Disruption Of Function Research Articles

Feasibility of plasma proteomics in patients with immune thrombocytopenia.

ITP is an acquired autoimmune bleeding disorder characterized by an isolated thrombocytopenia. The pathophysiology is highly multifactorial and involves antibody- and/or cytotoxic T cell-mediated killing of platelets and disruption of megakaryocyte function hampering platelet production. ITP remains a diagnosis of exclusion, and due to the high degree of variability between patients, it remains challenging to predict disease courses and responses to therapeutic agents. Hence, diagnostic and therapeutic laboratory biomarkers are highly warranted. To address this issue, in their paper, Jiang and colleagues have performed plasma proteomics in ITP patients (n = 40), in comparison to patients with thrombocytopenia due to other causes than ITP (non-ITP thrombocytopenia, n = 19) and healthy controls (n = 18). The data underscore that patients with ITP have a distinct plasma proteomic signature compared to non-ITP thrombocytopenia patients and healthy individuals. The findings should be further validated and investigated but suggest that the application of plasma proteomics is feasible and promising with respect to the search for potential biomarkers in patients with ITP. Commentary on: Jiang etal. Targeted proteomics profiling reveals valuable biomarkers in the diagnosis of primary immune thrombocytopenia. Br J Haematol 2024 (Online ahead of print). doi: 10.1111/bjh.19760.

Novel biomarkers of mitochondrial dysfunction in Long COVID patients.

Coronavirus disease 2019 (COVID-19) can lead to severe acute respiratory syndrome, and while most individuals recover within weeks, approximately 30-40% experience persistent symptoms collectively known as Long COVID, post-COVID-19 syndrome, or post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC). These enduring symptoms, including fatigue, respiratory difficulties, body pain, short-term memory loss, concentration issues, and sleep disturbances, can persist for months. According to recent studies, SARS-CoV-2 infection causes prolonged disruptions in mitochondrial function, significantly altering cellular energy metabolism. Our research employed transmission electron microscopy to reveal distinct mitochondrial structural abnormalities in Long COVID patients, notably including significant swelling, disrupted cristae, and an overall irregular morphology, which collectively indicates severe mitochondrial distress. We noted increased levels of superoxide dismutase 1 which signals oxidative stress and elevated autophagy-related 4B cysteine peptidase levels, indicating disruptions in mitophagy. Importantly, our analysis also identified reduced levels of circulating cell-free mitochondrial DNA (ccf-mtDNA) in these patients, serving as a novel biomarker for the condition. These findings underscore the crucial role of persistent mitochondrial dysfunction in the pathogenesis of Long COVID. Further exploration of the cellular and molecular mechanisms underlying post-viral mitochondrial dysfunction is critical, particularly to understand the roles of autoimmune reactions and the reactivation of latent viruses in perpetuating these conditions. This comprehensive understanding could pave the way for targeted therapeutic interventions designed to alleviate the chronic impacts of Long COVID. By utilizing circulating ccf-mtDNA and other novel mitochondrial biomarkers, we can enhance our diagnostic capabilities and improve the management of this complex syndrome.

UNDERSTANDING THE BENEFITS OF STEVIA REBAUDIANA BERTONI FOR DIABETES: A COMPREHENSIVE REVIEW

Diabetes Mellitus (DM) is a complicated metabolic condition defined by long-term elevated blood glucose levels. This chronic hyperglycemia induces metabolic dysfunctions that cause structural and functional disruptions in the vasculature, leading to macrovascular and microvascular complications. Stevia rebaudiana Bertoni, commonly known as Stevia, is a perennial shrub that contains various bioactive constituents responsible for its sweetness and several other activities. Many studies on Stevia have shown that it possesses various beneficial effects on health, including being zero-calorie, anti-obesity, anti-diabetic, anti-hypertensive, antioxidant, antimicrobial and anti-tumor. Several studies have found that neither gastric juice nor digestive enzymes decompose stevioside. The presence of bioactive phenolic and flavonoid compounds supports Stevia's medicinal properties and its potential use in both the food/nutraceutical and pharmaceutical industries. A significant antioxidant capacity of Stevia has been identified recently. It can also help limit essential nutrient supply to tumor cells. Research on Stevia's effects on the human body has largely found no negative side effects. The growing body of evidence underscores Stevia's potential role in managing various health conditions, particularly for diabetic patients, due to its minimal impact on blood sugar levels. However, to fully harness its benefits and meet the increasing global demand, further scientific research is essential to optimize its cultivation, enhance its chemical constituents and ensure its safety. Overall, Stevia stands out as a promising natural sweetener with significant health benefits for diabetic patients. In this review article, we explore different aspects of Stevia and its beneficial effects on diabetic patients.

A microglia-containing cerebral organoid model to study early life immune challenges.

Prenatal infections and activation of the maternal immune system have been proposed to contribute to causing neurodevelopmental disorders (NDDs), chronic conditions often linked to brain abnormalities. Microglia are the resident immune cells of the brain and play a key role in neurodevelopment. Disruption of microglial functions can lead to brain abnormalities and increase the risk of developing NDDs. How the maternal as well as the fetal immune system affect human neurodevelopment and contribute to NDDs remains unclear. An important reason for this knowledge gap is the fact that the impact of exposure to prenatal risk factors has been challenging to study in the human context. Here, we characterized a model of cerebral organoids (CO) with integrated microglia (COiMg). These organoids express typical microglial markers and respond to inflammatory stimuli. The presence of microglia influences cerebral organoid development, including cell density and neural differentiation, and regulates the expression of several ciliated and mesenchymal cell markers. Moreover, COiMg and organoids without microglia show similar but also distinct responses to inflammatory stimuli. Additionally, IFN-γ induced significant transcriptional and structural changes in the cerebral organoids, that appear to be regulated by the presence of microglia. Specifically, interferon-gamma (IFN-γ) was found to alter the expression of genes linked to autism. This model provides a valuable tool to study how inflammatory perturbations and microglial presence affect neurodevelopmental processes.

Differences in Walking Speed of SACH Foot And Single Axis Foot in Transtibial Prosthesis User

Background: Lower limb amputation causes disruption of limb function, one of which is the ability to walk. One of the walking aids that can be used is a transtibial prosthesis. A transtibial prosthesis consists of a socket, shank and foot components. The choice of foot type and the use of a transtibial prosthesis is one of the factors that influence walking speed. SACH foot and single axis foot are the types of foot that are often used by prosthesis users Aims: To determine the difference in walking speed of SACH Foot and Single Axis Foot in transtibial prosthesis users. Method and Subjects: Using quantitative research, observational method with cross sectional design. The subjects of this research were users of transtibial prosthesis type SACH foot and single axis foot. The sample for this study consisted of 28 people. The measuring instruments used in this research are 10 MWT (Meter Walk Test). Results: Based on statistical tests, the results showed that there were differences in walking speed between SACH foot and single axis foot type transtibial prosthesis users. Where the p value <0.05 is 0.000 with an effect size of 0.81, which means it has a high or strong difference effect. Conclusion: There is a difference in walking speed, namely the walking speed of users of single axis foot transtibial prosthesis is faster than SACH foot. So, it is recommended to prefer using a single axis foot in users of transtibial prosthesis, especially at moderate activity levels. The limitations of this research are that there are not many subjects and the foot types are less diverse. Future research can be developed with other types of foot prosthesis and measurement of gait parameters

Kinase function of TgTKL1 is essential for its role in Toxoplasma propagation and pathogenesis.

Toxoplasma gondii is a protozoan parasite that can cause life-threatening disease in humans. Hence, identifying key factors required for parasite growth and pathogenesis is important to develop novel therapeutics. We have previously shown that a member of the TKL protein kinase family, TgTKL1, is a plant-like kinase that is required for effective Toxoplasma growth in vitro and essential for virulence in vivo. Herein, we show that the TgTKL1 is, indeed, a bona fide kinase, and loss of its kinase function in the Toxoplasma leads to similar defects seen in parasites with complete loss of TgTKL1. More specifically, the TgTKL1 kinase mutant exhibits defects in parasite growth, host-cell invasion, gene expression profile, and virulence in the animal model. Together, these findings suggest that TgTKL1 is a true kinase, and loss of its kinase activity leads to disruption of TgTKL1 function in Toxoplasma.

Cellular and Molecular Pathophysiology of Gestational Diabetes

Gestational diabetes (GD) is a metabolic disorder characterized by glucose intolerance during pregnancy, significantly impacting maternal and fetal health. Its global prevalence is approximately 14%, with risk factors including obesity, family history of diabetes, advanced maternal age, and ethnicity, which are linked to cellular and molecular disruptions in glucose regulation and insulin resistance. GD is associated with short- and long-term complications for both the mother and the newborn. For mothers, GD increases the risk of developing type 2 diabetes, cardiovascular diseases, and metabolic syndrome. In the offspring, exposure to GD in utero predisposes them to obesity, glucose intolerance, and metabolic disorders later in life. This review aims to elucidate the complex cellular and molecular mechanisms underlying GD to inform the development of effective therapeutic strategies. A systematic review was conducted using medical subject headings (MeSH) terms related to GD’s cellular and molecular pathophysiology. Inclusion criteria encompassed original studies, systematic reviews, and meta-analyses focusing on GD’s impact on maternal and fetal health, adhering to PRISMA guidelines. Data extraction captured study characteristics, maternal and fetal outcomes, key findings, and conclusions. GD disrupts insulin signaling pathways, leading to impaired glucose uptake and insulin resistance. Mitochondrial dysfunction reduces ATP production and increases reactive oxygen species, exacerbating oxidative stress. Hormonal influences, chronic inflammation, and dysregulation of the mammalian target of rapamycin (mTOR) pathway further impair insulin signaling. Gut microbiota alterations, gene expression, and epigenetic modifications play significant roles in GD. Ferroptosis and placental dysfunction primarily contribute to intrauterine growth restriction. Conversely, fetal macrosomia arises from maternal hyperglycemia and subsequent fetal hyperinsulinemia, resulting in excessive fetal growth. The chronic inflammatory state and oxidative stress associated with GD exacerbate these complications, creating a hostile intrauterine environment. GD’s complex pathophysiology involves multiple disruptions in insulin signaling, mitochondrial function, inflammation, and oxidative stress. Effective management requires early detection, preventive strategies, and international collaboration to standardize care and improve outcomes for mothers and babies.

Omega-3 Fatty Acids and Neuroinflammation in Depression: Targeting Damage-Associated Molecular Patterns and Neural Biomarkers

Major Depressive Disorder (MDD) is a prevalent mental health condition with a complex pathophysiology involving neuroinflammation, neurodegeneration, and disruptions in neuronal and glial cell function. Microglia, the innate immune cells of the central nervous system, release inflammatory cytokines in response to pathological changes associated with MDD. Damage-associated molecular patterns (DAMPs) act as alarms, triggering microglial activation and subsequent inflammatory cytokine release. This review examines the cellular mechanisms underlying MDD pathophysiology, focusing on the lipid-mediated modulation of neuroinflammation. We explore the intricate roles of microglia and astrocytes in propagating inflammatory cascades and discuss how these processes affect neuronal integrity at the cellular level. Central to our analysis are three key molecules: High Mobility Group Box 1 (HMGB1) and S100 Calcium Binding Protein β (S100β) as alarmins, and Neuron-Specific Enolase (NSE) as an indicator of neuronal stress. We present evidence from in vitro and ex vivo studies demonstrating how these molecules reflect and contribute to the neuroinflammatory milieu characteristic of MDD. The review then explores the potential of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) as neuroinflammation modulators, examining their effects on microglial activation, cytokine production, and neuronal resilience in cellular models of depression. We critically analyze experimental data on how ω-3 PUFA supplementation influences the expression and release of HMGB1, S100β, and NSE in neuronal and glial cultures. By integrating findings from lipidomic and cellular neurobiology, this review aims to elucidate the mechanisms by which ω-3 PUFAs may exert their antidepressant effects through modulation of neuroinflammatory markers. These insights contribute to our understanding of lipid-mediated neuroprotection in MDD and may inform the development of targeted, lipid-based therapies for both depression and neurodegenerative disorders.

Mild cognitive impairment in amyotrophic lateral sclerosis: current view.

Amyotrophic lateral sclerosis (ALS) is a fatal multi-system neurodegenerative disorder with no effective treatment or cure. Although primarily characterized by motor degeneration, cognitive dysfunction is an important non-motor symptom that has a negative impact on patient and caregiver burden. Mild cognitive deficits are present in a subgroup of non-demented patients with ALS, often preceding motor symptoms. Detailed neuropsychological assessments reveal deficits in a variety of cognitive domains, including those of verbal fluency and retrieval, language, executive function, attention and verbal memory. Mild cognitive impairment (MCI), a risk factor for developing dementia, affects between 10% and over 50% of ALS patients. Neuroimaging revealed atrophy of frontal and temporal cortices, disordered white matter Integrity, volume reduction in amygdala and thalamus, hypometabolism in the frontal and superior temporal gyrus and anterior insula. Neuronal loss in non-motor brain areas, associated with TDP-43 deposition, one of the morphological hallmarks of ALS, is linked to functional disruption of frontostriatal and frontotemporo-limbic connectivities as markers for cognitive deficits in ALS, the pathogenesis of which is still poorly understood. Early diagnosis by increased cerebrospinal fluid or serum levels of neurofilament light/heavy chain or glial fibrillary acidic protein awaits confirmation for MCI in ALS. These fluid biomarkers and early detection of brain connectivity signatures before structural changes will be helpful not only in establishing early premature diagnosis but also in clarifying the pathophysiological mechanisms of MCI in ALS, which might serve as novel targets for prohibition/delay and future adequate treatment of this debilitating disorder.

Impaired striatal glutathione-ascorbate metabolism induces transient dopamine increase and motor dysfunction.

Identifying initial triggering events in neurodegenerative disorders is critical to developing preventive therapies. In Huntington's disease (HD), hyperdopaminergia-probably triggered by the dysfunction of the most affected neurons, indirect pathway spiny projection neurons (iSPNs)-is believed to induce hyperkinesia, an early stage HD symptom. However, how this change arises and contributes to HD pathogenesis is unclear. Here, we demonstrate that genetic disruption of iSPNs function by Ntrk2/Trkb deletion in mice results in increased striatal dopamine and midbrain dopaminergic neurons, preceding hyperkinetic dysfunction. Transcriptomic analysis of iSPNs at the pre-symptomatic stage showed de-regulation of metabolic pathways, including upregulation of Gsto2, encoding glutathione S-transferase omega-2 (GSTO2). Selectively reducing Gsto2 in iSPNs in vivo effectively prevented dopaminergic dysfunction and halted the onset and progression of hyperkinetic symptoms. This study uncovers a functional link between altered iSPN BDNF-TrkB signalling, glutathione-ascorbate metabolism and hyperdopaminergic state, underscoring the vital role of GSTO2 in maintaining dopamine balance.

Biotinidase Deficiency and Aplasia Cutis Congenita with Ecterodactyly Syndrome (ACCES) in a case of Moya Moya Disease: A Missing Link

Biotinidase Deficiency (BD) is a rare autosomal recessive disorder caused by mutations in the BTD gene, leading to impaired biotin recycling and disruption in energy metabolism, oxidative stress, and blood-brain barrier function. This condition increases the risk of neurovascular events such as strokes. In parallel, the UBA2 gene's loss of function, through various mutations, results in Aplasia Cutis Congenita with Ectrodactyly (ACCES) syndrome, an autosomal dominant disorder with highly variable expressivity. ACCES syndrome commonly presents with scalp defects and less frequently with ectrodactyly, alongside other subtle skeletal anomalies, early growth deficiency, and neurodevelopmental delay. This case report discusses a 6-year-old child presenting with an acute stroke and distinct dysmorphic features, highlighting a rare association between Biotinidase Deficiency and ACCES syndrome, which likely contributed to the development of Moya Moya Disease (MMD), a rare progressive cerebrovascular disorder. The case suggests that the combination of neurovascular stress due to both BD and ACCES may increase the risk of stroke and MMD in affected individuals. This underscores the importance of recognizing overlapping genetic conditions that could lead to severe neurovascular complications.

Drosophila Trus, the orthologue of mammalian PDCD2L, is required for proper cell proliferation, larval developmental timing, and oogenesis.

Ribosomes are essential macromolecular machines required for decoding mRNA to make proteins, the major biomolecules that carry out all central cellular functions. As such, their structural and operational integrity is critical to organismal survival, and mutations that disrupt proper stoichiometry or assembly of ribosomes produce serious pathological consequences during an organism's development and/or adult life. The ribosome assembly factor PDCD2L is highly conserved from yeast to man, yet its overall function and requirement during development is poorly understood. By examining the developmental consequences of null mutations in trus , which encodes the Drosophila PDCD2L homolog, we demonstrate an essential role for this factor in cell-cycle regulation. Furthermore, disruption of Trus function in mitotically dividing imaginal tissue activates the Xrp1-dilp8 stress response pathway which limits production of ecdysone, the major arthropod molting hormone, leading to severe developmental delay during larval stages. These studies provide new insights on the requirements of this highly conserved ribosome assemble factor during development.

Shared and unique lifetime stressor characteristics and brain networks predict adolescent anxiety and depression.

Exposure to major life stressors and aberrant brain functioning have been linked to anxiety and depression, especially during periods of heighted functional brain plasticity, such as adolescence. However, it remains unclear if specific characteristics of major life stressors and functional network disruptions differentially predict anxiety and depression symptoms over time and, if so, whether they act independently or jointly. We collected baseline lifetime stressor exposure data and resting-state functional magnetic resonance imaging data in a longitudinal sample of 107 adolescents enriched for anxiety and depressive disorders. We examined five stressor characteristics: physical danger, interpersonal loss, humiliation, entrapment, and role change/disruption. Anxiety and depression symptoms were assessed at baseline, 6-month and 12-month follow-ups. Linear mixed effect models tested if these stressor characteristics, functional connectivity within and between frontoparietal, default, and ventral attention networks, and their interactions differentially predicted anxiety and depression symptoms at 6-month and 12-month follow-ups. Greater lifetime severity of physical danger and humiliation prospectively predicted increased anxiety symptoms at both follow-ups, whereas greater lifetime entrapment severity prospectively predicted higher anxiety and depression symptoms. Only the effects of lifetime entrapment severity were robust to including within- and between-network functional connectivity metrics and other significantly predictive stressor characteristics. Lifetime entrapment severity more strongly predicted anxiety symptoms in youth with higher default network connectivity. Greater functional connectivity between frontoparietal and default networks prospectively predicted increased depression symptoms. Taken together, these results underscore the critical importance of using stressor characteristics and functional connectivity jointly to study predictors for adolescent anxiety and depression.

The Interplay of the Mammalian Brain and Thyroid Hormones, and the Threat of Endocrine-Disrupting Chemicals

Introduction: During the formation of neural circuits, the developing brain demonstrates extraordinary plasticity, heavily influenced by hormones. These chemical messengers interact with specific receptors to regulate vital physiological functions. The thyroid gland plays a pivotal role in maintaining hormonal balance and guiding brain development. However, emerging threats like endocrine-disrupting chemicals (EDCs) can interfere with this intricate system. EDCs are exogenous substances that can mimic, enhance, or block the actions of endogenous hormones, disrupting hormonal signaling in the brain at various developmental stages. Exposure can impair cognitive function and behavior due to disruptions in thyroid function. Studies indicate that mixtures of EDCs negatively impact brain development, leading to lower IQ and behavioral problems. Reducing EDC exposure through regulations and public awareness is crucial, and further research is needed to elucidate their mechanisms. Conclusions: Protecting vulnerable populations, such as pregnant women and children, is essential through prompt regulatory measures.

Integrated systems biology identifies disruptions in mitochondrial function and metabolism as key contributors to heart failure with preserved ejection fraction (HFpEF).

Heart failure with preserved ejection fraction (HFpEF) accounts for ∼50% of HF cases, with no effective treatments. The ZSF1-obese rat model recapitulates numerous clinical features of HFpEF including hypertension, obesity, metabolic syndrome, exercise intolerance, and LV diastolic dysfunction. Here, we utilized a systems-biology approach to define the early metabolic and transcriptional signatures to gain mechanistic insight into the pathways contributing to HFpEF development. Male ZSF1-obese, ZSF1-lean hypertensive controls, and WKY (wild-type) controls were compared at 14w of age for extensive physiological phenotyping and LV tissue harvesting for unbiased metabolomics, RNA-sequencing, and assessment of mitochondrial morphology and function. Utilizing ZSF1-lean and WKY controls enabled a distinction between hypertension-driven molecular changes contributing to HFpEF pathology, versus hypertension + metabolic syndrome. ZSF1-obese rats displayed numerous clinical features of HFpEF. Comparison of ZSF1-lean vs WKY (i.e., hypertension-exclusive effects) revealed metabolic remodeling suggestive of increased aerobic glycolysis, decreased β-oxidation, and dysregulated purine and pyrimidine metabolism with few transcriptional changes. ZSF1-obese rats displayed worsened metabolic remodeling and robust transcriptional remodeling highlighted by the upregulation of inflammatory genes and downregulation of the mitochondrial structure/function and cellular metabolic processes. Integrated network analysis of metabolomic and RNAseq datasets revealed downregulation of nearly all catabolic pathways contributing to energy production, manifesting in a marked decrease in the energetic state (i.e., reduced ATP/ADP, PCr/ATP). Cardiomyocyte ultrastructure analysis revealed decreased mitochondrial area, size, and cristae density, as well as increased lipid droplet content in HFpEF hearts. Mitochondrial function was also impaired as demonstrated by decreased substrate-mediated respiration and dysregulated calcium handling. Collectively, the integrated omics approach applied here provides a framework to uncover novel genes, metabolites, and pathways underlying HFpEF, with an emphasis on mitochondrial energy metabolism as a potential target for intervention.

Method for disrupting the reproductive pheromone bond of the cotton bollworm on sunflower crops

Background: Synthetic analogs of sexual pheromones provide an effective method of biorational control of the number of phytophagous insects based on the directed disruption of reproductive functions in populations of the target pest on the protected crop without affecting the integrity of the agrocenosis. The work aims to determine the biological effectiveness of methods of mass trapping and disorientation of the cotton bollworm (Helicoverpa armigera) to protect sunflower (Helianthus annuus) crops.Methods: The experiments were carried out in 2022-2023 in the Central Zone of the Krasnodar Territory, Russia in the stationary scientific crop rotation at the Federal Research Center for Biological Plant Protection, Krasnodar (2.5 ha) and the Kononenko farm, Novovelichkovskaya village, Dinsky district (10 ha). The biological effectiveness of elimination and disorientation methods was judged by the degree of damage to plants and buds. The disorientation effect was calculated by the number of males captured at the disorientation sites compared to the control sites.Result: The decrease in males’ search activity (disorientation effect) reached 85.3%. The damage to buds by the pest in this variant was 2.0% compared to 10.8% in the control group. In the mass trapping variant, it equaled 1.5-3.0 and 7.5%, respectively, indicating the prospects of including these techniques in the H. armigera biorational control system.Conclusion: Our findings could aid future research on insect chemical communication to develop effective biological control methods.Keywords: Biological plant protection; Sunflower; Cotton bollworm; Synthetic sex pheromones; Elimination; Disorientation; Biological effectiveness

Functional network disruptions in youth with concussion using the Adolescent Brain Cognitive Development study

ABSTRACT Objective This study aimed to compare psychosocial outcomes and functional neuroimaging among youth with concussion, youth with anxiety, and age- and sex-matched controls. Methods Using archival data from the Adolescent Brain Cognitive DevelopmentSM Study, we analyzed between-group differences in psychosocial outcomes measured by the Child Behavior Checklist’s internalizing and externalizing problem scales, and assessed brain function using resting-state fMRI network-region connectivity (specifically frontoparietal network (FPN) and default mode network (DMN) connectivity with the amygdala). Results Significant differences in psychosocial outcomes were found across all groups, with the anxiety group reporting the most internalizing problems, followed by the concussion group which significantly differed from controls. Additionally, FPN-amygdala connectivity was significantly reduced in the concussion group only; this reduced connectivity did not predict psychosocial outcomes across groups. Conclusion This study provided preliminary findings that brain connectivity is reduced exclusively in individuals with concussion. Although disruptions were observed in the concussion group, further investigation is warranted to understand how disruptions may be associated with concussion symptoms. Studies that utilize well-defined control and study groups, and comprehensive cognitive and mental health measures will offer a deeper understanding of the relationship between brain function and psychosocial outcomes.

Regulation of Mitochondrial and Peroxisomal Metabolism in Female Obesity and Type 2 Diabetes.

Obesity and type 2 diabetes (T2D) are widespread metabolic disorders that significantly impact global health today, affecting approximately 17% of adults worldwide with obesity and 9.3% with T2D. Both conditions are closely linked to disruptions in lipid metabolism, where peroxisomes play a pivotal role. Mitochondria and peroxisomes are vital organelles responsible for lipid and energy regulation, including the β-oxidation and oxidation of very long-chain fatty acids (VLCFAs), cholesterol biosynthesis, and bile acid metabolism. These processes are significantly influenced by estrogens, highlighting the interplay between these organelles' function and hormonal regulation in the development and progression of metabolic diseases, such as obesity, metabolic dysfunction-associated fatty liver disease (MAFLD), and T2D. Estrogens modulate lipid metabolism through interactions with nuclear receptors, like peroxisome proliferator-activated receptors (PPARs), which are crucial for maintaining metabolic balance. Estrogen deficiency, such as in postmenopausal women, impairs PPAR regulation, leading to lipid accumulation and increased risk of metabolic disorders. The disruption of peroxisomal-mitochondrial function and estrogen regulation exacerbates lipid imbalances, contributing to insulin resistance and ROS accumulation. This review emphasizes the critical role of these organelles and estrogens in lipid metabolism and their implications for metabolic health, suggesting that therapeutic strategies, including hormone replacement therapy, may offer potential benefits in treating and preventing metabolic diseases.

Ameliorative Effects of N-Acetyl Cysteine and Zinc Sulfate on Reproductive Dysfunction Induced by Short-Term Crude Oil Exposure in Male Wistar Rats

Background: Crude oil contamination by accidental or voluntary ingestion is prevalent in the Niger Delta region of Nigeria. One of the possible impacts of crude oil contamination is reproductive toxicity leading to infertility. The present study evaluated the potential protective effects of N-Acetyl Cysteine (NAC) and Zinc Sulfate (ZnSO4) in mitigating reproductive dysfunction caused by short-term Bonny Light Crude oil (BLCO) exposure in male Wistar rats. Materials and Methods: Fifty (50) male Wistar (180 – 200g) were used for the study. They were divided into ten (10) groups of five (5) animals each. Groups I and II served as the control and negative control and received distilled water and BLCO (600mg/kg) respectively while groups III to X served as the experimental groups and received NAC (100 and 200mg/kg) and ZnSO4 (0.5mg/kg and 1mg/kg) orally for three (3) weeks. Animals were euthanized, and blood and semen were collected for biochemical and seminal analysis. Results: The results of this current study show that BLCO exposure caused a disruption in reproductive functions in rats by decreasing reproductive hormones and semen quality parameters in Wistar rats. NAC and ZnSO4 administration significantly improved semen quality parameters by improving sperm count, sperm motility and morphology in experimental rats. Conclusion: Evidence from the present study suggests that NAC and ZnSO4 protected the testes, preventing reproductive alterations linked to BLCO exposure.

AIBP Protects Müller Glial Cells Against Oxidative Stress-Induced Mitochondrial Dysfunction and Reduces Retinal Neuroinflammation.

Glaucoma, an optic neuropathy with the loss of retinal ganglion cells (RGCs), is a leading cause of irreversible vision loss. Oxidative stress and mitochondrial dysfunction have a significant role in triggering glia-driven neuroinflammation and subsequent glaucomatous RGC degeneration in the context of glaucoma. It has previously been shown that apolipoprotein A-I binding protein (APOA1BP or AIBP) has an anti-inflammatory function. Moreover, Apoa1bp-/- mice are characterized by retinal neuroinflammation and RGC loss. In this study, we found that AIBP deficiency exacerbated the oxidative stress-induced disruption of mitochondrial dynamics and function in the retina, leading to a further decline in visual function. Mechanistically, AIBP deficiency-induced oxidative stress triggered a reduction in glycogen synthase kinase 3β and dynamin-related protein 1 phosphorylation, optic atrophy type 1 and mitofusin 1 and 2 expression, and oxidative phosphorylation, as well as the activation of mitogen-activated protein kinase (MAPK) in Müller glia dysfunction, leading to cell death and inflammatory responses. In vivo, the administration of recombinant AIBP (rAIBP) effectively protected the structural and functional integrity of retinal mitochondria under oxidative stress conditions and prevented vision loss. In vitro, incubation with rAIBP safeguarded the structural integrity and bioenergetic performance of mitochondria and concurrently suppressed MAPK activation, apoptotic cell death, and inflammatory response in Müller glia. These findings support the possibility that AIBP promotes RGC survival and restores visual function in glaucomatous mice by ameliorating glia-driven mitochondrial dysfunction and neuroinflammation.