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Foliar architecture and physio-biochemical plasticity determines survival of Typha domingensis pers. Ecotypes in nickel and salt affected soil.

Environ Pollut 2021 May 7;286:117316. Epub 2021 May 7.

Department of Botany, Government College University, Faisalabad, Pakistan. Electronic address:

Six ecotypes of Typha domingensis Pers. Jahlar (E), Sheikhupura (E), Sahianwala (E), Gatwala (E), Treemu (E) and Knotti (E) from different ecological regions were collected to evaluate the leaf anatomical and biochemical attributes under different levels of salinity and nickel stress viz; L (control), L (100 mM + 50 mg kg), L (200 mM + 100 mg kg) and L (300 mM + 150 mg kg). Presence of salt and Ni in rooting medium consistently affected growth, anatomical and physio-biochemical attributes in all Typha ecotypes. Read More

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Improving pollutants environmental risk assessment using a multi model toxicity determination with in vitro, bacterial, animal and plant model systems: The case of the herbicide alachlor.

Environ Pollut 2021 Apr 27;286:117239. Epub 2021 Apr 27.

Department of Life Sciences, University of Coimbra, 3000-456 Coimbra, Portugal; CNC - Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, IIIUC - Institute for Interdisciplinary Research, Coimbra, Portugal. Electronic address:

Several environmental pollutants, including pesticides, herbicides and persistent organic pollutants play an important role in the development of chronic diseases. However, most studies have examined environmental pollutants toxicity in target organisms or using a specific toxicological test, losing the real effect throughout the ecosystem. In this sense an integrative environmental risk of pollutants assessment, using different model organisms is necessary to predict the real impact in the ecosystem and implications for target and non-target organisms. Read More

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Thymoquinone sensitizes human hepatocarcinoma cells to TRAIL-induced apoptosis via oxidative DNA damage.

DNA Repair (Amst) 2021 Apr 15;103:103117. Epub 2021 Apr 15.

Department of General Surgery, the First Hospital Affiliated of Shandong First Medical University (Qianfoshan Hospital), Jinan, Shandong, 250014, China. Electronic address:

Introduction: Hepatocellular carcinoma (HCC) remains one of the most predominant types of digestive system malignancies worldwide. TNF-related apoptosis-inducing ligand (TRAIL) is a biological cytokine with the mentioned specificity, but some tumor cells' resistance limits its use as a therapeutic approach. The present study aimed to investigate thymoquinone (TQ) and TRAIL's combined effect and the potential mechanisms in human hepatic HepG2 carcinoma cells. Read More

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microRNA-210/ Long non-coding RNA MEG3 axis inhibits trophoblast cell migration and invasion by suppressing EMT process.

Placenta 2021 May 5;109:64-71. Epub 2021 May 5.

Department of Obstetrics and Gynecology, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710061, China. Electronic address:

Introduction: Pre-eclampsia is characterized by insufficient spiral artery remodeling, and trophoblast dysfunction plays an important role in this process. Noncoding RNAs (microRNAs (miRNAs) and long noncoding RNAs (LncRNAs) are included) can regulate trophoblasts. MicroRNA-210 (miR-210) can decrease trophoblast cell migration and invasion and may act as a biomarker for preeclampsia. Read More

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Functionally active cyclin-dependent kinase 9 is essential for porcine reproductive and respiratory syndrome virus subgenomic RNA synthesis.

Mol Immunol 2021 May 11;135:351-364. Epub 2021 May 11.

College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan Province, China; International Joint Research Center of National Animal Immunology, Henan Agricultural University, Zhengzhou, Henan Province, China. Electronic address:

Cyclin-dependent kinase 9 (CDK9) is a key regulator of RNA-polymerase II and a candidate therapeutic target for various virus infections such as respiratory syncytial virus, herpes simplex virus, human adenovirus, human cytomegalovirus, hepatitis virus B, and human papillomavirus. We employed CDK9-IN-1, a selective CDK9 inhibitor, to investigate the role of CDK9 in porcine reproductive and respiratory syndrome virus (PRRSV) infection. CDK9-IN-1 dose-dependently reduced PRRSV replication without cytotoxicity in the infected cells. Read More

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Elevated CO improves the nutritive value, antibacterial, anti-inflammatory, antioxidant and hypocholestecolemic activities of lemongrass sprouts.

Food Chem 2021 Mar 31;357:129730. Epub 2021 Mar 31.

Department of Medicinal and Aromatic Plants, Desert Research Centre, Cairo, Egypt. Electronic address:

Sprouts have been regarded as a big store for bioactive compounds with a wide range of biological activities. Elevated CO (eCO, 620 μmol mol)was employed to enhance the nutritive and health promoting values of sprouts of two species of lemongrass, i.e. Read More

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Endothelium-derived Cdk5 deficit aggravates air pollution-induced peripheral vasoconstriction through ATR upregulation.

Ecotoxicol Environ Saf 2021 May 11;219:112314. Epub 2021 May 11.

Department of Physiology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China. Electronic address:

PM infiltrates into circulation and increases the risk of systemic vascular dysfunction. As the first-line barrier against external stimuli, the molecular mechanism of the biological response of vascular endothelial cells to PM exposure remains unclear. In this study, 4-week-old mice were exposed to Hangzhou 'real' airborne PM for 2 months and were found to display bronchial and alveolar damage. Read More

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CCT128930 is a novel and potent antagonist of TRPM7 channel.

Biochem Biophys Res Commun 2021 May 11;560:132-138. Epub 2021 May 11.

Center for Neurological and Psychiatric Research and Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 201203, China. Electronic address:

Transient receptor potential melastatin 7 (TRPM7) channels represent a major magnesium (Mg)-uptake component in mammalian cells and are negatively modulated by internal Mg. However, few TRPM7 modulators were identified so far, which hindered the understanding of the TRPM7 channel functions. In this study, we identified that CCT128930, an ATP-competitive protein kinase B inhibitor reported previously, was a potent TRPM7 channel antagonist. Read More

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Sodium butyrate supplementation inhibits hepatic steatosis by stimulating liver kinase B1 and insulin-induced gene.

Cell Mol Gastroenterol Hepatol 2021 May 11. Epub 2021 May 11.

Center for Fatty Liver, Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China;; Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 200092, China;. Electronic address:

Background And Aims: Butyric acid is an intestinal microbiota-produced short-chain fatty acid, which exerts salutary effects on alleviating nonalcoholic fatty liver disease (NAFLD). However, the underlying mechanism of butyrate on regulating hepatic lipid metabolism is largely unexplored.

Methods: A mouse model of NAFLD was induced with HFD feeding, and sodium butyrate (NaB) intervention was initiated at the 8th week and lasted for eight weeks. Read More

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A lack of red blood cell swelling in five elasmobranch fishes following air exposure and exhaustive exercise.

Comp Biochem Physiol A Mol Integr Physiol 2021 May 11:110978. Epub 2021 May 11.

Department of Fisheries Science, Virginia Institute of Marine Science, William & Mary, Gloucester Point, VA 23062, United States of America.

In teleost fishes, catecholamine-induced increases in the activity of cation exchangers compensate for decreases in hemoglobin oxygen affinity and maximum blood oxygen carrying capacity caused by decreases in plasma pH (i.e., metabolic acidosis). Read More

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Cellular Antioxidant Mechanisms Control Immunoglobulin Light Chain-Mediated Proximal Tubule Injury.

Free Radic Biol Med 2021 May 11. Epub 2021 May 11.

Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, 35294-0007; Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, 35294-0007; Department of Veterans Affairs Medical Center, Birmingham, AL, 35233. Electronic address:

A major cause of morbidity and mortality in multiple myeloma is kidney injury from overproduction of monoclonal immunoglobulin light chains (FLC). FLC can induce damage through the production of hydrogen peroxide, which activates pro-inflammatory and pro-apoptotic pathways. The present study focused on catalase, a highly conserved antioxidant enzyme that degrades hydrogen peroxide. Read More

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Systematic review of Ethiopian medicinal plants used for their anti-inflammatory and wound healing activities.

J Ethnopharmacol 2021 May 11:114179. Epub 2021 May 11.

Centre for Global Health Research, Brighton and Sussex Medical School, University of Sussex, Brighton, BN1 9PX, United Kingdom; School of Public Health, Addis Ababa University, Addis Ababa, Ethiopia.

Ethnopharmacological Relevance: Plant materials are used worldwide as complementary and alternative therapeutics for the treatment of various illnesses. In Ethiopia, folk medicines are utilized across a wide range of cultures and settings. Ethiopia has numerous plant species of which around 12% are endemic, making it a rich source of medicinal plants that are potentially important for human wellbeing. Read More

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Blocking TLR4-NF-κB pathway protects mouse islets from the combinatorial impact of high fat and fetuin-A mediated dysfunction and restores ability for insulin secretion.

Mol Cell Endocrinol 2021 May 11:111314. Epub 2021 May 11.

Cell Signalling Laboratory, Department of Zoology, Visva-Bharati University, Santiniketan- 731 235, India. Electronic address:

Lipid mediated pancreatic β-cell dysfunction during Type 2 diabetes is known to be regulated by activation of TLR4 (Toll Like Receptor 4) and NF-κB (Nuclear factor kappa B). Recently we have reported that MIN6 cells (mouse insulinoma cells) secrete fetuin-A on stimulation by palmitate that aggravates β-cell dysfunction, but the mechanism involve in-vivo has not been demonstrated and thus remained unclear. Here we attempted to dissect the role of palmitate and fetuin-A on insulin secretion using high fat diet (HFD) fed mice model. Read More

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EFFECT OF TYPE 2 DIABETES MELLITUS ON PLACENTAL EXPRESSION AND ACTIVITY OF NUTRIENT TRANSPORTERS AND THEIR ASSOCIATION WITH BIRTH WEIGHT AND NEONATAL ADIPOSITY.

Mol Cell Endocrinol 2021 May 11:111319. Epub 2021 May 11.

Department of Obstetrics and Gynecology, Division of Reproductive Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA; Department of Pediatrics, Section of Neonatology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.

Aims: Infants born to women with Type 2 Diabetes Mellitus (T2DM) are at risk of being born large for gestational age due to excess fetal fat accretion. Placental nutrient transport determines fetal nutrient availability, impacting fetal growth. The aims of the study were to evaluate the effect of T2DM on placental insulin signaling, placental nutrient transporters and neonatal adiposity. Read More

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Recent developments in animal venom peptide nanotherapeutics with improved selectivity for cancer cells.

Biotechnol Adv 2021 May 11:107769. Epub 2021 May 11.

Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA. Electronic address:

Animal venoms are a rich source of bioactive peptides that efficiently modulate key receptors and ion channels involved in cellular excitability to rapidly neutralize their prey or predators. As such, they have been a wellspring of highly useful pharmacological tools for decades. Besides targeting ion channels, some venom peptides exhibit strong cytotoxic activity and preferentially affect cancer over healthy cells. Read More

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PEG-polyaminoacid based micelles for controlled release of doxorubicin: Rational design, safety and efficacy study.

J Control Release 2021 May 11. Epub 2021 May 11.

Department of Pharmaceutical and Pharmacological Sciences, University of Padova, via F. Marzolo 5, 35131 Padova, Italy.

A library of amphiphilic monomethoxypolyethylene glycol (mPEG) terminating polyaminoacid co-polymers able to self-assemble into colloidal systems was screened for the delivery and controlled release of doxorubicin (Doxo). mPEG-Glu/Leu random co-polymers were generated by Ring Opening Polymerization from 5 kDa mPEG-NH macroinitiator using 16:0:1, 8:8:1, 6:10:1, 4:12:1 γ-benzyl glutamic acid carboxy anhydride monomer/leucine N-carboxy anhydride monomer/PEG molar ratios. Glutamic acid was selected for chemical conjugation of Doxo, while leucine units were introduced in the composition of the polyaminoacid block as spacer between adjacent glutamic repeating units to minimize the steric hindrance that could impede the Doxo conjugation and to promote the polymer self-assembly by virtue of the aminoacid hydrophobicity. Read More

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Attached-growth configuration outperforms continuously stirred tank anaerobic membrane bioreactors in alleviating membrane biofouling.

Environ Res 2021 May 11:111272. Epub 2021 May 11.

King Abdullah University of Science and Technology (KAUST), Water Desalination and Reuse Center (WDRC), Biological and Environmental Sciences & Engineering Division (BESE), Thuwal, 23955-6900, Saudi Arabia. Electronic address:

Biofouling impedes the performance of anaerobic membrane bioreactors (AnMBR). Two reactors, one in an up-flow attachment-growth AnMBR (UA-AnMBR) configuration, and the other, as a continuously stirred AnMBR (CS-AnMBR) were evaluated for differences in membrane fouling rate. TMP increment in UA-AnMBR was slower than CS-AnMBR, although both reactors had similar COD removal efficiency (ca. Read More

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Inhibition of miR-1224 suppresses hypoxia/reoxygenation-induced oxidative stress and apoptosis in cardiomyocytes through targeting GPX4.

Exp Mol Pathol 2021 May 11:104645. Epub 2021 May 11.

Department of Cardiology, Zhuji People's Hospital of Zhejiang Province, Zhuji Affiliated Hospital of Shaoxing University, Zhuji, Zhejiang 311800, China. Electronic address:

We have focused on the underlying role of miR-1224 in cardiomyocyte injury stimulated by hypoxia/reoxygenation (H/R). In the current study, the rat cardiomyocyte cell line H9C2 was used to construct a H/R cell model to validate the cardioprotective effects of miR-1224. Data from the dual-luciferase assay revealed that the glutathione peroxidase 4 (GPX4) was a direct target of miR-1224. Read More

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The role of salt-inducible kinases on the modulation of renal and intestinal Na,K-ATPase activity during short- and long-term high-salt intake.

Eur J Pharmacol 2021 May 11:174153. Epub 2021 May 11.

Unit of Pharmacology and Therapeutics, Department of Biomedicine, Faculty of Medicine, University of Porto, 4200 Porto, Portugal; MedInUp - Center for Drug Discovery and Innovative Medicines, University of Porto, 4200 Porto, Portugal; Division of Research and Development, BIAL-Portela & C(a), S.A, 4745-457 Coronado (S. Mamede & S. Romão), Portugal. Electronic address:

Type 1 salt-inducible kinases (SIK1) has been shown to act as a mediator during the cellular adaptation to variations in intracellular sodium in a variety of cell types. Type 2 SIK (SIK2) modulates various biological functions and acts as a signal transmitter in various pathways. To evaluate the role of both SIK isoforms in renal and intestinal Na,K-ATPase (NKA) activity, we made use of constitutive sik1 (SIK1-KO), sik2 (SIK2-KO), double sik1sik2 (double SIK1*2-KO) knockout and wild-type (WT) mice challenged to a standard (0. Read More

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Molecular Docking and Dynamic Studies of a Potential Therapeutic Target Inhibiting Glyoxalase System: metabolic action of the 3, 3 '- [3- (5-chloro-2-hydroxyphenyl) -3-oxopropane-1, 1-diyl] - bis-4-hydroxycoumarin leads overexpression of the intracellular level of methylglyoxal and induction of a pro-apoptotic phenomenon in a hepatocellular carcinoma model.

Chem Biol Interact 2021 May 11:109511. Epub 2021 May 11.

QOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal. Electronic address:

Methylglyoxal is a dicarbonyl compound recruited as a potential cytotoxic marker, initially presents in cells and considered as a metabolite of the glycolytic pathway. Our aim is to demonstrate the inhibitory effect of 3, 3'-[3-(5-chloro-2-hydroxyphenyl)-3-oxopropane-1, 1-diyl] Bis (4-hydroxycoumarin) on the glyoxalase system, and indirectly its anticancer activity. The docking of OT-55 was conducted by using Flexible docking protocol, ChiFlex and libdock tools inside the active site of Glo-I indicated that both hydrogen bonding and hydrophobic interactions contributed significantly in establishing potent binding with the active site which is selected as a strong inhibitor with high scoring values and maximum Gibbs free energy. Read More

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Endogenous vitamin E metabolites mediate allosteric PPARγ activation with unprecedented co-regulatory interactions.

Cell Chem Biol 2021 May 12. Epub 2021 May 12.

Institute of Pharmaceutical Chemistry, Goethe University Frankfurt, Frankfurt 60438, Germany. Electronic address:

Vitamin E exhibits pharmacological effects beyond established antioxidant activity suggesting involvement of unidentified mechanisms. Here, we characterize endogenously formed tocopherol carboxylates and the vitamin E mimetic garcinoic acid (GA) as activators of the peroxisome proliferator-activated receptor gamma (PPARγ). Co-stimulation of PPARγ with GA and the orthosteric agonist pioglitazone resulted in additive transcriptional activity. Read More

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Hyperleukocytosis in Solid Tumors: A Rare Paraneoplastic Syndrome Associated with Poor Prognosis.

Am J Med Sci 2021 May 11. Epub 2021 May 11.

Department of Anatomical Pathology, Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal. Electronic address:

Hematological paraneoplastic syndromes are fairly uncommon. While mild leukocytosis in solid tumors is well reported, white blood cell (WBC) count over 50,000 u/L, described as paraneoplastic leukemoid reaction (PLR), is not. Indeed, when found, it is usually associated with a higher burden of disease, tumor activity and worse clinical outcomes. Read More

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Pembrolizumab plus cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma: an open-label, multi-arm, non-randomised, multicentre, phase 2 trial.

Lancet Oncol 2021 May 11. Epub 2021 May 11.

Moores Comprehensive Cancer Center, University of California, San Diego, La Jolla, CA, USA.

Background: Pembrolizumab (PD-1 inhibitor) and cetuximab (EGFR inhibitor) are active as single agents and in combination with cytotoxic chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). Given each drug's single agent activity and unique mechanism of action, we aimed to evaluate the anti-tumour activity of PD-1 blockade with EGFR inhibition in recurrent or metastatic HNSCC.

Methods: This study is an open-label, non-randomised, multi-arm, phase 2 trial done at four academic centres in the USA. Read More

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Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial.

Lancet Oncol 2021 May 11. Epub 2021 May 11.

Department of Oncology and Haematology, Humanitas Clinical and Research Center, IRCCS, Humanitas University, Milan, Italy.

Background: Patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who do not respond to or who have progressive disease after salvage therapies have a poor prognosis. Loncastuximab tesirine is a CD19-directed antibody-drug conjugate with encouraging phase 1 single-agent antitumour activity and acceptable safety in non-Hodgkin lymphoma. We aimed to evaluate the antitumour activity and safety of loncastuximab tesirine in patients with relapsed or refractory DLBCL. Read More

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Tracking self-performance in the prefrontal cortex: It's layered.

Cell 2021 May;184(10):2534-2536

Center for Neural Science, New York University, New York, USA. Electronic address:

In this issue of Cell, Spellman and colleagues record and manipulate the activity of neurons in the medial prefrontal cortex of mice performing a task in which they must pay attention to different stimuli. They show that this brain region is important for monitoring the animals' performance, and neurons that appear to contribute to behavior reside in deep cortical layers. Read More

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Rab34 GTPase mediates ciliary membrane formation in the intracellular ciliogenesis pathway.

Curr Biol 2021 May 8. Epub 2021 May 8.

Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511, USA. Electronic address:

The primary cilium is an essential organizing center for signal transduction, and ciliary defects cause congenital disorders known collectively as ciliopathies. Primary cilia form by two pathways that are employed in a cell-type- and tissue-specific manner: an extracellular pathway in which the cilium grows out from the cell surface and an intracellular pathway in which the nascent cilium first forms inside the cell. After exposure to the external environment, cilia formed via the intracellular pathway may have distinct functional properties, as they often remain recessed within a ciliary pocket. Read More

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Bipartite binding of the N terminus of Skp2 to cyclin A.

Structure 2021 May 11. Epub 2021 May 11.

Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON M5G 1X5, Canada; Department of Molecular Genetics, University of Toronto, ON M5S 1A8, Canada; Department of Biochemistry, University of Toronto, ON M5S 1A8, Canada. Electronic address:

Skp2 and cyclin A are cell-cycle regulators that control the activity of CDK2. Cyclin A acts as an activator and substrate recruitment factor of CDK2, while Skp2 mediates the ubiquitination and subsequent destruction of the CDK inhibitor protein p27. The N terminus of Skp2 can interact directly with cyclin A but is not required for p27 ubiquitination. Read More

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Antibody-Functionalized Nanowires: A Tuner for the Activation of T Cells.

Nano Lett 2021 May 14. Epub 2021 May 14.

T cells sense both chemical cues delivered by antigen molecules and physical cues delivered by the environmental elasticity and topography; yet, it is still largely unclear how these cues cumulatively regulate the immune activity of T cells. Here, we engineered a nanoscale platform for stimulation of T cells based on antigen-functionalized nanowires. The nanowire topography and elasticity, as well as the immobilized antigens, deliver the physical and chemical cues, respectively, enabling the systematic study of the integrated effect of these cues on a T cell's immune response. Read More

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Hyperglycemia minimally alters primary self-renewing human colonic epithelial cells while TNFα-promotes severe intestinal epithelial dysfunction.

Integr Biol (Camb) 2021 May 15. Epub 2021 May 15.

Department of Bioengineering, University of Washington, Seattle, WA, USA.

Hyperglycemia is thought to increase production of inflammatory cytokines and permeability of the large intestine. Resulting intestinal inflammation is then often characterized by excess secretion of tumor necrosis factor alpha (TNFα). Thus, hyperglycemia in hospitalized patients suffering from severe trauma or disease is frequently accompanied by TNFα secretion, and the combined impact of these insults on the intestinal epithelium is poorly understood. Read More

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Zinc limitation triggers anticipatory adaptations in Mycobacterium tuberculosis.

PLoS Pathog 2021 May 14;17(5):e1009570. Epub 2021 May 14.

School of Life Sciences, University of Hawai'i at Mānoa, Honolulu, Hawaii, United States of America.

Mycobacterium tuberculosis (Mtb) has complex and dynamic interactions with the human host, and subpopulations of Mtb that emerge during infection can influence disease outcomes. This study implicates zinc ion (Zn2+) availability as a likely driver of bacterial phenotypic heterogeneity in vivo. Zn2+ sequestration is part of "nutritional immunity", where the immune system limits micronutrients to control pathogen growth, but this defense mechanism seems to be ineffective in controlling Mtb infection. Read More

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