bluuebunny/crossref_metadata_2025_split huggingface dataset:
Active vitamin D regulates macrophage M1/M2 phenotypes via the STAT‐1‐TREM‐1 pathway in diabetic nephropathy
Authors: Zhang Xiaoliang , Zhao Yu , Zhu Xiaodong , Guo Yinfeng , Yang Ying , Jiang Yuteng , Liu Bicheng 
Published: November 2018

AbstractAimImbalance of M1/M2 macrophages phenotype activation is a key point in diabetic nephropathy (DN). This study aimed to investigate whether active vitamin D (VD) suppresses macrophage transition to the M1 phenotype via inhibiting the high glucose‐induced STAT‐1 phosphorylation to reduce TREM‐1 expression.MethodsIn vivo, pathological changes in kidney tissue were detected and the expression of CD68 TREM‐1, STAT‐1, M1 makers, and M2 makers were acquired in renal tissue of patients with DN and 18w DN rats. In vitro, RAW 264.7 cells were incubated in the presence of high glucose with or without VD. Silencing and overexpression of TREM‐1 and silencing and activate of STAT‐1 were explored to elucidate the underlying mechanism. The expression of TREM‐1 and STAT‐1 and the changes of macrophage phenotype were examined separately by western blot and immunofluorescence staining.Results(a) Expression of TREM‐1, p‐STAT‐1, and M1 markers (iNOS and TNF‐α) were increased and positively correlated in kidneys from patients with DN. (b) In DN rats, the enlargement of glomerular surface area, expansion of glomerular mesangial matrix, the expression of CD68, TREM‐1, p‐STAT‐1, and M1 marker (iNOS) were significantly increased in comparison with the normal control group, whereas above changes were markedly decreased in the diabetic group treated with the VD group. (c) In vitro, VD significantly decreased high glucose‐induced CD68, TREM‐1, p‐STAT‐1, and M1 marker (iNOS) expression. However, above‐mentioned effects of VD are abolished when TREM‐1 is overexpressed or STAT‐1 is activated. Reductions in STAT‐1 expression decreased the TREM‐1 expression.ConclusionVD can inhibit macrophage transition to the M1 phenotype through the STAT‐1/TREM‐1 pathway.
Intersectin‐Cdc42 interaction is required for orderly meiosis in porcine oocytes
Authors: Li Xiaoyan , Gao Min , He Yongfu , Xiong Bo , Liu Honglin , Gu Ling 
Published: November 2018

AbstractIntersectins (ITSNs) have been shown to act as adaptor proteins that govern multiple cellular events via regulating Cdc42 activity. However, it remains to be determined whether the ITSN‐Cdc42 pathway is functional in porcine oocytes. To address this question, we used a small molecule, ZCL278, to selectively disrupt the ITSN2‐Cdc42 interaction. In the present study, we find that porcine oocytes exposed to ZCL278 are unable to completely progress through meiosis. Meanwhile, the spindle defects and chromosomal congression failure are frequently detected in these oocytes. In support of this, we observed the accumulated distribution of vesicle‐like ITSN2 signals around the chromosome/spindle region during porcine oocyte maturation. In addition, our results also showed that inhibition of the ITSN‐Cdc42 interaction impairs the actin polymerization in porcine oocytes. In summary, the findings support a model where ITSNs, through the interaction with Cdc42, modulates the assembly of meiotic apparatus and actin polymerization, consequently ensuring the orderly meiotic progression during porcine oocyte maturation.
MicroRNA‐145 induces the senescence of activated hepatic stellate cells through the activation of p53 pathway by ZEB2
Authors: Yang Junfa , Lu Yuchen , Yang Peipei , Chen Qingfeng , Wang Yang , Ding Qi , Xu Tao , Li Xiaofeng , Li Changyao , Huang Cheng , Meng Xiaoming , Li Jun , Zhang Lei , Wang Xiao 
Published: November 2018

AbstractActivation of quiescent hepatic stellate cells (HSCs) is the major event in liver fibrosis, along with enhancement of cell proliferation and overproduction of extracellular matrix. Recent findings suggest that senescence of activated HSCs might limit the development of liver fibrosis. The p53, a guardian of the genome is associated with liver fibrosis, has been shown to regulate HSCs senescence. In this study, we report that microRNA‐145 (miR‐145) and p53 were downregulated in vivo and in vitro, concomitant with the enhanced expression of zinc finger E‐box binding homeobox 2 (ZEB2). In addition, overexpression of miR‐145 and p53 led to upregulation of the number of senescence‐associated β‐galactosidase‐positive HSCs and the expression of senescence markers p16 and p21, along with the reduced abundance of HSC activation markers α‐smooth muscle actin and type I collagen in activated HSCs. Furthermore, silencing of ZEB2 promoted senescence of activated HSCs. Moreover, we also demonstrated that miR‐145 specifically targeted the 3′‐untranslated regions of ZEB2. In vitro promoter regulation studies show that ZEB2 could bind to the E‐box of the p53 promoter as well as inhibit its promoter activity and thus suppress the expression of p53, which in turn repressed activated HSCs senescence. Taken together, our results describe a novel miR‐145‐ZEB2‐p53 regulatory line might participate in the senescence of activated HSCs and might carry potential therapeutic targets for restraining liver fibrosis.
Expression and regulatory networks of Mycobacterium tuberculosis PE/PPE family antigens
Authors: Li Wu , Deng Wanyan , Xie Jianping 
Published: November 2018

AbstractPE/PPE family antigens are distributed mainly in pathogenic mycobacteria and serve as potential antituberculosis (TB) vaccine components. Some PE/PPE family antigens can regulate the host innate immune response, interfere with macrophage activation and phagolysosome fusion, and serve as major sources of antigenic variation. PE/PPE antigens have been associated with mycobacteria pathogenesis; pe/ppe genes are mainly found in pathogenic mycobacteria and are differentially expressed between Mtb and Mycobacterium bovis. PE/PPE proteins were essential for the growth of Mtb, and PE/PPE proteins were differentially expressed under a variety of conditions. Multiple mycobacterial‐virulence‐related transcription factors, sigma factors, the global transcriptional regulation factor Lsr2, MprAB, and PhoPR two‐component regulatory systems, and cyclic adenine monophosphate‐dependent regulators, regulate the expression of PE/PPE family antigens. Multiple‐scale integrative analysis revealed the expression and regulatory networks of PE/PPE family antigens underlying the virulence and pathogenesis of Mtb, providing important clues for the discovery of new anti‐TB measures.
Redefining the signaling pathways from pluripotency to pancreas development: In vitro β‐cell differentiation
Authors: Hashemitabar Mahmoud , Heidari Elham 
Published: November 2018

AbstractPancreatic β‐cells are destroyed by the immune system, in type 1 diabetes (T1D) and are impaired by glucose insensitivity in type 2 diabetes (T2D). Islet‐cells transplantation is a promising therapeutic approach based on in vitro differentiation of pluripotent stem cells (PSCs) to insulin‐producing cells (IPCs). According to evolutionary stages in β‐cell development, there are several distinct checkpoints; each one has a unique characteristic, including definitive endoderm (DE), primitive gut (PG), posterior foregut (PF), pancreatic epithelium (PE), endocrine precursor (EP), and immature β‐cells up to functional β‐cells. A better understanding of the gene regulatory networks (GRN) and associated transcription factors in each specific developmental stage, guarantees the achievement of the next successful checkpoints and ensures an efficient β‐cell differentiation procedure. The new findings in signaling pathways, related to the development of the pancreas are discussed here, including Wnt, Activin/Nodal, FGF, BMP, retinoic acid (RA), sonic hedgehog (Shh), Notch, and downstream regulators, required for β‐cell commitment. We also summarized different approaches in the IPCs protocol to conceptually define a standardized system, leading to the creation of a reproducible method for β‐cell differentiation. To normalize blood glucose level in diabetic mice, the replacement therapy in the early differentiation stage, such as EP stages was associated with better outcome when compared with the fully differentiated β‐cells’ graft.
Comparative transcriptome analysis reveals PERP upregulated duringSalmonellaEnteritidis challenge in laying ducks
Authors: Zhang Yu , Gu Tian‐tian , Chen Yang , Huang Yu , Du Jinping , Lu Lizhi , Zhu Guo‐qiang , Xu Qi , Chen Guo‐hong 
Published: November 2018

AbstractSalmonellaEnteritidis (SE) can be transmitted to eggs through cecum or the ovary from infected layers and causes food poisoning in humans. The mechanism of cecal transmission has been extensively studied. However, the mechanism and route of transovarian transmission of SE remain unclear. In this study, the ducks were orally inoculated with SE, and the ovarian follicles and stroma were collected to detect SE infection. The immune responses were triggered and the innate and adaptive immune genes (TLR4, NOD1, AvβD7, and IL‐1β) were upregulated significantly during the SE challenge. Moreover, the ovary tissues (small follicle and stroma) of susceptible and resistant–laying ducks were performed by RNA sequencing. We obtained and identified 23 differentially expressed genes (DEGs) between susceptible and resistant–laying ducks in both small follicle and stroma tissues (p < 0.05). The DEGs were predominately identified in the p53 signaling pathway. The expression of key genes (p53, MDM2, PERP, caspase‐3, and Bcl‐2) involved in the signaling pathway was significantly higher in granulosa cells (dGCs) from SE‐infected ducks than those from uninfected ducks. Moreover, the overexpression of PERP resulted in further induction of p53, MDM2, caspase‐3, and Bcl‐2 during SE infection in dGCs. Whereas, an opposite trend was observed with the knockdown of PERP. Besides, it is further revealed that the PERP could enhance cell apoptosis, SE adhesion, and SE invasion in SE‐infected dGCs overexpression. Altogether, our results demonstrate the duck PERP involved in the ovarian local immune niche through p53 signaling pathway in dGCs challenged with SE.
α‐2‐Macroglobulin induces the shedding of microvesicles from cutaneous wound myofibroblasts
Authors: Laberge Alexandra , Ayoub Akram , Arif Syrine , Larochelle Sébastien , Garnier Alain , Moulin Véronique J. 
Published: November 2018

AbstractMicrovesicles (MVs) are recognized as an important class of cell‐to‐cell messengers. Although the properties of MVs are increasingly documented, the mechanisms regulating MV biogenesis remain debated. Myofibroblasts are a key cellular component of wound healing and have been shown to produce MVs upon stimulation with serum. However, the mediator(s) responsible for the observed effect of serum on MV release have yet to be identified. To isolate the molecule(s) of interest, serum proteins were sequentially separated using chromatography, selective precipitation, and electrophoresis. MV production was assessed throughout the purification and after stimulation of myofibroblasts with two potent purified molecules. α‐2‐Macroglobulin (A2M) was thereby found to dose‐dependently stimulate MV release. We confirmed the presence of the A2M receptor, low‐density lipoprotein receptor‐related protein‐1 (LRP1), on myofibroblasts. Inhibition of LRP1 resulted in a significant decrease in MV production. Together, our results suggest that A2M positively regulates MV shedding through the activation of LRP1 on myofibroblasts.
Long noncoding RNA LINC00460 promotes carcinogenesis via sponging miR‐613 in papillary thyroid carcinoma
Authors: Feng Li , Yang Bin , Tang Xiao‐Di 
Published: November 2018

AbstractLong intergenic noncoding RNA 460 (LINC00460) has been identified as a critical regulator for multiple types of cancers. However, the biological role and underlying mechanism in human papillary thyroid carcinoma (PTC) still remain unclear and need to be uncovered. This study was aimed to ascertain the biological role and molecular mechanism of LINC00460 in PTC progression. Our findings revealed that the level of LINC00460 was significantly upregulated in PTC tissues and cell lines, which was positively correlated with advanced tumor–node–metastasis (TNM) stage and lymph node metastasis. Cellular experiments exhibited that knockdown of LINC00460 decreased proliferative, migratory, and invasive abilities of PTC cells. Mechanism assays noted that knockdown of LINC00460 suppressed cell proliferation, migration, and invasion, and inhibited expression of sphingosine kinase 2 (SphK2, a target of miR‐613) in PTC cells, at least in part, by regulating miR‐613. These findings suggested that LINC00460 could function as a competing endogenous RNA to regulate SphK2 expression by sponging miR‐613 in PTC. Targeting LINC00460 could be a promising therapeutic strategy for patients with PTC.
The possible role of bacteria, viruses, and parasites in initiation and exacerbation of irritable bowel syndrome
Authors: Shariati Aref , Fallah Fateme , Pormohammad Ali , Taghipour Ali , Safari Hossein , chirani Alireza salami , Sabour Sahar , Alizadeh‐Sani Mahmood , Azimi Taher 
Published: November 2018

AbstractIrritable bowel syndrome (IBS) is a prolonged and disabling functional gastrointestinal disorder with the incidence rate of 18% in the world. IBS could seriously affect lifetime of patients and cause high economic burden on the community. The pathophysiology of the IBS is hardly understood, whereas several possible mechanisms, such as visceral hypersensitivity, irregular gut motility, abnormal brain–gut relations, and the role of infectious agents, are implicated in initiation and development of this syndrome. Different studies demonstrated an alteration in B‐lymphocytes, mast cells (MC), T‐lymphocytes, and cytokine concentrations in intestinal mucosa or systemic circulation that are likely to contribute to the formation of the IBS. Therefore, IBS could be developed in those with genetic predisposition. Infections’ role in initiation and exacerbation of IBS has been investigated by quite several clinical studies; moreover, the possible role of some pathogens in development and exacerbation of this disease has been described. It appears that the main obligatory pathogens correspond with the IBS disease, Clostridium difficile, Escherichia coli, Mycobacterium avium subspecies paratuberculosis, Campylobacter concisus, Campylobacter jejuni, Chlamydia trachomatis, Helicobacter pylori, Pseudomonas aeruginosa, Salmonella spp, Shigella spp, and viruses, particularly noroviruses. A number of pathogenic parasites (Blastocystis, Dientamoeba fragilis, and Giardia lamblia) may also be involved in the progression and exacerbation of the disease. Based on the current knowledge, the current study concludes that the most common bacterial, viral, and parasitic pathogens may be involved in the development and progression of IBS.
Tracing individuals and populations of the tambaqui, Colossoma macropomum (Cuvier, 1818), from Brazilian hatcheries using microsatellite markers
Authors: Aguiar Jonas da Paz , Fazzi‐Gomes Paola F , Hamoy Igor G , dos Santos Sidney EB , Sampaio Iracilda 
Published: November 2018

AbstractBACKGROUNDIn recent years, tracing of alimentary produce of animal origin has become increasingly important, for economic, food safety and ecological reasons. The tambaqui, Colossoma macropomum, is the native fish most farmed in Brazil. The reliable identification of the origin of tambaquis (wild or farmed) offered for sale to the general public has become necessary to satisfy regulatory norms and uphold consumer confidence. Molecular methods based on the analysis of DNA sequences have often been used to evaluate the potential for tracing farmed fish, given their reliability and precision.RESULTSFull likelihood and Bayesian approaches proved to be the most efficient for the identification, respectively, of individuals and populations for most of the fish sampled from seven hatcheries and one wild stock. The exclusion method and genetic distances were the least effective approaches for the identification of individuals and populations. The Bayesian method identified correctly more than 99% of the fry from most stocks, except those of the Santarém hatchery and River Amazon wild stock, which presented the best results for individual identification.CONCLUSIONSThe identification of populations was effective for most hatcheries, although the identification of individuals from most stocks was hampered by the reduced genetic variability. © 2018 Society of Chemical Industry
Specific prognostic factors in hepatitis B virus‐related and non‐hepatitis B virus–related intrahepatic cholangiocarcinoma after macroscopic curative resection
Authors: Huang Jianbo , Wang Xiangyu , Zhu Ying , Wang Zheng , Li Jianhua , Xu Da , Wang Shenghao , Li Tian‐En , Lu Lu 
Published: November 2018

BackgroundThe hepatitis B virus (HBV)‐related intrahepatic cholangiocarcinoma (iCCA) was recognized as a unique subtype of iCCA, within particular features in demography, clinicopathology, and genealogy. However, how they predict prognosis, in particular, for HBV‐ and non‐HBV–related iCCA is still unclear.MethodsDemographic, clinicopathologic, and genetic features were retrospectively collected and reviewed to determine the specific prognostic factors, precisely predicting the overall survival (OS) in HBV‐related (n = 119) and non‐HBV–related (
n = 149) iCCA patients, respectively.ResultsIn HBV‐related iCCA, TP53 mutation, vascular invasion, extrahepatic metastasis, and serum levels of alpha‐fetoprotein (AFP) were independent prognostic factors for OS. In non‐HBV–related iCCA, RAS/
RAF mutation and lymphatic metastasis independently predicted the OS of patients. Tumor differentiation and serum levels of CA19‐9 were significantly associated with OS in both HBV‐ and non‐HBV–related iCCA patients. In a subset analysis, TP53 and RAS/RAF mutations were consistently related to poorer outcome in HBV‐ and non‐HBV–related iCCA, respectively.ConclusionsThe HBV‐ and non‐HBV–related iCCA have different prognostic factors for the OS.
Hypomethylation of mismatch repair genes MLH1 and MSH2 is associated with chemotolerance of breast carcinoma: Clinical significance
Authors: Dasgupta Hemantika , Islam Saimul , Alam Neyaz , Roy Anup , Roychoudhury Susanta , Panda Chinmay Kumar 
Published: November 2018

Background and ObjectivesThe aim of the study was to understand the importance of mismatch repair genes MLH1 and MSH2 in chemotolerance and prognosis of breast carcinoma (BC).MethodsFirst, the alterations (deletion/methylation/expression) of MLH1 and MSH2 were analyzed in 45 neoadjuvant chemotherapy (NACT)‐treated and 133 pretherapeutic BC samples. The chemotolerant BC cells were characterized by treating two BC cell lines MCF‐7 and MDA MB 231 with two anthracycline antitumor antibiotics, doxorubicin and nogalamycin.ResultsThe deletion frequencies were 32% to 38% in MLH1/MSH2 genes and promoter methylation frequencies were 49% to 62% in MLH1 and 41% to 51% in MSH2 in both NACT‐treated and pretherapeutic samples. The overall alteration of MLH1 and MSH2 was 58% to 71% in the samples. Reduced messenger RNA (mRNA) and protein expression were found in both the genes and it showed concordance with the molecular alterations. NACT‐treated patients showed better prognosis. The chemotherapeutic drug induced increased mRNA/protein expression of the genes in BC cell lines was due to their promoter hypomethylation, as analyzed by quantitative methylation assay. This phenomenon was also evident in NACT‐treated BC samples.ConclusionMLH1/MSH2 genes play a critical role in the development of BC. Hypomethylation of MLH1/MSH2 genes might be important in chemotolerance of the disease.
The impact of failure to achieve symptom control after resection of functional neuroendocrine tumors: An 8‐institution study from the US Neuroendocrine Tumor Study Group
Authors: Zaidi Mohammad Y. , Lopez‐Aguiar Alexandra G. , Poultsides George A. , Dillhoff Mary , Rocha Flavio G. , Idrees Kamran , Nathan Hari , Winslow Emily R. , Fields Ryan C. , Cardona Kenneth , Maithel Shishir K. ,   and other members of the US Neuroendocrine Tumor Study Group
Published: November 2018

BackgroundThe goals of resection of functional neuroendocrine tumors (NETs) are two‐fold: Oncological benefit and symptom control. The interaction between the two is not well understood.MethodsAll patients with functional NETs of the pancreas, duodenum, and ampulla who underwent curative‐intent resection between 2000 and 2016 were identified. Using Cox regression analysis, factors associated with reduced recurrence‐free survival (RFS) were identified.ResultsTwo‐hundred and thirty patients underwent curative‐intent resection. Fifty‐three percent were insulinomas, 35% gastrinomas, and 12% were other types. Twenty‐one percent had a known genetic syndrome, 23% had lymph node (LN) positivity, 80% underwent an R0 resection, and 14% had no postoperative symptom improvement (SI). Factors associated with reduced RFS included noninsulinoma histology, the presence of a known genetic syndrome, LN positivity, R1 margin, and lack of SI. On multivariable analysis, only the failure to achieve SI following resection was associated with reduced RFS. Considering only those patients with an R0 resection, failure to achieve SI was associated with worse 3‐year RFS compared with patients having SI (36% vs 80%; P = 0.006).ConclusionsFailure to achieve symptomatic improvement after resection of functional NETs is associated with worse RFS. These patients may benefit from short‐interval surveillance imaging postoperatively to assess for earlier radiographical disease recurrence.
Clinico‐pathological features and survival of patients with malignant exocrine pancreatic neoplasms: The AC Camargo Cancer Center experience
Authors: Fonseca de Jesus Victor Hugo , Guedes Camandaroba Marcos Pedro , Spina Donadio Mauro Daniel , Cabral Audrey , Pimentel Muniz Thiago , de Moura Leite Luciana , Ferreira Sant’Ana Lucas , Luiz da Costa Wilson , Curado Maria Paula , Coimbra Felipe José Fernandez 
Published: November 2018

BackgroundPancreatic cancer plays an important role in cancer‐related mortality. Few studies have been performed in Brazil to characterize patients affected by this disease. We aimed to describe the clinico‐pathological characteristics and the survival of patients with pancreatic cancer seen at AC Camargo Cancer Center (ACCCC).MethodsWe included patients ≥ 18‐year old, with a histologically confirmed diagnosis of exocrine pancreatic cancer, that attended at least one visit at ACCCC from 2008 to 2016.ResultsThe study included 739 patients. Median age at diagnosis was 64 years. Most patients were male. About 5% presented a family history of pancreatic cancer. A total of 40% had diabetes and 51.4% presented with ECOG performance status 1. Tumors most often arose in the pancreatic head and roughly half of the patients had metastatic disease at presentation. Median overall survival of patients with potentially resectable disease submitted to surgery at ACCCC was 35.4 months. Median overall survival times of patients with the unresectable and metastatic disease were 14.1 and 9.3 months, respectively.ConclusionsThe features of our population match those of studies done in developed countries. We believe multicentric data from patients with pancreatic cancer in Brazil could enable more effective preventive and therapeutic approaches to the disease.