Women and men are suggested to have differences in vulnerability to neuropsychiatric disorders, including major depressive disorder (MDD), generalized anxiety disorder (GAD), schizophrenia, eating ...disorders, including anorexia nervosa, and bulimia nervosa, neurodevelopmental disorders, such as autism spectrum disorder (ASD), and neurodegenerative disorders including Alzheimer's disease, Parkinson's disease. Genetic factors and sex hormones are apparently the main mediators of these differences. Recent evidence uncovers that reciprocal interactions between sex-related features (e.g., sex hormones and sex differences in the brain) and gut microbiota could play a role in the development of neuropsychiatric disorders via influencing the gut-brain axis. It is increasingly evident that sex-microbiota-brain interactions take part in the occurrence of neurologic and psychiatric disorders. Accordingly, integrating the existing evidence might help to enlighten the fundamental roles of these interactions in the pathogenesis of neuropsychiatric disorders. In addition, an increased understanding of the biological sex differences on the microbiota-brain may lead to advances in the treatment of neuropsychiatric disorders and increase the potential for precision medicine. This review discusses the effects of sex differences on the brain and gut microbiota and the putative underlying mechanisms of action. Additionally, we discuss the consequences of interactions between sex differences and gut microbiota on the emergence of particular neuropsychiatric disorders.
In the last three decades,the understanding of the renin angiotensin system(RAS)has been changed by the discoveries of functional local systems,novel biologically active peptides,additional specific ...receptors,alternative pathways of angiotensin(Ang)?Ⅱ?generation,and new roles for enzymes and precursor components other than those in Ang?Ⅱ?synthesis.In this regard,the discovery that Ang-(1-7)opposes the pressor,proliferative,pro-fibrotic,and pro-inflammatory effects mediated by Ang?Ⅱ?has contributed to the realization that the RAS is composed of two axes.The first axis consists of the angiotensin-converting enzyme(ACE),with Ang?Ⅱ?as the end product,and the angiotensin type 1(AT1)receptor as the main effector mediating the biological actions of Ang?Ⅱ.The second axis results from ACE2-mediated hydrolysis of Ang?Ⅱ,leading to the production of Ang-(1-7),with the Mas receptor as the main effector conveying the vasodilatory,antiproliferative,anti-fibrotic,and anti-inflammatory effects of Ang-(1-7).Experimental and clinical studies have shown that both axes of the RAS may take part in the pathogenesis of liver diseases.In this manuscript,we summarize the current evidence regarding the role of RAS in hepatic cirrhosis and its complications,including hemodynamic changes and hepatorenal syndrome.The therapeutic potential of the modulation of RAS molecules in liver diseases is also discussed.
Cerebral malaria (CM) is a clinical syndrome resulting from Plasmodium falciparum infection. A wide range of clinical manifestations follow the disease including cognitive dysfunction, seizures and ...coma. CM pathogenesis remains incompletely understood and without treatment this condition is invariably fatal. Artesunate has been accepted as the most effective drug for treating severe malaria. Besides its antiparasitic activity, an anti-inflammatory property has also been reported. In the current study, the immunomodulatory role of artesunate was investigated using a Plasmodium berghei ANKA model of CM, trough evaluation of behavioural changes and cytokines expression in hippocampus and in frontal cortex.
C57Bl/6 mice were infected with P. berghei by intraperitoneal route, using a standardized inoculation of 106 parasitized erythrocytes. Memory function was evaluated using the step-down inhibitory avoidance test. The mRNA expression of IFN-γ, IL-1β, IL-6 and TNF in the frontal cortex and hippocampus of control and infected mice on day 5 post-infection were estimated by quantitative real time PCR. Plasmodium berghei -infected mice also received intraperitoneally a single dose of artesunate (32 mg/kg) on day 4 post-infection, and 24 hours after treatment behavioural and immunological analysis were performed. The protein levels of cytokines IL-2, IL-6, IL-10, IL-17, IFN-γ, TNF in the serum, frontal cortex and hippocampus of controls and P. berghei -infected mice treated or not treated with artesunate were determined using a cytometric bead array (CBA) kit. The survival and neurological symptoms of CM were also registered.
CM mice presented a significant impairment of aversive memory compared to controls on day 5 post-infection. A higher mRNA expression of pro-inflammatory cytokines was found in the hippocampus and frontal cortex of infected mice. A single dose of artesunate was also able to decrease the expression of inflammatory cytokines in the hippocampus and frontal cortex of P. berghei-infected mice. In parallel, a significant improvement in neurological symptoms and survival were observed in artesunate treated mice.
In summary, the current study provided further evidence that CM affects key brain areas related to cognition process. In addition, different patterns of cytokine expression during the course of CM could be modulated by a single administration of the anti-malarial artesunate.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Depression is among the psychiatric sequelae of COVID-19, affecting more than 20% of the convalescents. Its underlying pathophysiology remains unclear. Interleukin 6 (IL-6), a pro-inflammatory ...cytokine, plays a critical role in the COVID-19-associated cytokine storm, has been implicated in depressive disorders, and may thus be involved in post-COVID-19 depression.
: PubMed, Scopus, Embase, and Web of Science were systematically searched for relevant studies assessing peripheral IL-6 levels in convalescents who developed depression after COVID-19 vs. convalescents who did not.
Five studies were included in our systematic review, and four entered the meta-analysis. The meta-analysis revealed that post-COVID people with
depression did not have statistically significant differences in IL-6 levels compared to those without depression (standardized mean difference (SMD) = 0.09, 95% confidence interval (CI) = -0.35, 0.54, p-value = 0.68)
Although convalescents with depression did not have significantly higher IL-6 levels than convalescents without depression, the results should be interpreted considering the limited sample size and the low power of the included studies.
Neuropsychiatric disorders (i.e., mood disorders and schizophrenia) and inflammation are closely intertwined, and possibly powering each other in a bidirectional loop. Depression facilitates ...inflammatory reactions and inflammation promotes depression and other neuropsychiatric disorders. Patients with neuropsychiatric disorders exhibit all cardinal features of inflammation, including increased circulating levels of inflammatory inducers, activated sensors, and inflammatory mediators targeting all tissues. Inflammation may contribute to the pathophysiology and clinical progression of these disorders. Of note, proinflammatory cytokines modulate mood behavior and cognition by reducing brain monoamine levels, activating neuroendocrine responses, promoting excitotoxicity (increased glutamate levels), and impairing brain plasticity. What are the sources of this chronic inflammation? Increasing evidence indicates that changes in neuroendocrine regulation, metabolism, diet/microbiota, and negative health behaviors are important triggers of inflammation. Finally, recent data indicate that early‐life stress is associated with overt inflammation prior to the development of neuropsychiatric disorders.
Neuropsychiatric disorders (notably, mood disorders and schizophrenia) and inflammation are closely intertwined. Increasing evidence indicates that depression and inflammation are powering each other. This article will present the reader with an overview of the inflammatory phenomenon present in neuropsychiatric disorders, especially in mood disorders and schizophrenia. The review will focus on pre‐clinical and clinical evidence that sterile inflammation may contribute to the pathophysiology and clinical progression of these disorders.
Abstract Evidence suggests that maternal and fetal immune dysfunction may impact fetal brain development and could play a role in neurodevelopmental disorders, although the definitive ...pathophysiological mechanisms are still not completely understood. Stress, malnutrition and physical inactivity are three maternal behavioral lifestyle factors that can influence immune and central nervous system (CNS) functions in both the mother and fetus, and may therefore, increase risk for neurodevelopmental/psychiatric disorders. First, we will briefly review some aspects of maternal-fetal immune system interactions and development of immune tolerance. Second, we will discuss the bidirectional communication between the immune system and CNS and the pathways by which immune dysfunction could contribute to neurodevelopmental disorders. Third, we will discuss the effects of prenatal stress and malnutrition (over and undernutrition) on perinatal programming of the CNS and immune system, and how this might influence neurodevelopment. Finally, we will discuss the beneficial impact of physical fitness during pregnancy on the maternal-fetal unit and infant and how regular physical activity and exercise can be an effective buffer against stress- and inflammatory-related disorders. Although regular physical activity has been shown to promote neuroplasticity and an anti-inflammatory state in the adult, there is a paucity of studies evaluating its impact on CNS and immune function during pregnancy. Implementing stress reduction, proper nutrition and ample physical activity during pregnancy and the childbearing period may be an efficient strategy to counteract the impact of maternal stress and malnutrition/obesity on the developing fetus. Such behavioral interventions could have an impact on early development of the CNS and immune system and contribute to the prevention of neurodevelopmental and psychiatric disorders. Further research is needed to elucidate this relationship and the underlying mechanisms of protection. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease.
•COVID-19 is not associated with higher risks of relapses in multiple sclerosis.•Results of expanded disability status scale shifts after COVID-19 are heterogeneous.•COVID-19 is not associated with ...an increase in the expanded disability status scale.
Upper respiratory viral infections have long been considered triggers for multiple sclerosis (MS) relapse and exacerbation. The possible effects of SARS-CoV-2 infection on MS relapse and deterioration remain controversial.
We systematically searched PubMed, Scopus, Embase, Cochrane, and Web of Science databases to find relevant studies assessing changes in relapse rates or Expanded Disability Status Scale (EDSS) following COVID-19 in people with MS. Meta-analyses were performed, and to investigate sources of heterogeneity, subgroup analysis, meta-regression, and sensitivity analysis were conducted.
We included 14 studies in our systematic review and meta-analysis. The meta-analysis demonstrated that COVID-19 was not associated with a rise in relapse rate (risk ratio (RR): 0.97, 95 % confidence interval (CI): 0.67, 1.41, p-value: 0.87) or a rise in EDSS (standardized mean difference (SMD): −0.09, 95 % CI: −0.22, 0.03, p-value: 0.13). The analysis of EDSS changes indicated a significant heterogeneity (I2: 55 %, p-value: 0.01). Other analyses were not statistically significant.
COVID-19 infection was not associated with an increased risk of relapse and clinical deterioration in people with MS.
Despite intensive research, the etiopathogenesis of preeclampsia (PE) remains uncertain. Inflammatory and angiogenic factors are thought to play considerable roles in this disease. The objective of ...this study was to investigate the association between soluble endoglin (sEng), transforming growth factor beta-1 (TGF-β1) and tumor necrosis factor alpha soluble receptors (sTNF-Rs) and the clinical manifestations of PE.
Plasma levels of sEng, TGF-β1 and sTNF-Rs were determined by ELISA in 23 non-pregnant, 21 normotensive pregnant and 43 PE women. PE women were stratified into subgroups according to the severity mild (n = 12) and severe (n = 31) and onset-time of the disease early (n = 19) and late (n = 24).
Pregnancy was associated with higher levels of sEng, sTNF-R1 and sTNF-R2 than the non-pregnant state. Moreover, PE women had higher levels of sEng and sTNF-R1 than normotensive pregnant women. No difference was found in TGF-β1 levels, comparing the three study groups. Late PE had higher levels of sTNF-R1 and sTNF-R2 than early PE. No significant differences were found in sEng and TGF-β1 comparing early and late PE. sEng levels were higher in severe PE than in mild PE and no difference was found for TGF-β1, sTNF-R1 and sTNF-R2 levels. There was a positive correlation among sEng, TNF-R1 and sTNF-2 levels. Logistic regression analysis revealed that primiparity and sEng levels are independently associated with the development of PE. Furthermore, sEng levels are independently associated with the disease severity.
These results suggest that pregnancy is a condition associated with higher levels of anti-angiogenic and pro-inflammatory factors than the non-pregnant state and that PE is associated with an imbalance of these factors in the maternal circulation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Encephalitis is caused by autoimmune or infectious agents marked by brain inflammation. Investigations have reported altered concentrations of the cytokines in encephalitis. This study was conducted ...to determine the relationship between encephalitis and alterations of cytokine levels in cerebrospinal fluid (CSF) and serum. We found possibly suitable studies by searching PubMed, Embase, Scopus, and Web of Science, systematically from inception to August 2021. 23 articles were included in the meta-analysis. To investigate sources of heterogeneity, subgroup analysis and sensitivity analysis were conducted. The protocol of the study has been registered in PROSPERO with a registration ID of CRD42021289298. A total of 23 met our eligibility criteria to be included in the meta-analysis. A total of 12 cytokines were included in the meta-analysis of CSF concentration. Moreover, 5 cytokines were also included in the serum/plasma concentration meta-analysis. According to the analyses, patients with encephalitis had higher CSF amounts of IL-6, IL-8, IL-10, CXCL10, and TNF-alpha than healthy controls. The alteration in the concentration of IL-2, IL-4, IL-17, CCL2, CXCL9, CXCL13, and IFN-gamma was not significant. In addition, the serum/plasma levels of the TNF-alpha were increased in encephalitis patients, but serum/plasma concentration of the IL-6, IL-10, CXCL10, and CXCL13 remained unchanged. This meta-analysis provides evidence for higher CSF concentrations of IL-6, IL-8, IL-10, CXCL10, and TNF-alpha in encephalitis patients compared to controls. The diagnostic and prognostic value of these cytokines and chemokines should be investigated in future studies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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