonstrated that pharmacological inhibition of the Notch signaling pathway enhances cisplatin efficacy against several cancer cells. However, whether augmentation of the anti-cancer effect of cisplatin by Notch inhibition comes at the cost of increased kidney injury is unclear...
November 8, 2018: Journal of Cellular and Molecular Medicine
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