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PI3K, mTOR AND GSK3 MODULATE CYTOKINES' PRODUCTION IN PERIPHERAL LEUKOCYTE IN TEMPORAL LOBE EPILEPSY.

Neurosci Lett 2021 May 9:135948. Epub 2021 May 9.

Neuroscience Program, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Department of Pharmacology, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. Electronic address:

Introduction: Epilepsy is a common pathological condition that predisposes individuals to seizures, as well as cognitive and emotional dysfunctions. Different studies have demonstrated that inflammation contributes to the pathophysiology of epilepsy. Indeed, seizures change the peripheral inflammatory pattern, which, in turn, could contribute to seizures. Read More

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IL-6 deficiency promotes colitis by recruiting Ly6C monocytes into inflamed colon tissues in a CCL2-CCR2-dependent manner.

Eur J Pharmacol 2021 May 9:174165. Epub 2021 May 9.

Center for New Drug Safety Evaluation and Research, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, 211198, PR China. Electronic address:

Interleukin 6 (IL-6) is a pleiotropic cytokine that is elevated in inflammatory bowel disease. However, the role of IL-6 deficiency in colitis is not well-defined. Some IL-6 and IL-6 receptor antagonists are associated with severe gastrointestinal immune adverse effects, but the mechanisms of the effects are not clear. Read More

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A novel human arterial wall-on-a-chip to study endothelial inflammation and vascular smooth muscle cell migration in early atherosclerosis.

Lab Chip 2021 May 12. Epub 2021 May 12.

School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore, 639798, Singapore. and Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 308232, Singapore.

Mechanistic understanding of atherosclerosis is largely hampered by the lack of a suitable in vitro human arterial model that recapitulates the arterial wall structure, and the interplay between different cell types and the surrounding extracellular matrix (ECM). This work introduces a novel microfluidic endothelial cell (EC)-smooth muscle cell (SMC) 3D co-culture platform that replicates the structural and biological aspects of the human arterial wall for modeling early atherosclerosis. Using a modified surface tension-based ECM patterning method, we established a well-defined intima-media-like structure, and identified an ECM composition (collagen I and Matrigel mixture) that retains the SMCs in a quiescent and aligned state, characteristic of a healthy artery. Read More

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Inhibitory effects of β-type glycosidic polysaccharide from on dextran sodium sulfate-induced colitis in mice.

Food Funct 2021 May;12(9):3831-3841

Department of Food Science, University of Massachusetts, Amherst, MA 01002, USA.

The aim of the present study was to determine the inhibitory effects and the potential underlying mechanisms of a novel Pleurotus eryngii β-type glycosidic polysaccharide (WPEP) on colitis. To achieve this, sixty CD-1 (ICR) mice were divided into six groups including healthy and colitic mice treated with or without WPEP at two different doses (n = 10). The results showed that WPEP displayed a significant inhibitory effect on colitis as indicated by the lowered disease activity index in the treated colitic mice compared to the untreated colitic mice (2. Read More

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from human breast milk ameliorates ulcerative colitis in mice gut microbiota modulation.

Food Funct 2021 May 12. Epub 2021 May 12.

Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, 127 Youyi West Road, Xi'an, Shaanxi Province 710072, China.

Gut microbiota imbalance is one of the major causes of ulcerative colitis (UC). L. rhamnosus SHA113 (LRS), a strain isolated from healthy human milk, influences the regulation of gut flora. Read More

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Aggravation of airway inflammation in RSV-infected asthmatic mice following infection-induced alteration of gut microbiota.

Ann Palliat Med 2021 May 10. Epub 2021 May 10.

Department of Traditional Chinese Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.

Background: This study aimed to confirm the relationship between asthma, respiratory syncytial virus (RSV) infection, and the gut environment by analyzing the alterations in the gut microbiota of RSV-infected asthmatic mice.

Methods: Twenty-four male BALB/c mice were randomly separated into a control group (CON), ovalbumin (OVA) group, and an OVA + RSV group, (n=8 mice/group). At the end of experiments, we evaluated the RSV-infected asthma model using Wright-Giemsa staining, histopathology and immunoglobulin E (IgE) level using enzyme-linked immunosorbent assays (ELISA). Read More

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Anti-inflammatory Treatment and Cardiovascular Outcomes: Results of Clinical Trials.

Eur Cardiol 2021 Feb 23;16:e15. Epub 2021 Apr 23.

DAMIC Medical Institute, Rusculleda Foundation for Research Cordoba, Argentina.

Atherosclerosis is a chronic inflammatory disorder of the vasculature where cholesterol accumulates in the arterial wall stimulating infiltration of immune cells. This plays an important role in plaque formation, as well as complications caused by its build up. Pro-inflammatory cytokines and chemokines are implicated throughout the progression of the disease and different therapies that aim to resolve this chronic inflammation, reduce cardiovascular (CV) events and improve clinical outcomes have been tested. Read More

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February 2021

Human umbilical cord Wharton's jelly-derived mesenchymal stem cell transplantation could improve diabetic intracavernosal pressure.

Asian J Androl 2021 May 4. Epub 2021 May 4.

Department of Urology, Shanghai General Hospital of Nanjing Medical University, Shanghai 200080, China.

Mesenchymal stem cells (MSCs) secrete various cytokines with angiogenic and neuroprotective effects. This study aimed to assess the effects of human umbilical cord Wharton's jelly-derived MSCs (hWJ-MSCs) on diabetes-related intracavernosal pressure (ICP) impairment in rats. hWJ-MSCs were isolated from human umbilical cord Wharton's jelly and transplanted into the corpus cavernosum of streptozotocin (STZ)-induced diabetic rats by unilateral injection. Read More

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Biophysical Characterization of a Novel Tri-layer Placental Allograft Membrane.

Adv Wound Care (New Rochelle) 2021 May 11. Epub 2021 May 11.

Integra LifeSciences Corp, 17583, Princeton, New Jersey, United States;

Objective: Placental tissues, including membranes composed of amnion and chorion, are promising options for the treatment of chronic wounds. Amnion and chorion contain multiple extracellular matrix (ECM) proteins as well as a multitude of growth factors and cytokines that, when used clinically, assist in the progression of difficult to heal wounds through restoration of a normal healing process. The objective of this study was to characterize the in vitro physical and biological properties of a dehydrated tri-layer placental allograft membrane (TPAM) consisting of a chorion layer sandwiched between 2 layers of amnion. Read More

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Impact of interval training with probiotic (L. plantarum / Bifidobacterium bifidum) on passive avoidance test, ChAT and BDNF in the hippocampus of rats with Alzheimer's disease.

Neurosci Lett 2021 May 8:135949. Epub 2021 May 8.

Department of Physical Education and Sport Sciences, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran.

It has been suggested that gut microbiota dysbiosis can lead to Alzheimer's disease (AD), inducing the production of many AD-related pre-inflammatory cytokines. On the other hand, daily probiotic administration and regular exercise training are assumed to improve clinical AD-related symptoms. To take this line of research further, this study was aimed at investigating the impact of moderate-intensity interval training (MIIT) with a combined administration of Lactobacillus plantarum and Bifidobacterium bifidum (probiotic, BROB) on the passive avoidance test (Shuttle Box), choline acetyltransferase (ChAT) and the brain derived neurotrophic factor (BDNF) in the hippocampus of a rat model of AD. Read More

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Elucidating of oxidative distress in COVID-19 and methods of its prevention.

Chem Biol Interact 2021 May 8:109501. Epub 2021 May 8.

Intraoperative Imaging Unit, Chair and Department of Neurosurgery and Neurotraumatology, Karol Marcinkowski University of Medical Sciences, Przybyszewskiego 49, 60-355, Poznan, Poland; Department of Neurosurgery and Neurotraumatology, Heliodor Swiecicki Clinical Hospital, Przybyszewskiego 49, 60-355, Poznan, Poland. Electronic address:

The pandemic of SARS-CoV-2 stimulates significant efforts and approaches to understand its global spread. Although the recent introduction of the vaccine is a crucial prophylactic step, the effective treatment for SARS-CoV-2 is still undiscovered. An in-depth analysis of symptoms and clinical parameters, as well as molecular changes, is necessary to comprehend COVID-19 and propose a remedy for affected people to fight that disease. Read More

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Changes in peripheral blood regulatory T cells, and IL-6 and IL-10 levels predict response of pediatric medulloblastoma and germ cell tumors with residual or disseminated disease to craniospinal irradiation.

Int J Radiat Oncol Biol Phys 2021 May 8. Epub 2021 May 8.

Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA. Electronic address:

Purpose: Radiotherapy modulates immune cells and cytokines resulting in both clinically beneficial and detrimental effects. The changes in peripheral blood T lymphocyte subsets and cytokines during radiotherapy for pediatric brain tumors and the association of these changes with therapeutic outcomes have not been well described.

Methods And Materials: The study population consisted of children (n=83, ages 3∼18) with primary brain tumors (medulloblastoma, glioma, germ cell tumors, and CNS embryonal tumor-NOS), with or without residual or disseminated (R/D) diseases who were starting standard post-operative focal or craniospinal-irradiation (CSI). Read More

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Compromised long-lived memory CD8+ T cells are associated with reduced IL-7 responsiveness in HIV-infected immunological non-responders.

Eur J Immunol 2021 May 11. Epub 2021 May 11.

Department of Infectious Diseases, Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.

Immune deficiency is one of the hallmarks of HIV infection and a major cause of adverse outcomes in people living with HIV (PLWH). Long-lived memory CD8 T cells (LLMCs) are essential executors of long-term protective immunity; however, the generation and maintenance of LLMCs during chronic HIV infection are not well understood. In the present study, we analyzed circulating LLMCs in healthy controls (HCs) and PLWH with different disease statuses, including treatment naïve patients (TNs), complete responders (CRs), and immunological non-responders (INRs). Read More

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Genetic variants and immune responses in a cohort of patients with varicella zoster virus encephalitis.

J Infect Dis 2021 May 11. Epub 2021 May 11.

Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.

Background: Infection with varicella zoster virus (VZV) may involve different central nervous system (CNS) manifestations, including meningitis, encephalitis, and vasculitis. In cases where otherwise healthy individuals are affected, an inborn error of immunity may underlie increased susceptibility or severity of infection.

Methods: We collected a cohort of 17 adults who experienced VZV encephalitis and performed whole exome sequencing. Read More

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Mesenchymal stromal cells reduce evidence of lung injury in patients with ARDS.

JCI Insight 2021 May 11. Epub 2021 May 11.

Cardiovascular Research Institute, University of California, San Francisco, San Francisco, United States of America.

Background: Whether airspace biomarkers add value to plasma biomarkers in studying ARDS is not well understood. Mesenchymal stromal cells (MSCs) are an investigational therapy for ARDS, and airspace biomarkers may provide mechanistic evidence for MSCs' impact in patients with ARDS.

Methods: We carried out a nested cohort study within a phase 2a safety trial of treatment with allogeneic MSCs for moderate to severe ARDS. Read More

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A role for IL-33-activated ILC2s in eosinophilic vasculitis.

JCI Insight 2021 May 11. Epub 2021 May 11.

Department of Internal Medicine, Cochin Hospital, Paris, France.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare but serious disease with poorly understood mechanisms. Here we report that patients with EGPA have elevated levels of TSLP, IL-25, and sST2, well characterized cytokine "alarmins" that activate or modulate type 2 innate lymphoid cells (ILC2s). Patients with active EGPA have a concurrent reduction in circulating ILC2s, suggesting a role for ILC2s in the pathogenesis of this disease. Read More

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Declining neutrophil production despite increasing G-CSF levels is associated with chronic inflammation in elderly rhesus macaques.

J Leukoc Biol 2021 May 11. Epub 2021 May 11.

Division of Immunology, Tulane National Primate Research Center, Tulane University, Covington, Louisiana, USA.

Aging is characterized by a loss of bone marrow hematopoietic tissue, systemic chronic inflammation, and higher susceptibility to infectious and noninfectious diseases. We previously reported the tightly regulated kinetics and massive daily production of neutrophils during homeostasis in adult rhesus macaques aged 3 to 19 yr (equivalent to approximately 10 to 70 yr of age in humans). In the current study, we observed an earlier release of recently dividing neutrophils from bone marrow and greater in-group variability of neutrophil kinetics based on in vivo BrdU labeling in a group of older rhesus macaques of 20-26 yr of age. Read More

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CCR2-dependent monocyte-derived cells restrict SARS-CoV-2 infection.

bioRxiv 2021 May 4. Epub 2021 May 4.

SARS-CoV-2 has caused a historic pandemic of respiratory disease (COVID-19) and current evidence suggests severe disease is associated with dysregulated immunity within the respiratory tract. However, the innate immune mechanisms that mediate protection during COVID-19 are not well defined. Here we characterize a mouse model of SARS-CoV-2 infection and find that early CCR2-dependent infiltration of monocytes restricts viral burden in the lung. Read More

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The Efficacy of Herbal Supplements and Nutraceuticals for Prevention of Migraine: Can They Help?

Cureus 2021 May 6;13(5):e14868. Epub 2021 May 6.

Research, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.

Migraine is a common neurological disorder associated with or without aura. Although the pathophysiology of migraine is not very well understood, pro-inflammatory cytokines and oxidative stress biomarkers are found to be increased in migraine. Multiple studies have been done to see if alternative medicine such as herbal supplements and nutraceuticals are effective in the prevention and treatment of migraine headaches. Read More

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Allopurinol ameliorates high fructose diet induced hepatic steatosis in diabetic rats through modulation of lipid metabolism, inflammation, and ER stress pathway.

Sci Rep 2021 May 10;11(1):9894. Epub 2021 May 10.

Department of Endocrinology and Metabolism, Kyung Hee University School of Medicine, Kyung Hee University Hospital at Gangdong, #892 Dongnam-ro, Gangdong-gu, Seoul, 05278, Korea.

Excess fructose consumption contributes to development obesity, metabolic syndrome, and nonalcoholic fatty liver disease (NAFLD). Uric acid (UA), a metabolite of fructose metabolism, may have a direct role in development of NAFLD, with unclear mechanism. This study aimed to evaluate role of fructose and UA in NAFLD and explore mechanisms of allopurinol (Allo, a UA lowering medication) on NAFLD in Otsuka Long-Evans Tokushima Fatty (OLETF) rats fed a high fructose diet (HFrD), with Long-Evans Tokushima Otsuka (LETO) rats used as a control. Read More

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Human adipose tissue-derived mesenchymal stem cells and their extracellular vesicles modulate lipopolysaccharide activated human microglia.

Cell Death Discov 2021 May 10;7(1):98. Epub 2021 May 10.

Interventional Regenerative Medicine and Imaging Laboratory, Department of Radiology, Stanford University, Palo Alto, CA, 94304, USA.

Neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), are driven by neuroinflammation triggered by activated microglial cells; hence, the phenotypic regulation of these cells is an appealing target for intervention. Human adipose tissue-derived mesenchymal stem cells (hAD-MSCs) may be a potential therapeutic candidate to treat NDs given their immunomodulatory properties. Evidence suggests that the mechanism of action of hAD-MSCs is through their secretome, which includes secreted factors such as cytokines, chemokines, or growth factors as well as extracellular vesicles (EVs). Read More

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Human-relevant near-organ neuromodulation of the immune system via the splenic nerve.

Proc Natl Acad Sci U S A 2021 May;118(20)

Clinical Sciences and Services, The Royal Veterinary College, Hatfield AL9 7TA, United Kingdom;

Neuromodulation of immune function by stimulating the autonomic connections to the spleen has been demonstrated in rodent models. Consequently, neuroimmune modulation has been proposed as a new therapeutic strategy for the treatment of inflammatory conditions. However, demonstration of the translation of these immunomodulatory mechanisms in anatomically and physiologically relevant models is still lacking. Read More

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IL-9-triggered lncRNA Gm13568 regulates Notch1 in astrocytes through interaction with CBP/P300: contribute to the pathogenesis of experimental autoimmune encephalomyelitis.

J Neuroinflammation 2021 May 11;18(1):108. Epub 2021 May 11.

Xuzhou Key Laboratory of Neurobiology, Department of Neurobiology and Anatomy, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, People's Republic of China.

Background: Interleukin 9 (IL-9), produced mainly by T helper 9 (Th9) cells, has been recognized as an important regulator in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Astrocytes respond to IL-9 and reactive astrocytes always associate with blood-brain barrier damage, immune cell infiltration, and spinal injury in MS and EAE. Several long non-coding RNAs (lncRNAs) with aberrant expression have been identified in the pathogenesis of MS. Read More

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Deletion of a putative promoter-proximal Tnfsf11 regulatory region in mice does not alter bone mass or Tnfsf11 expression in vivo.

PLoS One 2021 10;16(5):e0250974. Epub 2021 May 10.

Center for Musculoskeletal Disease Research, University of Arkansas for Medical Sciences, Little Rock, AR, United States of America.

The cytokine RANKL is essential for osteoclast formation during physiological and pathological bone resorption. RANKL also contributes to lymphocyte production, development of lymph nodes and mammary glands, as well as other biological activities. Transcriptional control of the Tnfsf11 gene, which encodes RANKL, is complex and involves distant regulatory regions. Read More

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The immune protection induced by a serine protease from the Trichinella spiralis adult against Trichinella spiralis infection in pigs.

PLoS Negl Trop Dis 2021 May 10;15(5):e0009408. Epub 2021 May 10.

Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China.

Trichinellosis is a major foodborne parasitosis caused by Trichinella spiralis. In the present study, a serine protease gene from an adult T. spiralis (Ts-Adsp) cDNA library was cloned, expressed in Escherichia coli and purified by Ni-affinity chromatography. Read More

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Fecal microbiota composition associates with the capacity of human peripheral blood monocytes to differentiate into immunogenic dendritic cells .

Gut Microbes 2021 Jan-Dec;13(1):1-20

Laboratory for Molecular Microbiology (LMM), Institute of Molecular Genetics and Genetic Engineering (IMGGI), University of Belgrade, Belgrade, Serbia.

Although promising for active immunization in cancer patients, dendritic cells (DCs) vaccines generated display high inter-individual variability in their immunogenicity, which mostly limits their therapeutic efficacy. Gut microbiota composition is a key emerging factor affecting individuals' immune responses, but it is unknown how it affects the variability of donors' precursor cells to differentiate into immunogenic DCs . By analyzing gut microbiota composition in 14 healthy donors, along with the phenotype and cytokines production by monocyte-derived DCs, we found significant correlations between immunogenic properties of DC and microbiota composition. Read More

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A protective variant of the autophagy receptor CALCOCO2/NDP52 in Multiple Sclerosis (MS).

Autophagy 2021 May 10:1-3. Epub 2021 May 10.

IRCCS Fondazione Santa Lucia, Rome, Italy.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system, which has been found associated with dysfunctional mitochondria. In order to advance our understanding of the complex molecular mechanisms underlying this disease, we analyzed mitophagy, a process fundamental for the elimination of damaged mitochondria through the autophagic process, in peripheral blood mononuclear cells (PBMCs) of MS patients. Through a genetic analysis carried out on 203 MS patients and 1000 healthy controls, we identified a natural variant of CALCOCO2/NDP52, a well-known autophagic receptor, associated with and protective in MS. Read More

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Therapeutic Potential of Cytokines in Demyelinating Lesions After Stroke.

J Mol Neurosci 2021 May 10. Epub 2021 May 10.

Department of Rehabilitation Medicine, Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, Shanghai, 201318, China.

White matter damage is a component of most human stroke and usually accounts for at least half of the lesion volume. Subcortical white matter stroke (WMS) accounts for 25% of all strokes and causes severe motor and cognitive dysfunction. The adult brain has a very limited ability to repair white matter damage. Read More

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Induction of renal tumor necrosis factor-alpha and other autacoids and the beneficial effects of hypertonic saline in acute decompensated heart failure.

Am J Physiol Renal Physiol 2021 May 10. Epub 2021 May 10.

Department of Pharmacology, New York Medical College, United Statesgrid.260917.b.

While administration of Hypertonic Saline (HSS) in combination with diuretics has yielded improved weight loss, preservation of renal function, and reduction in hospitalization time in the clinical setting of patients with acute decompensated heart failure (ADHF), the mechanisms that underlie these beneficial effects remain unclear and additional studies are needed before this approach can be adopted on a more consistent basis. As high salt conditions stimulate production of several renal autacoids that exhibit natriuretic effects, renal physiologists can contribute to the understanding of mechanisms by which HSS leads to increased diuresis both as an individual therapy, as well as in combination with loop diuretics. For instance, since HSS increases TNF-α production by proximal tubule (PT) and thick ascending limb of Henle's loop (TAL) epithelial cells, this 'Perspective article' is aimed at highlighting how the effects of TNF-α produced by these cell types may contribute to the beneficial effects of HSS in patients with ADHF. Read More

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Cowpea Mosaic Virus Promotes Anti-Tumor Activity and Immune Memory in a Mouse Ovarian Tumor Model.

Adv Ther (Weinh) 2019 May 25;2(5). Epub 2019 Feb 25.

Department of NanoEngineering, University of California, San Diego, La Jolla, CA 92093, USA.

Cowpea mosaic virus (CPMV) is a promising platform nanotechnology with applications as a cancer therapeutic. To understand the therapeutic potential of CPMV in more detail, its antitumor mechanisms are investigated using a syngeneic immunocompetent murine orthotopic ovarian cancer model (ID8-Defb29/Vegf-A). CPMV treatment in situ promotes tumor regression and prevents tumor recurrence. Read More

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