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Serum levels of tissue factor pathway inhibitor: Potential association with Raynaud's phenomenon and telangiectasia in patients with systemic sclerosis.

J Dermatol 2021 Apr 13. Epub 2021 Apr 13.

Department of Dermatology, University of Tokyo Graduate School of Medicine, Tokyo, Japan.

Vasculopathy is a critical step of systemic sclerosis (SSc) development, bridging between autoimmune inflammation and tissue fibrosis. Impaired coagulation system is a part of SSc vasculopathy, but the role of tissue factor pathway inhibitor (TFPI), a critical regulator of the extrinsic coagulation pathway, remained unknown. Therefore, we evaluated the clinical correlation of serum TFPI levels in SSc patients. Read More

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Verapamil as an Adjunct Therapy to Reduce tPA Toxicity in Hyperglycemic Stroke: Implication of TXNIP/NLRP3 Inflammasome.

Mol Neurobiol 2021 Apr 13. Epub 2021 Apr 13.

Department of Anatomy and Neurobiology, College of Medicine, The University of Tennessee Health Science Center, 875 Monroe Avenue, Wittenborg Bldg, Room-231, Memphis, TN, 38163, USA.

Thrombolytic therapy has remained quite challenging in hyperglycemic patients for its association with poor prognosis and increased hemorrhagic conversions. We recently showed that tissue plasminogen activator (tPA)-induced cerebrovascular damage is associated with thioredoxin-interacting protein (TXNIP) upregulation, which has an established role in the detrimental effects of hyperglycemia. In the present work, we investigated whether verapamil, an established TXNIP inhibitor, may provide protection against hyperglycemic stroke and tPA-induced blood-brain barrier (BBB) disruption. Read More

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Red blood cell distribution width as a novel prognostic marker after myocardial revascularization or cardiac valve surgery.

Sci Rep 2021 Apr 12;11(1):7889. Epub 2021 Apr 12.

Department of Medicine and Surgery, University of Parma, Parma, Italy.

The red blood cell distribution width (RDW) measures the variability in the size of circulating erythrocytes. Previous studies suggested a powerful correlation between RDW obtained from a standard complete blood count and cardiovascular diseases in both primary and secondary cardiovascular prevention. The current study aimed to evaluate the prognostic role of RDW in patients undergoing cardiac rehabilitation after myocardial revascularization and/or cardiac valve surgery. Read More

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Decoding allosteric regulation by the acyl carrier protein.

Proc Natl Acad Sci U S A 2021 Apr;118(16)

Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA 92093-0358;

Enzymes in multistep metabolic pathways utilize an array of regulatory mechanisms to maintain a delicate homeostasis [K. Magnuson, S. Jackowski, C. Read More

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Biological pathway expression complementation contributes to biomass heterosis in .

Proc Natl Acad Sci U S A 2021 Apr;118(16)

School of Advanced Agricultural Sciences and School of Life Sciences, State Key Laboratory of Protein and Plant Gene Research, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China;

The mechanisms underlying heterosis have long remained a matter of debate, despite its agricultural importance. How changes in transcriptional networks during plant development are relevant to the continuous manifestation of growth vigor in hybrids is intriguing and unexplored. Here, we present an integrated high-resolution analysis of the daily dynamic growth phenotypes and transcriptome atlases of young seedlings (parental ecotypes [Col-0 and Per-1] and their F hybrid). Read More

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Astrogliosis and episodic memory in late life: higher GFAP is related to worse memory and white matter microstructure in healthy aging and Alzheimer's disease.

Neurobiol Aging 2021 Feb 26;103:68-77. Epub 2021 Feb 26.

Department of Neurology, University of Colorado Alzheimer's & Cognition Center, Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Astrocytes play a formative role in memory consolidation during physiological conditions; when dysregulated, astrocytes release glial fibrillary acidic protein (GFAP), which has been linked with negative memory outcomes in animal studies. We examined the association between blood GFAP, memory, and white matter (WM) integrity, accounting for blood markers of AD pathology (i.e. Read More

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February 2021

Overexpression of MtRAV3 enhances osmotic and salt tolerance and inhibits growth of Medicago truncatula.

Plant Physiol Biochem 2021 Apr 4;163:154-165. Epub 2021 Apr 4.

Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100193, China. Electronic address:

Related to ABI3/VP1 (RAV) transcription factors play important roles in regulating plant growth and stress tolerance, which have been studied in many plant species, but have remained largely unidentified in legumes. To functionally characterize RAV in legumes, MtRAV3 from legume model plant Medicago truncatula was isolated and its function was investigated by overexpressing MtRAV3 in M. truncatula. Read More

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Design of novel peptide-inhibitors against the conserved bacterial transcription terminator, Rho.

J Biol Chem 2021 Apr 9:100653. Epub 2021 Apr 9.

Laboratory of Transcription, Center for DNA Fingerprinting and Diagnostics, Inner Ring Road, Uppal, Hyderabad-39, India. Electronic address:

The transcription terminator Rho regulates many physiological processes in bacteria, such as antibiotic sensitivity, DNA repair, RNA-remodeling, etc, and hence, is a potential antimicrobial target, which is unexplored. The bacteriophage P4 capsid protein, Psu, moonlights as a natural Rho antagonist. Here, we report the design of novel peptides based on the C-terminal region of Psu using phenotypic screening methods. Read More

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Integrin β1 regulates proliferation, apoptosis, and migration of trophoblasts through activation of phosphoinositide 3 kinase/protein kinase B signaling.

J Obstet Gynaecol Res 2021 Apr 11. Epub 2021 Apr 11.

Department of Sport Medicine, The First Hospital of Jilin University, Jilin University, Changchun, Jilin, China.

Aims: Abnormal trophoblast invasion is one of the onsets of preeclampsia (PE). Studies found that integrin β1 (ITGB1) is closely related to PE, but the role of ITGB1 in the progression of trophoblast remained unclear. Therefore, we studied the functional role of ITGB1 in PE and its effects on trophoblast. Read More

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Antivirulence DsbA inhibitors attenuate serovar Typhimurium fitness without detectable resistance.

FASEB Bioadv 2021 Apr 10;3(4):231-242. Epub 2021 Feb 10.

Institute of Health and Biomedical Innovation School of Biomedical Sciences Queensland University of Technology Herston QLD Australia.

Inhibition of the DiSulfide Bond (DSB) oxidative protein folding machinery, a major facilitator of virulence in Gram-negative bacteria, represents a promising antivirulence strategy. We previously developed small molecule inhibitors of DsbA from K-12 (EcDsbA) and showed that they attenuate virulence of Gram-negative pathogens by directly inhibiting multiple diverse DsbA homologues. Here we tested the evolutionary robustness of DsbA inhibitors as antivirulence antimicrobials against serovar Typhimurium under pathophysiological conditions in vitro. Read More

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Protective effects and molecular mechanisms of polypeptide k on Schwann cells.

Ann Transl Med 2021 Mar;9(5):381

Key Laboratory of Neuroregeneration of Jiangsu, Ministry of Education, Jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair, Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, China.

Background: polypeptide k (ABPPk) is an active ingredient used in traditional Chinese medicine separated from polypeptides. So far, the role of ABPPk in peripheral nerve protection has not been comprehensively studied.

Methods: In this study, primary Schwann cells exposed to serum deprivation were treated with ABPPk or nerve growth factor (NGF) . Read More

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MICAL2 Facilitates Gastric Cancer Cell Migration via MRTF-A-Mediated CDC42 Activation.

Front Mol Biosci 2021 24;8:568868. Epub 2021 Mar 24.

Department of Physiology, Nanjing Medical University, Nanjing, China.

Cell migration is driven by the reorganization of the actin cytoskeleton. Although MICAL2 is known to mediate the oxidation of actin filaments to regulate F-actin dynamics, relatively few studies have investigated the potential role of MICAL2 during cancer cell migration. The migratory ability of gastric cancer cells was measured by wound healing and transwell assays. Read More

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Growth on Formic Acid Is Dependent on Intracellular pH Homeostasis for the Thermoacidophilic Methanotroph sp. RTK17.1.

Front Microbiol 2021 24;12:651744. Epub 2021 Mar 24.

School of Biological Sciences, University of Canterbury, Christchurch, New Zealand.

Members of the genus , a clade of metabolically flexible thermoacidophilic methanotrophs from the phylum Verrucomicrobia, can utilize a variety of substrates including methane, methanol, and hydrogen for growth. However, despite sequentially oxidizing methane to carbon dioxide methanol and formate intermediates, growth on formate as the only source of reducing equivalents (i.e. Read More

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Ektacytometry Analysis of Post-splenectomy Red Blood Cell Properties Identifies Cell Membrane Stability Test as a Novel Biomarker of Membrane Health in Hereditary Spherocytosis.

Front Physiol 2021 25;12:641384. Epub 2021 Mar 25.

Central Diagnostic Laboratory-Research, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.

Hereditary spherocytosis (HS) is the most common form of hereditary chronic hemolytic anemia. It is caused by mutations in red blood cell (RBC) membrane and cytoskeletal proteins, which compromise membrane integrity, leading to vesiculation. Eventually, this leads to entrapment of poorly deformable spherocytes in the spleen. Read More

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Inhibition of Shear-Induced Platelet Aggregation by Xueshuantong via Targeting Piezo1 Channel-Mediated Ca Signaling Pathway.

Front Pharmacol 2021 22;12:606245. Epub 2021 Mar 22.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.

XueShuanTong (XST) comprising therapeutically active ginsenosides, a lyophilized extract of roots, is extensively used in traditional Chinese medicine to treat ischemic heart and cerebrovascular diseases. Our recent study shows that treatment with XST inhibits shear-induced thrombosis formation but the underlying mechanism remained unclear. This study aimed to investigate the hypothesis that XST inhibited shear-induced platelet aggregation via targeting the mechanosensitive Ca-permeable Piezo1 channel by performing platelet aggregation assay, Ca imaging and Western blotting analysis. Read More

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[A case of young hepatocellular carcinoma with non-B, non-C, non-cirrhotic background].

Nihon Shokakibyo Gakkai Zasshi 2021 ;118(4):348-357

Department of Internal Medicine, Saiseikai Matsusaka General Hospital.

A man in his 20s visited a local physician because of upper abdominal pain, and an abdominal ultrasonography revealed hepatic tumors. He was then referred to our hospital. The patient had no history of blood transfusion, tattoos, habitual alcohol consumption, or narcotic drug use. Read More

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Effect of co-encapsulation using a calcium alginate matrix and fructooligosaccharides with gelatin coating on the survival of Lactobacillus paracasei cells.

Braz J Microbiol 2021 Apr 10. Epub 2021 Apr 10.

Laboratory of Food Microbiology, Federal University of Tocantins (UFT), Palmas, TO, Brazil.

The demand for functional foods is increasing each year because consumers are gaining awareness about the importance of a healthy diet in the proper functioning of the body. Probiotics are among the most commonly known, commercialized, and studied foods. However, the loss of viability of probiotic products is observed during their formulation, processing, and storage. Read More

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Bintrafusp Alfa, a Bifunctional Fusion Protein Targeting TGFβ and PD-L1, in Patients with Esophageal Squamous Cell Carcinoma: Results from a Phase 1 Cohort in Asia.

Target Oncol 2021 Apr 11. Epub 2021 Apr 11.

National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.

Background: Patients with esophageal squamous cell carcinoma (SCC) have limited treatment options. Blocking transforming growth factor-β (TGFβ), which can be overexpressed in these tumors, may enhance responses to programmed cell death protein 1/programmed death-ligand 1 [PD-(L)1] inhibitors. Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the TGFβ receptor II (TGFβRII) (a TGFβ "trap") fused to a human IgG1 monoclonal antibody blocking PD-L1. Read More

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Acute alcohol consumption increases systemic endotoxin bioactivity for days in healthy volunteers-with reduced intestinal barrier loss in female.

Eur J Trauma Emerg Surg 2021 Apr 11. Epub 2021 Apr 11.

Department of Trauma, Hand and Reconstructive Surgery, Goethe University, Frankfurt, Germany.

Objective: Trauma is the most common cause of death among young adults. Alcohol intoxication plays a significant role as a cause of accidents and as a potent immunomodulator of the post-traumatic response to tissue injury. Polytraumatized patients are frequently at risk to developing infectious complications, which may be aggravated by alcohol-induced immunosuppression. Read More

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The PaO2/FiO2 ratio on admission is independently associated with prolonged hospitalization in COVID-19 patients.

J Infect Dev Ctries 2021 Mar 31;15(3):353-359. Epub 2021 Mar 31.

Department of Medical, Surgical and Experimental Sciences, University of Sassari, Sassari, Italy.

Introduction: The early identification of factors that predict the length of hospital stay (HS) in patients affected by coronavirus desease (COVID-19) might assist therapeutic decisions and patient flow management.

Methodology: We collected, at the time of admission, routine clinical, laboratory, and imaging parameters of hypoxia, lung damage, inflammation, and organ dysfunction in a consecutive series of 50 COVID-19 patients admitted to the Respiratory Disease and Infectious Disease Units of the University Hospital of Sassari (North-Sardinia, Italy) and alive on discharge.

Results: Prolonged HS (PHS, >21 days) patients had significantly lower PaO2/FiO2 ratio and lymphocytes, and significantly higher Chest CT severity score, C-reactive protein (CRP) and lactic dehydrogenase (LDH) when compared to non-PHS patients. Read More

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The C99 domain of the amyloid precursor protein resides in the disordered membrane phase.

J Biol Chem 2021 Apr 8:100652. Epub 2021 Apr 8.

Department of Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, 37232. Electronic address:

Processing of the amyloid precursor protein (APP) via the amyloidogenic pathway is associated with the etiology of Alzheimer's disease. The cleavage of APP by β-secretase to generate the transmembrane 99-residue C-terminal fragment (C99) and subsequent processing of C99 by γ-secretase to yield amyloid-β (Aβ) peptides are essential steps in this pathway. Biochemical evidence suggests amyloidogenic processing of C99 occurs in cholesterol- and sphingolipid-enriched liquid-ordered phase membrane rafts. Read More

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Native cyclase-associated protein and actin from Xenopus laevis oocytes form a unique 4:4 complex with a tripartite structure.

J Biol Chem 2021 Apr 8:100649. Epub 2021 Apr 8.

Departments of Pathology and Cell Biology, Emory University School of Medicine, Atlanta, Georgia, USA; Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, USA. Electronic address:

Cyclase-associated protein (CAP) is a conserved actin-binding protein that regulates multiple aspects of actin dynamics, including polymerization, depolymerization, filament severing, and nucleotide exchange. CAP has been isolated from different cells and tissues in an equimolar complex with actin, and previous studies have shown that a CAP-actin complex contains six molecules each of CAP and actin. Intriguingly, here, we successfully isolated a complex of Xenopus cyclase-associated protein 1 (XCAP1) with actin from oocyte extracts which contained only four molecules each of XCAP1 and actin. Read More

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Waste streams in onion production: Bioactive compounds, quercetin and use of antimicrobial and antioxidative properties.

Waste Manag 2021 Apr 7;126:476-486. Epub 2021 Apr 7.

Department of Food Science and Technology, Biotechnical Faculty, University of Ljubljana, Jamnikarjeva 101, SI-1000 Ljubljana, Slovenia; The Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins (CipKeBiP), Jamova 39, SI-1000, Ljubljana, Slovenia. Electronic address:

Onion production generates abundant waste with high contents of bioactive compounds. These might have several beneficial functional properties for fortification of foods. To understand the variety and potential for further use, we examined various parts of the plants (edible/inedible waste/outer skin of onion), as well as extraction in water/ethanol and by shaking/sonication. Read More

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Viral reduction of human blood by UVA photosensitized vitamin K5.

J Med Virol 2021 Apr 10. Epub 2021 Apr 10.

Division of Blood Components and Devices, OBRR, CBER, FDA, Silver Spring, MD, USA.

Blood product transfusion can transmit viral pathogens. Pathogen reduction methods for blood products have been developed but, so far, are not available for whole blood. We evaluated if Vitamin K5 (VK5) and ultraviolet light A (UVA) irradiation could be used for virus inactivation in plasma and whole blood. Read More

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Induction of resistance to sugarcane mosaic virus by RNA interference targeting coat protein gene silencing in transgenic sugarcane.

Mol Biol Rep 2021 Apr 10. Epub 2021 Apr 10.

Laboratory of Molecular Biology and Biotechnology, Center for Development of Advanced Science and Technology (CDAST), Jember University, Jln. Kalimantan 37, Jember, 68121, Indonesia.

Sugarcane mosaic virus (SCMV) is a serious disease of monocotyledonous plants, including sugarcane, causing deterioration in both growth and productivity. RNA interference (RNAi) inhibits gene expression through RNA-mediated sequence-specific interactions and is considered an effective approach to control viral infection in plants. In this study, the SCMVCp gene encoding the coat protein (CP) was inserted into the pGreen-0179 plasmid in both sense and antisense orientations. Read More

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Serum inflammatory markers in patients with multiple sclerosis and their association with clinical manifestations and MRI findings.

Acta Neurol Belg 2021 Apr 9. Epub 2021 Apr 9.

Epilepsy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Inflammation in a myelinated portion of the nervous system is the mainstay of multiple sclerosis (MS). Elevation of inflammatory markers such as procalcitonin, ESR and hs-CRP is suspected to occur in MS patients. However, their prognostic role and their relationship with the severity of clinical symptoms of MS and MRI evidences has remained unnoticed in the literature. Read More

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The circulating soluble form of the CD40 costimulatory immune checkpoint receptor and liver metastasis risk in rectal cancer.

Br J Cancer 2021 Apr 9. Epub 2021 Apr 9.

Department of Oncology, Akershus University Hospital, Lørenskog, Norway.

Background: In colorectal cancer, the inflamed tumour microenvironment with its angiogenic activities is immune- tolerant and incites progression to liver metastasis. We hypothesised that angiogenic and inflammatory factors in serum samples from patients with non-metastatic rectal cancer could inform on liver metastasis risk.

Methods: We measured 84 angiogenic and inflammatory markers in serum sampled at the time of diagnosis within the population-based cohort of 122 stage I-III patients. Read More

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T cell reactivity to regulatory factor X4 in type 1 narcolepsy.

Sci Rep 2021 Apr 9;11(1):7841. Epub 2021 Apr 9.

Department of Psychiatry and Behavioral Sciences, Stanford University Center for Sleep Sciences, Stanford University School of Medicine, Palo Alto, CA, USA.

Type 1 narcolepsy is strongly (98%) associated with human leukocyte antigen (HLA) class II DQA1*01:02/DQB1*06:02 (DQ0602) and highly associated with T cell receptor (TCR) alpha locus polymorphism as well as other immune regulatory loci. Increased incidence of narcolepsy was detected following the 2009 H1N1 pandemic and linked to Pandemrix vaccination, strongly supporting that narcolepsy is an autoimmune disorder. Although recent results suggest CD4+ T cell reactivity to neuropeptide hypocretin/orexin and cross-reactive flu peptide is involved, identification of other autoantigens has remained elusive. Read More

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Kinetic analysis reveals that independent nucleation events determine the progression of polyglutamine aggregation in .

Proc Natl Acad Sci U S A 2021 Mar;118(11)

Department of Molecular Biosciences, Rice Institute for Biomedical Research, Northwestern University, Evanston, IL 60208-3500;

Protein aggregation is associated with a wide range of degenerative human diseases with devastating consequences, as exemplified by Alzheimer's, Parkinson's, and Huntington's diseases. In vitro kinetic studies have provided a mechanistic understanding of the aggregation process at the molecular level. However, it has so far remained largely unclear to what extent the biophysical principles of amyloid formation learned in vitro translate to the complex environment of living organisms. Read More

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Fragile-Tough Mechanical Reversion of Silk Materials via Tuning Supramolecular Assembly.

ACS Biomater Sci Eng 2021 Apr 9. Epub 2021 Apr 9.

Department of Biomedical Engineering, Tufts University, Medford, Massachusetts 02155, United States.

Regenerated silk nanofibers are interesting as protein-based material building blocks due to their unique structure and biological origin. Here, a new strategy based on control of supramolecular assembly was developed to regulate interactions among silk nanofibers by changing the solvent, achieving tough mechanical features for silk films. Formic acid was used to replace water related to charge repulsion of silk nanofibers in solution, inducing interactions among the nanofibers. Read More

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