Decrease of IL-1β and TNF in the Spinal Cord Mediates Analgesia Produced by Ankle Joint Mobilization in Complete Freund Adjuvant-Induced Inflammation Mice Model

ObjectiveThis study aims to investigate the effects of ankle joint mobilization (AJM) on mechanical hyperalgesia and peripheral and central inflammatory biomarkers after intraplantar (i.pl.) Complete Freund’s Adjuvant (CFA)-induced inflammation.MethodsMale Swiss mice were randomly assigned to 3 groups (n = 7): Saline/Sham, CFA/Sham, and CFA/AJM. Five AJM sessions were carried out at 6, 24, 48, 72, and 96 h after CFA injection. von Frey test was used to assess mechanical hyperalgesia. Tissues from paw skin, paw muscle and spinal cord were collected to measure pro-inflammatory (TNF, IL-1β) and anti-inflammatory cytokines (IL-4, IL-10, and TGF-β1) by ELISA. The macrophage phenotype at the inflammation site was evaluated by Western blotting assay using the Nitric Oxide Synthase 2 (NOS 2) and Arginase-1 immunocontent to identify M1 and M2 macrophages, respectively.ResultsOur results confirm a consistent analgesic effect of AJM following the second treatment session. AJM did not change cytokines levels at the inflammatory site, although it promoted a reduction in M2 macrophages. Also, there was a reduction in the levels of pro-inflammatory cytokines IL-1β and TNF in the spinal cord.ConclusionTaken together, the results confirm the anti-hyperalgesic effect of AJM and suggest a central neuroimmunomodulatory effect in a model of persistent inflammation targeting the pro-inflammatory cytokines IL-1β and TNF.

Proinflammatory adipokines and cytokines in abdominal obesity as a factor in the development of atherosclerosis and renal pathology

In recent decades, there has been an increase in the prevalence of overweight and obesity. Obesity has become an underestimated pandemic and a public health threat around the world. Adipose tissue is positioned as an endocrine organ that secretes a wide range of pro-inflammatory cytokines and adipokines, inducing a state of chronic subinflammation. The results of epidemiological studies over the past 30 years have also shown that visceral adipose tissue is an independent risk factor for the development of atherosclerosis, cardiometabolic diseases and chronic kidney disease. We performed a systematic review to summarize important aspects of the state of chronic subinflammation in the context of its effect on the decrease in glomerular filtration rate and the development of chronic kidney disease. The review deals with the etiology and pathogenesis of obesity, the hormonal profile of adipose tissue, the molecular mechanisms of the effect of pro-inflammatory cytokines and adipokines on the kidneys, and the pathophysiology of renal diseases. Information on the topic from publications based on the Pubmed database has been used.

Impact of the COVID-19 Pandemic on Chronic Neurological Disorders: Focus on Patients with Dementia

The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) represents a public health problem worldwide. COVID-19 triggers a maladaptive cytokine release commonly referred to as cytokine storm syndrome with increased production of pro-inflammatory cytokines, which also appears to contribute to chronic neuro-inflammation and neurodegenerative disorders’ appearance, including multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease. In this context, SARS-CoV-2 might enter the central nervous system through binding with the angiotensin converting enzyme 2 receptors which are highly expressed in glial cells and neurons. For this reason, an association between COVID-19, its dependent cytokine storm, and the development and/or progression of neurodegenerative disorders might be evaluated. Therefore, the aim of this review was to assess the impact of COVID-19 on neurodegenerative disorders focusing on the possible increased mortality risk and/or deterioration of clinical course of pre-existing chronic neurological diseases in patients with dementia.

Associations Between Oral Health Status, Perceived Stress, and Neuropsychiatric Symptoms Among Community Individuals With Alzheimer's Disease: A Mediation Analysis

Community individuals with Alzheimer's disease (AD) experience oral disease alongside neuropsychiatric symptoms (NPS) with disease progression. Despite growing evidence for the link between oral health and cognitive status, few studies have investigated the associations between oral health and NPS, especially based on individuals' experience of AD. The primary aim of this study was to examine (a) the difference in oral health-related stressors among individuals with AD, mild cognitive impairment (MCI), and subjective cognitive decline (SCD); and (b) the associations of these stressors with NPS under the framework of the stress process model (SPM). A cross-sectional study was conducted among individuals diagnosed with AD (n = 35), MCI (n = 36) or SCD (n = 35), matched for age, sex education, and body mass index (BMI). Multiple regression and mediation model analyses were performed to explore predictors and their relationships with NPS based on the SPM. Data collection comprised four sections: (a) individual context; (b) oral health-related stressors, including dental caries, periodontal status, oral hygiene, the geriatric oral health assessment index (GOHAI), oral salivary microbiota, pro-inflammatory cytokines, and oral health behavior; (c) subjective stressors (i.e., perceived stress [PS]); and (d) NPS. Decayed, missing, and filled teeth (DMFT), missing teeth (MT), loss of attachment (LoA), plaque index (PLI), PS, oral health behavior, GOHAI, pro-inflammatory cytokines, and salivary bacterial composition were significantly different among the three groups; these parameters were poorer in the AD group than SCD and/or MCI group. LoA, PLI, PS, and pain or discomfort in the GOHAI were directly associated with NPS. PLI, LoA, and psychosocial function in the GOHAI indirectly affected NPS, and this relationship was mediated by PS. Individuals with AD reported greater oral health-related stressors. This study identifies direct and indirect associations linking oral health-related stressors and PS with NPS in individuals with AD. Our findings suggest that targeted dental care and oral-related stressor control may be valuable for managing NPS.

MiR-200c-3p inhibits LPS-induced M1 polarization of BV2 cells by targeting RIP2

Background Microglia are important immune cells, which can be induced by lipopolysaccharide (LPS) into M1 phenotype that express pro-inflammatory cytokines. Some studies have shown that microRNAs play critical roles in microglial activation. Objective This study was designed to investigate the role of miR-200c-3p in regulating inflammatory responses of LPS-treated BV2 cells. Methods The expression of miR-200c-3p in BV2 cells was detected by real-time PCR. Receptor-interacting protein 2 (RIP2) was predicted as a target gene of miR-200c-3p. Their relationship was verified by dual-luciferase reporter assay. The function of miR-200c-3p and RIP2 in microglial polarization and NF-κB signaling was further evaluated. Results LPS treatment reduced miR-200c-3p expression in a dose-dependent and time-dependent manner in BV2 cells. LPS treatment increased the expression of M1 phenotype markers inducible nitric oxide synthase (iNOS) and major histocompatibility complex class (MHC)-II, promoted the release of pro-inflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α, and enhanced the nuclear translocation and phosphorylation of nuclear factor-kappaB (NF-κB) p65. Reversely, miR-200c-3p mimics down-regulated the levels of these inflammatory factors. Furthermore, RIP2 was identified to be a direct target of miR-200c-3p. RIP2 knockdown had a similar effect to miR-200c-3p mimics. Overexpression of RIP2 eliminated the inhibitory effect of miR-200c-3p on LPS-induced M1 polarization and NF-κB activation in BV2 cells. Conclusions MiR-200c-3p mimics suppressed LPS-induced microglial M1 polarization and NF-κB activation by targeting RIP2. MiR-200c-3p/RIP2 might be a potential therapeutic target for the treatment of neuroinflammation-associated diseases.

Endogenous and exogenous serotonin, but not sumatriptan, ameliorate seizures and neuroinflammation in the pentylenetetrazole-induced seizure model in rats

ABSTRACT Background: Epilepsy has neuropsychiatric comorbidities such as depression, bipolar disorder, and anxiety. Drugs that target epilepsy may also be useful for its neuropsychiatric comorbidities. Objective: To investigate the effects of serotonergic modulation on pro-inflammatory cytokines and the seizures in pentylenetetrazole (PTZ)-induced seizure model in rats. Methods: Male Wistar rats were injected intraperitoneally with serotonin, selective serotonin reuptake inhibitor fluoxetine, 5-HT1B/D receptor agonist sumatriptan, or saline 30 min prior to PTZ treatment. Behavioral seizures were assessed by the Racine's scale. Concentrations of IL-1β, IL-6, and TNF-α in serum and brain tissue were determined by ELISA. Results: Serotonin and fluoxetine, but not sumatriptan, alleviated PTZ-induced seizures by prolonging onset times of myoclonic-jerk and generalized tonic-clonic seizures. The anti-seizure effect of fluoxetine was greater than that of serotonin. Likewise, serotonin and fluoxetine, but not sumatriptan, reduced PTZ-induced increases in the levels of IL-1β and IL-6 in both serum and brain tissue. None of the administered drugs including PTZ affected TNF-α concentrations. Conclusions: Our findings suggest that endogenous and exogenous serotonin exhibits anticonvulsant effects by suppressing the neuroinflammation. It seems that 5-HT1B/D receptors do not mediate anticonvulsant and anti-neuroinflammatory effects of serotonin.

Plasmapheresis with Convalescent Plasma as a Rescue Therapy for COVID-19 Patients: A Case Series

: On December 29, 2019, an epidemic of an infectious disease caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was declared in Wuhan, China. The first case of COVID-19 in Iran (Qom Province) was reported in February 2020, and within a short period, the number of infected cases increased rapidly around the country. Evidence suggests that the levels of pro-inflammatory cytokines are high in critically ill patients, and there is a correlation between the high level of cytokines and the pathogenesis of COVID-19; consequently, COVID-19 may have complications, such as acute respiratory distress syndrome (ARDS) and even death. These inflammatory factors can lead to a cytokine storm, while counteracting this storm seems to be an effective therapeutic approach. In this case series, we reported two critically ill patients with COVID-19, undergoing plasmapheresis with convalescent plasma, corticosteroid therapy, and interferon administration.

Selenium-Enriched Yeast Relieves Hexavalent Chromium Toxicity by Inhibiting NF-κB Signaling Pathway in Broiler Spleens

This study was conducted to investigate the molecular mechanisms of selenium (Se) antagonism of hexavalent chromium (Cr6+)-induced toxicity. Potassium dichromate (K2Cr2O7) and selenium-enriched yeast (SeY) were used to construct the single Cr6+ and combined Se/Cr6+ exposure broiler models, and then the broilers were randomly divided into four groups (C group, Se group, Se/Cr6+ group, and Cr6+ group). After a 42-day experiment, the spleen tissues of broilers were excised and weighted. The antagonistic mechanisms of Se and Cr6+ were evaluated using histopathological assessment, serum biochemical tests, oxidative stress kits, ELISA, qPCR, and Western blotting. On the whole, there were no significant changes between the C and Se groups. The spleen organ index in the Cr6+ group was significantly decreased, but SeY increased spleen organ index to a certain extent. The levels of SOD and GSH were reduced, and the MDA content was elevated by Cr6+; however, these changes were mitigated by Se/Cr6+ exposure. Importantly, Cr6+ exposure induced a series of histopathological injuries in broiler spleen tissues, while these symptoms were significantly relieved in the Se/Cr6+group. Furthermore, Cr6+ significantly decreased the levels of T-globulin, IgA, IgM, and IgG in serum. Contrarily, dramatically more T-globulin IgA, IgM, and IgG were found in the Se/Cr6+group than in the Cr6+ group. Revealed by the results of qPCR and WB, the expressions of NF-κB, IκBα, and p-IκBα were upregulated in Cr6+ groups, while they were downregulated in Se/Cr6+ group compared to that in Cr6+ group. Besides IFN-γ and IL-2, the expressions of pro-inflammatory cytokines were significantly increased by Cr6+ exposure, but the SeY supplement relived the expression levels mediated by Cr6+ exposure. In conclusion, our findings suggest SeY has biological activity that can protect broiler spleens from immunosuppression and inflammation induced by Cr6+, and we speculate that the NF-κB signaling pathway is one of its mechanisms.

Periostin in Angiogenesis and Inflammation in CRC—A Preliminary Observational Study

Background and Objectives: To assess the periostin level and the concentrations of pro-inflammatory cytokines: TNFα, IFN-γ, IL-1β and IL-17 in tumor and marginal tissues of CRC and to investigate the influence of periostin on angiogenesis by MVD (microvessel density) and concentration of VEGF-A in relation to clinicopathological parameters of patients. Materials and Methods: The study used 47 samples of tumor and margin tissues derived from CRC patients. To determinate the concentration of periostin, VEGF-A, TNFα, IFNγ, IL-1β and IL-17, we used the commercially available enzyme- linked immunosorbent assay kit. MVD was assessed on CD34-stained specimens. The MVD and budding were assessed using a light microscope Results: We found significantly higher concentrations of periostin, VEGF-A, IFN-γ, IL-1 β, IL-17 and TNFα in the tumor samples compared with surgical tissue margins. The tumor concentrations of periostin were correlated with tumor levels of VEGF-A, IFN-γ, IL-1β and TNFα. We observed significant correlation between margin periostin and VEGF-A, IFN-γ, IL-17 and TNFα in tumor and margin specimens. Additionally, we found a significantly negative correlation between periostin tumor concentration and microvessel density at the invasive front. Tumor periostin levels were also correlated positively with tumor budding. Conclusions: Periostin activity may be associated with pro-inflammatory cytokine levels: TNFα, IFN-γ, IL-1β and IL-17. Our results also suggest the role of periostin in angiogenesis in CRC and its upregulation in poorly vascularized tumors. Further research on the regulations between periostin and cytokines are necessary to understand the interactions between tumor and immune tumor microenvironment, which could be helpful in the development of new targeted therapy.