bluuebunny/crossref_metadata_2025_split huggingface dataset:
What role does pyroptosis play in microbial infection?
Authors: Xia Xiaojing , Wang Xin , Zheng Yi , Jiang Jinqing , Hu Jianhe 
Published: December 2018

AbstractPyroptosis, a type of programmed cell death mediated by gasdermin, is characterized by the swelling and rupture of cells, release of cellular contents and a strong inflammatory response, which is critical for controlling microbial infection. Pattern recognition receptors recognize the intracellular and extracellular pathogenic microbial components and stimulate the organism's inflammatory response by activating the pyroptosis signaling pathway and releasing interleukin‐1β (IL‐1β), IL‐18, and other inflammatory factors to promote pathogen clearance and prevent infection. In the process of continuous evolution, pathogens have developed multiple strategies to modulate the occurrence of pyroptosis and thus enhance their ability to induce disease; that is, the competition between host cells and pathogens controls the occurrence of pyroptosis. Competition can directly affect tissue inflammation outbreaks and even alter cell survival. Studies have shown that various bacterial infections, including Shigella flexneri, Salmonella, Listeria monocytogenes, and Legionella pneumophila, can lead to pyroptosis. Pyroptosis is associated with the occurrence and development of various diseases caused by microbial infection, and the identification of molecules related to the pyroptosis signaling pathway may provide new drug targets for the treatment of related diseases. This study reviews the molecular mechanisms of pyroptosis and the role of pyroptosis in microbial infection‐related diseases.
Interleukin‐10 responses from acute exercise in healthy subjects: A systematic review
Authors: Cabral‐Santos Carolina , de Lima Junior Edson Alves , Fernandes Isabela Maia da Cruz , Pinto Rafael Zambelli , Rosa‐Neto José César , Bishop Nicolette Charllote , Lira Fábio Santos 
Published: December 2018

AbstractPurposeInterleukin 10 (IL‐10) is a cytokine that plays a critical role with potent anti‐inflammatory properties when produced during exercise, limiting host immune response to pathogens and preventing tissue damage. The purpose of this systematic review was to assess the response of IL‐10 after acute exercise session in healthy adults.MethodsDatabases of Ovid Medline (1978–2016), CINAHL (1998–2016), EMBASE (2003–2016), SportDiscus (1990–2016), and Web of Science library (1990–2016) were carefully screened. Clinical trials comparing exercise types in healthy individuals were included for pooled analysis. The trials of exercise were methodologically appraised by PEDro Scale.ResultsTwelve randomized controlled and crossover trials containing 176 individuals were identified for inclusion. The Kruskal‐Wallis test showed no significant differences between type of exercise and the corresponding values in IL‐10 [X2(4) = 2.878; p = 0.449]. The duration of exercise was significantly correlated with increase in IL‐10 changes (Pearson's r = 1.00, 95%CI: 0.015–0.042, p < 0.0001) indicating that 48% of the variation in IL‐10 levels can be explained by the duration of the exercise performed. In addition, despite a linear increase, we did not find a significant correlation with the intensity of exercise and IL‐10 changes (Pearson's r = 0.218, 95%CI: −0.554–0.042, p < 0.035).ConclusionOverall, the duration of the exercise is the single most important factor determining the magnitude of the exercise‐induced increase of plasma IL‐10.
Coenzyme Q10 protects against β‐cell toxicity induced by pravastatin treatment of hypercholesterolemia
Authors: Lorza‐Gil Estela , de Souza Jane C. , García‐Arévalo Marta , Vettorazzi Jean F. , Marques Ana Carolina , Salerno Alessandro G. , Trigo Jose Roberto , Oliveira Helena C. F. 
Published: December 2018

AbstractNew onset of diabetes is associated with the use of statins. We have recently demonstrated that pravastatin‐treated hypercholesterolemic LDL receptor knockout (LDLr−/−) mice exhibit reductions in insulin secretion and increased islet cell death and oxidative stress. Here, we hypothesized that these diabetogenic effects of pravastatin could be counteracted by treatment with the antioxidant coenzyme Q
10 (CoQ
10), an intermediate generated in the cholesterol synthesis pathway. LDLr
−/− mice were treated with pravastatin and/or CoQ
10 for 2 months. Pravastatin treatment resulted in a 75% decrease of liver CoQ
10 content. Dietary CoQ
10 supplementation of pravastatin‐treated mice reversed fasting hyperglycemia, improved glucose tolerance (20%) and insulin sensitivity (>2‐fold), and fully restored islet glucose‐stimulated insulin secretion impaired by pravastatin (40%). Pravastatin had no effect on insulin secretion of wild‐type mice. In vitro, insulin‐secreting INS1E cells cotreated with CoQ
10 were protected from cell death and oxidative stress induced by pravastatin. Simvastatin and atorvastatin were more potent in inducing dose‐dependent INS1E cell death (10–15‐fold), which were also attenuated by CoQ
10 cotreatment. Together, these results demonstrate that statins impair β‐cell redox balance, function and viability. However, CoQ
10 supplementation can protect the statins detrimental effects on the endocrine pancreas.
Exosomes as a novel cell‐free therapeutic approach in gastrointestinal diseases
Authors: Baghaei Kaveh , Tokhanbigli Samaneh , Asadzadeh Hamid , Nmaki Saeed , Reza Zali Mohammad , Hashemi Seyed Mahmoud 
Published: December 2018

AbstractCell communication through extracellular vesicles (EVs) has been defined for many years and it is not limited only to neighboring cells, but also distant ones in organisms receive these signals. These vesicles are secreted from the variety of cells and are composed of a distinctive component such as proteins, lipids, and nucleic acids. EVs have different classified subgroups regarding their cell origin, in this context, exosomes are the most appealing particles in cell biology, especially clinical in recent years and are represented as novel therapeutic agents with numerous advantages alongside and/or over cell therapy. However, cell therapy had a hopeful outcome in gastrointestinal diseases which have minimal alternatives in their treatments. Inflammatory bowel disease (IBD), liver fibrosis, gastrointestinal cancers are the examples that cell therapy and immunotherapy were applied in their treatment, therefore, the cell products like exosomes are the beneficial option in their treatment even cancers with promising results in animal models. In this review, we consider the main defined biogenesis, function, and component of secreted exosomes in different cells with a specific focus on the potential application of these exosomes as a cell‐free therapeutic approach in gastrointestinal diseases like IBD, gastric cancer, and colon cancer. Additionally, exosomes role as therapeutic reagents mainly mesenchymal stem cells and dendritic cell‐derived exosomes in different studies have been under intense investigation and even they are being studied in different clinical trials. Therefore, all these striking functions described for secretome implies the importance of these biocarriers.
EP2 and EP4 receptor antagonists: Impact on cytokine production and β2‐adrenergic receptor desensitization in human airway smooth muscle
Authors: Bradbury Peta , Rumzhum Nowshin N. , Ammit Alaina J. 
Published: December 2018

AbstractProstaglandin E2 (PGE2) is a key prostanoid known to have both proinflammatory and anti‐inflammatory impact in the context of chronic respiratory diseases. We hypothesize that these opposing effects may be the result of different prostanoid E (EP) receptor‐mediated signaling pathways. In this study, we focus on two of the four EP receptors, EP2 and EP4, as they are known to induce cyclic adenosine monophosphate (cAMP)‐dependent signaling pathways. Using primary human airway smooth muscle (ASM) cells, we first focussed on the PGE2‐induced production of two cAMP‐dependent proinflammatory mediators: interleukin 6 (IL‐6) and cyclo‐oxygenase 2 production. We show that PGE2‐induced IL‐6 protein secretion occurs via an EP2‐mediated pathway, in a manner independent of receptor‐mediated effects on messenger RNA (mRNA) expression and temporal activation kinetics of the transcription factor cAMP response element binding. Moreover, stimulation of ASM with PGE2 did not establish a positive, receptor‐mediated, feedback loop, as mRNA expression for EP2 and EP4 receptors were not upregulated and receptor antagonists were without effect. Our studies revealed that the EP2, but not the EP4, receptor is responsible for β2‐adrenergic desensitization induced by PGE2. We demonstrate that PGE2‐induced heterologous receptor desensitization responsible for tachyphylaxis to short‐ (salbutamol) or long‐ (formoterol) β2‐agonists (measured by cAMP release) can be reversed by the EP2 receptor antagonist PF‐04418948. Importantly, this study highlights that inhibiting the EP2 receptor restores β2‐adrenergic receptor function in vitro and offers an attractive novel therapeutic target for treating infectious exacerbations in people suffering from chronic respiratory diseases in the future.
Attenuation of aquaporin‐3 and epidermal growth factor receptor expression and activation in systemic sclerosis dermal fibroblasts
Authors: Farhadi Elham , Mahmoudi Mahdi , Rahmani Farzaneh , Yousefi Bahman , Sarafnejad Abdolfattah , Kavosi Hoda , Karimizadeh Elham , Jamshidi Ahmadreza , Gharibdoost Farhad 
Published: December 2018

AbstractObjectivesImpaired wound healing and skin dehydration are the mainstay of systemic sclerosis (SSc) cutaneous manifestations. Aquaporin‐3 (AQP3) has a pivotal role in skin hydration and wound healing. Epidermal growth factor receptor (EGFR) activation is impaired in SSc fibroblasts. It is unclear whether AQP3 downregulation or epidermal growth factor (EGF) signaling are the primary points of dysregulation in SSc patients.MethodsSkin punch biopsies were obtained from 10 SSc patients and 10 healthy subjects. The mRNA and/or protein expression levels of AQP3, EGFR/p‐EGFR, matrix metalloproteinase‐1/2/9 (MMP‐1/2/9), and tissue inhibitors of metalloproteinase‐1 (TIMP1) at baseline and after EGF and transforming growth factor‐β1 (TGF‐β1) treatment was evaluated in extracted fibroblasts using real‐time polymerase chain reaction and western blot analysis.ResultsSSc fibroblasts expressed lower AQP3 and EGFR, compared with normal fibroblasts. Normal fibroblasts increased AQP3 expression in response to EGF whereas AQP3 expression had no change in EGF‐treated‐SSc fibroblasts. Likewise, EGFR was activated in response to EGF in the normal group but not SSc group. Baseline expression of MMP‐1/2/9 and TIMP1 was not different between SSc and controls. EGF treatment did not result in alteration of any MMPs expression in either of the groups. Combination treatment resulted in a significant upregulation of MMP‐1 in normal fibroblasts compared with SSc fibroblasts, while in SSc fibroblasts MMP‐9 expression was upregulated in response to treatment with TGF‐β1 only.ConclusionDownregulation of AQP3 expression in SSc fibroblasts may be related to reduced EGFR expression and activation. TGF‐β1 (alone or in combination with EGF) only can upregulate AQP3 expression in SSc fibroblasts so, TGF‐β1 affect MMP‐1 and MMP‐9 just in SSc fibroblasts.
Transforming growth factor‐β signaling: Tumorigenesis and targeting for cancer therapy
Authors: Ahmadi Amirhossein , Najafi Masoud , Farhood Bagher , Mortezaee Keywan 
Published: December 2018

AbstractTransforming growth factor (TGF)‐β is a multitasking cytokine such that its aberrant expression is related to cancer progression and metastasis. TGF‐β is produced by a variety of cells within the tumor microenvironment (TME), and it is responsible for regulation of the activity of cells within this milieu. TGF‐β is a main inducer of epithelial–mesenchymal transition (EMT), immune evasion, and metastasis during cancer progression. TGF‐β exerts most of its functions by acting on TβRI and TβRII receptors in canonical (Smad‐dependent) or noncanonical (Smad‐independent) pathways. Members of mitogen‐activated protein kinase, phosphatidylinositol 3‐kinase/protein kinase B, and nuclear factor κβ are involved in the non‐Smad TGF‐β pathway. TGF‐β acts by complex signaling, and deletion in one of the effectors in this pathway may influence the outcome in a diverse way by taking even an antitumor role. The stage and the type of tumor (contextual cues from cancer cells and/or the TME) and the concentration of TGF‐β are other important factors determining the fate of cancer (progression or repression). There are a number of ways for targeting TGF‐β signaling in cancer, among them the special focus is on TβRII suppression.
Mutual inhibitions between epidermal growth factor receptor signaling and miR‐124a control pancreatic progenitor proliferation
Authors: Zhang Zhenwu , Zhai Wenjun , Liang Jie , Chen Zhenbao , Ma Mingjun , Zhao Yicheng , Liang Yang , Li Xuyan , Teng Chun‐Bo 
Published: December 2018

AbstractPancreatic stem/progenitor cells convert from a proliferative to a differentiated fate passing through proliferation cease to a resting state. However, the molecular mechanisms of cell cycle arrest are poorly understood. In this study, we demonstrated that the microRNA‐124a (miR‐124a) inhibited the proliferation of pancreatic progenitor cells both in vitro and ex vivo and promoted a quiescent state. The miR‐124a directly targeted SOS Ras/Rac guanine nucleotide exchange factor 1 (SOS1), IQ motif‐containing GTPase‐activating protein 1 (IQGAP1), signal transducer and activator of transcription 3 (STAT3), and cyclin D2 (CCND2), thereby inactivating epidermal growth factor receptor (EGFR) downstream signaling pathways including mitogen‐activated protein kinase/extracellular signal‐regulated kinase (MEK/ERK), phosphatidylinositol 3‐kinase‐protein kinase B (PI3K/AKT) and Janus kinase (JAK)/STAT3. miR‐124a blocked cell proliferation mainly through targeting STAT3 to inhibit PI3K/AKT and JAK/STAT3 signaling. Moreover, miR‐124a expression was negatively regulated by EGFR downstream PI3K/AKT signaling. These results indicated that miR‐124a and EGFR signaling mutually interact to form a regulating circuit that determines the proliferation of pancreatic progenitor cells.
Dynamic recognition and repair of DNA complex damage
Authors: Yan Junfang , Xie Yi , Zhang Qianjing , Gan Lu , Wang Fang , Li Hongyan , Si Jing , Zhang Hong 
Published: December 2018

AbstractIrradiation (IR) can be used to treat cancer by inducing complex and irreparable DNA damage in the cancer cells, which may lead to their apoptotic death. However, little is known about the molecular mechanism of this DNA damage. Here, the non‐small‐cell lung cancer cell line A549 was treated with either X‐ray or carbon ion combined with bleomycin (BLM). The cell survival rate, frequency of double‐strand breaks (DSBs), dynamic changes in γH2AX, and p53 binding protein 1 (53BP1), and protein expression of Ku70, Rad51, and XRCC1 were determined by the clone formation assay, agarose gel electrophoresis, immunofluorescence, and western blot analysis. The results showed that the most obvious complex DSBs occurred in the carbon IR + BLM group. The number of γH2AX and 53BP1 foci in the 0.5 hr X‐ray IR + BLM group was the highest (p < 0.001) among all the groups. γH2AX foci were detected in the nucleus at 0.5, 1, 2, and 4 hr, but were distributed throughout the cell at 6 hr after IR in the carbon ion IR + BLM group. The expression of Ku70 increased and XRCC1 decreased at 2 and 6 hr after IR. Our data indicate that a DNA damage frequency of 13.4/Mbp is caused by clustered DNA damage and further show a correlation between γH2AX, 53BP1, and XRCC1 levels and the extent of DNA damage. The results of this study provide insights into DNA damage recognition and a rationale for the clinical use of radiotherapy.
Mechanical loading releases osteoclastogenesis‐modulating factors through stimulation of the P2X7 receptor in hematopoietic progenitor cells
Authors: Bratengeier Cornelia , Bakker Astrid D. , Fahlgren Anna 
Published: December 2018

AbstractMechanical instability of bone implants stimulate osteoclast differentiation and peri‐implant bone loss, leading to prosthetic loosening. It is unclear which cells at the periprosthetic interface transduce mechanical signals into a biochemical response, and subsequently facilitate bone loss. We hypothesized that mechanical overloading of hematopoietic bone marrow progenitor cells, which are located near to the inserted bone implants, stimulates the release of osteoclast‐inducing soluble factors. Using a novel in vitro model to apply mechanical overloading, we found that hematopoietic progenitor cells released adenosine triphosphate (ATP) after only 2 min of mechanical loading. The released ATP interacts with its specific receptor P2X7 to stimulate the release of unknown soluble factors that inhibit (physiological loading) or promote (supraphysiological loading) the differentiation of multinucleated osteoclasts derived from bone marrow cultures. Inhibition of ATP‐receptor P2X7 by Brilliant Blue G completely abolished the overloading‐induced stimulation of osteoclast formation. Likewise, stimulation of P2X7 receptor on hematopoietic cells by BzATP enhanced the release of osteoclastogenesis‐stimulating signaling molecules to a similar extent as supraphysiological loading. Supraphysiological loading affected neither gene expression of inflammatory markers involved in aseptic implant loosening (e.g., interleukin‐1β (IL‐1β), IL‐6, tumor necrosis factor‐α, and PTGES2) nor expression of the osteoclast modulators receptor activator of nuclear factor κ‐Β ligand and osteoprotegerin. Our findings suggest that murine hematopoietic progenitor cells are a potential key player in local mechanical loading‐induced bone implant loosening via the ATP/P2X7‐axis. Our approach identifies potential therapeutic targets to prevent prosthetic loosening.
Validation of the albumin–indocyanine green evaluation model in patients with resected hepatocellular carcinoma and comparison with the albumin–bilirubin score
Authors: Russolillo Nadia , Forchino Fabio , Conci Simone , Mele Caterina , Langella Serena , Ruzzenente Andrea , Scoleri Iolanda , Giuliante Felice , Guglielmi Alfredo , Ferrero Alessandro 
Published: December 2018

AbstractBackgroundThe albumin–indocyanine green evaluation (ALICE) model based on serum albumin and indocyanine retention rate has been shown to be an effective method for predicting postoperative outcomes in hepatocellular carcinoma patients. Aim of the study was to validate the ALICE model in a large Western cohort of patients by comparing the albumin–bilirubin (ALBI) score and Child–Turcotte–Pugh (CTP) score.MethodsA total of 400 patients who underwent hepatic resection from January 2005 to June 2016 at three centers were enrolled. The ALICE, ALBI, and CTP scores were computed for all patients.ResultsThe ALICE score correlated better with ALBI (r = 0.428) than with CTP score (r = 0.302). Both the ALICE (grade 1: 49%; grade 2: 51%) and the ALBI (grade 1: 52.5%; grade 2: 47.5%) scores stratified the CTP class A patients into two distinct classes. The incidence of ascites (grades 1–3: ALICE 11%, 20%, 58%; ALBI 11%, 23%, 50%) and severe liver failure (ALICE 8.7%, 10.5%, 41.7%; ALBI 8.6%, 12%, 50%) increased with increasing ALBI and ALICE grade and were similar for the same grade.ConclusionsThe ALICE model can assess hepatic functional reserve and predict postoperative outcomes with efficacy comparable with the ALBI grade and better than the CTP score.
Beyond the mean: Understanding firm‐level consequences of variability in diversity climate perceptions
Authors: Reinwald Max , Huettermann Hendrik , Bruch Heike 
Published: December 2018

SummaryWe develop and test an organizational‐level model of the consequences of diversity climate for company performance. Drawing from affective events theory and the organizational climate literature, we highlight the role of idiosyncrasies in employees' diversity climate perceptions. Specifically, we consider diversity climate strength (i.e., agreement in employees' climate perceptions) as a boundary condition of diversity climate's organizational‐level effects and expect high climate strength to be particularly beneficial in demographically diverse organizations. Moreover, we introduce collective positive affect as an underlying mechanism of diversity climate's conditional effects on company performance. Hypotheses are tested in a study of 82 German small‐and‐medium‐sized companies with 13,695 surveyed employees. Results show a moderated mediation relationship where diversity climate is only positively related to organizational performance (via collective positive affect) at relatively high diversity climate strength. Although this finding holds for both demographically diverse and homogeneous organizations, post hoc analyses provide initial evidence that a strong climate only helps to realize the effects of diversity climate on collective positive affect when members of age‐ and gender‐related demographic subgroups converge in their climate perceptions. Our study contributes to a better understanding of diversity climate as an effective lever for managing diversity.
Quantification of pentaerythritol tetrastearate, a mold release agent used in polycarbonate, by non‐aqueous RP HPLC method
Authors: Indira Polasa , Arun Kumar , Ramesh Narayana 
Published: December 2018

AbstractA new non‐aqueous high‐performance liquid chromatography method for the quantitative determination of mold release agent pentaerythritol tetrastearate in polycarbonate matrix has been developed and validated. The analyte calibration curve was linear over range of 0.05–0.2 mg/mL (Coefficient of determination > 0.999), with limit of detection of 0.03 mg/mL. The repeatability of method was satisfactory with relative standard deviation of 1.6%. The obtained recovery was ranging from 100–101%. Detailed high‐resolution mass spectrometric characterization of the principle peak confirmed that all the five components of pentaerythritol tetrastearate elutes as a single peak under the established chromatographic conditions. The new method is reliable and independent of any variation in composition of analyte in the samples compared to pentaerythritol tetrastearate reference standard used for calibration. The new high‐performance liquid chromatography method is robust and easy to implement in quality control laboratories for quantitative estimation of the mold release agent added in commercial polymer.