Search Results (120)

Schizophrenia is a challenging multifactorial neuropsychiatric disease that involves interactions between genetic susceptibility and environmental insults. Increasing evidence implicates viral infections as significant environmental contributors, particularly during sensitive neurodevelopmental periods. This review synthesises current findings on the viral hypothesis of schizophrenia, encompassing a wide array of neurotropic viruses, including influenza viruses, herpesviruses (HSV-1 and 2, CMV, VZV, EBV, HHV-6 and 8), hepatitis B and C viruses, HIV, HERVs, HTLV, Zika virus, BoDV, coronaviruses (including SARS-CoV-2), and others. These pathogens can contribute to schizophrenia through mechanisms such as direct microinvasion, persistent central nervous system infection, immune-mediated neuroinflammation, molecular mimicry, and the disturbance of the blood–brain barrier. Prenatal exposure to viral infections can trigger maternal immune activation, resulting in cytokine-mediated alterations in the neurological development of the foetus that persist into adulthood. Genetic studies highlight the role of immune-related loci, including major histocompatibility complex polymorphisms, in modulating susceptibility to infection and neurodevelopmental outcomes. Clinical data also support the “mild encephalitis” hypothesis, suggesting that a subset of schizophrenia cases involve low-grade chronic neuroinflammation. Although antipsychotics have some immunomodulatory effects, adjunctive anti-inflammatory therapies show promise, particularly in treatment-resistant cases. Despite compelling associations, pathogen-specific links remain inconsistent, emphasising the need for longitudinal studies and integrative approaches such as viromics to unravel causal relationships. This review supports a “multi-hit” model in which viral infections interfere with hereditary and immunological susceptibilities, enhancing schizophrenia risk. Elucidating these virus–immune–brain interactions may facilitate the discovery of biomarkers, targeted prevention, and novel therapeutic strategies for schizophrenia. Full article

Alzheimer’s Disease (AD) is a multifactorial process. Amyloid plaque formation constitutes the main characteristic of the disease. Despite the identification of numerous factors associated with AD, the mechanism remains unclear in several aspects. Disturbances in intestinal and blood–brain barrier (BBB) penetration, observed in AD, may facilitate immunologic response to food-derived antigens. In the present study, antibodies against egg albumin, bovine-casein, and N-Glycolyl-Neuraminic acid (Neu5Gc) were measured in the cerebrospinal fluid (CSF) and serum of the patients using an enzyme-linked immunosorbent assay (ELISA). Zero anti-Neu5Gc and low concentrations of anti-casein antibodies were detected. Increased anti-native egg albumin antibodies were present in the serum of patients of all stages with 65% positivity (p < 0.001) in mild disease and a higher percentage in females (81.9%, p < 0.001). Lower serum positivity to anti-denatured egg albumin antibodies was observed, showing a gradual increase with severity and higher prevalence also in females. In the CSF, anti-native and anti-denatured egg albumin antibodies were mainly observed in severely ill patients with accumulative positivity to either antigen, reaching 61.8% in severe vs. 15% in mild disease (p < 0.001). Increased values were mainly observed in males. Anti-egg albumin antibodies may be implicated in the disease mechanism through sequence/structural similarity with human proteins, mainly serpins, and it would be worth consideration in further investigations and therapeutic strategies. Full article

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrosing lung disease characterized by chronic inflammation, vascular remodeling, and immune dysregulation. COVID-19, caused by SARS-CoV-2, shares several systemic immunohematologic disturbances with IPF, including cytokine storms, endothelial injury, and prothrombotic states. Unlike general comparisons of viral infections and chronic lung disease, this review offers a focused analysis of the shared hematologic and immunologic mechanisms between COVID-19 and IPF. Our aim is to better understand how SARS-CoV-2 infection may worsen disease progression in IPF and identify converging pathophysiological pathways that may inform clinical management. We conducted a narrative synthesis of the peer-reviewed literature from PubMed, Scopus, and Web of Science, focusing on clinical, experimental, and pathological studies addressing immune and coagulation abnormalities in both COVID-19 and IPF. Both diseases exhibit significant overlap in inflammatory and fibrotic signaling, particularly via the TGF-β, IL-6, and TNF-α pathways. COVID-19 amplifies coagulation disturbances and endothelial dysfunction already present in IPF, promoting microvascular thrombosis and acute exacerbations. Myeloid cell overactivation, impaired lymphocyte responses, and fibroblast proliferation are central to this shared pathophysiology. These synergistic mechanisms may accelerate fibrosis and increase mortality risk in IPF patients infected with SARS-CoV-2. This review proposes an integrative framework for understanding the hematologic and immunologic convergence of COVID-19 and IPF. Such insights are essential for refining therapeutic targets, improving prognostic stratification, and guiding early interventions in this high-risk population. Full article

Background: Depression is a mental disorder characterized by a combination of somatic and cognitive disturbances, in which a predominantly sad or irritable mood significantly interferes with the patient’s functioning. This condition can affect individuals of all ages and socioeconomic backgrounds. Currently, various studies are exploring a possible association between oral dysbiosis and depression—an increasingly relevant topic, as confirmation of such a relationship could position the oral microbiota as a potential etiological or diagnostic factor for depression, given its accessibility and ease of analysis. Aim: To present a qualitative synthesis of studies addressing how oral dysbiosis influences the onset of depression, as well as the importance of controlling this alteration of the oral microbiota to aid in the prevention of the disease. Materials and Methods: The PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) outline the procedures to be followed for conducting this systematic review. The article search was carried out on 22 May 2025, across the PubMed, Scopus, Scielo, and The Cochrane Library databases, using terms related to “depression” and “oral dysbiosis”. Studies published within the last 10 years that addressed the potential association between oral dysbiosis, and depression were included. Furthermore, the quality of the studies was assessed using various tools depending on their design: the Newcastle–Ottawa Scale (NOS) was applied to case-control and cohort studies; the Joanna Briggs Institute (JBI) critical appraisal checklist was used for cross-sectional studies; and experimental studies were evaluated using SYRCLE’s Risk of Bias Tool. Results: A total of eleven studies were included in this systematic review. The findings suggest the presence of alterations in the oral microbiota of patients with depression, particularly in terms of composition, structure, and diversity. A reduction in alpha diversity—an indicator of local microbial balance—was observed, along with an increase in beta diversity, indicating greater inter-individual variability, which may be associated with inflammatory processes or immunological dysfunctions. Some studies reported differing results, which may be attributable to methodological variability regarding study design, or the populations sampled. Conclusions: This systematic review suggests that the oral microbiome could be considered a diagnostic biomarker and therapeutic target for depression, as the analyzed studies demonstrate a significant association between oral microbiome dysbiosis and this mental disorder. However, the methodological heterogeneity among the studies highlights the need for further research to confirm this potential relationship. Full article

Introduction: Unilateral cleft lip and palate (CLP) is a severe orofacial birth defect characterized by improper fusion of facial parts and disturbed orofacial functions. The defect manifests as a gap in the orofacial tissues that is accompanied by defective healing patterns and chronic inflammation. The immune system’s defense factors modulate immunity, inflammation, and healing. Angiogenesis factors control blood-vessel formation. Therefore, these factors are vital in the immunological assessment and understanding of CLP morphopathogenesis. The aim of the study is to assess the distribution of vascular endothelial growth factor (VEGF), transforming growth factor beta 1 (TGF- β1), the total macrophage population and the M2 subtype, heat-shock proteins (HSP) 60 and 70, and nuclear factor kappa B (NF-κB) p50 and p65 subtypes in the affected tissue of children with CLP before and during primary dentition. Materials and Methods: Tissue samples were obtained from 15 patients aged from 3 to 8 months during veloplastic surgery. Five controls were used for comparison of data. Immunohistochemistry, light microscopy, semi-quantitative evaluation (from 0 to ++++), and statistics (Mann–Whitney U test and Spearman’s rank correlation) were used to evaluate the data for statistically significant differences and correlations between the groups. Results: Epithelial tissues affected by CLP presented with statistically significant increases in levels of VEGF (p = 0.007), total macrophages (p = 0.007), HSP60 (p = 0.001), NF-κB p65 (p = 0.000), and p50 (p = 0.045), but with a decrease in M2 macrophages (p = 0.025). Blood vessels in CLP-affected tissues showed a statistically significant increase in levels of NF-κB p65 (p = 0.003) and a statistically significant decrease in M2 numbers (p = 0.014). Connective tissue presented with no statistically significant differences. Spearman’s rank correlation revealed multiple statistically significant correlations—26 positive and 5 negative. Conclusions: Statistically significant changes in levels of VEGF and both NF-κB subtypes and numbers of total macrophages and M2 macrophages suggest a possible alteration of variable immune and inflammatory reactions and macrophage functions associated with the initiation and maintenance of the chronic process and the resulting damage. Full article

Autistic traits—such as social communication deficits, cognitive rigidity, and repetitive behaviors—are increasingly recognized in individuals with schizophrenia, particularly in early-onset cases and subtypes with predominant negative symptoms. This overlap has prompted investigations into shared pathophysiological mechanisms. One emerging area of focus is the role of neuroinflammation in schizophrenia, which may contribute to the manifestation of autistic features. Immunological research indicates the presence of chronic low-grade inflammation, microglial activation, and disruption of the blood–brain barrier in schizophrenia. In particular, an imbalance in T-helper (Th) cell responses—specifically a shift toward Th2 dominance or concurrent Th1/Th2 activation—may lead to dysregulated cytokine production and disturbances in neural function. These findings highlight the importance of exploring immunological pathways as a basis for specific symptom profiles. Additionally, current efforts aim to identify reliable inflammatory biomarkers in schizophrenia that could support diagnosis, predict disease course, and guide treatment. Evaluating neuroinflammatory markers in patients with autistic features may provide novel insight into schizophrenia subtypes and help tailor immunomodulatory therapies. This review explores the expression of autistic traits in schizophrenia and examines the role of neuroinflammation and Th1/Th2 imbalance as potential mechanisms and biomarkers. Full article

Background: Herpes zoster (HZ), resulting from the reactivation of latent varicella-zoster virus, has been increasingly observed in individuals following COVID-19. Given the shared immunological disturbances between the two conditions, this study aimed to investigate whether HZ following COVID-19 is associated with an elevated risk of renal, infectious, and autoimmune complications. Methods: This retrospective cohort study utilized data from the TriNetX global federated health network, encompassing over 9 million adults diagnosed with COVID-19 between January 2020 and January 2022. Patients who developed HZ within one year following COVID-19 diagnosis were compared to 1:1 propensity score-matched controls without HZ. Time-to-event analyses over a three-year follow-up period were conducted to estimate the risks of major adverse kidney events (MAKE; defined as acute kidney injury, dialysis dependence, or severely reduced kidney function with eGFR <30 mL/min/1.73 m²), sepsis, systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA), using Kaplan–Meier survival curves and Cox proportional hazards models. Results: HZ following COVID-19 was significantly associated with increased risks of all four outcomes: MAKE (HR 1.940, 95% CI: 1.866–2.017), sepsis (HR 2.362, 95% CI: 2.250–2.479), SLE (HR 2.667, 95% CI: 2.254–3.156), and RA (HR 2.484, 95% CI: 2.267–2.730). Subgroup analyses identified older age, diabetes, impaired renal function, and elevated inflammatory markers as key risk-enhancing factors. Conclusions: HZ following COVID-19 may serve as a clinical indicator of systemic immune dysregulation and is independently associated with increased long-term risks of renal, infectious, and autoimmune sequelae. Enhanced monitoring of this high-risk population is warranted. Full article

Systemic autoimmune rheumatic diseases (SARDs), such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren’s syndrome (SS), are traditionally characterized by chronic inflammation and immune-mediated damage to joints and other tissues. However, many patients also experience symptoms such as widespread pain, persistent fatigue, cognitive dysfunction, and autonomic disturbances that cannot be attributed directly or entirely to peripheral inflammation or structural pathology. These conditions suggest the involvement of interactions between the nervous and immune systems, which probably include both peripheral and central components. This review summarizes the current knowledge of neurological and neuroimmune mechanisms that may contribute to these symptoms in SARDs. Glial cell activation and neuroinflammation within the central nervous system (CNS), small-fiber neuropathy (SFN) affecting peripheral nociceptive pathways, central pain sensitization, and autonomic nervous system dysfunction will be discussed. In addition, the role of molecular mediators, including cytokines, neuropeptides, and microRNAs, that could potentially modulate neuroimmune signaling will be highlighted. Integrating findings from pathology, immunology, and neuroscience, this review seeks to provide a useful framework for understanding neuroimmune dysregulation in SARDs. It also highlights the clinical relevance of these mechanisms and summarizes new directions for diagnosis and treatment. Full article

The human gut microbiome is integral to maintaining systemic physiological balance, with accumulating evidence emphasizing its critical role in reproductive health. This review investigates the bidirectional interactions between the gut microbiota and the female reproductive system, mediated by neuroendocrine, immune, and metabolic pathways, constituting the gut–reproductive axis. Dysbiosis, characterized by microbial imbalance, has been linked to reproductive disorders such as polycystic ovary syndrome (PCOS), endometriosis, infertility, impaired spermatogenesis, and pregnancy complications. These associations can be explained by immunological dysregulation, systemic inflammation, altered sex hormone metabolism, and hypothalamic–pituitary–gonadal (HPG) axis disturbances. This review aims to clarify the molecular and cellular mechanisms underpinning gut–reproductive interactions and to evaluate the feasibility of microbiome-targeted therapies as clinical interventions for improving reproductive outcomes. Full article

Background: Neuralgic amyotrophy (NA), also known as Parsonage–Turner syndrome, brachial neuritis, and idiopathic brachial plexopathy, is a rare and potentially debilitating peripheral nerve disorder characterized by acute-onset shoulder pain followed by progressive motor deficits. It is often under-recognized, with an estimated incidence of 1 to 3 per 100,000 annually, though some studies suggest the actual prevalence may be significantly higher. The condition typically progresses through three phases, an acute painful phase, a phase of weakness, and a recovery phase, with sensory disturbances common in addition to motor weakness. The exact pathogenesis of NA remains unclear, though it is thought to involve a combination of genetic, environmental, and immunological factors. While neurologic complications following hematopoietic stem cell transplantation (HSCT), such as neuropathies and myopathies, have been documented, NA remains exceedingly rare in this context, with only a few reported cases. The pathophysiology in HSCT patients is hypothesized to involve immune dysregulation, graft-versus-host disease (GvHD), infection, and the effects of immunosuppressive therapy. Diagnosis is primarily clinical, supported by electrodiagnostic studies and MRI, though no laboratory markers exist. The management of NA is largely supportive and multimodal, focusing on pain control and rehabilitation. Objectives: The objective of this study was to describe the characteristics, clinical course, and outcomes of patients admitted for HSCT who were subsequently diagnosed with NA. Study Design: This retrospective case series from a single institution examined nine (N = 9) patients who developed acute shoulder pain following HSCT. We collected data on demographics, transplant details, clinical features, MRI findings, and electrodiagnostic studies, summarized using descriptive statistics. The diagnosis of neurologic amyotrophy was based on clinical presentation and corroborated by imaging and electrodiagnostic results. Long-term follow-up was assessed to evaluate symptom recovery. Results: Between August 2020 and July 2022, nine patients (44% male, median age 60) were diagnosed with NA following autologous (n = 4) or allogeneic (n = 5) HSCT. The onset of severe shoulder pain occurred at a median of 9 days post-transplant (range 1–21 days), with the majority of patients experiencing unilateral pain, predominantly affecting the right shoulder (55%). Neurologic weakness developed on average 5.1 days after pain onset, and sensory deficits were observed in all but one patient. MRI findings revealed muscle edema, atrophy, and enhancement in six patients, while electromyography confirmed NA in five. Due to the small sample size, statistical analyses, including p-values, confidence intervals, and trend comparisons, were not performed, and thus no conclusions can be drawn regarding associations between variables such as early onset and worse outcomes. Shoulder pain resolved after a median of 23 days (range 8–40 days). Long-term follow-up (>1 year) showed that three patients achieved full or near-full recovery, four partially recovered, and two showed minimal improvement. Conclusions: NA should be highly suspected in patients with acute shoulder pain and neurologic symptoms post-HSCT. To improve diagnostic accuracy and clinical outcomes, we recommend enhanced clinician awareness, the implementation of targeted diagnostic protocols (such as MRI and electrodiagnostic studies), and the establishment of standardized long-term follow-up protocols. Full article

Pregnancy orchestrates profound neurological, hormonal, and anatomical transformations in the maternal brain, preparing it for caregiving and infant bonding. Neuroimaging reveals structural changes such as gray matter reductions and white matter reorganization during pregnancy, followed by partial recovery postpartum. These adaptations are modulated by fluctuating levels of estradiol, progesterone, prolactin, and oxytocin, which coordinate neuroplasticity and behavioral readiness. At the molecular and cellular levels, pregnancy hormones drive synaptic remodeling, neurogenesis, and glial activity. Together, these changes support maternal motivation, attachment, and responsiveness, highlighting the maternal brain’s dynamic plasticity across gestation and the postpartum period. Also, pregnancy induces profound physiological changes, particularly in vascular, hormonal, and neurologic systems, to support maternal and fetal health. While these adaptations are essential, they can predispose pregnant individuals to various neurologic and ophthalmic pathologies. This review explores how pregnancy-related changes—including hypercoagulability, pituitary enlargement, hormonal fluctuations, and immunological modulation—contribute to conditions such as stroke, idiopathic intracranial hypertension, preeclampsia-associated visual disturbances, and demyelinating disorders like neuromyelitis optica spectrum disorder and multiple sclerosis. Additionally, ocular manifestations of systemic diseases like diabetic retinopathy and thyroid orbitopathy are discussed. Understanding these complex interactions is critical for prompt recognition, accurate diagnosis, and appropriate management of vision-threatening and neurologically significant complications during pregnancy. Nevertheless, many aspects of physiological and pathological changes during and after pregnancy remain unknown and warrant further investigation. Full article

The amygdala, especially its central nucleus (CeA), is one of the key brain structures regulating fear, anxiety and stress responses and is also involved in gut microbiota signal processing. Amygdala hyperactivity, as well as microbiota alterations, plays an important role in the pathophysiology of anxiety disorders, depression or post-traumatic stress disorder (PTSD). The present study determines whether 3 weeks of galactooligosaccharide (GOS) supplementation alleviates behavioural, haematological, immunological and gut microbiota disturbances induced by long-term electrical stimulation of the CeA in rats (Stim). The unsupplemented Stim group showed locomotor hyperactivity and higher anxiety (measured with an actometer and the elevated plus maze, respectively), as well as a decrease in white blood cells (WBCs), lymphocytes (LYMs), red blood cells (RBCs) and platelets (PLTs); an elevation of TNFα; a reduction in IL-10 concentration in plasma; and microbiota alterations as compared to the control (Sham) group. GOS supplementation alleviated all these Stim-induced adverse effects or even normalised them to the sham group level. The effect of GOS was comparable to citalopram and even more effective in WBC and PLT normalisation and IL-10 induction. The obtained results indicate the high therapeutic potential of GOS in anxiety and stress-related disorders. GOS supplementation may support conventional therapy or the prevention of PTSD, depression and anxiety disorders. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM), is a rapidly growing global health concern, often accompanied by chronic kidney disease (CKD) and metabolic disturbances. Obesity-related indices, such as the visceral adiposity index (VAI) and body adiposity index (BAI), have been linked to cardiovascular and renal complications in diabetic patients. However, studies integrating both the atherogenic coefficient (AC) and prognostic nutritional index (PNI) for evaluating diabetic nephropathy (DN) remain limited. This study aimed to assess the associations of obesity-related indices with immunological and nutritional factors in patients with T2DM and prediabetes (PreDM). Methods: A retrospective, cross-sectional study was conducted over six months at a university clinical hospital in Dolj County, Romania. The study enrolled 268 newly diagnosed T2DM patients and 150 PreDM patients. Anthropometric parameters, laboratory tests, and demographic data were collected. AC and PNI were calculated using standard formulas, and statistical analyses were performed to determine their associations with metabolic and inflammatory markers. Results: Our study found that T2DM patients had significantly lower PNI values, indicating mild malnutrition, while PreDM patients maintained a normal nutritional status. AC was significantly higher in T2DM patients, correlating with lipid profile alterations and systemic inflammation. Obesity indices, particularly VAI, were significantly elevated in T2DM patients with higher AC values. Statistically significant differences in total cholesterol, low-density lipoprotein cholesterol (LDL-c), and triglycerides were observed between AC subgroups, reinforcing its role in cardiovascular risk assessment. Conclusions: The findings highlight the potential of AC and PNI as biomarkers for assessing nutritional, inflammatory, and lipemic status in diabetic patients. The significant associations between obesity-related indices, lipid profiles, and inflammation markers suggest that early assessment of these parameters may potentially aid in predicting diabetic complications. Further studies are needed to explore the clinical utility of AC and PNI in managing T2DM and CKD progression. Future research should investigate how the lipidic spectrum alters the progression of DN across various patient groups with diabetes and prediabetes Full article

Background: Chronic venous disease (CVD) is a vascular disorder common among pregnant women, due to the impairment in the venous function associated with the mechanical, hemodynamical, and hormonal changes that occur during pregnancy. CVD is linked to venous hypertension, inflammation, oxidative stress, and hypoxia, which alter placental structure and function, as demonstrated in previous works. The placenta fulfills several roles in fetal development and maternal well-being by mediating nutrient exchange; acting as a mechanical, chemical, and immunological shield; and producing essential hormones, making it crucial to investigate the effects of CVD in this organ. Patients and methods: This work specifically analyzes the gene expression of circadian markers (CLOCK, BMAL1, PER1, and PER2), epigenetic regulators (HAT1 and associated molecules like histones H3, H4, RBBP7, and ASF1), and the anti-aging protein KLOTHO in placental tissue of pregnant women with CVD (CVD-PW, N = 98) compared to healthy pregnant controls (HC-PW, N = 82), using RT-qPCR and immunohistochemistry (IHC) to determine protein expression. Results: Our study demonstrates that the placentas of CVD-PW exhibit the reduced gene and protein levels of circadian regulators (clock, bmal1, per1, and per2), increased expression of hat1 and related proteins (h3, h4, rbbp7, and asf1), and decreased klotho expression, indicative of accelerated aging. Conclusions: These findings highlight profound molecular disturbances in the placentas of women with CVD, offering insights into the disease’s pathophysiology and potential implications for maternofetal well-being. While this study deepens our understanding of the relationship between CVD and placental dysfunction, further research is required to fully elucidate these mechanisms and their long-term effects. Full article

The COVID-19 pandemic has raised significant concerns regarding its potential impact on maternal and neonatal health. This study aimed to investigate the immunologic and hemostatic profiles of neonates exposed to SARS-CoV-2 during the peripartum period (0–14 days prior to delivery). This retrospective study included 28 neonates born to COVID-19-positive mothers during the peripartum period and a control group of 54 neonates born to mothers who never tested positive for SARS-CoV-2 during pregnancy. Arterial blood samples were collected from all neonates on the second day of life for the simultaneous assessment of full blood count, C-reactive protein (CRP), serum interleukin-6 (IL-6), and Interferon gamma-induced protein 10 (IP-10) levels, as well as Rotational Thromboelastometry (ROTEM) tests (EXTEM, INTEM, and NATEM). Neonates born to COVID-19-positive mothers and those born to COVID-19-negative mothers exhibited similar coagulation profiles based on ROTEM analysis. Multiple linear regression analysis revealed that peripartum COVID-19 infection was associated with higher IP-10 levels in neonates (coefficient: +16.8, 95% CI: +9.0 to +24.6, p < 0.0001). Our study findings suggest that the presence of immunologic disturbance in neonates is related to recent peripartum exposure to maternal SARS-CoV-2 infection, as evidenced by increased IP-10 levels in blood samples obtained from neonates born to SARS-CoV-2-positive mothers. However, peripartum exposure to maternal SARS-CoV-2 did not appear to disrupt the hemostatic profile of the exposed newborns based on ROTEM test results. Full article