scholarly journals On inflammatory hypothesis of depression: what is the role of IL-6 in the middle of the chaos?

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Elnaz Roohi ◽  
Nematollah Jaafari ◽  
Farshad Hashemian
Keyword(s):  
Inflammatory Responses ◽  
The Body ◽  
Research Review ◽  
Original Research ◽  
Journal Articles ◽  
Major Depressive ◽  
Treatment And Prevention ◽  
Depression Symptomatology ◽  
The Brain

AbstractMany patients with major depressive disorder (MDD) are reported to have higher levels of multiple inflammatory cytokines including interleukin 6 (IL-6). Recent studies both pre-clinical and clinical have advocated for the functional role of IL-6 in development of MDD and suggested a great potential for targeting this cytokine to open new avenues in pharmacotherapy of depression. The purpose of the present narrative review was to provide an integrated account of how IL-6 may contribute to development of depression. All peer-reviewed journal articles published before July 2020 for each area discussed were searched by WOS, PubMed, MEDLINE, Scopus, Google Scholar, for original research, review articles, and book chapters. Publications between 1980 and July 2020 were included. Alterations in IL-6 levels, both within the periphery and the brain, most probably contribute to depression symptomatology in numerous ways. As IL-6 acts on multiple differing target tissues throughout the body, dysregulation of this particular cytokine can precipitate a multitude of events relevant to depression and blocking its effects can prevent further escalation of inflammatory responses, and potentially pave the way for opening new avenues in diagnosis, treatment, and prevention of this debilitating disorder.

scholarly journals Modulation of Macrophages M1/M2 Polarization Using Carbohydrate-Functionalized Polymeric Nanoparticles

Polymers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 88
Author(s):  
Raquel G. D. Andrade ◽  
Bruno Reis ◽  
Benjamin Costas ◽  
Sofia A. Costa Lima ◽  
Salette Reis
Keyword(s):  
Inflammatory Responses ◽  
Polymeric Nanoparticles ◽  
Interaction Mechanism ◽  
Mannose Receptor ◽  
The Body ◽  
Receptor Expression ◽  
Production Methods ◽  
Polymeric Nanocarriers ◽  
Efficient Delivery

Exploiting surface endocytosis receptors using carbohydrate-conjugated nanocarriers brings outstanding approaches to an efficient delivery towards a specific target. Macrophages are cells of innate immunity found throughout the body. Plasticity of macrophages is evidenced by alterations in phenotypic polarization in response to stimuli, and is associated with changes in effector molecules, receptor expression, and cytokine profile. M1-polarized macrophages are involved in pro-inflammatory responses while M2 macrophages are capable of anti-inflammatory response and tissue repair. Modulation of macrophages’ activation state is an effective approach for several disease therapies, mediated by carbohydrate-coated nanocarriers. In this review, polymeric nanocarriers targeting macrophages are described in terms of production methods and conjugation strategies, highlighting the role of mannose receptor in the polarization of macrophages, and targeting approaches for infectious diseases, cancer immunotherapy, and prevention. Translation of this nanomedicine approach still requires further elucidation of the interaction mechanism between nanocarriers and macrophages towards clinical applications.

scholarly journals Millimeter (MM) wave and microwave frequency radiation produce deeply penetrating effects: the biology and the physics

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Martin L. Pall
Keyword(s):  
Magnetic Fields ◽  
Electric Fields ◽  
Cardiac Activity ◽  
Maximum Level ◽  
Voltage Sensor ◽  
The Body ◽  
Time Varying ◽  
The Brain ◽  
Mm Waves

Abstract Millimeter wave (MM-wave) electromagnetic fields (EMFs) are predicted to not produce penetrating effects in the body. The electric but not magnetic part of MM-EMFs are almost completely absorbed within the outer 1 mm of the body. Rodents are reported to have penetrating MM-wave impacts on the brain, the myocardium, liver, kidney and bone marrow. MM-waves produce electromagnetic sensitivity-like changes in rodent, frog and skate tissues. In humans, MM-waves have penetrating effects including impacts on the brain, producing EEG changes and other neurological/neuropsychiatric changes, increases in apparent electromagnetic hypersensitivity and produce changes on ulcers and cardiac activity. This review focuses on several issues required to understand penetrating effects of MM-waves and microwaves: 1. Electronically generated EMFs are coherent, producing much higher electrical and magnetic forces then do natural incoherent EMFs. 2. The fixed relationship between electrical and magnetic fields found in EMFs in a vacuum or highly permeable medium such as air, predicted by Maxwell’s equations, breaks down in other materials. Specifically, MM-wave electrical fields are almost completely absorbed in the outer 1 mm of the body due to the high dielectric constant of biological aqueous phases. However, the magnetic fields are very highly penetrating. 3. Time-varying magnetic fields have central roles in producing highly penetrating effects. The primary mechanism of EMF action is voltage-gated calcium channel (VGCC) activation with the EMFs acting via their forces on the voltage sensor, rather than by depolarization of the plasma membrane. Two distinct mechanisms, an indirect and a direct mechanism, are consistent with and predicted by the physics, to explain penetrating MM-wave VGCC activation via the voltage sensor. Time-varying coherent magnetic fields, as predicted by the Maxwell–Faraday version of Faraday’s law of induction, can put forces on ions dissolved in aqueous phases deep within the body, regenerating coherent electric fields which activate the VGCC voltage sensor. In addition, time-varying magnetic fields can directly put forces on the 20 charges in the VGCC voltage sensor. There are three very important findings here which are rarely recognized in the EMF scientific literature: coherence of electronically generated EMFs; the key role of time-varying magnetic fields in generating highly penetrating effects; the key role of both modulating and pure EMF pulses in greatly increasing very short term high level time-variation of magnetic and electric fields. It is probable that genuine safety guidelines must keep nanosecond timescale-variation of coherent electric and magnetic fields below some maximum level in order to produce genuine safety. These findings have important implications with regard to 5G radiation.

scholarly journals Metabolic Acidosis in Patients with CKD: Epidemiology, Pathogenesis, and Treatment

2021 ◽  
pp. 1-16
Author(s):  
Marcin Adamczak ◽  
Stanisław Surma
Keyword(s):  
Metabolic Acidosis ◽  
Sodium Bicarbonate ◽  
Current Knowledge ◽  
Venous Blood ◽  
The Body ◽  
Hydrogen Ions ◽  
Ckd Progression ◽  
New Drug ◽  
Treatment And Prevention

<b><i>Background:</i></b> Metabolic acidosis in CKD is diagnosed in patients with plasma or venous blood bicarbonate concentration lower than 22 mmol/L. Metabolic acidosis occurs in about 20% of patients with CKD. Metabolic acidosis may lead to dysfunction of many systems and organs as well as CKD progression. Currently, sodium bicarbonate is mainly used for pharmacological treatment of metabolic acidosis in patients with CKD. Veverimer is a new drug dedicated to treatment of metabolic acidosis in patients with CKD. Orally given veverimer binds hydrogen ions in the intestines and subsequently is excreted from the body with feces. Clinical studies have shown that veverimer is effective in increasing serum bicarbonate concentrations in CKD patients with metabolic acidosis. Here, we present review of the epidemiology, pathogenesis, diagnosis, treatment, and prevention of metabolic acidosis in CKD patients. <b><i>Summary:</i></b> Metabolic acidosis is common in patients with CKD and contributes to CKD progression and many complications, which worsen the prognosis in these patients. Currently, sodium bicarbonate is mainly used in metabolic acidosis treatment. The role of the new drug veverimer in the metabolic acidosis therapy needs further studies. <b><i>Key Message:</i></b> The aim of this review article is to summarize the current knowledge concerning the epidemiology, pathogenesis, diagnosis, treatment, and prevention of metabolic acidosis in CKD patients.

CCM3 Loss-Induced Lymphatic Defect Is Mediated by the Augmented VEGFR3-ERK1/2 Signaling

2021 ◽  
Author(s):  
Lingfeng Qin ◽  
Haifeng Zhang ◽  
Busu Li ◽  
Quan Jiang ◽  
Francesc Lopez ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Fluorescein Isothiocyanate ◽  
The Body ◽  
Blue Dye ◽  
Transcriptional Level ◽  
Dependent Manner ◽  
Cavernous Malformations ◽  
Morphological Alterations ◽  
The Brain

Objective: Cerebral cavernous malformations (CCMs) can happen anywhere in the body, although they most commonly produce symptoms in the brain. The role of CCM genes in other vascular beds outside the brain and retina is not well-examined, although the 3 CCM-associated genes ( CCM1 , CCM2 , and CCM3 ) are ubiquitously expressed in all tissues. We aimed to determine the role of CCM gene in lymphatics. Approach and Results: Mice with an inducible pan–endothelial cell (EC) or lymphatic EC deletion of Ccm3 ( Pdcd10 ECKO or Pdcd10 LECKO ) exhibit dilated lymphatic capillaries and collecting vessels with abnormal valve structure. Morphological alterations were correlated with lymphatic dysfunction in Pdcd10 LECKO mice as determined by Evans blue dye and fluorescein isothiocyanate(FITC)-dextran transport assays. Pdcd10 LECKO lymphatics had increased VEGFR3 (vascular endothelial growth factor receptor-3)-ERK1/2 signaling with lymphatic hyperplasia. Mechanistic studies suggested that VEGFR3 is primarily regulated at a transcriptional level in Ccm3-deficient lymphatic ECs, in an NF-κB (nuclear factor κB)–dependent manner. CCM3 binds to importin alpha 2/KPNA2 (karyopherin subunit alpha 2), and a CCM3 deletion releases KPNA2 to activate NF-κB P65 by facilitating its nuclear translocation and P65-dependent VEGFR3 transcription. Moreover, increased VEGFR3 in lymphatic EC preferentially activates ERK1/2 signaling, which is critical for lymphatic EC proliferation. Importantly, inhibition of VEGFR3 or ERK1/2 rescued the lymphatic defects in structure and function. Conclusions: Our data demonstrate that CCM3 deletion augments the VEGFR3-ERK1/2 signaling in lymphatic EC that drives lymphatic hyperplasia and malformation and warrant further investigation on the potential clinical relevance of lymphatic dysfunction in patients with CCM.

scholarly journals Prevailing role of mucosal immunoglobulins and B cells in teleost skin immune responses to bacterial infection

2020 ◽  
Author(s):  
Xiao-Ting Zhang ◽  
Yong-Yao Yu ◽  
Hao-Yue Xu ◽  
Zhen-Yu Huang ◽  
Xia Liu ◽  
...  
Keyword(s):  
B Cells ◽  
Bacterial Infection ◽  
Inflammatory Responses ◽  
The Body ◽  
Innate Immune ◽  
Flavobacterium Columnare ◽  
First Line ◽  
Skin Mucus ◽  
Skin Mucosa

AbstractThe skin of vertebrates is the outermost organ of the body and serves as the first line of defense against external aggressions. In contrast to mammalian skin, that of teleost fish lacks keratinization and has evolved to operate as a mucosal surface containing a skin-associated lymphoid tissue (SALT). Thus far, IgT representing the prevalent immunoglobulin (Ig) in SALT have only been reported upon infection with a parasite. However, very little is known about the types of B cells and Igs responding to bacterial infection in the teleost skin mucosa, as well as the inductive or effector role of the SALT in such responses. To address these questions, here we analyzed the immune response of trout skin upon infection with one of the most widespread fish skin bacterial pathogens, Flavobacterium columnare. This pathogen induced strong skin innate immune and inflammatory responses at the initial phases of infection. More critically, we found that the skin mucus of fish having survived the infection contained significant IgT-but not IgM- or IgD-specific titers against the bacteria. Moreover, we demonstrate the local proliferation and production of IgT+ B-cells and specific IgT titers respectively within the SALT upon bacterial infection. Thus, our findings represent the first demonstration that IgT is the main Ig isotype induced by the skin mucosa upon bacterial infection, and that because of the large surface of the skin, its SALT probably represents a prominent IgT inductive site in fish.

scholarly journals Monocyte Transmodulation: The Next Novel Therapeutic Approach in Overcoming Ischemic Stroke?

2020 ◽  
Vol 11 ◽  
Author(s):  
Joohyun Park ◽  
Ji Young Chang ◽  
Jong Youl Kim ◽  
Jong Eun Lee
Keyword(s):  
Ischemic Stroke ◽  
Blood Cells ◽  
Inflammatory Responses ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Great Opportunity ◽  
Reparative Process ◽  
The Brain ◽  
Vital Element

The immune response following neuroinflammation is a vital element of ischemic stroke pathophysiology. After the onset of ischemic stroke, a specialized vasculature system that effectively protects central nervous system tissues from the invasion of blood cells and other macromolecules is broken down within minutes, thereby triggering the inflammation cascade, including the infiltration of peripheral blood leukocytes. In this series of processes, blood-derived monocytes have a significant effect on the outcome of ischemic stroke through neuroinflammatory responses. As neuroinflammation is a necessary and pivotal component of the reparative process after ischemic stroke, understanding the role of infiltrating monocytes in the modulation of inflammatory responses may offer a great opportunity to explore new therapies for ischemic stroke. In this review, we discuss and highlight the function and involvement of monocytes in the brain after ischemic injury, as well as their impact on tissue damage and repair.

scholarly journals GPR110 (ADGRF1) mediates anti-inflammatory effects of N-docosahexaenoylethanolamine

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Taeyeop Park ◽  
Huazhen Chen ◽  
Hee-Yong Kim
Keyword(s):  
Inflammatory Cytokine ◽  
Inflammatory Responses ◽  
Cytokine Expression ◽  
Regulatory Function ◽  
Enzyme Linked Immunosorbent Assay ◽  
Inflammatory Condition ◽  
Wild Type ◽  
Knock Out ◽  
The Brain

Abstract Background Neuroinflammation is a widely accepted underlying condition for various pathological processes in the brain. In a recent study, synaptamide, an endogenous metabolite derived from docosahexaenoic acid (DHA, 22:6n-3), was identified as a specific ligand to orphan adhesion G-protein-coupled receptor 110 (GPR110, ADGRF1). Synaptamide has been shown to suppress lipopolysaccharide (LPS)-induced neuroinflammation in mice, but involvement of GPR110 in this process has not been established. In this study, we investigated the possible immune regulatory role of GPR110 in mediating the anti-neuroinflammatory effects of synaptamide under a systemic inflammatory condition. Methods For in vitro studies, we assessed the role of GPR110 in synaptamide effects on LPS-induced inflammatory responses in adult primary mouse microglia, immortalized murine microglial cells (BV2), primary neutrophil, and peritoneal macrophage by using quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA) as well as neutrophil migration and ROS production assays. To evaluate in vivo effects, wild-type (WT) and GPR110 knock-out (KO) mice were injected with LPS intraperitoneally (i.p.) or TNF intravenously (i.v.) followed by synaptamide (i.p.), and expression of proinflammatory mediators was measured by qPCR, ELISA, and western blot analysis. Activated microglia in the brain and NF-kB activation in cells were examined microscopically after immunostaining for Iba-1 and RelA, respectively. Results Intraperitoneal (i.p.) administration of LPS increased TNF and IL-1β in the blood and induced pro-inflammatory cytokine expression in the brain. Subsequent i.p. injection of the GPR110 ligand synaptamide significantly reduced LPS-induced inflammatory responses in wild-type (WT) but not in GPR110 knock-out (KO) mice. In cultured microglia, synaptamide increased cAMP and inhibited LPS-induced proinflammatory cytokine expression by inhibiting the translocation of NF-κB subunit RelA into the nucleus. These effects were abolished by blocking synaptamide binding to GPR110 using an N-terminal targeting antibody. GPR110 expression was found to be high in neutrophils and macrophages where synaptamide also caused a GPR110-dependent increase in cAMP and inhibition of LPS-induced pro-inflammatory mediator expression. Intravenous injection of TNF, a pro-inflammatory cytokine that increases in the circulation after LPS treatment, elicited inflammatory responses in the brain which were dampened by the subsequent injection (i.p.) of synaptamide in a GPR110-dependent manner. Conclusion Our study demonstrates the immune-regulatory function of GPR110 in both brain and periphery, collectively contributing to the anti-neuroinflammatory effects of synaptamide under a systemic inflammatory condition. We suggest GPR110 activation as a novel therapeutic strategy to ameliorate inflammation in the brain as well as periphery.

scholarly journals Concentrations of the Selected Biomarkers of Endothelial Dysfunction in Response to Antiepileptic Drugs: A Literature Review

2019 ◽  
Vol 25 ◽  
pp. 107602961985942 ◽  
Author(s):  
Beata Sarecka-Hujar ◽  
Izabela Szołtysek-Bołdys ◽  
Ilona Kopyta ◽  
Barbara Dolińska ◽  
Andrzej Sobczak
Keyword(s):  
Risk Factors ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Literature Review ◽  
Antiepileptic Drug ◽  
Asymmetric Dimethylarginine ◽  
The Body ◽  
Biochemical Processes ◽  
The Brain

Epilepsy is a disease arising from morphological and metabolic changes in the brain. Approximately 60% of patients with seizures can be controlled with 1 antiepileptic drug (AED), while in others, polytherapy is required. The AED treatment affects a number of biochemical processes in the body, including increasing the risk of cardiovascular diseases (CVDs). It is indicated that the duration of AED therapy with some AEDs significantly accelerates the process of atherosclerosis. Most of AEDs increase levels of homocysteine (HCys) as well as may affect concentrations of new, nonclassical risk factors for atherosclerosis, that is, asymmetric dimethylarginine (ADMA) and homoarginine (hArg). Because of the role of these parameters in the pathogenesis of CVD, knowledge of HCys, ADMA, and hArg concentrations in patients with epilepsia treated with AED, both pediatric and adult, appears to be of significant importance.

scholarly journals Co-occuring Toxoplasma Infection and Psychotic Symptoms : Case Report

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Carla R Marchira ◽  
Andrian F Kusumadewi ◽  
Patricia Wulandari
Keyword(s):  
Life Support ◽  
The United States ◽  
The Body ◽  
Psychotic Symptoms ◽  
Toxoplasma Infection ◽  
Case Presentation ◽  
The Family ◽  
Brain Neurotransmitter ◽  
The Brain

Abstract   Introduction Schizophrenia is a neuropsychiatric disease that is global and is experienced by 1% of the population in the United States and Europe. This study raises awareness of the role of infectious agents in the initiation of psychotic symptoms in schizophrenia. Case Presentation A 20-year-old man is taken by the family to the emergency department because he has decreased consciousness, and the body suddenly stiffens. Patients begin to experience changes in behavior in the form of difficulty sleeping, when invited to talk quietly, laughing alone and whispering without the other person. TORCH examination found an increase in anti-toxoplasma IgM and IgG. This patient is then given basic life support in the form of ABC (airway, breathing, circulation support) and seizure management. Also given risperidone 2 mg / 12 hours, pyrimethamine 1-II (1x200 mg), pyrimethamine day III-XXI (1x 25 mg), intravenous Cefotaxim 2g / 8 hours, Clindamycin 500 mg / 8 hours. The patient experienced improvement after the second week of treatment. Conclusion Toxoplasmosis causes lesions in the brain that cause changes in brain neurotransmitter pathways, which lead to changes in patient behavior.

scholarly journals Prevention and treatment of COVID-19 infection by earthing

2020 ◽  
Author(s):  
Haider Abdul-Lateef Mousa
Keyword(s):  
Oxygen Supply ◽  
Blood Oxygenation ◽  
The Body ◽  
Oxygen Level ◽  
Blood Oxygen Level ◽  
Antipyretic Effect ◽  
Treatment And Prevention ◽  
Taste And Smell ◽  
Chest Ct Scan

Background: Earthig is a contact with earth by several means that could cause influx of electron into the body with subsequent anti-inflammatory effect, immunity enhancement, anticoagulation, rising blood oxygenation, and possible antipyretic effect. All these effects of earthing might have a substantial role in the management of patients with COVID-19 infection without deleterious side effects of ordinary medications.Objective: to investigate the role of earthing in treatment and prevention of COVID-19 infection.Design: Observational studySetting: University of Basrah, College of Medicine, Iraq.Patients: The study included 59 cases with COVID-19 infection.Interventions: All patients conducted earthing through direct contact with earth or connecting apparatus for about 15 min-3 hours/day.Measurements and Main Results: The diagnosis was confirmed by PCR test with or without chest CT-scan. There was spectacular response in a severely ill patient who was unable to speak due to dyspnea with blood oxygen level 38% on continuous oxygen supply. On the second day of three hours daily earthing, his oxygen level raised to 95% with oxygen supply and 77% without oxygen supply. After 1-3 days of earthing, most patients revealed improvement of the following symptoms: fever, dyspnea, cough, weakness, headache, chest pain, taste and smell sense loss, anorexia, and body pain. Six people were in contact with COVID-19 patients that had performed preventive earthing. They contracted mild or short-lived illness although their household were severely affected.Conclusions: The outcome of patients with COVID-19 who had performed regular and sufficient earthing showing significant curing or preventive effects that more studies on larger sample size are advocated.

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