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Mult Scler Relat Disord 2021 May 21;53:103033. Epub 2021 May 21.

Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark; Brain Research InterDisciplinary Guided Excellence (BRIDGE), University of Southern Denmark, Denmark. Electronic address:

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an antibody-mediated autoimmune inflammatory disease of the central nervous system (CNS), resulting in primary astrocytopathy. We have previously shown that Angiotensin AT2-receptor (AT2R) stimulation with the specific agonist Compound 21 (C21) attenuated NMOSD-like pathology. Recent studies have proposed that the mechanism behind protective effects of AT2R includes induction of brain derived neurotrophic factor (BDNF). Read More

Evid Based Complement Alternat Med 2021 7;2021:5510552. Epub 2021 May 7.

Division of Chinese Internal Medicine, Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.

Methods: The adults with body mass index (BMI) more than 27 kg/m were enrolled in the study. General personal information, physical condition, TCMBC, biochemical, and SNPs were collected for eligible subjects. The body constitution questionnaire (BCQ) was used to evaluate the relationships between TCMBC tendency, biochemical values, and obesity-related SNPs. Read More

Clin Rev Allergy Immunol 2021 May 29. Epub 2021 May 29.

Department of Translational Medical Sciences, University of Naples Federico II, 80131, Naples, Italy.

Hereditary angioedema (HAE) is a rare genetic disease, characterized by recurrent and unexpected potentially life-threatening mucosal swelling. HAE may be further classified into HAE with C1-inhibitor deficiency (C1-INH-HAE) and HAE with normal C1-INH activity (nlC1-INH-HAE), mostly due to mutations leading to increased vascular permeability. Recent evidence implicates also the innate and adaptive immune responses in several aspects of angioedema pathophysiology. Read More

Curr Opin Immunol 2021 May 15;72:126-134. Epub 2021 May 15.

Division of Rheumatology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, 63110, USA. Electronic address:

Membrane cofactor protein (MCP; CD46), a ubiquitously expressed complement regulatory protein, serves as a cofactor for serine protease factor I to cleave and inactivate C3b and C4b deposited on host cells. However, CD46 also plays roles in human reproduction, autophagy, modulating T cell activation and effector functions and is a member of the newly identified intracellular complement system (complosome). CD46 also is a receptor for 11 pathogens ('pathogen magnet'). Read More

Postgrad Med 2021 May 17. Epub 2021 May 17.

Dept of Internal Medicine, Northern CA VA Health Care System, Martinez Outpatient Clinic.

The majority of angioedema cases encountered in clinical practice are histamine-mediated (allergic); however, some cases are bradykinin-related (non-allergic) and do not respond to standard anti-allergy medications. Among bradykinin-related angioedema, hereditary angioedema (hae) is a rare, but chronic and debilitating condition. The majority of hae is caused by deficiency (type 1) or abnormal function (type 2) of the naturally occurring protein, c1-inhibitor (c1-inh)-a major inhibitor of proteases in the contact (kallikrein-bradykinin cascade), fibrinolytic pathway, and complement systems. Read More

Evid Based Complement Alternat Med 2021 14;2021:9834856. Epub 2021 Apr 14.

Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.

Objective: Huangqi-Honghua herb pair is known for its medicinal value to treat Qi deficiency and blood stasis syndrome with a long history in clinical practice. To understand its possible mechanism in a systematic study, a network pharmacological method was addressed.

Methods: Detailed information on the HH compounds was obtained from two public databases, and oral bioavailability (OB) and drug-like (DL) of the compounds were evaluated. Read More

Curr Obes Rep 2021 Apr 28. Epub 2021 Apr 28.

Section of Endocrinology, Diabetes, Nutrition, and Weight Management, Department of Medicine, Boston University School of Medicine and Boston Medical Center, Doctor's Office Building, 720 Harrison Avenue, Suite, Boston, MA, 8100, USA.

Purpose Of Review: A growing body of evidence suggests that obesity and increased visceral adiposity are strongly and independently linked to adverse outcomes and death due to COVID-19. This review summarizes current epidemiologic data, highlights pathogenetic mechanisms on the association between excess body weight and COVID-19, compares data from previous pandemics, discusses why COVID-19 challenges the "obesity paradox," and presents implications in prevention and treatment as well as future perspectives.

Recent Findings: Data from meta-analyses based on recent observational studies have indicated that obesity increases the risks of infection from SARS-CoV-2, severe infection and hospitalization, admission to the ICU and need of invasive mechanical ventilation (IMV), and the risk of mortality, particularly in severe obesity. Read More

Peptides 2021 Apr 24;142:170556. Epub 2021 Apr 24.

Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa, Nagoya, 464-8602, Japan. Electronic address:

In recent decades, small secreted peptides have been recognized as a new class of intercellular signaling phytohormones in plants. Tyrosine sulfation plays crucial roles in peptide hormone bioactivities in plants. The Arabidopsis tyrosylprotein sulfotransferase mutant tpst-1 causes severe abnormalities in the root tip due to deficiency in the biosynthesis of all functional tyrosine-sulfated peptides. Read More

Mol Genet Metab Rep 2021 Jun 9;27:100753. Epub 2021 Apr 9.

Faculty of Health and Medical Sciences, University of Surrey, GU2 7AL Guildford, United Kingdom.

Mitochondrial dysfunction underlying metabolic disorders such as obesity and diabetes mellitus is strongly associated with cardiac arrhythmias. Murine Pgc-1α hearts replicate disrupted mitochondrial function and model the associated pro-arrhythmic electrophysiological abnormalities. Quantitative PCR, western blotting and histological analysis were used to investigate the molecular basis of the electrophysiological changes associated with mitochondrial dysfunction. Read More

Nat Commun 2021 04 20;12(1):2335. Epub 2021 Apr 20.

Cancer Research UK Edinburgh Centre, MRC Institute of Genetics & Molecular Medicine, The University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK.

Current therapeutic options for treating colorectal cancer have little clinical efficacy and acquired resistance during treatment is common, even following patient stratification. Understanding the mechanisms that promote therapy resistance may lead to the development of novel therapeutic options that complement existing treatments and improve patient outcome. Here, we identify RAC1B as an important mediator of colorectal tumourigenesis and a potential target for enhancing the efficacy of EGFR inhibitor treatment. Read More

Commun Biol 2021 Mar 25;4(1):401. Epub 2021 Mar 25.

Department of Molecular and Cellular Biology, School of Biological Sciences, University of Adelaide, Adelaide, Australia.

Vitamin D deficiency remains a global concern. This 'sunshine' vitamin is converted through a multistep process to active 1,25-dihydroxyvitamin D (1,25D), the final step of which can occur in macrophages. Here we demonstrate a role for vitamin D in innate immunity. Read More

Evid Based Complement Alternat Med 2021 20;2021:4652492. Epub 2021 Feb 20.

College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China.

Introduction: Traditional Chinese medicine (TCM) believes that the pathogenic factors of colorectal cancer (CRC) are "deficiency, dampness, stasis, and toxin," and Fuzheng-Jiedu Decoction (FJD) can resist these factors. In this study, we want to find out the potential targets and pathways of FJD in the treatment of CRC and also explain from a scientific point of view that FJD multidrug combination can resist "deficiency, dampness, stasis, and toxin."

Methods: We get the composition of FJD from the TCMSP database and get its potential target. Read More

Scand J Immunol 2021 May 15;93(5):e13025. Epub 2021 Feb 15.

Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, Poznan, Poland.

Background: Complex interactions between the environment and the mucosal immune system underlie inflammatory bowel disease (IBD). The involved cytokine signalling pathways are modulated by a number of transcription factors, one of which is runt-related transcription factor 3 (RUNX3).

Objective: To systematically review the immune roles of RUNX3 in immune regulation, with a focus on the context of IBD. Read More

Proc Natl Acad Sci U S A 2021 01;118(4)

Whitehead Institute for Biomedical Research, Cambridge, MA 02142;

In mammalian cells, nutrients and growth factors signal through an array of upstream proteins to regulate the mTORC1 growth control pathway. Because the full complement of these proteins has not been systematically identified, we developed a FACS-based CRISPR-Cas9 genetic screening strategy to pinpoint genes that regulate mTORC1 activity. Along with almost all known positive components of the mTORC1 pathway, we identified many genes that impact mTORC1 activity, including , , , , , and Using the genome-wide screening data, we generated a focused sublibrary containing single guide RNAs (sgRNAs) targeting hundreds of genes and carried out epistasis screens in cells lacking nutrient- and stress-responsive mTORC1 modulators, including GATOR1, AMPK, GCN2, and ATF4. Read More

Front Immunol 2020 9;11:571489. Epub 2020 Dec 9.

Department of Biomedical Engineering, University of California, Davis, Davis, CA, United States.

Superparamagnetic iron oxide nanoparticles (SPION) are employed as diagnostics and therapeutics following intravenous delivery for the treatment of iron deficiency anemia (IDA) in adult patients with chronic kidney failure. Neutrophils are the first defense against blood borne foreign insult and recruit to vascular sites of inflammation a sequential process that is characterized by adhesive capture, rolling, and shear resistant arrest. A primary chemotactic agonist presented on the glycocalyx of inflamed endothelium is IL-8, which upon binding to its cognate membrane receptor (CXCR1/2) activates a suite of responses in neutrophils. Read More

Blood Adv 2020 12;4(24):6086-6097

Cardiac Anesthesia Division, Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA.

β2 integrins are well-known leukocyte adhesion molecules consisting of 4 members: CD11a-d. Their known biological functions range widely from leukocyte recruitment, phagocytosis, to immunological synapse formation, but the studies have been primarily focused on CD11a and CD11b. CD11c is 1 of the 4 members and is extremely homologous to CD11b. Read More

BMC Immunol 2020 12 14;21(1):61. Epub 2020 Dec 14.

Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, USA.

Background: C1q is a soluble pattern recognition protein that regulates multiple leukocyte functions, and deficiency in C1q results in autoimmunity. C1q stimulates enhanced phagocytic function through multiple mechanisms including the rapid enhancement of Fcγ receptor (FcγR) -mediated phagocytosis. The molecular mechanism responsible for this rapid enhancement of phagocytic function is unknown. Read More

Biochem Biophys Res Commun 2021 01 10;534:34-40. Epub 2020 Dec 10.

Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian, China. Electronic address:

Abnormal crosstalk between gut immune and the liver was involved in nonalcoholic steatohepatitis (NASH). Mice with methionine choline-deficient (MCD) diet-induced NASH presented an imbalance of pro-(IL-6 and IFN-γ) and anti-inflammatory cytokines (IL-10) in the intestine. We also clarified that the ratio of CD4 T cells and found that the NASH mesenteric lymph node (MLN) presents decreased numbers of CD4Th17 cells but increased numbers of CD4CD8FoxP3 regulatory T cells (Tregs). Read More

Nat Commun 2020 12 2;11(1):6171. Epub 2020 Dec 2.

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

While effective in specific settings, adoptive chimeric antigen receptor (CAR) T cell therapy for cancer requires further improvement and optimization. Our previous results show that CD40L-overexpressing CAR T cells mobilize endogenous immune effectors, resulting in improved antitumor immunity. However, the cell populations required for this protective effect remain to be identified. Read More

Elife 2020 12 1;9. Epub 2020 Dec 1.

Department of Neurology, Washington University School of Medicine in St. Louis, St. Louis, United States.

The circadian clock regulates various aspects of brain health including microglial and astrocyte activation. Here, we report that deletion of the master clock protein BMAL1 in mice robustly increases expression of complement genes, including and , in the hippocampus. BMAL1 regulates expression of the transcriptional repressor REV-ERBα, and deletion of REV-ERBα causes increased expression of transcript in neurons and astrocytes as well as C3 protein primarily in astrocytes. Read More

Egypt J Immunol 2020 Jan;27(1):109-118

Department of Pediatric, Faculty of Medicine, Assiut University, Assiut, Egypt.

This study intended to measure the expression of complement regulatory proteins CD55 and CD59 on RBCs membrane in patients with β-thalassemia (β- thal) major in addition to investigate if splenectomy affects their expression pattern. This was a case-control study, participants were allocated in three groups. The study group 1 consisted of β-thal patients who underwent splenectomy. Read More

J Neuroinflammation 2020 Nov 11;17(1):336. Epub 2020 Nov 11.

The Jackson Laboratory, Bar Harbor, ME, USA.

Background: The risk of glaucoma increases significantly with age and exposure to elevated intraocular pressure, two factors linked with neuroinflammation. The complement cascade is a complex immune process with many bioactive end-products, including mediators of inflammation. Complement cascade activation has been shown in glaucoma patients and models of glaucoma. Read More

Gastroenterology 2021 Feb 2;160(3):863-874. Epub 2020 Nov 2.

Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Diego, California. Electronic address:

Background & Aims: Liver CRIg (complement receptor of the immunoglobulin superfamily) macrophages play a critical role in filtering bacteria and their products from circulation. Translocation of microbiota-derived products from an impaired gut barrier contributes to the development of obesity-associated tissue inflammation and insulin resistance. However, the critical role of CRIg macrophages in clearing microbiota-derived products from the bloodstream in the context of obesity is largely unknown. Read More

Am J Physiol Endocrinol Metab 2021 01 2;320(1):E87-E92. Epub 2020 Nov 2.

Department of Pathology and Cell Biology, College of Physicians and Surgeons, Naomi Berrie Diabetes Center, New York, New York.

Obesity is a potent risk factor for atherosclerotic morbidity and mortality. Cytokines secreted from adipose tissue, namely, adipokines, have been suggested to be actively involved in atherosclerosis. One of the most abundant adipokines, adipsin, is downregulated in obesity. Read More

Front Immunol 2020 7;11:583853. Epub 2020 Oct 7.

The Department of Medicine, Stony Brook University, Stony Brook, NY, United States.

Genetic deficiency in C1q is a strong susceptibility factor for systemic lupus erythematosus (SLE). There are two major hypotheses that potentially explain the role of C1q in SLE. The first postulates that C1q deficiency abrogates apoptotic cell clearance, leading to persistently high loads of potentially immunogenic self-antigens that trigger autoimmune responses. Read More

Asian Pac J Allergy Immunol 2020 Dec;38(4):233-238

Department of Otolaryngology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.

This article aims to review the literature regarding the immune response to fungi in diabetic patients with invasive fungal rhinosinusitis. Systematic searches of Medline, EMBASE, and Cochrane Library databases were performed to include articles from 1988 to 2019 which assessed 'immune response to fungi in normal host', 'immune deficiency in diabetes mellitus', or 'immune response to fungi in diabetic patients'. Fungal cell wall activated pattern recognition receptors, resulting in recruitment of innate immune cells and an adaptive immune response. Read More

J Immunol 2020 11 7;205(10):2834-2839. Epub 2020 Oct 7.

School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, St Lucia, Queensland 4072, Australia

Neutrophil infiltration to ischemic tissues following reperfusion worsens injury. A key driver of neutrophil recruitment and activation is the complement factor C5a, which signals through two receptors, C5aR1 and C5aR2. In this study, we used a neutrophil-dependent mouse model of intestinal ischemia-reperfusion (IR) injury to investigate the underexplored role of C5aR2 in neutrophil mobilization, recruitment, and disease outcomes. Read More

Front Immunol 2020 8;11:2124. Epub 2020 Sep 8.

Institute of Physiology II, University Hospital Münster, Münster, Germany.

The importance of the intracellular Ca concentration ([Ca]) in neutrophil function has been intensely studied. However, the role of the intracellular Na concentration ([Na]) which is closely linked to the intracellular Ca regulation has been largely overlooked. The [Na] is regulated by Na transport proteins such as the Na/Ca-exchanger (NCX1), Na/K-ATPase, and Na-permeable, transient receptor potential melastatin 2 (TRPM2) channel. Read More

Proteomics Clin Appl 2020 11 14;14(6):e2000053. Epub 2020 Oct 14.

Center for Translational Biomedical Research, North Carolina Research Campus, University of North Carolina at Greensboro, Kannapolis, NC, 28081, USA.

Purpose: Type 1 diabetes (T1D) is characterized by autoimmune mediated self-destruction of the pancreatic islet beta cells and the resultant insulin deficiency. However, little is known about the underlying molecular pathogenesis at the pancreatic tissue level given the limited availability of clinical specimens.

Experimental Design: Quantitative proteomic studies is performed on age-matched T1D and healthy cadaveric pancreatic tissues (n = 18 each) using TMT 10plex-based isobaric labeling and BoxCar-based label-free LC-MS/MS approaches. Read More

Immunobiology 2020 09 28;225(5):152003. Epub 2020 Aug 28.

Department of Medicine, Division of Nephrology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA. Electronic address:

Complement (C) system is a double edge sword acting as the first line of defense on the one hand and causing aggravation of disease on the other. C activation when unregulated affects different organs including muscle regeneration. However, the effect of factor H (FH), a critical regulator of the alternative C pathway in muscle remains to be studied. Read More