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Abstract Background Metabolic syndrome (MetS) is highly prevalent in individuals with schizophrenia (SZ), leading to negative consequences like premature mortality. Gut dysbiosis, which refers to an imbalance of the microbiota, and chronic inflammation are associated with both SZ and MetS. However, the relationship between gut dysbiosis, host immunological dysfunction, and SZ comorbid with MetS (SZ-MetS) remains unclear. This study aims to explore alterations in gut microbiota and their correlation with immune dysfunction in SZ-MetS, offering new insights into its pathogenesis. Methods and results We enrolled 114 Chinese patients with SZ-MetS and 111 age-matched healthy controls from Zhejiang, China, to investigate fecal microbiota using Illumina MiSeq sequencing targeting 16 S rRNA gene V3-V4 hypervariable regions. Host immune responses were assessed using the Bio-Plex Pro Human Cytokine 27-Plex Assay to examine cytokine profiles. In SZ-MetS, we observed decreased bacterial α-diversity and significant differences in β-diversity. LEfSe analysis identified enriched acetate-producing genera (Megamonas and Lactobacillus), and decreased butyrate-producing bacteria (Subdoligranulum, and Faecalibacterium) in SZ-MetS. These altered genera correlated with body mass index, the severity of symptoms (as measured by the Scale for Assessment of Positive Symptoms and Scale for Assessment of Negative Symptoms), and triglyceride levels. Altered bacterial metabolic pathways related to lipopolysaccharide biosynthesis, lipid metabolism, and various amino acid metabolism were also found. Additionally, SZ-MetS exhibited immunological dysfunction with increased pro-inflammatory cytokines, which correlated with the differential genera. Conclusion These findings suggested that gut microbiota dysbiosis and immune dysfunction play a vital role in SZ-MetS development, highlighting potential therapeutic approaches targeting the gut microbiota. While these therapies show promise, further mechanistic studies are needed to fully understand their efficacy and safety before clinical implementation.

Cerebral vasculitis is a rare but severe complication of Systemic Lupus Erythematosus (SLE), presenting significant challenges in management due to its potential for devastating neurological consequences and poor prognosis. We present a case of an 18-year-old female with known SLE who presented with seizures, declining cognitive function, and unresponsiveness. Neurological examination, laboratory investigations, and radiological imaging supported the diagnosis of cerebral vasculitis secondary to SLE. Despite aggressive immunosuppressive therapy, the patient’s neurological status continued to deteriorate, leading to respiratory failure and multiorgan dysfunction. Ultimately, the patient succumbed to multiorgan failure attributed to severe CNS vasculitis and its complications. This case underscores the importance of early recognition and aggressive management of cerebral vasculitis in SLE while highlighting the need for further research into more effective therapeutic strategies to improve patient outcomes.

Cerebral vasculitis is a rare but severe complication of Systemic Lupus Erythematosus (SLE), presenting significant challenges in management due to its potential for devastating neurological consequences and poor prognosis. We present a case of an 18-year-old female with known SLE who presented with seizures, declining cognitive function, and unresponsiveness. Neurological examination, laboratory investigations, and radiological imaging supported the diagnosis of cerebral vasculitis secondary to SLE. Despite aggressive immunosuppressive therapy, the patient’s neurological status continued to deteriorate, leading to respiratory failure and multiorgan dysfunction. Ultimately, the patient succumbed to multiorgan failure attributed to severe CNS vasculitis and its complications. This case underscores the importance of early recognition and aggressive management of cerebral vasculitis in SLE while highlighting the need for further research into more effective therapeutic strategies to improve patient outcomes.

Schizophrenia is a complex psychiatric condition that may involve immune system dysregulation. Since most putative disease mechanisms in schizophrenia have been derived from genetic association studies and fluid-based molecular analyses, this review aims to summarize the emerging evidence on clinical correlates to immune system dysfunction in this psychiatric disorder. We conclude this review by attempting to develop a unifying hypothesis regarding the relative contributions of microglia and various immune cell populations to the development of schizophrenia. This may provide important translational insights that can become useful for addressing the multifaceted clinical presentation of schizophrenia. [ABSTRACT FROM AUTHOR]

Due to the presence of the ACE2 receptor in different tissues (nasopharynx, lung, nervous tissue, intestine, liver), the COVID-19 disease involves several organs in our bodies. SARS-CoV-2 is able to infect different cell types, spreading to different districts. In the host, an uncontrolled and altered immunological response is triggered, leading to cytokine storm, lymphopenia, and cellular exhaustion. Hence, respiratory distress syndrome (ARDS) and systemic multi-organ dysfunction syndrome (MODS) are established. This scenario is also reflected in the composition of the microbiota, the balance of which is regulated by the interaction with the immune system. A change in microbial diversity has been demonstrated in COVID-19 patients compared with healthy donors, with an increase in potentially pathogenic microbial genera. In addition to other symptoms, particularly neurological, the occurrence of dysbiosis persists after the SARS-CoV-2 infection, characterizing the post-acute COVID syndrome. This review will describe and contextualize the role of the immune system in unbalance and dysbiosis during SARS-CoV-2 infection, from the acute phase to the post-COVID-19 phase. Considering the tight relationship between the immune system and the gut–brain axis, the analysis of new, multidistrict parameters should be aimed at understanding and addressing chronic multisystem dysfunction related to COVID-19. [ABSTRACT FROM AUTHOR]

Background: Tic disorder is a neurodevelopmental disorder characterized by motor and phonic tic symptoms. Tourette syndrome (TS) is a subtype of tic disorder that shows more persistent tic symptoms. The etiological mechanism of TS concerning immune dysfunction remains unclear due to limited evidence, especially for pediatric TS patients. Method: In the present study, a meta-analysis was performed to confirm the identified changes in proinflammatory cytokines and T cells of pediatric TS patients. A total of five databases, including PubMed, Web of Science, PsycINFO, Google Scholar and the China National Knowledge Infrastructure (CNKI), were used for the literature search. The standardized mean difference (SMD) and mean difference (MD) with a 95% confidence interval (CI) were used to present the effect size of each type of proinflammatory cytokine and T cell. Sensitivity analysis, subgroup analysis and meta-regression analysis were used to explore the heterogeneity of the meta-analysis. This meta-analysis was registered in the International Platform of Registered Systematic Review and Meta-analysis Protocols (number: INPLASY2021110079). Results: In the 25 studies included in this meta-analysis, thirteen studies focused on the levels of T cells, and twelve studies focused on the levels of proinflammatory cytokines. Based on the random-effects model, the pooled MDs are -1.45 (95% CI: -3.44, 0.54) for CD3 cells, -4.44 (95% CI: -6.80, -2.08) for CD4 cells, and 1.94 (95% CI: -0.08, 3.97) for CD8 cells. The pooled SMDs are1.36 for IL-6 (95% CI: 0.00, 2.72) and 2.39 for tumor necrosis factor alpha (TNF-α) (95% CI: 0.93, 3.84). Conclusion: We provided evidence of immune dysfunction in pediatric TS patients, with elevated levels of particular proinflammatory cytokines and disproportionate changes in T-cell subpopulations. Small to large effect sizes were identified for increased IL-6 levels as well as a reduced number of T helper cells, while a large effect size was identified for increased TNF-α levels. These results indicate a close association between peripheral immune activation and TS. However, the most direct and meaningful interaction between peripheral immune status and microglial activation in the central nervous system in TS patients requires further exploration. [ABSTRACT FROM AUTHOR]

BackgroundTic disorder is a neurodevelopmental disorder characterized by motor and phonic tic symptoms. Tourette syndrome (TS) is a subtype of tic disorder that shows more persistent tic symptoms. The etiological mechanism of TS concerning immune dysfunction remains unclear due to limited evidence, especially for pediatric TS patients.MethodIn the present study, a meta-analysis was performed to confirm the identified changes in proinflammatory cytokines and T cells of pediatric TS patients. A total of five databases, including PubMed, Web of Science, PsycINFO, Google Scholar and the China National Knowledge Infrastructure (CNKI), were used for the literature search. The standardized mean difference (SMD) and mean difference (MD) with a 95% confidence interval (CI) were used to present the effect size of each type of proinflammatory cytokine and T cell. Sensitivity analysis, subgroup analysis and meta-regression analysis were used to explore the heterogeneity of the meta-analysis. This meta-analysis was registered in the International Platform of Registered Systematic Review and Meta-analysis Protocols (number: INPLASY2021110079).ResultsIn the 25 studies included in this meta-analysis, thirteen studies focused on the levels of T cells, and twelve studies focused on the levels of proinflammatory cytokines. Based on the random-effects model, the pooled MDs are -1.45 (95% CI: -3.44, 0.54) for CD3 cells, -4.44 (95% CI: -6.80, -2.08) for CD4 cells, and 1.94 (95% CI: -0.08, 3.97) for CD8 cells. The pooled SMDs are1.36 for IL-6 (95% CI: 0.00, 2.72) and 2.39 for tumor necrosis factor alpha (TNF-α) (95% CI: 0.93, 3.84).ConclusionWe provided evidence of immune dysfunction in pediatric TS patients, with elevated levels of particular proinflammatory cytokines and disproportionate changes in T-cell subpopulations. Small to large effect sizes were identified for increased IL-6 levels as well as a reduced number of T helper cells, while a large effect size was identified for increased TNF-α levels. These results indicate a close association between peripheral immune activation and TS. However, the most direct and meaningful interaction between peripheral immune status and microglial activation in the central nervous system in TS patients requires further exploration.

Exposure through arsenic-contaminated air and food caused by the burning of coal is a major environmental public health concern in Guizhou Province of China. Previous studies have shown that immunological dysfunction is involved in the pathogenesis and carcinogenesis of arsenic; however, knowledge regarding effective prevention measures have not been fully examined. The effect of Ginkgo biloba extract (EGb761) on arsenic-induced skin damage of human immortalized keratinocyte cells (HaCaT) was first evaluated in this study. The results showed that 200 μg/mL EGb761 can reduce the expression of miR-155-5p, and the indicators reflecting arsenic-induced skin damage (Krt1, Krt6c and Krt10) in arsenic-exposed cells (P < 0.05), the expression levels of NF-AT1; the indicators reflecting arsenic-induced immunological dysfunction (IL-2, IFN-γ) in cells; and the levels of secreted IL-2 and IFN-γ in cell supernatants were significantly increased (P < 0.05). Further randomized controlled double-blind experiments showed that compared to the placebo control group, the expression level of miR-155-5p in the plasma of the Ginkgo biloba intervention group, the indicators in the serum reflecting arsenic-induced skin damage (Krt1, Krt6c, and Krt10) and the epithelial-mesenchymal transformation (EMT) vimentin were significantly reduced (P < 0.05), but the levels of NF-AT1 and the indicators reflecting arsenic-induced immunological dysfunction (IL-2, IFN-γ) and EMT (E-cadherin) in serum were significantly increased (P < 0.05). Our study provides some limited evidence that Ginkgo biloba L. can increase the expression of NF-AT1 by downregulating the level of miR-155-5p, alleviating immunological dysfunction, and decreasing the expression of EMT biomarkers, thus indirectly improving arsenic-induced skin damage. [ABSTRACT FROM AUTHOR]

Sepsis-induced acute kidney injury (AKI) is a frequent complication in critically ill patients, refractory to conventional treatments. Aberrant activation of innate immune system may affect organ damage with poor prognosis for septic patients. Here, we investigated the efficacy of polymethyl methacrylate membrane (PMMA)-based continuous hemofiltration (CVVH) in modulating systemic and tissue immune activation in a swine model of LPS-induced AKI. After 3 h from LPS infusion, animals underwent to PMMA-CVVH or polysulfone (PS)-CVVH. Renal deposition of terminal complement mediator C5b-9 and of Pentraxin-3 (PTX3) deposits were evaluated on biopsies whereas systemic Complement activation was assessed by ELISA assay. Gene expression profile was performed from isolated peripheral blood mononuclear cells (PBMC) by microarrays and the results validated by Real-time PCR. Endotoxemic pigs presented oliguric AKI with increased tubulo-interstitial infiltrate, extensive collagen deposition, and glomerular thrombi; local PTX-3 and C5b-9 renal deposits and increased serum activation of classical and alternative Complement pathways were found in endotoxemic animals. PMMA-CVVH treatment significantly reduced tissue and systemic Complement activation limiting renal damage and fibrosis. By microarray analysis, we identified 711 and 913 differentially expressed genes with a fold change >2 and a false discovery rate

Sepsis-induced acute kidney injury (AKI) is a frequent complication in critically ill patients, refractory to conventional treatments. Aberrant activation of innate immune system may affect organ damage with poor prognosis for septic patients. Here, we investigated the efficacy of polymethyl methacrylate membrane (PMMA)-based continuous hemofiltration (CVVH) in modulating systemic and tissue immune activation in a swine model of LPS-induced AKI. After 3 h from LPS infusion, animals underwent to PMMA-CVVH or polysulfone (PS)-CVVH. Renal deposition of terminal complement mediator C5b-9 and of Pentraxin-3 (PTX3) deposits were evaluated on biopsies whereas systemic Complement activation was assessed by ELISA assay. Gene expression profile was performed from isolated peripheral blood mononuclear cells (PBMC) by microarrays and the results validated by Real-time PCR. Endotoxemic pigs presented oliguric AKI with increased tubulo-interstitial infiltrate, extensive collagen deposition, and glomerular thrombi; local PTX-3 and C5b-9 renal deposits and increased serum activation of classical and alternative Complement pathways were found in endotoxemic animals. PMMA-CVVH treatment significantly reduced tissue and systemic Complement activation limiting renal damage and fibrosis. By microarray analysis, we identified 711 and 913 differentially expressed genes with a fold change >2 and a false discovery rate <0.05 in endotoxemic pigs and PMMA-CVVH treated-animals, respectively. The most modulated genes were Granzyme B, Complement Factor B, Complement Component 4 Binding Protein Alpha, IL-12, and SERPINB-1 that were closely related to sepsis-induced immunological process. Our data suggest that PMMA-based CVVH can efficiently modulate immunological dysfunction in LPS-induced AKI. [ABSTRACT FROM AUTHOR]

Sepsis is a major cause of morbidity and mortality worldwide despite numerous attempts to identify effective therapeutics. While some sepsis deaths are attributable to tissue damage caused by inflammation, most mortality is the result of prolonged immunosuppression. Ex vivo, immunosuppression during sepsis is evidenced by a sharp decrease in the production of pro-inflammatory cytokines by T cells and other leukocytes and increased lymphocyte apoptosis. This allows suppressive cytokines to exert a greater inhibitory effect on lymphocytes upon antigen exposure. While some pre-clinical and clinical trials have demonstrated utility in targeting cytokines that promote lymphocyte survival, this has not led to the approval of any therapies for clinical use. As cytokines with a more global impact on the immune system are also altered by sepsis, they represent novel and potentially valuable therapeutic targets. Recent evidence links interleukin (IL)-17, IL-27, and IL-33 to alterations in the immune response during sepsis using patient serum and murine models of peritonitis and pneumonia. Elevated levels of IL-17 and IL-27 are found in the serum of pediatric and adult septic patients early after sepsis onset and have been proposed as diagnostic biomarkers. In contrast, IL-33 levels increase in patient serum during the immunosuppressive stage of sepsis and remain high for more than 5 months after recovery. All three cytokines contribute to immunological dysfunction during sepsis by disrupting the balance between type 1, 2, and 17 immune responses. This review will describe how IL-17, IL-27, and IL-33 exert these effects during sepsis and their potential as therapeutic targets.

Sepsis is a major cause of morbidity and mortality worldwide despite numerous attempts to identify effective therapeutics. While some sepsis deaths are attributable to tissue damage caused by inflammation, most mortality is the result of prolonged immunosuppression. Ex vivo , immunosuppression during sepsis is evidenced by a sharp decrease in the production of pro-inflammatory cytokines by T cells and other leukocytes and increased lymphocyte apoptosis. This allows suppressive cytokines to exert a greater inhibitory effect on lymphocytes upon antigen exposure. While some pre-clinical and clinical trials have demonstrated utility in targeting cytokines that promote lymphocyte survival, this has not led to the approval of any therapies for clinical use. As cytokines with a more global impact on the immune system are also altered by sepsis, they represent novel and potentially valuable therapeutic targets. Recent evidence links interleukin (IL)-17, IL-27, and IL-33 to alterations in the immune response during sepsis using patient serum and murine models of peritonitis and pneumonia. Elevated levels of IL-17 and IL-27 are found in the serum of pediatric and adult septic patients early after sepsis onset and have been proposed as diagnostic biomarkers. In contrast, IL-33 levels increase in patient serum during the immunosuppressive stage of sepsis and remain high for more than 5 months after recovery. All three cytokines contribute to immunological dysfunction during sepsis by disrupting the balance between type 1, 2, and 17 immune responses. This review will describe how IL-17, IL-27, and IL-33 exert these effects during sepsis and their potential as therapeutic targets. [ABSTRACT FROM AUTHOR]

Activation of extracellular signal-regulated kinase (ERK) signalling, alteration of the uterine microenvironment and a reduction in human chorionic gonadotrophin production have been linked with fetal trisomy 16-induced early embryonic death (EED). However, the detailed biological mechanism of EED remains unclear. Using quantitative proteomics we successfully screened differentially expressed proteins in the villous tissues from patients with EED and fetal trisomy 16 (EEDT16), patients with EED but normal fetal chromosomes (EEDNC) and patients undergoing elective abortion with normal fetal chromosomes (EANC) as the reference group. Compared with the reference group, we identified 337 and 220 differentially expressed proteins in EEDT16 patients and EEDNC patients respectively; these were involved in critical biological processes including immune response, superoxide metabolism, inflammatory responses and so on. We found that differential expression of immunological function-related molecules, such as human leukocyte antigen-g (HLA-G), HLA-C, Fc Fragment Of IgG Receptor III (FcγR III), also named CD16, interleukin 18 (IL-18) and transforming growth factor β1 (TGF-β1), might induce EED in both EEDT16 and EEDNC patients. More severe immunological dysfunction was observed in EEDT16 patients than that in EEDNC patients. Furthermore, differential expression of implantation and invasion-related molecules, such as cytochrome b-245 light chain (CYBA), neutrophil cytosol factor 2 (NCF2), Mitogen-activated protein kinase kinase kinase 4 (MAP3K4), matrix metalloproteinase 2 (MMP2), MMP9 and tumour necrosis factor α (TNF-α) might induce EED in both EEDT16 and EEDNC patients, although more severe dysfunction in the implantation and invasion ability of villous tissues was observed in EEDT16 patients. Since the detailed biological mechanism of EEDT16 remains unclear, this study used quantitative proteomics to screen differentially expressed proteins in the villous tissues from patients with EEDT16, EEDNC and EANC. Dysfunction in immunological function and in the implantation and invasion ability was observed in EEDT16 and EEDNC patients. [ABSTRACT FROM AUTHOR]

Although numerous studies have demonstrated that titanium dioxide nanoparticles (TiO2 NPs) can be accumulated in various animal organs and can cause toxicity, there is currently only limited data regarding reproductive toxicity especially on the toxic mechanisms of TiO2 NPs in Sertoli cells. In order to investigate the mechanism of reproductive toxicity, primary cultured rat Sertoli cells were exposed to 5, 15, or 30 μg/mL TiO2 NPs for 24 h, and TiO2 NPs internalization, expression of PKC (p-PKC) and p38 MAPK (p-p38 MAPK) as well as calcium homeostasis were examined. Our findings demonstrated that TiO2 NPs crossed the membrane into the cytoplasm or nucleus, and significantly suppressed cell viability of primary cultured rat Sertoli cells in a concentration-dependent manner. Furthermore, immunological dysfunction caused by TiO2 NPs was involved in the increased expression of NF-κB, TNF-α, and IL-1β, and decreased IκB expression. TiO2 NPs significantly decreased Ca2+-ATPase and Ca2+/Mg2+-ATPase activity and enhanced intracellular Ca2+ levels, and up-regulated the expression of p-PKC and p-p38 MAPK in a dose-dependent manner in primary cultured rat Sertoli cells. Taken together, these findings indicate that TiO2 NPs may induce immunological dysfunction of primary cultured rat Sertoli cells by stimulating the Ca2+/PKC/p38 MAPK cascade, which triggers NF-κB activation and ultimately induces the expression of inflammatory cytokines in primary cultured rat Sertoli cells. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1374-1382, 2017. [ABSTRACT FROM AUTHOR]

Very few cases of patients with myasthenia gravis (MG) who later developed amyotrophic lateral sclerosis (ALS) have been described, although some studies showed that significantly more cases than expected have ALS associated with a prior diagnosis of autoimmune diseases. Our aim was to investigate whether the association of ALS and MG was higher than expected in a population-based study and to describe the clinical features characterizing these patients. In Emilia Romagna Region of Italy, a prospective registry has been collecting all incident ALS cases since 1.1.2009. For each patient, detailed clinical information is collected by caring physicians, including comorbidities. From 1.1.2009 to 31.12.2014, 671 patients were diagnosed with ALS; five patients (0.75%) were also affected by MG. Considering Western Countries incidence rates the occurrence of both the diseases should be a really exceptional event (7.5/109), compared to our findings (1.87/107) (p < 0.01). Patients with ALS and MG had more frequently a bulbar onset and a fast progressive course. These cases of ALS after MG raise the possibility of potential shared immunological dysfunctions, which may be expression of common pathogenic mechanisms, as well as of shared disease-course modulating events. [ABSTRACT FROM AUTHOR]

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We report a novel missense mutation p.T145K in the insulin-like growth factor (IGF) acid-labile subunit (IGFALS) gene identified in a Turkish patient with normal growth, transient pancytopenic episodes and signs of immunological dysfunction. Because of recurrent cutaneous mycoses and absence of pubertal development until the age of 14.75 years we determined several endocrine parameters in order to rule out autoimmune-polyendocrine syndromes. Despite a normal height between the 25th and 50th percentile we found severely decreased IGF-1 and undetectably low IGFBP-3 levels. Laboratory signs of immunological dysfunction included reduced total lymphocyte count with diminished B and T helper cell fractions, decreased serum concentrations of IgM and IgG subclass 4, and elevated antinuclear antibody and anti-dsDNA titers as well as persistently high interleukin-2-receptor levels. Further endocrine work-up revealed elevated fasting insulin and undetectably low ALS serum levels, leading to the diagnosis of ALS deficiency. Sequencing of the coding region of the IGFALS gene showed a novel homozygous missense mutation (c.434C>A; p.T145K). Since immunological abnormalities have not been reported in more than 20 ALS-deficient patients so far and our patient was born to consanguineous parents, a second autosomal recessive defect is likely to underlie the immunological phenotype, although a causative role of IGFALS p.T145K cannot be entirely ruled out. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Introduction: Pegylated interferon and ribavirin (PEG-IFN/RBV) therapy for recurrent hepatitis C after liver transplantation (LT) is associated with a lower sustained virological response (SVR) rate as well as more frequent side effects compared to non-transplant patients. We aimed to determine the incidence and clinical characteristics of LT recipients with recurrent hepatitis C who developed immunological dysfunction (ID) during or after PEG-IFN/RBV therapy and to assess its impact on patient and graft survival. Methods: Seventy-four deceased donor LT recipients with histological recurrence of hepatitis C were treated with PEG-IFN/RBV from 1/00 to 12/08. ID was defined as biopsy-proven rejection or moderate plasma cell hepatitis. Patients were followed up until death, re-LT or 30 September 2011. Results: Twelve patients (16 %) had ID, 8 (10.7 %) had cholestasis without ID, while 54 had no ID/cholestasis during or after discontinuation of PEG-IFN/RBV therapy. Biopsy-proven acute cellular rejection prior to (hazard ratio = 4.87, p = 0.009) and type of immunosuppression at the time of initiation of PEG-IFN/RBV were the only independent predictors of ID. Patients who were on tacrolimus at the time of initiation of PEG-IFN/RBV had a significantly lower risk of ID compared to those who were on cyclosporine (HR 0.254, p = 0.023). Patients with ID had a trend toward a lower SVR rate (25 vs. 54 %, p = 0.18) and a significantly higher rate of graft failure (33 vs. 4 %, p = 0.004) compared to patients with no ID/cholestasis. Conclusions: ID is common during or after PEG-IFN/RBV therapy for recurrent hepatitis C and frequently associated with decreased graft survival, trending toward low rates of SVR. Careful monitoring of liver biochemistries during or after PEG-IFN/RBV therapy with a low threshold to biopsy patients and particularly those receiving cyclosporine-based immunosuppression may improve outcomes in these patients. [ABSTRACT FROM AUTHOR]

Abstract: Tourette syndrome (TS) is a neurodevelopmental disorder associated with motor and phonic tics. While the aetiology has been debated, no single causative agent has been implicated in the development of TS. This systematic review aims to evaluate original studies investigating the role of immunological abnormalities in both tic expression and susceptibility to infection in patients with TS. A comprehensive literature search using the databases ‘EMBase’, ‘PsycInfo’, ‘Pubmed’, ‘Thomson World of Science’ and ‘Medline’ generated 21 original studies that met inclusion criteria. Results found that abnormalities related to lymphocytes, cytokines, antineuronal antibodies and immunoglobulins were relatively common in TS populations. In addition, abnormalities in immunoglobulin concentrations could be linked to a propensity to the development of infections in selected individuals with TS. While these results support the initial research question, further studies with fewer confounding factors are required to establish a definite association between immune dysfunction, TS and infection. [Copyright &y& Elsevier]

Tourette syndrome (TS) is a condition characterized by tics produced because of neuropsychiatric malfunctioning occurring in childhood, which becomes less severe in adulthood, followed by a difference in the severity of tics between two persons. TS is a diverse variable in which symptoms vary in different patients. It is associated with comorbidities like obsessive-compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), and depression, and hampers the quality of life. Comorbid disorders must be investigated and treated as part of the clinical approach for all TS patients. Clinicians should be aware of the infrequent but serious neurological problems that can occur in these patients and recommend aggressively treating tics. Currently, there is more emphasis on symptom-based treatments by medicines, but as etiological knowledge improves, we will divert to disease-modifying medications in the future. Behavioral, pharmacological, and surgical methods can treat TS. Neuroleptics, other drugs, and behavioral therapies are the first-line options. Deep brain stimulation is evolving but has its pros and cons. The main focus of this review is on tics characteristics, how to manage and assess them, and limitations in the clinical spectrum., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Ramteke et al.)

Abstract: An inappropriate glycogen accumulation in preeclamptic placentas was described as secondary to biochemical alterations. Insulin resistance is widely accepted to be associated with preeclampsia, although its basis remain unclear. A family of putative insulin mediators, namely inositol phosphoglycans, were described to exert many insulin-like effects on lipid and glucose metabolism. A definite association between the P-type mediator (P-IPG) and preeclampsia was reported, being increased in placenta, urine, amniotic fluid and cord blood from human preeclamptic pregnancies. A strong link exists between insulin resistance and inflammation. Clear features of insulin resistance and systemic inflammatory activation were described in preeclampsia. It may be a consequence of the immunological dysfunction that occurs in preeclampsia that is temporized during sperm exposure and co-habitation which confuses the maternal immune network to perceive ‘danger’. The over-expression of P-IPG during preeclampsia may be a counter-regulatory mechanism to insulin resistance since these molecules mimic insulin action. Besides, the lipidic form of P-IPG was reported to be similar to endotoxins, and may represent the ‘danger signa’. We propose here a novel working theory on insulin resistance and preeclampsia. [Copyright &y& Elsevier]

The immunosuppressive therapy in systemic vasculitis leads to immunological dysfunctions. The consequences of granulocytopenia and cellular immune deficits are infections of different etiologies in up to 50% of vasculitis patients. The leading severe infections are sepsis and pneumonia induced by a broad spectrum of pathogens (extra- and intra-cellular growing bacteria, fungi, parasites and viruses). The contribution of infections to the mortality of vasculitis patients is important and should induce early and careful control of these events. [ABSTRACT FROM AUTHOR]

Background: In the present study, immunological alterations were investigated as one possible factor contributing towards the pathogenesis of schizophrenia. Specifically cellular changes, deviating cytokine production and interfering variables were studied in order to improve our understanding of how these factors interact. Method: 44 acutely ill schizophrenics were compared with matched healthy controls. Cell numbers were determined by flow cytometry and cytokine production by whole blood assay and ELISA. A criss-cross technique was employed for the assessment of interfering serum factors. Results: Cell counts for leukocytes, lymphocytes, pan T cells, activated T cells and the absolute B cell count of the schizophrenic patients were all within normal limits. The absolute and relative monocyte counts, the number of IL-2 receptor carrying T cells and the relative B cell count were slightly elevated. IL-2 and IFN-γ production were increased while IL-10 production, the sIL-2R and cortisol levels remained unchanged. No interfering serum factors were detected. Conclusion: The deficient production of TH-1 cytokines in schizophrenia is not due either to a changed number of immunocompetent cells or to a counterregulation of the TH-2 cytokine IL-10. Serum factors in in vitro testing are not responsible for the deficient cytokine production. [ABSTRACT FROM AUTHOR]

Chronic tic disorder and Tourette syndrome are common childhood-onset neurological diseases. However, the pathophysiology underlying these disorders is unclear, and most studies have focused on the disinhibition of the corticostriatal–thalamocortical circuit. An autoimmune dysfunction has been proposed in the pathogenetic mechanism of Tourette syndrome and related neuropsychiatric disorders such as obsessive–compulsive disorder, autism, and attention-deficit/hyperactivity disorder. This is based on evidence from animal model studies and clinical findings. Herein, we review and give an update on the clinical characteristics, clinical evidence, and genetic studies in vitro as well as animal studies regarding immune dysfunction in Tourette syndrome. [ABSTRACT FROM AUTHOR]

Environmental exposure to arsenic is a major public health challenge worldwide. In detailing the hallmark signs of chronic arsenic exposure, previous studies have shown that epigenetic and immune dysfunction are associated with arsenic-induced skin lesions; however, knowledge regarding interactions between the mechanisms listed above is limited. In this study, a total of 106 skin samples were collected over the past 20 years. Based on the presence or absence of high arsenic exposure, the participants were divided into arsenic exposure (72) and reference (34) groups. Additionally, the arsenic exposure group was further divided into the non-cancer group (31, including skin hyperpigmentation and hyperkeratosis) and the skin cancer group (41, including Bowen's disease, basal cell carcinoma and squamous cell carcinoma) according to a skin histopathological examination. First, the associations among miR-155, NF-AT1 with immunological dysfunction and arsenic-induced skin lesions and carcinogenesis were confirmed using these skin samples. In the arsenic-exposed group, miR-155–5p, keratin 1(Krt1), keratin 10 (Krt10), and keratin 6c (Krt6c) were significantly increased in the skin (p < 0.05), while NF-AT1, interleukin-2 (IL-2), and interferon-γ (IFN-γ) were significantly decreased (p < 0.05). Clear correlations were observed among these factors (p < 0.05). In immortalized human keratinocytes, silencing and overexpression of NF-AT1 could alter the expression and secretion of immunological dysfunction indicators (IL-2 and IFN-γ) that are induced by arsenic exposure (p < 0.05); however, miR-155–5p levels did not change significantly (p > 0.05). The miR-155–5p mimic and inhibitor could regulate the NF-AT1-mediated immunological dysfunction caused by arsenic (p < 0.05). Our study provides some limited evidence that miR-155–5p regulates the NF-AT1-mediated immunological dysfunction that is involved in the pathogenesis and carcinogenesis of arsenic. The second major finding was that Krt1 and Krt10 are markers of hyperkeratosis caused by arsenic, and Krt6c is a potential biomarker that can reflect arsenic carcinogenesis. Image 1 • miR-155 regulates NF-AT1-mediated immunological dysfunction. • Krt1 and Krt10 are markers of hyperkeratosis caused by arsenic. • Krt6c is a potential biomarker that reflects the carcinogenesis of arsenic. miR-155–5p regulates the NF-AT1-mediated immunological dysfunction involved in the pathogenesis and carcinogenesis of arsenic. [ABSTRACT FROM AUTHOR]

Introduction : Autoimmune diseases (ADs) are idiopathic and heterogeneous disorders with contentious pathophysiology. Great strides have been made in epigenetics and its involvement in ADs. Zeste homolog 2 (EZH2) has sparked extensive interest because of its pleiotropic roles in distinct pathologic contexts. Areas covered : This review summarizes the epigenetic functions and the biological significance of EZH2 in the etiology of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), inflammatory bowel disease (IBD), multiple sclerosis (MS), and systemic sclerosis (SSc). A brief recapitulation of the therapeutic potential of EZH2 targeting is provided. Expert opinion : There are questions marks and controversies surrounding the feasibility and safety of EZH2 targeting; it is recommended in RA and SLE, but queried in T1D, IBD, MS, and SSc. Future work should focus on contrast studies, systematic analyses and preclinical studies with optimizing methodologies. Selective research studies conducted in a stage-dependent manner are necessary because of the relapsing-remitting clinical paradigms.

Although numerous studies have demonstrated that titanium dioxide nanoparticles (TiO 2 NPs) can be accumulated in various animal organs and can cause toxicity, there is currently only limited data regarding reproductive toxicity especially on the toxic mechanisms of TiO 2 NPs in Sertoli cells. In order to investigate the mechanism of reproductive toxicity, primary cultured rat Sertoli cells were exposed to 5, 15, or 30 μg/mL TiO 2 NPs for 24 h, and TiO 2 NPs internalization, expression of PKC (p-PKC) and p38 MAPK (p-p38 MAPK) as well as calcium homeostasis were examined. Our findings demonstrated that TiO 2 NPs crossed the membrane into the cytoplasm or nucleus, and significantly suppressed cell viability of primary cultured rat Sertoli cells in a concentration-dependent manner. Furthermore, immunological dysfunction caused by TiO 2 NPs was involved in the increased expression of NF-κB, TNF-α, and IL-1β, and decreased IκB expression. TiO 2 NPs significantly decreased Ca 2+ -ATPase and Ca 2+ /Mg 2+ -ATPase activity and enhanced intracellular Ca 2+ levels, and up-regulated the expression of p-PKC and p-p38 MAPK in a dose-dependent manner in primary cultured rat Sertoli cells. Taken together, these findings indicate that TiO 2 NPs may induce immunological dysfunction of primary cultured rat Sertoli cells by stimulating the Ca 2+ /PKC/p38 MAPK cascade, which triggers NF-κB activation and ultimately induces the expression of inflammatory cytokines in primary cultured rat Sertoli cells. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1374-1382, 2017., (© 2017 Wiley Periodicals, Inc.)

Major trauma induces profound immune dysfunction, which subsequently results in sepsis and multiple organ dysfunction syndromes (MODS). The functionally conducive immune cells are of paramount important in the early recovery and development of the post-traumatic organ failure. In this study, we investigated the immune deregulation after severe trauma by means of detecting the differentiation of CD4(+) T cells. Seven male patients with thoracic trauma (aged 29.8 ± 7.6 years) hospitalized in the Intensive Care Units (ICU) in our hospital were enrolled in the study. Peripheral blood was collected from all the patients on the 1st, 7th, 14th and 21st day of admission, respectively. Flow cytometry was carried out to determine the percentage of CD4(+) T cells differentiated into Th1, Th2, Th17 and Treg subsets, based on which the ratios of Th1/Th2 and Th17/Treg were also calculated. Twenty-five healthy male individuals (aged 34 ± 7 years) in the hospital in the same period of time served as controls. The frequencies of all the four subsets in the traumatic patients showed significant dynamic changes compared with those of the controls at the defined time points. The ratios of Th1/Th2 and Th17/Treg showed significant decrease at the study interval. Notably, the value of Th1/Th2 was significantly higher (P=0.004) in the trauma group than that of control group on the 1st day after admission, which was reversed on the 14th day (P=0.014). The imbalance of Th1/Th2 and Th17/Treg at the present study all reflected the immune dysfunction of CD4 T cells followed by the severe thoracic trauma.