Search Results (1,428)

Neuroinflammation is the major contributor to the pathology of neonatal hypoxic–ischemic (HI) brain injury. Our previous studies have demonstrated that microRNA210 (miR210) inhibition with antisense locked nucleic acid (LNA) inhibitor mitigates neuroinflammation and provides neuroprotection after neonatal HI insult. However, the underlying mechanisms remain elusive. In the present study, using miR210 knockout (KO) mice and microglial cultures, we tested the hypothesis that miR210 promotes microglial activation and neuroinflammation through suppressing mitochondrial function in microglia after HI. Neonatal HI brain injury was conducted on postnatal day 9 (P9) wild-type (WT) and miR210 knockout (KO) mouse pups. We found that miR210 KO significantly reduced brain infarct size at 48 h and improved long-term locomotor functions assessed by an open field test three weeks after HI. Moreover, miR210 KO mice exhibited reduced IL1β levels, microglia activation and immune cell infiltration after HI. In addition, in vitro studies of microglia exposed to oxygen–glucose deprivation (OGD) revealed that miR210 inhibition with LNA reduced OGD-induced expression of Il1β and rescued OGD-mediated downregulation of mitochondrial iron–sulfur cluster assembly enzyme (ISCU) and mitochondrial oxidative phosphorylation activity. To validate the link between miR210 and microglia activation, isolated primary murine microglia were transfected with miR210 mimic or negative control. The results showed that miR210 mimic downregulated the expression of mitochondrial ISCU protein abundance and induced the expression of proinflammatory cytokines similar to the effect observed with ISCU silencing RNA. In summary, our results suggest that miR210 is a key regulator of microglial proinflammatory activation through reprogramming mitochondrial function in neonatal HI brain injury. Full article

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

Fungi, from saprophytes to pathogens, face predictable daily fluctuations in light, temperature, humidity, and nutrient availability. To cope, they have evolved an internal circadian clock that confers a major adaptive advantage. This review critically synthesizes current knowledge on the molecular architecture and physiological relevance of fungal circadian systems, moving beyond the canonical Neurospora crassa model to explore the broader phylogenetic diversity of timekeeping mechanisms. We examine the core transcription-translation feedback loop (TTFL) centered on the FREQUENCY/WHITE COLLAR (FRQ/WCC) system and contrast it with divergent and non-canonical oscillators, including the metabolic rhythms of yeasts and the universally conserved peroxiredoxin (PRX) oxidation cycles. A central theme is the clock’s role in gating cellular defenses against oxidative, osmotic, and nutritional stress, enabling fungi to anticipate and withstand environmental insults through proactive regulation. We provide a detailed analysis of chrono-pathogenesis, where the circadian control of virulence factors aligns fungal attacks with windows of host vulnerability, with a focus on experimental evidence from pathogens like Botrytis cinerea, Fusarium oxysporum, and Magnaporthe oryzae. The review explores the downstream pathways—including transcriptional cascades, post-translational modifications, and epigenetic regulation—that translate temporal signals into physiological outputs such as developmental rhythms in conidiation and hyphal branching. Finally, we highlight critical knowledge gaps, particularly in understudied phyla like Basidiomycota, and discuss future research directions. This includes the exploration of novel clock architectures and the emerging, though speculative, hypothesis of “chrono-therapeutics”—interventions designed to disrupt fungal clocks—as a forward-looking concept for managing fungal infections. Full article

While IPV is often studied as a predictor of housing insecurity, few U.S. studies explore how different forms of housing instability may contribute to intimate partner violence (IPV) risk. Using a mixed-methods approach and a cross-sectional design, this study examined the association between four housing instability domains and IPV among a sample of tenants that had either experienced eviction or were at high risk for eviction. Tenants in Harris and Travis counties (Texas, USA) completed an online survey (n = 1085; March–July 2024). Housing instability was assessed across four domains: homelessness, lease violations, utility hardship, and poor housing quality. IPV was measured using the Hurt, Insult, Threaten, Scream Screener. Covariate-adjusted logistic regression models suggest indicators within the four housing instability domains were associated with IPV risk. Within the homelessness domain, experiences with lifetime homelessness (AOR = 1.92, 95%CI 1.61–2.28), in the past 12 months living in unconventional spaces (AOR = 2.10, 95%CI 1.92–2.29), and moving in with others (AOR = 1.20, 95%CI 1.06–1.36) were associated with IPV. Within the lease violations domain, missed rent payments (AOR = 1.69, 95%CI 1.68–1.71) and non-payment lease violations (AOR = 2.50, 95%CI 2.29–2.73) in the past 12 months were associated with IPV. Utility shutoffs (AOR = 1.62, 95%CI 1.37–1.91) and unsafe housing (AOR = 1.65, 95%CI 1.31–2.09) in the past 12 months were associated with IPV. Homelessness, housing-related economic hardships and substandard living conditions predict an elevated risk of IPV. Full article

As voice cloning technology rapidly advances, the risk of personal voices being misused by malicious actors for fraud or other illegal activities has significantly increased, making the collection of speech data increasingly challenging. To address this issue, this study proposes a data augmentation method based on XText-to-Speech (XTTS) synthesis to tackle the challenges of small-sample, multi-class speech recognition, using profanity as a case study to achieve high-accuracy keyword recognition. Two models were therefore evaluated: a CNN model (Proposed-I) and a CNN-Transformer hybrid model (Proposed-II). Proposed-I leverages local feature extraction, improving accuracy on a real human speech (RHS) test set from 55.35% without augmentation to 80.36% with XTTS-enhanced data. Proposed-II integrates CNN’s local feature extraction with Transformer’s long-range dependency modeling, further boosting test set accuracy to 88.90% while reducing the parameter count by approximately 41%, significantly enhancing computational efficiency. Compared to a previously proposed incremental architecture, the Proposed-II model achieves an 8.49% higher accuracy while reducing parameters by about 98.81% and MACs by about 98.97%, demonstrating exceptional resource efficiency. By utilizing XTTS and public corpora to generate a novel keyword speech dataset, this study enhances sample diversity and reduces reliance on large-scale original speech data. Experimental analysis reveals that an optimal synthetic-to-real speech ratio of 1:5 significantly improves the overall system accuracy, effectively addressing data scarcity. Additionally, the Proposed-I and Proposed-II models achieve accuracies of 97.54% and 98.66%, respectively, in distinguishing real from synthetic speech, demonstrating their strong potential for speech security and anti-spoofing applications. Full article

With good reason, Vatican II encourages the Eastern ecclesial realities to preserve and, if necessary, to rediscover their own traditions (also, even if not only, for ecumenical reasons). There are, however, certain aspects of the heritage of the Eastern Churches that require urgent revision in a spirit of consistency with the teachings of the Council. This is undoubtedly the case with regard to the anti-Jewish elements so specific to the entire Christian tradition (more or less generalised insults and judgments; substitutionary and appropriative perspectives; a purely instrumental use of the Jewish scriptures) and, in the absence of full reception of the Council, still reflected in the public prayers of the Romanian Greek-Catholic Church, to the detriment of that spirit of respect, fraternity, and dialogue theoretically embraced throughout the Catholic world today. In the light of Nostra aetate §4 and the subsequent developments that flowed from it, I shall try in this contribution to outline some possible criteria for reforming the offices of Holy Week, aiming to show that—at least in this particular case—it is not enough merely to refer to the OE, let alone to use it to justify a comfortable tendency towards inertia. Apart from the fact that it is this very Decree that speaks of a possible and necessary organic progress, we cannot ignore the more general spirit of renewal of the Council and its other documents (the NA, the SC, the DV, the GS). The challenge would be to engender a creative fidelity, which—while preserving the best of tradition—surpasses certain of its contingent elements. Full article

Background: Sudden-onset bilateral mixed hearing loss in adults is an extremely rare condition but challenging to diagnose and treat. Conductive hearing loss is associated with otitis media, while the simultaneous presence of a sensorineural component requires supplementary investigation for possible shared pathophysiological mechanisms. Case Presentation: We report the case of a 41-year-old male who was admitted to our hospital with a 48 h history of bilateral, fast progressive hearing loss following a viral illness. The audiologic testing revealed bilateral severe mixed hearing loss. Tympanometry indicated the presence of middle-ear effusion, and myringotomy confirmed the existence of pressurized serous fluid. Treatment consisted of systemic and intratympanic corticosteroids, antibiotics, and supportive therapy. The patient had an unexpected full recovery of auditory function within one month. Discussion: Multiple hypotheses were considered. We hypothesized the coexistence of unrelated conductive and sensorineural hearing loss or a unifying pathological process. Theories discussed include a direct viral insult to the cochlear structures or even pressure-mediated damage to the basal cochlea due to the simultaneous inward displacement of the oval and round windows. The complete resolution of hearing loss is the indicator of a reversible etiology, possibly due to transient inner ear dysfunction secondary to middle-ear pathology or viral infection. Conclusions: This case illustrates the complexity of diagnosing acute mixed hearing loss. This report emphasizes a rare case of sudden-onset bilateral mixed hearing loss with a complete recovery, contributing valuable insight into under-reported and diagnostically complex presentations. Full article

Background: Post-concussion syndrome (PCS) and Functional Neurological Disorder (FND), including Functional Cognitive Disorder (FCD), are two frequently encountered but diagnostically complex conditions. While PCS is conceptualized as a sequela of mild traumatic brain injury (mTBI), FND/FCD encompasses symptoms incompatible with recognized neurological disease, often arising in the absence of structural brain damage. Yet, both conditions exhibit considerable clinical overlap—particularly in the domains of cognitive dysfunction, emotional dysregulation, and symptom persistence despite negative investigations. Objective: This review critically examines the shared and divergent features of PCS and FND/FCD. We explore their respective epidemiology, diagnostic criteria, and risk factors—including personality traits and trauma exposure—as well as emerging insights from neuroimaging and biomarkers. We propose the “Functional Overlay Model” as a clinical tool for navigating diagnostic ambiguity in patients with persistent post-injury symptoms. Results: PCS and FND/FCD frequently share features such as subjective cognitive complaints, fatigue, anxiety, and heightened somatic vigilance. High neuroticism, maladaptive coping, prior psychiatric history, and trauma exposure emerge as common risk factors. Neuroimaging studies show persistent network dysfunction in both PCS and FND, with overlapping disruption in fronto-limbic and default mode systems. The Functional Overlay Model helps to identify cases where functional symptomatology coexists with or replaces an initial organic insult—particularly in patients with incongruent symptoms and normal objective testing. Conclusions: PCS and FND/FCD should be conceptualized along a continuum of brain dysfunction, shaped by injury, psychology, and contextual factors. Early recognition of functional overlays and stratified psychological interventions may improve outcomes for patients with persistent, medically unexplained symptoms after head trauma. This review introduces the Functional Overlay Model as a novel framework to enhance diagnostic clarity and therapeutic planning in patients presenting with persistent post-injury symptoms. Full article

Obesity and pediatric fatty liver disease are increasingly prevalent, yet the underlying mechanisms linking these conditions to heightened inflammatory and immune responses remain poorly understood. Using a murine model reflecting early-life obesity and hepatic steatosis, we tested the hypothesis that obesity-driven hepatic inflammation intensifies systemic immune responses and exacerbates vascular dysfunction following innate immune activation. Newly weaned C57BL/6 mice were fed either a high-saturated-fat, high-cholesterol diet (HFD) or a control diet (CD) for four weeks, modeling adolescence in humans. HFD-fed mice exhibited hepatic and splenic enlargement, elevated plasma cholesterol levels, increased activity levels of liver enzymes (alanine and aspartate aminotransferases), and higher plasma serum amyloid A (SAA) concentrations. Following a sublethal dose of lipopolysaccharide (LPS), the expression of hepatic inflammatory genes (VCAM-1 and iNOS) was significantly elevated in HFD-fed mice, indicating an exaggerated local immune response. Mice fed an HFD also showed significant impairment in endothelium-dependent vasorelaxation compared to CD mice and saline-treated controls, while endothelium-independent responses remained intact. These vascular changes occurred in the context of hepatic inflammation, suggesting that early-life diet-induced steatosis sensitizes the vasculature to inflammatory insult. These findings suggest that obesity-driven hepatic inflammation primes exaggerated systemic immune responses to innate immune stimuli, potentially contributing to the vascular dysfunction and variable clinical morbidity observed in pediatric inflammatory conditions. Full article

Chronic ethanol use can lead to alcoholic cardiomyopathy (ACM), while the impact on the molecular and cellular aspects of the myocardium is unclear. Accordingly, male Sprague-Dawley rats were exposed to an ethanol-containing diet for 16 weeks and compared with a control group that was fed an isocaloric diet. Histological measurements from H&E slides revealed no significant differences in cell size. A proteomic approach revealed that alcohol exposure leads to enhanced mitochondrial lipid metabolism, and electron microscopy revealed impairments in mitochondrial morphology/density. Cardiac myosin purified from the hearts of ethanol-exposed animals demonstrated a 15% reduction in high-salt ATPase activity, with no significant changes in the in vitro motility and low-salt ATPase or formation of the super-relaxed (SRX) state. A protein carbonyl assay indicated a 20% increase in carbonyl incorporation, suggesting that alcohol may impact cardiac myosin through oxidative stress mechanisms. In vitro oxidation of healthy cardiac myosin revealed a dramatic decline in ATPase activity and in vitro motility, demonstrating a link between myosin protein oxidation and myosin mechanochemistry. Collectively, this study suggests alcohol-induced metabolic remodeling may be the initial insult that eventually leads to defects in the contractile machinery in the myocardium of ACM hearts. Full article

Introduction: Methadone, a synthetic opioid used for opioid substitution therapy (OST), is typically associated with arrhythmias rather than direct myocardial depression. Neurological complications, especially with concurrent antipsychotic use, have also been reported. Acute left ventricular failure in young adults is uncommon and often linked to genetic or infectious causes. We present a rare case of reversible cardiogenic shock and cerebellar insult due to methadone toxicity. Case Presentation: A 37-year-old man with a history of drug abuse on OST with methadone (130 mg/day) was admitted to the ICU with hemodynamic instability, seizures, and focal neurological deficits. Diagnostic workup revealed low cardiac output syndrome and a right cerebellar insult, attributed to methadone toxicity. The patient received individualized catecholamine support. After 10 days in the ICU, he was transferred to a general ward for ongoing cardiac and neurological rehabilitation and discharged in stable condition seven days later. Conclusions: Methadone-induced reversible left ventricular failure, particularly when accompanied by cerebellar insult, is rare but potentially life-threatening. Early recognition and multidisciplinary management are essential for full recovery in such complex toxicological presentations. Full article

Background/Objectives: Diets high in simple carbohydrates and saturated fats, commonly consumed in Westernized countries, have been linked to a greater predisposition to metabolic disorders, which are partly attributed to oxidative stress. This study aimed to investigate the impact of an obesogenic diet consumed during the pregnancy and lactation periods on hepatic metabolism and REDOX balance in rats. Methods: Sixteen pregnant Wistar rats were divided into two groups: control (CD), which received a vivarium diet, and obesogenic (OD), which received an obesogenic diet (high-fat diet plus condensed milk), from early pregnancy to late lactation. Thirty-six hours after weaning, the rats were euthanized, and blood, adipose tissue, and liver samples were collected for analysis. Results: These results demonstrate that exposure to an obesogenic diet during pregnancy and lactation in rats leads to adverse changes in hepatic metabolic, inflammatory, and REDOX balance. This experimental animal model serves as a valuable tool for investigating the mechanisms of metabolic dysfunction associated with diets that mimic human eating habits. However, it is essential to note that these findings pertain to an experimental model and therefore require validation in clinical studies to confirm their relevance and applicability in human health. Conclusions: The consumption of an obesogenic diet during pregnancy and lactation in rats induces adverse alterations in hepatic metabolic, inflammatory, and redox homeostasis. This animal model helps investigate the mechanisms of metabolic dysfunctions associated with human dietary habits. However, these findings still need to be confirmed in clinical studies to verify their relevance in humans. Full article

The success of in vitro fertilization (IVF) and female reproductive capacity are significantly determined by oocyte quality. Increasing data highlights the significance of oxidative stress—a state of imbalance between reactive oxygen species (ROS) and antioxidant defenses—in regulating oocyte competence. Normal folliculogenesis and ovulation rely on optimal ROS levels; excessive oxidative stress (OS) can lead to DNA fragmentation, undermine meiotic spindle integrity, and trigger apoptosis in cumulus and granulosa cells. Molecular insults impair nuclear and cytoplasmic maturation, thereby impacting fertilization potential and embryonic development. Individuals with polycystic ovarian syndrome (PCOS), endometriosis, advanced maternal age, and metabolic disorders—conditions associated with suboptimal IVF outcomes—frequently exhibit redox imbalance. This narrative review examines significant oxidative markers in the follicular environment, exploring the molecular processes linking OS to diminished oocyte quality and discussing therapy techniques aimed at mitigating oxidative damage. Maintaining redox homeostasis in the ovarian milieu appears to be an effective strategy for enhancing oocyte competence and optimizing outcomes in assisted reproduction. Full article

Several soluble mediators are activated during myogenesis and progression, and severe neurodegeneration, with related biomarkers, characterizes high myopia-related retinal atrophy. Targets of oxidative stress, epigenetics and neurogenic inflammation have been reported in the prospecting of some bioindicators to mirror retinal insults occurring in high myopia. The aim of the present study was to assess the expression of a few selected biomarkers belonging to the neurotrophin (NGF and BDNF), oxidative (NO, KEAP1/NRF2), and epigenetic (DNMT3 and HD1) pathways. Sixty-five (65; 76.25 ± 9.40 years) specimens—aqueous, anterior capsule (AC), and lens epithelial cells (LEC)—were collected at the time of cataract surgery and used for ELISA (aqueous) and transcripts analysis (AC/LEC). Biosamples were grouped as emmetrope (23; 81.00 ± 6.70 years); myopia (24; 75.96 ± 7.30); and high (pathological) myopia (18; 70.56 ± 11.68 years), depending on axial length (AL) and refractive error (RE). Comparisons and correlations were carried out between myopic and high-myopic subgroups. NGF and BDNF were lowered in myopic samples; NGF and BDNF transcripts were differentially expressed in LEC, and their expression correlated positively with NGF and negatively with BDNF, with the expression of the αSMA phenotype. NGF and BDNF correlated negatively with NO and nitrites. Oxidative stress (iNOS/NOX1/NOX4 and KEAP1/NRF2) and epigenetic (DNMTα3/HD1) transcripts were upregulated in myopic LEC, compared with emmetropic ones. Herein, we prospect the contribution of NGF and BDNF in both neuroinflammation and neuroprotection occurring in this chronic disease. Full article

Endometriosis (EMS) is a long-term inflammatory disease. It represents one of the most prevalent gynecological conditions, impacting an estimated 5% of reproductive women. Therefore, endometriosis contributes to substantial worldwide health challenges and healthcare costs. In EMS disease, endometrial glandular and stromal tissues are abnormally located outside the uterus. Similarly to the natural endometrium, these tissues grow and proliferate in response to estrogen-dependent signals. The pain and limited effectiveness of treatments are often linked to the inflammatory reaction triggered by EMS-associated ectopic tissue. This is especially amplified during the peaks of estrogen release that occur as the menstrual cycle transitions from the proliferative phase to ovulation. Maintaining the integrity of the mucosal lining, defending against pathogenic insults, and controlling physiological processes are all made possible by a healthy, balanced state of gut biomass. Additionally, numerous intestinal bacteria have been discovered to possess estrogen-metabolizing enzymes, which affect the estrobolome and, consequently, influence estrogen-related disorders. Therefore, there is increasing interest in understanding the role of microbiota and the estrobolome in endometriosis pathogenesis. This review will focus on the role of microbiota and the impact of estrobolome alterations in endometriosis pathogenesis. Full article