bluuebunny/crossref_metadata_2025_split huggingface dataset:
MiR‐130b increases fibrosis of HMC cells by regulating the TGF‐β1 pathway in diabetic nephropathy
Authors: Ma Yujin , Shi Jingxia , Wang Feifei , Li Shipeng , Wang Jie , Zhu Chaoxia , Li Liping , Lu Haibo , Li Chun , Yan Junqiang , Zhang Xin , Jiang Hongwei 
Published: September 2018

AbstractBasement membrane thickening, glomerular hypertrophy, and deposition of multiple extracellular matrix characterize the pathological basis of diabetic nephropathy (DN), a condition which ultimately leads to glomerular and renal interstitial fibrosis. Here, we identified a novel microRNA, miR‐130b, and investigated its role and therapeutic efficacy in alleviating DN. Introduction of miR‐130b dramatically increased cell growth and fibrosis in DN cells. We found that transforming growth factor (TGF)‐β1 was a functional target of miR‐130b in human glomerular mesangial cells (HMCs) and overexpression of miR‐130b increased expressions of the downstream signaling molecules of TGF‐β1, t‐Smad2/3, p‐Smad2/3, and SMAD4. An ectopic application of miR‐130b increased messenger RNA and protein expressions of collagen type I (colI), colIV, and fibronectin, whose expression levels were correlated with the expression of miR‐130b. Taken together, the findings of this study reveal that miR‐130b in HMC cells plays an important role in fibrosis regulation and may thus be involved with the pathogenesis of DN. Therefore, miR‐130b may serve as a novel therapeutic target for the prevention and the treatment of DN.
Individual or combination treatments with lapatinib and paclitaxel cause potential bone loss and bone marrow adiposity in rats
Authors: Lee Alice M. C. , Bowen Joanne M. , Su Yu‐Wen , Plews Erin , Chung Rosa , Keefe Dorothy M. K. , Xian Cory J. 
Published: September 2018

AbstractCancer treatments with cytotoxic drugs have been shown to cause bone loss. However, effects on bone are less clear for ErbB‐targeting tyrosine kinase inhibitors or their combination use with cytotoxic drugs. This study examined the effects of individual or combination treatments with breast cancer drugs lapatinib (a dual ErbB1/ErbB2 inhibitor) and paclitaxel (a microtubule‐stabilizing cytotoxic agent) on bone and bone marrow of rats. Wistar rats received lapatinib (240 mg/kg) daily, paclitaxel (12 mg/kg) weekly, or their combination for 4 weeks, and effects on bone/bone marrow were examined at the end of week 4. Microcomputed tomographical structural analyses showed a reduction in trabecular bone volume in tibia following the lapatinib, paclitaxel or their combination treatments (
P < 0.05). Histomorphometry analyses revealed marked increases in bone marrow adipocyte contents in all treatment groups. Reverse transcription polymerase chain reaction gene expression studies with bone samples and cell culture studies with isolated bone marrow stromal cells showed that the all treatment groups displayed significantly reduced levels of osterix expression and osteogenic differentiation potential but increased expression levels of adipogenesis transcription factor peroxisome proliferator‐activated receptor γ. In addition, these treatments suppressed the expression of Wnt10b and/or increased expression of Wnt antagonists (secreted frizzled‐related protein 1, Dickkopf‐related protein 1 and/or sclerostin). Furthermore, all treatment groups showed increased numbers of bone‐resorbing osteoclasts on trabecular bone surfaces, although only the lapatinib group displayed increased levels of osteoclastogenic signal (receptor activator of nuclear factor κΒ ligand/osteoclastogenesis inhibitor osteoprotegrin expression ratio) in the bones. Thus, inhibiting ErbB1 and ErbB2 by lapatinib or blocking cell division by paclitaxel or their combination causes significant trabecular bone loss and bone marrow adiposity involving a switch in osteogenesis/adipogenesis potential, altered expression of some major molecules of the Wnt/β‐catenin signalling pathway, and increased recruitment of bone‐resorbing osteoclasts.
Continuous exposure of nicotine and cotinine retards human primary pterygium cell proliferation and migration
Authors: Yang Qichen , Jhanji Vishal , Tan Sze Qin , Chan Kwok Ping , Cao Di , Chu Wai Kit , Zhang Mingzhi , Pang Chi Pui , Ng Tsz Kin 
Published: September 2018

AbstractPterygium is a triangular‐shaped hyperplastic growth, characterized by conjunctivalization, inflammation, and connective tissue remodeling. Our previous meta‐analysis found that cigarette smoking is associated with a reduced risk of pterygium. Yet, the biological effect of cigarette smoke components on pterygium has not been studied. Here we reported the proliferation and migration properties of human primary pterygium cells with continuous exposure to nicotine and cotinine. Human primary pterygium cells predominantly expressed the α5, β1, and γ subunits of the nicotinic acetylcholine receptor. Continuous exposure to the mixture of 0.15 μM nicotine and 2 μM cotinine retarded pterygium cell proliferation by 16.04% (P = 0.009) and hindered their migration by 11.93% (
P = 0.039), without affecting cell apoptosis. SNAIL and α‐smooth muscle actin protein expression was significantly downregulated in pterygium cells treated with 0.15 μM nicotine‐2 μM cotinine mixture by 1.33‐ (
P = 0.036) and 1.31‐fold (
P = 0.001), respectively. Besides, the 0.15 μM nicotine‐2 μM cotinine mixture also reduced matrix metalloproteinase (MMP)‐1 and MMP‐9 expressions in pterygium cells by 1.56‐ (
P = 0.043) and 1.27‐fold (
P = 0.012), respectively. In summary, this study revealed that continuous exposure of nicotine and cotinine inhibited human primary pterygium cell proliferation and migration in vitro by reducing epithelial‐to‐mesenchymal transition and MMP protein expression, partially explaining the lower incidence of pterygium in cigarette smokers.
Artemisinin attenuates tubulointerstitial inflammation and fibrosis via the NF‐κB/NLRP3 pathway in rats with 5/6 subtotal nephrectomy
Authors: Wen Yi , Pan Ming‐Ming , Lv Lin‐Li , Tang Tao‐Tao , Zhou Le‐Ting , Wang Bin , Liu Hong , Wang Feng‐Mei , Ma Kun‐Ling , Tang Ri‐Ning , Liu Bi‐Cheng 
Published: September 2018

AbstractArtemisinin (Art) is isolated from Artemisia annua L. and known as the most effective antimalaria drugs. Previous studies demonstrated that it could exert an immune‐regulatory effect on autoimmune diseases. In this study, we first investigated its potential role in tubulointerstitial inflammation and fibrosis in rats with 5/6 nephrectomy. Subtotal nephrectomized (SNx) rats were orally administered Art (100 mg·kg
−1·d
−1) for 16 weeks. Blood and urine samples were collected for biochemical examination. Kidney tissues were collected for immunohistochemistry and Western blot analyses. Ang II‐induced injury of the human kidney 2 (HK‐2) cells was used for in vitro study. It was shown that Art could significantly attenuate the renal function decline in SNx rats compared with control. More importantly, Art treatment significantly reduced the tubulointerstitial inflammation and fibrosis, as demonstrated by the evaluation of renal pathology. Furthermore, Art inhibited the activation of NLRP3 inflammasome and NF‐κB in the kidneys. In in vitro study, Art pretreatment could significantly prevent the activation of NLRP3 inflammasome and NF‐κB in Ang II‐treated HK‐2 cells, while BAY11‐7082 (an inhibitor of NF‐κB) significantly inhibited Ang II‐induced NLRP3 inflammasome activation. This study suggested that Art could provide renoprotective role by attenuating the tubulointerstitial inflammation and fibrosis in SNx rats by downregulating the NF‐κB/NLRP3 signaling pathway.
Localization and characterization of a putative cysteine desulfurase in Chlamydia psittaci
Authors: Wen Yating , Chen Yanbo , Li Li , Xu Man , Tan Yuan , Li Yumeng , Wang Chuan , Chen Qian , Kuang Xingxing , Wu Yimou 
Published: September 2018

AbstractChlamydia psittaci is an obligate intracellular pathogen with a biphasic developmental life cycle. It is auxotrophic for a variety of essential metabolites and obtains amino acids from eukaryotic host cells. Chlamydia can develop inside host cells within chlamydial inclusions. A pathway secreting proteins from inclusions into the host cellular cytoplasm is the type III secretion system (T3SS). The T3SS is universal among several Gram‐negative bacteria. Here, we show that CPSIT_0959 of C. psittaci is expressed midcycle and secreted into the infected cellular cytoplasm via the T3SS. Recombinant CPSIT_0959 possesses cysteine desulfurase and PLP‐binding activity, which removes sulfur from cysteine to produce alanine, and helps chlamydial replication. Our study shows that CPSIT_0959 improve the infectivity of offspring elementary bodies and seems to promote the replication by its product. This phenomenon has inhibited by the PLP‐dependent enzymes inhibitor. Moreover, CPSIT_0959 increased expression of Bim and tBid, and decreased the mitochondrial membrane potential of host mitochondria to induce apoptosis in the latecycle for release of offspring. These results demonstrate that CPSIT_0959 has cysteine desulfurase and PLP‐binding activity and is likely to contribute to apoptosis of the infected cells via a mitochondria‐mediated pathway to improve the infectivity of progeny.
The inhibitory effects of ginsenoside Rd on the human glioma U251 cells and its underlying mechanisms
Authors: Gu Biao , Wang Jipeng , Song Yaqi , Wang Qi , Wu Qingquan 
Published: September 2018

AbstractObjectiveThe current study was designed to investigate the inhibitory effects of ginsenoside Rd (Gs‐Rd) on human glioma U251 cells in vitro and its possible underlying mechanisms.MethodsThe groups included blank control group, low concentration Gs‐Rd treatment group (20 μM), mid concentration Gs‐Rd treatment group (40 μM), and high concentration Gs‐Rd treatment group (80 μM). The proliferative activity of human glioma U251 cells was detected by the MTT assay. Flow cytometry was performed to measure cell apoptosis of human glioma U251 cells. In addition, the ELISA assay was used to measure the telomerase activities in different groups on 24 hours, 48 hours, and 72 hours. Furthermore, real‐time quantitative polymerase chain reaction (RT‐PCR) and Western blot analysis were performed to measure the expression of Bcl‐2, human telomerase catalytic subunit (hTERT), and caspase‐3 in different groups on 48 hours at both messenger RNA (mRNA) and protein levels.ResultsThe proliferation of U251 cells was inhibited by Gs‐Rd with different concentrations in the dose‐ and time‐dependent manners. In addition, Gs‐Rd promoted U251 cell apoptosis rate in a dose‐dependent manner. Gs‐Rd with different concentrations (20 μM, 40 μM, and 80 μM) significantly enhanced the expression of teleomerase on 24 hours and 48 hours. In addition, Gs‐Rd with different concentrations significantly increased caspase‐3 and decreased Bcl‐2 and hTERT expressions at both mRNA and protein levels.ConclusionThe Gs‐Rd can remarkably inhibit the proliferation and promote cell apoptosis of human glioma U251 cells. The possible underlying mechanisms could be related to inhibiting telomerase activity, downregulating expression of Bcl‐2 and hTERT, and upregulating expression of caspase‐3 of human glioma U251 cells.
Quantitative differences in TAD border strength underly the TAD hierarchy in Drosophila chromosomes
Authors: Luzhin Artem V. , Flyamer Ilya M. , Khrameeva Ekaterina E. , Ulianov Sergey V. , Razin Sergey V. , Gavrilov Alexey A. 
Published: September 2018

AbstractChromosomes in many organisms, including Drosophila and mammals, are folded into topologically associating domains (TADs). Increasing evidence suggests that TAD folding is hierarchical, wherein subdomains combine to form larger superdomains, instead of a sequence of nonoverlapping domains. Here, we studied the hierarchical structure of TADs in Drosophila. We show that the boundaries of TADs of different hierarchical levels are characterized by the presence of different portions of active chromatin, but do not vary in the binding of architectural proteins, such as CCCTC binding factor or cohesin. The apparent hierarchy of TADs in Drosophila chromosomes is not likely to have functional importance but rather reflects various options of long‐range chromatin folding directed by the distribution of active and inactive chromatin segments and may represent population average.
Oleuropein induces apoptosis via abrogating NF‐κB activation cascade in estrogen receptor–negative breast cancer cells
Authors: Liu Lian , Ahn Kwang Seok , Shanmugam Muthu K , Wang Hong , Shen Hongyuan , Arfuso Frank , Chinnathambi Arunachalam , Alharbi Sulaiman Ali , Chang Yung , Sethi Gautam , Tang Feng Ru 
Published: September 2018

AbstractOleuropein is one of the most abundant phenolic compounds found in olives. Epidemiological studies have indicated that an increasing intake of olive oil can significantly reduce the risk of breast cancer. However, the potential effect(s) of oleuropein on estrogen receptor (ER)‐negative breast cancer is not fully understood.This study aims to understand the anticancer effects and underlying mechanism(s) of oleuropein on ER‐negative breast cancer cells in vitro. The effect of oleuropein on the viability of breast cancer cell lines was examined by mitochondrial dye‐uptake assay, apoptosis by flow cytometric analysis, nuclear factor‐κB (NF‐κB) activation by DNA binding/reporter assays and protein expression by Western blot analysis. In the present report, thiazolyl blue tetrazolium bromide assay results indicated that oleuropein inhibited the viability of breast cancer cells, and its effects were more pronounced on MDA‐MB‐231 as compared with MCF‐7 cells. It was further found that oleuropein increased the level of reactive oxygen species and also significantly inhibited cellular migration and invasion. In addition, the activation of NF‐κB was abrogated as demonstrated by Western blot analysis, NF‐κB‐DNA binding, and luciferase assays. Overall, the data indicates that oleuropein can induce substantial apoptosis via modulating NF‐κB activation cascade in breast cancer cells.
In silico evidence of direct interaction between statins and β‐amyloid
Authors: Shakour Neda , Bianconi Vanessa , Pirro Matteo , Barreto George E. , Hadizadeh Farzin , Sahebkar Amirhossein 
Published: September 2018

AbstractIntroductionAggregation of amyloid‐β (Aβ) peptides represents a crucial step in the pathogenesis of Alzheimer disease (AD). Compelling evidence from preclinical studies has established that statins may reduce amyloidogenesis and Aβ‐mediated neurodegeneration, supporting a potential role of statin treatment in the prevention of AD. Different statins have been shown to interfere indirectly with Aβ production and clearance through either cholesterol‐dependent or cholesterol‐independent mechanisms. However, whether there may be a direct interaction between statins and Aβ metabolism is still unclear.Materials and methodsTo test the possible direct interaction between statins and Aβ, we performed an in silico study by testing the orientation of different ligands, including statins and sulindac (the standard ligand of Aβ), in the Aβ active site using molecular operating environment (MOE) software.ResultsDocking experiments showed that all the tested statins could directly interact with Aβ protofibrils. Among statins, pitavastatin had the strongest interaction with Aβ (pki = 7.66), followed by atorvastatin (pk
i = 7.63), rosuvastatin (pk
i = 6.99), fluvastatin (pk
i = 6.96), pravastatin (pk
i = 6.46), lovastatin (pk
i = 6.37), and simvastatin (pk
i = 5.90). According to the above‐mentioned results, pitavastatin, atorvastatin, rosuvastatin, and fluvastatin had a stronger binding to Aβ compared with the standard ligand sulindac (pk
i = 6.62).ConclusionThis study showed a direct interaction between statins and Aβ protofibrils, which may underlie the protective role of this widely used class of drugs against amyloidogenesis and Aβ‐mediated neurodegeneration.
A study on correlation between oxidative stress parameters and inflammatory markers in type 2 diabetic patients with kidney dysfunction in north Indian population
Authors: Neelofar Km , Arif Zarina , Arafat Mir Yasir , Alam Khursheed , Ahmad Jamal 
Published: September 2018

AbstractBackgroundResearch reports support the statement that oxidative stress and inflammation are well‐known risk factors for chronic kidney disease (CKD) in patients with diabetes. This study was designed to ascertain the associated role of oxidative stress parameters and inflammatory markers in diabetes and related CKD among the north Indian population.MethodsThe study was divided into three groups as healthy subjects (group 1), patients with diabetes without complication (group 2), and with CKD (group 3). Serum levels of malondialdehyde (MDA) and nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR) content were estimated in all individuals. Inflammatory cytokines interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α)‐α were determined by enzyme‐linked immuno‐sorbent assay.ResultsMDA, protein carbonyl, and NO were significantly elevated in patients with type 2 diabetes as compared with healthy subjects (P ≤ 0.05). Total thiols content were found to be significantly decreased in patients with diabetes with CKD. The activity of antioxidant enzymes SOD, CAT, and GR showed a significant suppression in patients with type 2 diabetes with or without CKD as compared with healthy subjects. Nevertheless, the levels of proinflammatory cytokines IL‐6 and TNF‐α were significantly upregulated (
P ≤ 0.05) as compared with healthy subjects.ConclusionDetermination of antioxidant defense parameters and inflammatory markers contributes to understand the relationship between oxidative stress and inflammation on the development and prevention of chronic kidney disease in Indian patients with diabetes.
Associations between the cyclooxygenase‐2 expression in circulating tumor cells and the clinicopathological features of patients with colorectal cancer
Authors: Cai Jinlin , Huang Liang , Huang Jun , Kang Liang , Lin Hongcheng , Huang Pinzhu , Zhu Peixuan , Wang Jianping , Dong Jianghui , Wang Liping , Xian Cory J. 
Published: September 2018

AbstractWhile previous studies have shown that the number of circulating tumor cells (CTCs) alone is not sufficient to reflect tumor progression and that cyclooxygenase‐2 (COX‐2) expression is correlated with colorectal cancer (CRC) metastasis, COX‐2 expression status and its potential functions in CTCs of CRC patients are unknown. Here, epithelial‐mesenchymal transition (EMT) phenotype‐based subsets of CTCs and the COX‐2 expression status in CTCs were identified and their potential clinical values were assessed in 91 CRC patients. CTCs were enumerated in peripheral blood and subsets of CTCs (epithelial [eCTCs], mesenchymal [mCTCs], and biophenotypic [bCTCs]) and the COX‐2 expression status were determined using the RNA in situ hybridization method. CTCs were detected in 80.2% (73 of 91) patients. Neither the total CTC nor eCTC numbers were found to significantly associate with any of the clinicopathological features. However, the number of mCTCs was significantly associated with distance metastasis (P = 0.035) and had a trend of being associated with lymph node metastasis (
P = 0.055). Among the 73 patients enrolled for evaluating COX‐2 expression, 52.5% (38 of 73) were found to express COX‐2 in CTCs, and COX‐2 expression in CTCs was not found to associate with the clinicopathological factors. However, COX‐2 expression in mCTCs tended to have a higher rate in patients with metastasis compared with those without metastasis (72.0% vs 42.8%;
P = 0.072). Furthermore, COX‐2 expression and mCTC marker expression correlated positively (
R = 0.287;
P = 0.017). Further studies are required to investigate the clinical value of the expression of COX‐2 in mCTCs, especially in CRC patients with the advanced tumor stage and distant metastasis.
Administration of resveratrol improved Parkinson’s disease‐like phenotype by suppressing apoptosis of neurons via modulating the MALAT1/miR‐129/SNCA signaling pathway
Authors: Xia Dongjian , Sui Rubo , Zhang Zhuang 
Published: September 2018

AbstractMetastasis‐associated lung adenocarcinoma transcript 1 (MALAT1) has been implicated in the pathogenesis of Parkinson’s disease (PD). In addition, resveratrol was shown to regulate the expression of MALAT1. Therefore, the objective of this study was to clarify the role of resveratrol in PD. During the study, luciferase assays were conducted to determine the effect of resveratrol on the transcription efficiency of MALAT1 promoter as well as the regulatory relationships among MALAT1, miR‐129, and SNCA. In addition, real‐time PCR, Western blot analysis, MTT and flow cytometry analyses were conducted to investigate the mechanism of resveratrol in PD. Furthermore, a PD mouse model was established to study the role of resveratrol in vivo. It was found that resveratrol increased the number of TH+ cells and the expression of miR‐129, while decreasing the expression of MALAT1 and SNCA. In addition, MALAT1 inhibited the expression of miR‐129, a negative regulator of SNCA, thus increasing the expression of SNCA. A further mechanistic study revealed that resveratrol inhibited MALAT1 expression by blocking the transcription of the MALAT1 promoter. Finally, MPTP treatment could decrease cell proliferation and increase cell apoptosis, while resveratrol could partly offset the effect of MPTP. In summary, the therapeutic effect of resveratrol in the treatment of PD can be attributed to its ability to modulate the MALAT1/miR‐129/SNCA signaling pathway.
Notch‐1 signaling activation sustains overexpression of interleukin 33 in the epithelium of nasal polyps
Authors: Chiappara G. , Sciarrino S. , Di Sano C. , Gallina S. , Speciale R. , Lorusso F. , Di Vincenzo S. , D’Anna C. , Bruno A. , Gjomarkaj M. , Pace E. 
Published: September 2018

AbstractBackgroundAlterations in the nasal epithelial barrier homeostasis and increased interleukin 33 (IL‐33) expression contribute to the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP).AimsAs Notch‐1 signaling is crucial in repair processes of mucosa, the current study assessed Notch‐1/Jagged‐1 signaling and IL‐33 in the epithelium of nasal polyps biopsies from allergic (A‐CRSwNP;n = 9) and not allergic (NA‐CRSwNP;n = 9) subjects by immunohistochemistry. We also assessed, in a model of nasal epithelial cells, the effects of stimulation of Notch‐1 with Jagged‐1 on the expression of IL‐33 (by flow cytometry, immunofluorescence, and immunocytochemistry), Jagged‐1 (by flow cytometry), and p‐CREB transcription factor (by western blot analysis).ResultsEx vivo (a) in normal epithelium, the expression of Notch‐1 and IL‐33 were higher in NA‐CRSwNP than in A‐CRSwNP; (b) in metaplastic epithelium, the expression of Notch‐1, Jagged‐1, and IL‐33 were higher in NA‐CRSwNP than in A‐CRSwNP; (c) in hyperplastic epithelium, the expression of Notch‐1, Jagged‐1, and IL‐33 were higher in A‐CRSwNP than in NA‐CRSwNP; and (d) in basal epithelial cells, no differences were observed in the expression of Jagged‐1, IL‐33, and Notch‐1. The expression of Notch‐1 significantly correlated with the expression of IL‐33. In vitro, stimulation of Notch‐1 with Jagged‐1 induced the expression of (a) Jagged‐1; (b) IL‐33; and (c) p‐CREB transcription factor. The inhibitor of Notch‐1, DAPT, reduced all the effects of Jagged‐1 on nasal epithelial cells.ConclusionsThe data herein provided support, for the first time, a putative role of Notch‐1/Jagged‐1 signaling in the overexpression of IL‐33 in the epithelium of nasal polyps from patients with CRSwNP.