bluuebunny/crossref_metadata_2025_split huggingface dataset:
A detailed image of rutin underlying intracellular signaling pathways in human SW480 colorectal cancer cells based on miRNAs‐lncRNAs‐mRNAs‐TFs interactions
Authors: Nasri Nasrabadi Parinaz , Zareian Somaye , Nayeri Zahra , Salmanipour Reza , Parsafar Soha , Gharib Ehsan , Asadzadeh Aghdaei Hamid , Zali Mohammad Reza 
Published: January 2019

AbstractNatural dietary ingredients like flavonoids are important for body improvement against diseases. The flavonol rutin is widely found in fruits and vegetables and shows significant anticancer properties. However, the underlined signaling pathways have not been elucidated yet. In this study, the impacts of various doses of rutin (400–700 mM/ml) have been examined on human colon cancer SW480 cells metabolism, cell cycle, and apoptosis. The transcriptome was analyzed by bioinformatics tools and the interactions between rutin modulated microRNAs (miRNAs), long noncoding RNAs (lncRNAs), messenger RNAs (mRNAs), and transcription factors (TFs) were built, filtered and enriched. A dose of 600 mM of rutin significantly decreased cells metabolic activity, halved the population and arrested the cell cycle at the sub‐G1 phase. The enrichment analysis of miRNAs‐lncRNAs‐mRNAs‐TFs network showed that these effects were mediated through alteration of glucose, lipid, and protein metabolism, modulating endoplasmic reticulum stress responses, negative regulation of cell cycle process, and inducing the extrinsic and intrinsic apoptotic signaling pathways. Additionally, the key parent nodes of each annotation were illustrated. These findings create a detailed image of rutin underlying intracellular signaling pathways in CRC and also help us to better understand the role of dietary natural compounds in cancer treatment.
miR‐545 promoted enterovirus 71 replication via directly targeting phosphatase and tensin homolog and tumor necrosis factor receptor‐associated factor 6
Authors: Sun Ying , Feng Long , Li Jiansheng , Xu Huaming , Mei Xue , Feng Lingyan , Sun Huijuan , Gao Jianfeng , Zhang Xiaoli 
Published: January 2019

AbstractEnterovirus 71 (EV71) is a small, nonenveloped icosahedral RNA virus and is the predominant causative pathogen of hand‐foot‐and‐mouth disease. Recently, microRNAs (miRNAs) are reported to play important roles in the pathogenesis of EV71 replication. This study investigated the role of miR‐545 in the EV71 replication and explored the underlying molecular mechanisms. We showed that miR‐545 was upregulated in the EV71‐infected human embryonic kidney (HEK) 293 cells and rhabdomyosarcoma (RD) cells. Overexpression of miR‐545 promoted the viral replication of EV71 and attenuated the inhibitory effects of EV71 on cell viability in HEK293 and RD cells; while knockdown of miR‐545 significantly suppressed the EV71 replication in these two cell lines. Bioinformatics analysis and luciferase reporter assay showed that miR‐545 directly targeted the 3′untranslated region of phosphatase and tensin homolog (PTEN) and tumor necrosis factor receptor‐associated factor 6 (TRAF6) in HEK293 cells. Furthermore, miR‐545 negatively regulated the messenger RNA (mRNA) and protein expression of PTEN and TRAF6. The mRNA and protein expression of PTEN and TRAF6 was also suppressed by EV71 infection, which was attenuated by miR‐545 knockdown in HEK293 cells. Overexpression of PTEN and TRAF6 both suppressed the EV71 replication in HKE293 cells, and also attenuated the enhanced effects of miR‐545 overexpression on the EV71 replication in HEK293 cells. Collectively, our study for the first time showed that miR‐545 had an enhanced effect on the EV71 replication in HEK293 and RD cells. Further mechanistic results indicated that miR‐545 promoted EV71 replication at least partly via targeting PTEN and TRAF6.
Hexose monophosphate shunt, the role of its metabolites and associated disorders: A review
Authors: Akram Muhammad , Ali Shah Syed Muhammad , Munir Naveed , Daniyal Muhammad , Tahir Imtiaz Mahmood , Mahmood Zahed , Irshad Muhammad , Akhlaq Muhammad , Sultana Sabira , Zainab Rida 
Published: January 2019

AbstractThe hexose monophosphate (HMP) shunt acts as an essential component of cellular metabolism in maintaining carbon homeostasis. The HMP shunt comprises two phases viz. oxidative and nonoxidative, which provide different intermediates for the synthesis of biomolecules like nucleotides, DNA, RNA, amino acids, and so forth; reducing molecules for anabolism and detoxifying the reactive oxygen species during oxidative stress. The HMP shunt is significantly important in the liver, adipose tissue, erythrocytes, adrenal glands, lactating mammary glands and testes. We have researched the articles related to the HMP pathway, its metabolites and disorders related to its metabolic abnormalities. The literature for this paper was taken typically from a personal database, the Cochrane database of systemic reviews, PubMed publications, biochemistry textbooks, and electronic journals uptil date on the hexose monophosphate shunt. The HMP shunt is a tightly controlled metabolic pathway, which is also interconnected with other metabolic pathways in the body like glycolysis, gluconeogenesis, and glucuronic acid depending upon the metabolic needs of the body and depending upon the biochemical demand. The HMP shunt plays a significant role in NADPH2 formation and in pentose sugars that are biosynthetic precursors of nucleic acids and amino acids. Cells can be protected from highly reactive oxygen species by NADPH
2. Deficiency in the hexose monophosphate pathway is linked to numerous disorders. Furthermore, it was also reported that this metabolic pathway could act as a therapeutic target to treat different types of cancers, so treatments at the molecular level could be planned by limiting the synthesis of biomolecules required for proliferating cells provided by the HMP shunt, hence, more experiments still could be carried out to find additional discoveries.
Mechanisms underlying the regulation of intracellular and luminal pH in vaginal epithelium
Authors: Zhang Yi‐Lin , Feng Jian‐Chang , Ke Li‐Jiao , Xu Jia‐Wen , Huang Ze‐Xin , Huang Jiehong , Zhu Yun‐Xin , Zhou Wen‐Liang 
Published: January 2019

AbstractThe vagina provides a characteristic low‐Na+ and low‐pH fluid microenvironment that is considered generally protective. Previous studies have shown that various types of epithelial cells harbor the capacity of intracellular pH (pHi) regulation. However, it remains elusive whether vaginal epithelium could actively regulate pHi by transporting acid–base ions. In this study, we verified that after transient exposure to NH4Cl, the pHi values could rapidly recover from acidification via Na+‐H+ exchanger (NHE), Na+‐HCO3− cotransporter (NBC), and carbonic anhydrase in human vaginal epithelial cell line VK2/E6E7. Positive expression of the main acid–base transporters including NHE1‐2, NBCe1‐2, and NBCn1 mRNA was also detected in VK2/E6E7 cells. Moreover, the in vivo study further showed that interfering with the function of V‐type H+‐ATPase, NHE or NBC expressed in vagina impaired vaginal luminal pH homeostasis in rats. Taken together, our study reveals the property of pH regulation in vaginal epithelial cells, which might provide novel insights into the potential role of vaginal epithelium in the formation of the vaginal acidic microenvironment.
Microbial population dynamics in temperature‐phased anaerobic digestion of municipal wastewater sludge
Authors: Hameed Syeda A , Riffat Rumana , Li Baoqiang , Naz Iffat , Badshah Malik , Ahmed Safia , Ali Naeem 
Published: January 2019

AbstractBACKGROUNDThe present study compared the performance and capability of thermophilic–mesophilic, temperature‐phased anaerobic digestion (TPAD) of wastewater sludge at 45 and 55 °C in terms of rate of hydrolysis and methanogenesis at two point interval times – December and January – with operational conditions kept constant (total solid content 6.5%, solids retention time 12.5 days).RESULTSThe reduction of volatile solids (VS) was 77% at 45 °C TPAD‐1 and 72% at 55 °C TPAD‐II. The accumulation of ammonia and volatile fatty acids (VFAs; propionic acid) were observed to be below the inhibitory range (>3000 mg L−1), whereas the methane (CH4) production (45 °C, 3.55 ± 0.47 L CH4 L−1 day−1; 35 °C, 1.44 ± 0.12 L CH4 L−1 day−1) remained considerably higher in TPAD‐I than TPAD‐II. Furthermore, the TPAD‐II system suffered from certain degree of instability due to high level of total VFAs (6087 ± 1578 mg L−1), low buffering capacity, increased level of total NH3 (2982 ± 219 mg L−1) and free NH3 (246 ± 25 mg L−1), and relatively reduced CH4 production (1.69 ± 0.1 L L−1 day). The bacterial and archaeal population of the TPADs investigated by 454 pyrosequencing and Illumina sequencing showed, in both TPAD systems, a bacterial community dominated by Firmicutes, followed by Bacteriodetes, Proteobacteria, Synergistetes and Actiniobacteria. The archaeal community was dominated by Methanimicrobia (74–84% Methanosarcina) and Methanobacteria (15–27% Methanobacterium). A progression from genus Clostridium to Coprothermobacter and Tepidanaerobacter, and Methanocarcina to Methanothermobacter and Methanobacterium was observed in TPAD‐II.CONCLUSIONSThis study proved the processes driving the dynamics of key microbial population and its correlation with hydrolytic functionality of TPAD systems. © 2019 Society of Chemical Industry
Diabetes mellitus burden among people living with HIV from the Asia‐Pacific region
Authors: Han Win M , Jiamsakul Awachana , Kiertiburanakul Sasisopin , Ng Oon T , Sim Benedict LH , Sun Ly P , Van Nguyen Kinh , Choi Jun Y , Lee Man P , Wong Wing W , Kamarulzaman Adeeba , Kumarasamy Nagalingeswaran , Zhang Fujie , Tanuma Junko , Do Cuong D , Chaiwarith Romanee , Merati Tuti P , Yunihastuti Evy , Pujari Sanjay , Ditangco Rossana , Khusuwan Suwimon , Ross Jeremy , Avihingsanon Anchalee ,   IeDEA Asia‐Pacific
Published: January 2019

AbstractIntroductionComorbidities including diabetes mellitus (DM) among people living with HIV (PLHIV) are of increasing clinical concerns in combination antiretroviral therapy (cART) era. We aimed to determine the incidence and risk factors of new‐onset DM among PLHIV in Asian settings.MethodsPLHIV from a regional observational cohort without DM prior to antiretroviral therapy (ART) initiation were included in the analysis. DM was defined as having a fasting blood glucose ≥126 mg/dL, glycated haemoglobin ≥6.5%, a two‐hour plasma glucose ≥200 mg/dL, or a random plasma glucose ≥200 mg/dL. A Cox regression model, stratified by site, was used to identify risk factors associated with DM.Results and discussionOf the 1927 participants included, 127 were diagnosed with DM after ART initiation. Median follow‐up time from ART initiation to DM diagnosis was 5.9 years (interquartile range (IQR): 2.8 to 8.9 years). The crude incidence rate of DM was 1.08 per 100 person‐years (100 PYS), 95% confidence interval (CI) (0.9 to 1.3). In the multivariate analysis, later years of follow‐up (2011 to 2013: HR = 2.34, 95% CI 1.14 to 4.79, p = 0.02; and 2014 to 2017: HR = 7.20, 95% CI 3.27 to 15.87, p < 0.001) compared to <2010, older age (41 to 50 years: HR = 2.46, 95% CI 1.39 to 4.36, p = 0.002; and >50 years: HR = 4.19, 95% CI 2.12 to 8.28, p < 0.001) compared to <30 years, body mass index (BMI) >30 kg/m2 (HR = 4.3, 95% CI 1.53 to 12.09, p = 0.006) compared to BMI <18.5 kg/m2, and high blood pressure (HR = 2.05, 95% CI 1.16 to 3.63, p = 0.013) compared to those without high blood pressure, were associated with developing DM. The hazard was reduced for females (HR = 0.47, 95% CI 0.28 to 0.80, p = 0.006).ConclusionsType 2 DM in HIV‐infected Asians was associated with later years of follow‐up, high blood pressure, obesity and older age. This highlights the importance of monitoring and routine screening for non‐communicable diseases including DM as PLHIV age.
Non‐F HBV/HDV‐3 coinfection is associated with severe liver disease in Western Brazilian Amazon
Authors: Melo Da Silva Edinete , Kay Alan , Lobato Cirley , Muwonge Richard , Zoulim Fabien , Brites Carlos , Parana Raymundo , Trepo Christian 
Published: January 2019

AbstractThe clinical outcome of hepatitis B virus (HBV) infection may be related to host and viral genetic factors, as well as to the type of infection (monoinfection and coinfection). To analyze the distribution/combination of HBV/hepatitis D virus (HDV) genotypes and the associated clinical characteristics, 409 serum samples from patients with chronic HBV (94 of them coinfected by HDV) followed at the Viral Hepatitis Referral Center of Rio Branco, Brazil were enrolled. HBV DNA and HDV RNA were amplified, respectively, by polymerase chain reaction (PCR) and nested PCR using specific primers in the PreC/C region and the S gene, and by reverse‐transcription PCR and seminested PCR using specific primers in the delta antigen region and sequenced. The proportion of women (56.1%) was significantly higher than males in this cohort (
P < 0.01). Women were significantly younger (39.8 years; 8‐77 years) than males (44.7 years; 12‐79 years;
P < 0.01). Sixty‐eight (18%) patients were infected with HBV‐F genotype and 264 (69.8%) with HBV/non‐F genotypes. Coinfection by HDV was detected in 23.9% (94 of 409) of this population and was more frequent in male (54.2%, 51 of 94) than in female patients (44.7%, 42 of 94;
P = 0.015). HDV‐3 was the most prevalent (88.9%) genotype. Almost 70% of HDV‐3 coinfected patients were infected with HBV/non‐F genotypes. Severe liver disease was diagnosed in 41 patients, 60.9% (25 of 41) of them coinfected with HDV. HBV/HDV coinfection was associated with male sex, age above 30 years, severe liver disease, and increased alanine aminotransferase levels. HBV/HDV‐3 coinfection is associated with severe liver disease, in Rio Branco, Brazil.
Clinical outcomes after the introduction of direct antiviral agents for patients infected with genotype 1b hepatitis C virus depending on the regimens: A multicenter study in Korea
Authors: Kwon Jung Hyun , Yoo Sun Hong , Nam Soon Woo , Kim Hee Yeon , Kim Chang Wook , You Chan Ran , Choi Sang Wook , Cho Se Hyun , Han Joon‐Yeol , Song Do Seon , Chang U Im , Yang Jin Mo , Lee Sung Won , Lee Hae Lim , Han Nam Ik , Kim Seok‐Hwan , Song Myeong Jun , Sung Pil Soo , Jang Jeong Won , Bae Si Hyun , Choi Jong Young , Yoon Seung Kew 
Published: January 2019

AbstractBackgroundA real‐life study is essential outside clinical trials. The aim is to evaluate the clinical outcomes of direct acting agents (DAA) for patients with chronic hepatitis C (CHC) in real practice.MethodsWe analyzed 590 consecutively enrolled patients with CHC‐1b who received DAAs since 2015, when DAAs were introduced in Korea. The patients were checked for resistance‐associated variants (RAV) against nonstructural protein 5A inhibitors and then daclatasvir/asunaprevir or sofosbuvir based regimens were chosen.ResultsThe frequency of patients with cirrhosis and prior hepatocellular carcinoma (HCC) was 29.2% and 4.7%, respectively. For the RAV test, 10% were positive and in 3.6% the result was “indeterminate.” Overall, 518 patients were treated with a 24‐week regimen of daclatasvir/asunaprevir, 72 patients (RAV positive 75%) were treated with 12 weeks regimen of ledipasvir/sofosbuvir or daclatasvir/sofosbuvir. The SVR12 was 94.0% in the daclatasvir/asunaprevir, 98.2% in the ledipasvir/sofosbuvir, and 100% in the daclatasvir/sofosbuvir group. A total of 93.3% of SVR12 in the RAV‐“indeterminate” patients was not difference 95.0% in the RAV‐negative patients. Up to 1 year, de novo HCC occurrence and recurrence developed in 2.6% and 17.8%, respectively. HCC was more frequent in cirrhotic patients than in noncirrhotic patients (P = 0.000). α Fetoprotein (AFP) level at the end of treatment was a predicting factor for de novo HCC.ConclusionsOptimizing the choice of DAAs according to RAV test resulted in high SVR among CHC‐1b Korean patients. This real practice multicenter cohort study suggests the importance of AFP and HCC surveillance in cirrhotic patients even after successful HCV therapy.
Viral evolution in the cell‐associated HIV‐1 DNA during early ART can lead to drug resistance and virological failure in children
Authors: Gopalan Bindu Parachalil , D’Souza Reena R. , Rajnala Niharika , Arumugam Karthika , Dias Mary , Ranga Udaykumar , Shet Anita 
Published: January 2019

AbstractUsing cell‐associated DNA and cell‐free RNA of human immunodeficiency virus type‐1 (HIV‐1), we investigated the role of drug‐resistant viral variants that emerged during early antiretroviral therapy (ART) in determining virological outcome. This case‐control study compared virologic nonresponder children (two viral loads [VLs] ≥ 200 copies/mL within 2 years of ART) and responder children (two VLs < 200 copies/mL after six months of ART) infected with HIV‐1 initiated on nonnucleoside reverse‐transcriptase inhibitor (NNRTI)‐based ART. The partial reverse‐transcriptase gene of HIV‐1 in cell‐associated DNA was genotyped using next‐generation sequencing (NGS; Illumina; threshold 0.5%; at baseline and month six of ART) and in cell‐free RNA (concurrently and at virological failure; VL > 1000 copies/mL at ≥ 12 months of ART) using the Sanger method. Among 30 nonresponders and 37 responders, baseline differences were insignificant while adherence, VL, and drug resistance mutations (DRMs) observed at month six differed significantly (
P ≥ 0.05). At month six, NGS estimated a higher number of DRMs compared with Sanger (50% vs 33%;
P = 0.001). Among the nonresponders carrying a resistant virus (86.6%) at virological failure, 26% harbored clinically relevant low‐frequency DRMs in the cell‐associated DNA at month six (0.5%‐20%; K103N, G190A, Y181C, and M184I). Plasma VL of > 3 log
10copies/mL (AOR, 30.4; 95% CI, 3.3‐281;
P = 0.003) and treatment‐relevant DRMs detected in the cell‐associated DNA at month six (AOR, 24.2; 95% CI, 2.6‐221;
P = 0.005) were independently associated with increased risk for early virological failure. Our findings suggest that treatment‐relevant DRMs acquired in cell‐associated DNA during the first six months of ART can predict virological failure in children initiated on NNRTI‐based ART.
The role of lipid rafts in cell entry of human metapneumovirus
Authors: Chen Suhua , He Hao , Yang Hui , Tan Bin , Liu Enmei , Zhao Xiaodong , Zhao Yao 
Published: January 2019

AbstractHuman metapneumovirus (hMPV) is a crucial pathogen in children. A cell entry is the first step for infection. Our previous study indicated that there was an endocytosis pathway for hMPV cell entry. Lipid raft is a specific structure at the cell surface and it has been demonstrated to play an important role in endocytosis process of many viruses. In this study, we investigated whether and how lipid raft can take part in the hMPV entry. The confocal microscope was used to detect colocalization of hMPV and lipid raft marker. We demonstrated that colocalizations were increased along with the viral infection and hMPV particles transferred to the perinuclear region with lipid raft. When specific lipid raft inhibitors: methyl‐β cyclodextrin and nystatin were used, hMPV cell entry was inhibited and viral titer decreased dramatically. With the replenishment of exogenous cholesterol, hMPV recovered quickly. These data suggest that lipid raft plays an important role in hMPV endocytosis and maybe one of the pathways for hMPV cell entry.
The association between consuming bivalves, and acute gastroenteritis and norovirus in Tokyo, Japan
Authors: Kobayashi Daiki , Saito Mayuko , Heike Yuji , Yokota Kyoko , Arioka Hiroko , Oshitani Hitoshi 
Published: January 2019

AbstractA prospective matched case‐control study was conducted to evaluate associations between dietary histories, including consumption of bivalves, diarrhea, and norovirus positive diarrhea in adult ambulatory patients at an outpatient clinic of a hospital in Tokyo, Japan. Ambulatory cases with diarrhea were matched with nondiarrheal control patients, who visited the same clinic. A standardized questionnaire was used to obtain patients’ information, including histories of food consumption and clinical information. Norovirus infection was confirmed using real‐time reverse transcription polymerase chain reaction. A total of 207 patients, including 69 diarrheal cases and 138 nondiarrheal cases were included in the analysis. Among them, 60 (29.0%) participants reported consuming bivalves. Norovirus was detected in 35% (24/69) of diarrheal cases. Of those, 10 (41.7%) reported consumption of bivalves and of those, 6 (60.0%) consumed raw bivalves. The proportion of those who consumed raw bivalves was significantly higher in norovirus‐positive diarrheal cases than in norovirus‐negative diarrheal cases (25.0% vs 6.7%; odds ratio [OR], 4.67; 95% confidence interval [CI], 1.1‐20.7) and matched nondiarrheal controls (25.0% vs 6.3%, OR: 5.00; 95% CI, 1.1‐22.2). The attributable fraction of consuming raw bivalves for norovirus‐associated diarrhea to matched nondiarrheal controls was 20.0%. Consuming raw bivalves was substantially attributed to norovirus‐associated diarrhea in adult ambulatory patients and preventive measures for reducing the risk associated with consumption of raw bivalves could decrease the incidence of norovirus‐associated diarrhea.
Dengue virus serotypes and genotypic characterization from northeast India
Authors: Chetry Sumi , Khan Siraj A. , Dutta Prafulla , Apum Basumoti , Medhi Pranita S. , Saikia Durlov C. , Temsu Temjen , Mawii Lalhming , Marak Bichitrani C. 
Published: January 2019

AbstractDengue is a rapidly spreading acute arboviral infection transmitted through a human and Aedes mosquito cycle. Though northeast region of India has been experiencing dengue outbreaks regularly for over a decade, reports on genetic characterization of the virus from this region are limited. The present study was undertaken to detect the genotype and genetic composition of circulating dengue virus (DENV) in this region. Blood samples were collected from 918 suspected dengue patients of five northeast Indian states. Serological investigations, viz, nonstructural 1 (NS1) enzyme‐linked immunosorbent assay (ELISA), immunoglobulin M (IgM) ELISA, and immunoglobulin G (IgG) ELISA were performed followed by molecular detection. Sequence analysis and phylogenetic tree construction based on capsid‐premembrane (C‐prM) gene junction was done by BioEdit and MEGA6 software, respectively. Serological detection showed 35.34% NS1 and 18.12% IgM positivity. Secondary infection was observed in 24.53%. All four serotypes were detected. Phylogenetic analysis demonstrated circulation of genotype III of DENV‐1, genotype IV of DENV‐2, and genotype III of DENV‐3. Sequences from this region form distinct clades in the phylogenetic tree. Characterization of the C‐prM gene junction reveals divergence among the DENV strains. As genetic variation within the DENV is known to be associated with diverse clinical outcomes, information regarding the genetic composition of circulating virus could be beneficial in designing an effective intervention strategy.