bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stabilizing proteins to prevent conformational changes required for amyloid fibril formation
Authors: Siddiqi Mohammad Khursheed , Alam Parvez , Malik Sadia , Majid Nabeela , Chaturvedi Sumit Kumar , Rajan Sudeepa , Ajmal Mohd Rehan , Khan Mohsin Vahid , Uversky Vladimir N , Khan Rizwan Hasan 
Published: September 2018

AbstractAmyloid fibrillation is associated with several human maladies, such as Alzheimer’s, Parkinson’s, Huntington’s diseases, prions, amyotrophic lateral sclerosis, and type 2 diabetes diseases. Gaining insights into the mechanism of amyloid fibril formation and exploring novel approaches to fibrillation inhibition are crucial for preventing amyloid diseases. Here, we hypothesized that ligands capable of stabilizing the native state of query proteins might prevent protein unfolding, which, in turn, may reduce the propensity of proteins to form amyloid fibrils. We demonstrated the efficient inhibition of amyloid formation of the human serum albumin (HSA) (up to 85%) and human insulin (up to 80%) by a nonsteroidal anti‐inflammatory drug, ibuprofen (IBFN). IBFN significantly increases the conformational stability of both HSA and insulin, as confirmed by differential scanning calorimetry (DSC). Moreover, increasing concentration of IBFN boosts its amyloid inhibitory propensity in a linear fashion by influencing the nucleation phase as assayed by thioflavin T fluorescence, transmission electron microscopy, and dynamic light scattering. Furthermore, circular dichroism analysis supported the DSC results, showing that IBFN binds to the native state of proteins and almost completely prevents their tendency to lose secondary and tertiary structures. Cell toxicity assay confirms that species formed in the presence of IBFN are less toxic to neuronal cells (SH‐SY5Y). These results demonstrate the feasibility of using a small molecule to stabilize the native state of proteins, thereby preventing the amyloidogenic conformational changes, which appear to be the common link in several human amyloid diseases.
Role of angiotensin‐converting enzyme insertion/deletion polymorphism in sudden cardiac arrest
Authors: Liu Aifen , Wang Sai , Zhang Chunxiao , Sun Di , Song Xiaozheng 
Published: September 2018

AbstractObjectiveThis study aimed to investigate the relationship between angiotensin‐converting enzyme (ACE) insertion/deletion (I/D) polymorphism and to understand sudden cardiac arrest (SCA) in the Chinese population.MethodsIn this study, 232 patients were divided into the SCA group and the coronary disease group with coronary disease, but no SCA occurred during the treatment period. After comparing the genotype frequencies of the two groups, all patients were further divided into three groups as the II homozygotes, ID heterozygotes, and DD homozygotes to investigate the relationship in ACE I/D polymorphism and other risk factors of SCA.ResultsThe frequencies of DD genotype in the SCA group were significantly higher than the coronary disease group, as well as the D allele frequencies in the SCA group were high when compared with the coronary disease group. According to the genotypes of the ACE I/D polymorphism, the distribution of patients’ characteristics had no significant differences among all the characteristics. Both, the patients who survived SCA, with II genotype and the ones who died of SCA, with DD genotype had significant higher percentages.ConclusionThe DD genotype was associated with a higher prevalence of SCA and might be a risk factor of survival rate in sudden cardiac death.
Liver stiffness assessed by transient elastography as a potential indicator of chronic kidney disease in patients with nonalcoholic fatty liver disease
Authors: Qin Shaoyou , Wang Song , Wang Xu , Wang Jiangbin 
Published: September 2018

BackgroundThis study was designed to determine the diagnostic value of liver stiffness measured by transient elastography (TE) in identifying chronic kidney disease (CKD) in individuals with ultrasonography‐diagnosed NAFLD.MethodsA total of 1439 adult patients with ultrasonography‐diagnosed NAFLD between October 2015 and August 2017 in China‐Japan union hospital of Jilin university were initially eligible. According to the exclusion criteria, 24 patients were excluded, and eventually, a total of 1415 patients were included in the study. The AST/ALT ratio and FIB‐4 score were calculated from blood tests, and liver stiffness was measured using TE.ResultsThe liver stiffness measured by TE, FIB‐4 score, ALT/AST ratio were significantly elevated in CKD patients, compared with those without CKD (P < 0.001). The areas under the curve (AUROC) of liver stiffness, FIB‐4 score and AST/ALT ratio were 0.694 (0.670‐0.718), 0.707 (0.682‐0.730), 0.712 (0.688‐0.736), showing no statistically significant difference between these three tests. Further, multivariate analysis identified four independent risk factors for CKD: age, diabetes mellitus, serum uric acid, and liver stiffness. Also, the performance of these four independent variables taken together in a logistic regression model for identifying CKD was 0.834 (AUROC; 95%CI: 0.814‐0.853), showing a higher diagnostic performance than that of a single application of liver stiffness.ConclusionsLiver stiffness assessed by TE is a potential indicator for CKD in ultrasonography‐diagnosed NAFLD patients. Further, a four‐variable model (liver stiffness, age, serum uric acid, and diabetes mellitus) could be a useful tool for identifying subjects at high risk for CKD in NAFLD patients.
Teeth‐derived stem cells: A source for cell therapy
Authors: Baniebrahimi Ghazaleh , Khanmohammadi Razieh , Mir Fatemeh 
Published: September 2018

AbstractCell therapy is one of the important therapeutic approaches in the treatment of many diseases such as cancer, degenerative diseases, and cardiovascular diseases. Among various cell types, which could be used as cell therapies, stem cell therapy has emerged as powerful tools in the treatment of several diseases. Multipotent stem cells are one of the main classes of stem cells that could originate from different parts of the body such as bone marrow, adipose, placenta, and tooth. Among several types of multipotent stem cells, tooth‐derived stem cells (TDSCs) are associated with special properties such as accessible, easy isolation, and low invasive, which have introduced them as a good source for using in the treatment of several diseases such as neural injuries, liver fibrosis, and Cohrn’s disease. Here, we provided an overview of TDSCs particular stem cells from human exfoliated deciduous teeth and clinical application of them. Moreover, we highlighted molecular mechanisms involved in the regulation of dental stem cells fate.
Ephrin A1 promotes proliferation of bovine endometrial cells with abundant expression of proliferating cell nuclear antigen and cyclin D1 changing the cell population at each stage of the cell cycle
Authors: Lim Whasun , Bae Hyocheol , Bazer Fuller W. , Song Gwonhwa 
Published: September 2018

AbstractEphrin A1 has a role in a variety of biological events, including cell proliferation, differentiation, migration, and angiogenesis. Ephrin A1 expression is abundant in trophoblasts and endometrial cells during the implantation period; however, its intracellular activities have not yet been reported in bovine endometrial (BEND) epithelial cells. The aim of this study was to identify the functional role of ephrin A1 in BEND cells, which have served as a good model system for investigating the regulation of signal transduction following treatment with interferon‐τ (IFNT) in vitro. Supplementation of ephrin A1 to BEND cells increased cell proliferation and increased levels of proliferating cell nuclear antigen and cyclin D1 protein in BEND cell nuclei. To investigate intracellular mechanisms regulated by ephrin A1, we performed Western blot analysis focused on mitogen‐activated protein kinase (MAPK) and phosphoinositide 3‐kinase (PI3K) signaling, which are significantly involved in the successful maintenance of pregnancy. Ephrin A1 dose‐dependently increased phosphorylation of extracellular signal‐regulated kinases (ERK)1/2, c‐Jun N‐terminal kinases (JNK), P38, protein kinase B (AKT), P70S6K, S6, and cyclin D1, and the activated proteins were suppressed by pharmacological inhibitors including wortmannin (a PI3K inhibitor), U0126 (an ERK1/2 inhibitor), and SP600125 (a JNK inhibitor). Among ephrin A1 receptors, abundant expression of EPHA2 and EPHA4 messenger RNA was detected in BEND cells by reverse transcription polymerase chain reaction analysis. Furthermore, tunicamycin‐induced endoplasmic reticulum (ER) stress was inactivated by ephrin A1 treatment of BEND cells. Our findings suggest that ephrin A1 promotes the development of BEND cells and likely enhances uterine capacity and maintenance of pregnancy by activating MAPK and PI3K signaling cascades and by restoring ER stress.
A genetic variant in CDKN2A/2B locus was associated with poor prognosis in patients with esophageal squamous cell carcinoma
Authors: Ghobadi Niloofar , Mehramiz Mehrane , ShahidSales Soodabeh , Rezaei Borojerdi Arezoo , Anvari Kazem , Khazaei Majid , Rezayi Majid , Sadegh Khorrami Mohammad , Joudi‐Mashhad Mona , Ramshini Hassan , Ahmadi‐Simab Saeideh , Moradi Ali , Hassanian Seyed Mahdi , Ghayour‐Mobarhan Majid , Boroushaki Mohammad Taher , Ferns Gordon A. , Avan Amir 
Published: September 2018

AbstractEsophageal squamous cell carcinoma (ESCC) is among the leading causes of cancer related death. Despite of extensive efforts in identifying valid cancer prognostic biomarkers, only a very small number of markers have been identified. Several genetic variants in the 9p21 region have been identified that are associated with the risk of multiple cancers. Here, we explored the association of two genetic variants in the 9p21 region, CDKN2A/B, rs10811661, and rs1333049 for the first time in 273 subjects with, or without ESCC. We observed that the patients with ESCC had a higher frequency of a TT genotype for rs10811661 than individuals in the control group, and this polymorphism was also associated with tumor size. Moreover, a CC genotype for the rs1333049 polymorphism was associated with a reduced overall survival (OS) of patients with ESCC. In particular, patients with a CC (rs1333049) genotype had a significantly shorter OS (CC genotype: 34.5 ± 8.9 months vs. CG+GG: 47.7 ± 5.9 months;
p value = 0.03). We have also shown the association of a novel genetic variant in CDKN2B gene with clinical outcome of patients with ESCC. Further investigations are warranted in a larger population to explore the value of emerging markers as a risk stratification marker in ESCC.
The genetic factors contributing to hypospadias and their clinical utility in its diagnosis
Authors: Joodi Marjan , Amerizadeh Forouzan , Hassanian Seyed Mahdi , Erfani Marjan , Ghayour‐Mobarhan Majid , Ferns Gordon A. , Khazaei Majid , Avan Amir 
Published: September 2018

AbstractHypospadias is among the most common congenital malformations in male neonates. It results from abnormal penile and urethral development, but is a multifactorial disorder that is highly heterogeneous, with several genetic and environmental determinants. Monogenic and chromosomal abnormalities are present in approximately 30% of cases, although the genetic factors contributing to hypospadias remain unknown in 70% of cases. While defects in androgen synthesis can lead to this malformation, mutational analyses have shown several genes, such as sonic hedgehog, fibroblast growth factors, bone morphogenetic proteins, homeobox genes, and the Wnt family, are involved in the normal development of male external genitalia. Mutations in the genes of penile development (e.g., HOX, FGF, Shh) and testicular determination (e.g., WT1, SRY), luteinizing hormone receptor, and androgen receptor have also been proposed to be implicated in hypospadias. Here we review the recent advances in this field and discuss the potential genes that could determine the risk of hypospadias.
Stromal vascular fraction cells plus sustained release VEGF/Ang‐1‐PLGA microspheres improve fat graft survival in mice
Authors: He Yucang , Yu Xiaofang , Chen Zhuojie , Li Liqun 
Published: September 2018

AbstractAutologous fat transplantation is increasingly applied in plastic and reconstructive surgery. Stromal vascular fraction cells (SVFs) combined with angiogenic factors, such as VEGF (vascular endothelial growth factor A) and Ang‐1 (angiogenin‐1), can improve angiogenesis, which is a critical factor for graft survival. However, direct transplant with such a mixture is insufficient owing to the short half‐life of angiogenic factors. In this study, we evaluated whether a double sustained release system of VEGF/ANG‐1‐PLGA (poly (lactic‐co‐glycolic acid)) microspheres plus SVFs can improve angiogenesis and graft survival after autologous fat transplantation. VEGF/ANG‐1‐PLGA‐sustained release microspheres were fabricated by a modified double emulsion–solvent evaporation technique. Human aspirated fat was mixed with SVF suspension plus VEGF/ANG‐1 sustained release microspheres (Group C), SVF suspension (Group B) alone, or Dulbecco’s modified Eagle’s medium as the control (Group A). Eighteen immunocompromised nude mice were injected with these three mixtures subcutaneously at random positions. After 8 weeks, the mean volume of grafts was greater in the SVFs plus VEGF/ANG‐1‐PLGA group than in the control and SVFs groups (1.08 ± 0.069 ml vs. 0.62 ± 0.036 ml, and 0.83 ± 0.059 ml, respectively). Histological assessments showed that lower fibrosis, but greater microvascular density in the SVFs plus VEGF/ANG‐1‐PLGA group than in the other groups, though the SVFs group also had an appropriate capillary density and reduced fibrosis. Our findings indicate that SVFs plus VEGF/ANG‐1‐PLGA‐sustained release microspheres can improve angiogenesis and graft survival after autologous fat transplantation.
Laminar shear stress‐provoked cytoskeletal changes are mediated by epigenetic reprogramming of TIMP1 in human primary smooth muscle cells
Authors: da Silva Rodrigo A. , Fernandes Célio Jr da C. , Feltran Geórgia da S. , Gomes Anderson M. , de Camargo Andrade Amanda Fantini , Andia Denise C. , Peppelenbosch Maikel P. , Zambuzzi Willian F. 
Published: September 2018

AbstractWhereas endothelial responses to shear stress are well‐characterized, the cell physiological effects of shear stress in smooth muscle cells (SMCs) remain largely obscure. As SMCs are directly challenged by shear stress after endothelial denuding injury following procedures such as angioplasty or endarterectomy, characterization of these responses represents an important scientific question. Hence we decided to contrast cytoskeletal reorganization, epigenetic reprogramming, signaling transduction, and changes in miRNA (miRs) profiles in primary human aortic smooth muscle cells (AoSMCs) between unstressed cells and cells exposed to shear stress. We observed that shear stress‐provoked reorganization of the actin cytoskeleton in an apparently Cofilin‐dependent fashion and which related to altered integrin signaling, apparently caused by remodeling of the extracellular matrix. The latter appeared a downstream effect of increased expression of matrix metalloproteinases and downregulation of tissue metalloproteinase inhibitor 1 (TIMP1) protein levels. In turn, these effects related to shear stress‐provoked changes in expression and nuclear localization of the epigenetic regulators demethylases TET1, TET2, DNMT1, DNMT3A and DNMT3B, HDAC6, and SIRT1. Accordingly, TIMP1 promotor CpG hypomethylation was a prominent effect, and resulted in a significant increase in TIMP1 transcription, which may also have related increased expression of miRs involved in modulating TIMP1 translation. Thus epigenetic‐reprogramming of TIMP1 emerges as critical element in smooth muscle responses to mechanical signals and as epigenetic machinery is amendable to pharmacological manipulation, this pathway may have important clinical consequences.
Genetics and rheumatoid arthritis susceptibility in Iran
Authors: Korani Shahla , Korani Mitra , Butler Alexandra E. , Sahebkar Amirhossein 
Published: September 2018

AbstractRheumatoid arthritis (RA) is an autoimmune disorder with a number of risk factors, including both genetic and environmental. A number of RA risk associated genomic loci has been identified. In this review, we summarize the association of genetic factors with RA reported in population studies in Iran. No significant association was found between the majority of genetic factors identified in other populations and risk for RA in the Iranian subjects. This conflicting result could be due to the ethnic differences and diversity that are present in Iran. We conclude that there is a need to investigate larger groups of Iranian subjects, encompassing different regions of Iran, to either prove or refute these initial findings.
Hypoxia induces ZEB2 in podocytes: Implications in the pathogenesis of proteinuria
Authors: Nakuluri Krishnamurthy , Mukhi Dhanunjay , Nishad Rajkishor , Saleem Moin A. , Mungamuri Sathish Kumar , Menon Ram K. , Pasupulati Anil Kumar 
Published: September 2018

AbstractThe glomerular filtration barrier (GFB) plays a critical role in ensuing protein free urine. The integrity of the GFB is compromised during hypoxia that prevails during extreme physiological conditions. However, the mechanism by which glomerular permselectivity is compromised during hypoxia remains enigmatic. Rats exposed to hypoxia showed a decreased glomerular filtration rate, podocyte foot‐processes effacement, and proteinuria. Accumulation of hypoxia‐inducible factor‐1α (HIF1α) in podocytes resulted in elevated expression of zinc finger E‐box binding homeobox 2 (ZEB2) and decreased expression of E‐ and P‐cadherin. We also demonstrated that HIF1α binds to hypoxia response element localized in the ZEB2 promoter. Furthermore, HIF1α also induced the expression of ZEB2‐natural antisense transcript, which is known to increase the efficiency of ZEB2 translation. Ectopic expression of ZEB2 induced loss of E‐ and P‐cadherin and is associated with enhanced motility of podocytes during hypoxic conditions. ZEB2 knockdown abrogated hypoxia‐induced decrease in podocyte permselectivity. This study suggests that hypoxia leads to activation of HIF1α–ZEB2 axis, resulting in podocyte injury and poor renal outcome.
Melatonin and cancer: From the promotion of genomic stability to use in cancer treatment
Authors: Farhood Bagher , Goradel Nasser Hashemi , Mortezaee Keywan , Khanlarkhani Neda , Najafi Masoud , Sahebkar Amirhossein 
Published: September 2018

AbstractCancer remains among the most challenging human diseases. Several lines of evidence suggest that carcinogenesis is a complex process that is initiated by DNA damage. Exposure to clastogenic agents such as heavy metals, ionizing radiation (IR), and chemotherapy drugs may cause chronic mutations in the genomic material, leading to a phenomenon named genomic instability. Evidence suggests that genomic instability is responsible for cancer incidence after exposure to carcinogenic agents, and increases the risk of secondary cancers following treatment with radiotherapy or chemotherapy. Melatonin as the main product of the pineal gland is a promising hormone for preventing cancer and improving cancer treatment. Melatonin can directly neutralize toxic free radicals more efficiently compared with other classical antioxidants. In addition, melatonin is able to regulate the reduction/oxidation (redox) system in stress conditions. Through regulation of mitochondrial nction and inhibition of pro‐oxidant enzymes, melatonin suppresses chronic oxidative stress. Moreover, melatonin potently stimulates DNA damage responses that increase the tolerance of normal tissues to toxic effect of IR and may reduce the risk of genomic instability in patients who undergo radiotherapy. Through these mechanisms, melatonin attenuates several side effects of radiotherapy and chemotherapy. Interestingly, melatonin has shown some synergistic properties with IR and chemotherapy, which is distinct from classical antioxidants that are mainly used for the alleviation of adverse events of radiotherapy and chemotherapy. In this review, we describe the anticarcinogenic effects of melatonin and also its possible application in clinical oncology.
Cholesterol burden in the liver induces mitochondrial dynamic changes and resistance to apoptosis
Authors: Domínguez‐Pérez Mayra , Simoni‐Nieves Arturo , Rosales Patricia , Nuño‐Lámbarri Natalia , Rosas‐Lemus Mónica , Souza Verónica , Miranda Roxana U. , Bucio Leticia , Uribe Carvajal Salvador , Marquardt Jens U. , Seo Daekwan , Gomez‐Quiroz Luis E. , Gutiérrez‐Ruiz María Concepción 
Published: September 2018

AbstractNon‐alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of histopathological changes ranging from non‐inflammatory intracellular fat deposition to non‐alcoholic steatohepatitis (NASH), which may progress into hepatic fibrosis, cirrhosis, or hepatocellular carcinoma. Recent data suggest that impaired hepatic cholesterol homeostasis and its accumulation are relevant to the pathogenesis of NAFLD/NASH. Despite a vital physiological function of cholesterol, mitochondrial dysfunction is an important consequence of dietary‐induced hypercholesterolemia and was, subsequently, linked to many pathophysiological conditions. The aim in the current study was to evaluate the morphological and molecular changes of cholesterol overload in mouse liver and particularly, in mitochondria, induced by a high‐cholesterol (HC) diet for one month. Histopathological studies revealed microvesicular hepatic steatosis and significantly elevated levels of liver cholesterol and triglycerides leading to impaired liver synthesis. Further, high levels of oxidative stress could be determined in liver tissue as well as primary hepatocyte culture. Transcriptomic changes induced by the HC diet involved disruption in key pathways related to cell death and oxidative stress as well as upregulation of genes related to glutathione homeostasis. Impaired liver function could be associated with a decrease in mitochondrial membrane potential and ATP content and significant alterations in mitochondrial dynamics. We demonstrate that cholesterol overload in the liver leads to mitochondrial changes which may render damaged hepatocytes proliferative and resistant to cell death whereby perpetuating liver damage.
Bibliographic title search for medical cardiological “signs” (eponyms)
Authors: Kanie Takayoshi , Mizuno Atsushi , Kawai Fujimi , Iri Takanobu , Suzuki Takahiro , Oshima Shinichirou , Fukui Sho , Son Raku , Matsuo Takahiro 
Published: September 2018

AbstractBackgroundThe word “sign” refers to important physical findings or observations that are useful in diagnosis; however, there are no scientific reviews of “signs.” The aim of this paper was to list and review these terms using a bibliographic approach.MethodsWe performed a title search of “sign” using a bibliographic search and review approach in MEDLINE and EMBASE.ResultsWe detected 398 papers including 217 medical signs in cardiology.ConclusionsThis is the first literature review of eponyms specifically for signs using a bibliographic method, which is useful for the discussion of the appropriateness of eponyms.