Yan-Shou Zhang, Lei Han, Chao Yang, Yun-Jiang Liu, Xiang-Mei Zhang
BACKGROUND: High expression of leucine-rich alpha-2-glycoprotein 1 (LRG1) is closely related to angiogenesis, which may play an important role in promoting invasion and metastasis. However, the current literature has yet to clarify the clinical significance of LRG1 in breast cancer. OBJECTIVES: The purpose of this work was to validate the correlation between LRG1 expression and prognosis in early breast cancer. METHODS: We utilized an LRG1 detection agent in 330 cases of early breast cancer...
November 26, 2020: Oncology Research and Treatment
Ankita Das, Shreya Adhikary, Amit Roy Chowdhury, Ananya Barui
Stem cell chirality or left-right (LR) asymmetry is an essential attribute observed during tissue regeneration. Ability to instruct the LR orientation of cells by biophysical manipulation can be a promising approach for recapitulating their inherent function. Despite remarkable progress in tissue engineering, development of LR chirality in stem cells has been largely unexplored. Here, we demonstrate the role of substrate stiffness on LR asymmetry of cultured mesenchymal stem cells (MSC). We found that MSC acquired higher asymmetricity when cultured on stiffer PCL/Collagen matrix...
November 26, 2020: Biomedical Materials
Sankha Subhra Das, Subhayan Das, Prasanna Kumar Byram, Motiur Rahaman, Tuphan Kanti Dolai, Anish Chatterjee, Nishant Chakravorty
Hemoglobin E (HbE)/β-thalassemia is a form of β-hemoglobinopathy that is well-known for its clinical heterogeneity. Individuals suffering from this condition are often found to exhibit increased fetal hemoglobin (HbF) levels - a factor that may contribute to their reduced blood transfusion requirements. This study hypothesized that the high HbF levels in HbE/β-thalassemia individuals may be guided by microRNAs and explored their involvement in the disease pathophysiology. The miRNA expression profile of hematopoietic progenitor cells in HbE/β-thalassemia patients was investigated and compared with that of healthy controls...
November 19, 2020: Blood Cells, Molecules & Diseases
Antoine Desilets, Félix Blanc-Durand, Sally Lau, Taiki Hakozaki, Rui Kitadai, Julie Malo, Wiam Belkaid, Corentin Richard, Meriem Messaoudene, Lena Cvetkovic, Suzanne Kazandjian, Mustapha Tehfe, Marie Florescu, Kevin Jao, Nathalie Daaboul, Scott Owen, Benjamin Shieh, Jason Agulnik, Victor Cohen, Chloé Charbonneau, Nicolas Marcoux, Normand Blais, Natasha B Leighl, Penelope A Bradbury, Geoffrey Liu, Frances A Shepherd, Houda Bahig, Bertrand Routy, Adrian Sacher, Arielle Elkrief
BACKGROUND: The PACIFIC trial demonstrated that durvalumab therapy following chemoradiation (CRT) was associated with improved overall survival (OS) in patients with stage III non-small cell lung cancer (NSCLC). It is unclear whether the results obtained as part of randomised controlled trials are a reflection of real-world (RW) data. Several questions remain unanswered with regard to RW durvalumab use, such as optimal time to durvalumab initiation, incidence of pneumonitis and response in PD-L1 subgroups...
November 23, 2020: European Journal of Cancer
Jibran Sualeh Muhammad, Maha Guimei, Manju Nidagodu Jayakumar, Jasmin Shafarin, Aisha Saleh Janeeh, Rola AbuJabal, Mohamed Ahmed Eladl, Anu Vinod Ranade, Amjad Ali, Mawieh Hamad
Increased expression of Yes-associated protein-1 (YAP1) was shown to correlate with reduced survival in breast cancer (BC) patients. However, the exact mechanism of YAP1 regulation in BC cells remains ambiguous. Genomic sequence search showed that the promoter region of the YAP1 gene contains CpG Islands, hence the likelihood of epigenetic regulation by DNA methylation. To address this possibility, the effect of estrogen (17β estradiol; E2) on YAP1 gene expression and YAP1 promoter methylation status was evaluated in BC cells...
November 23, 2020: Neoplasia: An International Journal for Oncology Research
Alejandro Matía, María M Lorenzo, Rafael Blasco
The potential of viruses as biotechnology platforms is becoming more appealing due to technological advances in synthetic biology techniques and to the increasing accessibility of means to manipulate virus genomes. Among viral systems, poxviruses, and their prototype member Vaccinia Virus, are one of the outstanding choices for different biotechnological and medical applications based on heterologous gene expression, recombinant vaccines or oncolytic viruses. The refinement of genetic engineering methods on Vaccinia Virus over the last decades have contributed to facilitate the manipulation of the genomes of poxviruses, and may aid in the improvement of virus variants designed for different goals through reverse genetic approaches...
November 23, 2020: Current Opinion in Virology
Dilyana Todorova, Yue Zhang, Qu Chen, Jingfeng Liu, Jingjin He, Xuemei Fu, Yang Xu
BACKGROUND: With their inherent capability of unlimited self-renewal and unique potential to differentiate into functional cells of the three germ layers, human embryonic stem cells (hESCs) hold great potential in regenerative medicine. A major challenge in the application of hESC-based cell therapy is the allogeneic immune rejection of hESC-derived allografts. METHODS: We derived dendritic cell-like cells (DCLs) from wild type and CTLA4-Ig/PD-L1 knock-in hESCs, denoted WT DCLs and CP DCLs...
November 23, 2020: EBioMedicine
Laurens F Reeskamp, Tycho R Tromp, Roeland Huijgen, Erik S G Stroes, G Kees Hovingh, Aldo Grefhorst
BACKGROUND AND AIMS: Statins suppress hepatic mRNA expression of ANGPTL3 encoding angiopoietin-like 3 in healthy subjects, but it is unknown if plasma ANGPTL3 concentrations are affected by statins prescribed to hypercholesterolemic patients in clinical practice. We therefore investigated the effect of statin treatment on plasma ANGPTL3 concentrations in hypercholesterolemic patients. In addition, we explored the underlying mechanism by which statins regulate ANGPTL3 in vitro. METHODS: Plasma ANGPTL3 concentrations were measured in 93 genetically confirmed familial hypercholesterolemia (FH) patients who were using statin therapy and 61 statin naïve FH patients...
November 18, 2020: Atherosclerosis
Yajun Cao, Hongyan Wu, Wanli Zhai, Ying Wang, Mengdi Li, Meng Li, Liu Yang, Ye Tian, Yunhao Song, Jun Li, Yinyin Wang, Qiang Ding, Linqi Zhang, Ming Cai, Zhijie Chang
Due to the multi-potential differentiation and immunomodulatory function, mesenchymal stem cells (MSCs) have been widely used in the therapy of chronic and autoimmune diseases. Recently, the novel coronavirus disease 2019 (COVID-19) has grown to be a global public health emergency but no effective drug is available to date. Several studies investigated MSCs therapy for COVID-19 patients. However, it remains unclear whether MSCs could be the host cells of SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) and whether they might affect the SARS-CoV-2 entry into other cells...
October 24, 2020: Stem Cell Research
Wen-Jing Zhang, Ren-Qi Wang, Lin-Tao Li, Wen Fu, Huan-Chun Chen, Zheng-Fei Liu
Many viruses utilize molecular chaperone heat shock protein 90 (Hsp90) for protein folding and stabilization, however, the role of Hsp90 in herpesvirus lifecycle is obscure. Here, we provide evidence that Hsp90 participates in pseudorabies virus (PRV) replication. Viral growth kinetics assays show that Hsp90 inhibitor geldanamycin (GA) abrogates PRV replication at the post-penetration step. Transmission electron microscopy demonstrates that dysfunction of Hsp90 diminishes the quantity of PRV nucleocapsids. Overexpression and knockdown of Hsp90 suggest that de novo Hsp90 is involved in PRV replication...
November 13, 2020: Virology
Antika Boonlaos, Wiriyachayon Wechsirisan, Pawitree Chaibuth, Vena Chupia, Suwit Chotinun, Phongsakorn Chuammitri
Herbal compound, quercetin, has previously been shown its modulatory effects on mammalian neutrophils and avian counterpart. However, at this instance it is not clear how quercetin promotes its effects on fungal and yeast killing in chicken heterophils. In the present study, we have proved that quercetin exerts the significant modulatory effects against pathogenic yeast (Candida albicans) in freshly isolated heterophils from Thai native broiler chicken. This substance is shown to facilitate heterophil effector functions through the reduction of ROS generation, and promotion of phagocytosis and candidacidal killing...
November 15, 2020: Comparative Immunology, Microbiology and Infectious Diseases
Thanich Sangsuwannukul, Kamonlapat Supimon, Jatuporn Sujjitjoon, Nattaporn Phanthaphol, Thaweesak Chieochansin, Naravat Poungvarin, Sopit Wongkham, Mutita Junking, Pa-Thai Yenchitsomanus
Current treatment of cholangiocarcinoma (CCA) - a lethal bile duct cancer - is ineffective because the disease is usually diagnosed at late and advanced stage. Thus, a novel therapeutic modality is urgently required. Fourth-generation chimeric antigen receptor (CAR4) T cells was created to target CD133, a well-known cancer stem cell marker, that is highly expressed and associates with cancer progression. The anti-CD133-CAR4 T cells showed high efficacy against CD133-expressing CCA cells. Tumour cell lysis occurred in a dose- and CD133 antigen-dependent manner, and significantly higher, up to 57...
November 23, 2020: International Immunopharmacology
Jin Wan, Jiao Zhang, Heng Yin, Daiwen Chen, Bing Yu, Jun He
Alginate oligosaccharide (AOS), produced by the depolymerisation of alginate (a polysaccharide naturally present in certain species of brown algae), has been shown to have versatile biological functions. In the present study, the porcine small intestinal epithelial cell line IPEC-J2 was used to assess the ameliorative effects of AOS on tumour necrosis factor-α (TNF-α)-induced intestinal epithelial cell injury. IPEC-J2 cells were pre-treated with or without AOS (600 μg/mL) in the presence or absence of TNF-α (50 ng/mL) for 24 h...
November 23, 2020: International Immunopharmacology
Jianning Guo, Yu Liu, Xiaoyao Guo, Yujiao Meng, Cong Qi, Jingxia Zhao, Tingting Di, Lu Zhang, Xinwei Guo, Yazhuo Wang, Yan Wang, Ping Li
Psoriasis is not only a chronic inflammatory skin disease but also a psychosomatic disorder. Depression is one of the most common associated diseases, which aggravates psoriatic skin lesions and affects the life quality of patients. Clinical experiments establish a correlation between psoriasis and depression; however, the mechanisms yet unclear because only a few related studies are available. Therefore, to investigate whether imiquimod-induced psoriasis-like mice showed depressive-like behavior, 5% imiquimod cream was smeared on the back of mice to induce psoriasis-like skin lesions for 8 days...
November 23, 2020: International Immunopharmacology
Kai Shi, Yingling Lu, Xiaolu Chen, Dongfeng Li, Wenxing Du, Minli Yu
Skeletal muscle development is an orchestrated progress that is primarily regulated by temporospatial expression of myogenic regulatory factors (MRFs). Recent studies demonstrated that DNA demethylation also exerted a critical role in myogenesis. However, the function of Tet2 in the regulation of chicken myogenesis still remains unknown. In the present study, the role of Tet2 in regulating myogenic differentiation was determined by using a model of primary myoblasts from chickens. The expression of Tet2 was significantly elevated during myoblast differentiation...
November 23, 2020: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
Elizabeth R Evans, Amir M Farnoud, Kristin M O'Brien, Elizabeth L Crockett
Antarctic notothenioids are noted for extreme stenothermy, yet underpinnings of their thermal limits are not fully understood. We hypothesized that properties of ventricular membranes could explain previously observed differences among notothenioids in temperature onset of cardiac arrhythmias and persistent asystole. Microsomes were prepared using ventricles from six species of notothenioids, including four species from the hemoglobin-less (Hb-) family Channichthyidae (icefishes), which also differentially express cardiac myoglobin (Mb), and two species from the (Hb+) Nototheniidae...
November 23, 2020: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
J Chalmers, Y C L Tung, C H Liu, C J O'Kane, S O'Rahilly, G S H Yeo
OBJECTIVE: More than 300 genetic variants have been robustly associated with measures of human adiposity. Highly penetrant mutations causing human obesity do so largely by disrupting satiety pathways in the brain and increasing food intake. Most of the common obesity-predisposing variants are in, or near, genes that are expressed highly in the brain, but little is known about their function. Exploring the biology of these genes at scale in mammalian systems is challenging. We sought to establish and validate the use of a multicomponent screen for feeding behaviour phenotypes taking advantage of the tractable model organism Drosophila melanogaster...
November 23, 2020: Molecular Metabolism
Nannan Sun, Huiling Hu, Fei Wang, Lanlan Li, Wanwan Zhu, Yan Shen, Jianbo Xiu, Qi Xu
The crosstalk between intestinal bacteria and the central nervous system, so called "the gut-brain axis", is critically important for maintaining brain homeostasis and function. This study aimed to investigate the integrity of the blood-brain barrier (BBB) and migration of bone marrow (BM)-derived cells to the brain parenchyma after intestinal microbiota depletion in adult mice. Gut microbiota dysbiosis was induced with 5 non-absorbable antibiotics in drinking water in mice that had received bone marrow transplantation (BMT) from green fluorescent protein (GFP) transgenic mice...
November 23, 2020: Brain, Behavior, and Immunity
Dario Breitel, Paul Brett, Saleh Alseekh, Alisdair R Fernie, Eugenio Butelli, Cathie Martin
L-DOPA, also known as Levodopa or L-3,4-dihydroxyphenylalanine, is a non-standard amino acid, and the gold standard drug for the treatment for Parkinson's Disease (PD). Recently, a gene encoding the enzyme that is responsible for its synthesis, as a precursor of the coloured pigment group betalains, was identified in beetroot, BvCYP76AD6. We have engineered tomato fruit enriched in L-DOPA through overexpression of BvCYP76AD6 in a fruit specific manner. Analysis of the transgenic fruit revealed the feasibility of accumulating L-DOPA in a non-naturally betalain-producing plant...
November 23, 2020: Metabolic Engineering
Sílvia Umeda Gallani, Gustavo Moraes Ramos Valladão, Lindomar de Oliveira Alves, Suzana Kotzent, Diogo Teruo Hashimoto, Geert Wiegertjes, Karina Kirsten, Luiz Carlos Kreutz, Fabiana Pilarski
The production of tambaqui Colossoma macropomum has recently reached a milestone, being considered the main native species produced in South American continental waters. Despite the importance of this fish, its immunity is not well understood. In this study we established some patterns of innate immunity for the species via two experiments. Both studies evaluated the fish in the absence (intraperitoneal saline) or presence (intraperitoneal, 3 x 107  CFU/mL of Aeromonas hydrophila at 0.1 mL/10 g of living weight) of infection at 5 points over time-course of 14 days (0 h, 6 h, 24 h, 7 d, 14 d)...
November 23, 2020: Microbial Pathogenesis
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