Alterations In Levels Research Articles

Kisspeptin and Endometriosis—Is There a Link?

This article presents a narrative review that explores the potential link between kisspeptin—a key regulator of the hypothalamic-pituitary-gonadal axis—and the pathogenesis of endometriosis. Kisspeptin plays a significant role in regulating reproductive functions by modulating the release of gonadotropin-releasing hormone (GnRH), which in turn stimulates the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Recent studies suggest that kisspeptin may also impact peripheral reproductive tissues and influence inflammatory processes involved in the development of endometriosis. Altered kisspeptin signaling has been associated with the abnormal hormonal environment observed in endometriosis, which affects menstrual cycles and ovarian function. Research indicates that women with endometriosis exhibit altered levels of kisspeptin and its receptor, KISS1R, in both eutopic and ectopic endometrial tissues, suggesting a role in disease progression, particularly in tissue invasion and lesion formation. Kisspeptin’s role in regulating matrix metalloproteinases (MMPs), enzymes essential for tissue remodeling, further supports its potential contribution to the pathophysiology of endometriosis. Moreover, kisspeptin-based therapeutic strategies are currently under investigation, with the aim of providing targeted treatments that reduce the side effects commonly associated with existing therapies. Despite promising findings, further research is needed to fully understand the mechanisms by which kisspeptin influences endometriosis.

Altered eotaxin-1 and interleukin-34 levels in obsessive-compulsive disorder: a case-control observational study in Bangladesh.

Obsessive-compulsive disorder (OCD) is a prevalent mental health condition that impacts daily life. It is thought to be associated with genetic, biological, and structural brain changes, serotonergic abnormalities, altered neuromodulation, and environmental factors. Limited observational studies have examined cytokines in Bangladeshi patients with OCD. This study aimed to assess the levels of eotaxin-1 and interleukin (IL)-34 in individuals with this disorder. This case-control observational study included 58 patients with OCD and 30 healthy controls (HCs) matched for age, sex, and body mass index. The severity of OCD was assessed using the Yale-Brown obsessive-compulsive scale (Y-BOCS). Psychiatrists evaluated participants according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Serum levels of eotaxin-1 and IL-34 were measured using enzyme-linked immunosorbent assay kits. Patients with OCD exhibited significantly higher serum eotaxin-1 levels (121.13±7.84 pg/mL) than HCs (85.52±9.42 pg/mL). Conversely, IL-34 levels were considerably lower in patients than in HCs (119.02±14.53 pg/mL vs. 179.96±27.88 pg/mL). The Cohen d values for eotaxin-1 and IL-34 were 0.55 and -0.48, respectively. Among patients with OCD, a significant positive correlation was found between serum eotaxin-1 level and Y-BOCS score, along with a negative correlation between serum eotaxin-1 and IL-34 levels. The findings suggest that altered eotaxin-1 and IL-34 levels may be associated with OCD. These chemokines and cytokines could serve as primary tools for assessing the risk of OCD, warranting further clinical investigation. This could potentially support more extensive research and the development of diagnostic and therapeutic strategies targeting these pathways.

Changes in Circulating Levels of Long Non-Coding RNA p5549 and p19461 Following Metabolic Bariatric Surgery (MBS): A Prospective Study.

Obesity is attributed to a combination of factors such as lifestyle, environmental influences, and genetic background. Nowadays, the issue of obesity has grown to an epidemic scale. Environmental changes, having contributed to the sharp rise in obesity prevalence, are not the only contributing etiologic factors. Inherent biological variables interact with environmental factors resulting in obesity. Epigenetic mechanisms may explain part of obesity heritability. One of the recently discovered epigenetic mechanisms for controlling gene expression is long non-coding RNAs (lncRNAs). Circulating lncRNA p5549 and p19461 levels were reported to be significantly lower in individuals with obesity. This study aimed to evaluate whether weight loss following metabolic/bariatric surgery (MBS) can be related to altered expression levels of those lncRNAs, which have been reported to be reduced in individuals with obesity. Comparison of circulating levels of lncRNA p5549 and p19461 before and 12weeks after MBS in thirty-four patients was conducted to evaluate whether MBS can revert the altered levels of these lncRNAs. None of the participating patients were lost to follow-up, and all underwent re-evaluation of post-surgical expression levels. lncRNA p5549 expression levels in serum were found to increase significantly in the postoperative samples compared to preoperative samples (fold increase: 4.63 ± 7.68, p = 0.014). Epigenetic changes in patients with obesity, specifically lncRNA-p5549 expression levels, are reversed after MBS. The postoperative increase in the expression levels of lncRNA- p19461 was not statistically significant.

Neurotransmitter Dysregulation in Sleep and Circadian Rhythms: Implications for Postpartum Depression

Postpartum depression (PPD) is a major mental health disorder that affects mothers both emotionally and physically, hindering their ability to care for the child. Other neurotransmitter imbalances during the postpartum period include serotonin, dopamine, melatonin, GABA, and orexin, which result in disturbances in sleep. The reduction in serotonin concentration is related to mood and sleep, while altered dopamine levels are related to alertness and coordinating circadian rhythms. Further, women postpartum demonstrates higher melatonin levels and a subsequent neuronal excitation due to lesser functioning GABA-A receptors, which in addition combine to cause disturbances with sleep. This paper reviews the literature to analyze the effects of neurotransmitter disorders in sleep and circadian rhythm on postpartum depression. The review provides emerging treatment options for postpartum depression including selective serotonin reuptake inhibitors (SSRIs), melatonin agonists, and benzodiazepines, which have shown promising results in relieving symptoms by modulating neurotransmitter pathways. However, more research needs to be undertaken in the field of non-pharmacological interventions, the long-term outcome of neurotransmitter dysregulation, and preventive measures during pregnancy that would go a long way toward improving overall outcomes for mothers as well as their infants.

A structure-based in silico analysis of the Kell blood group system

Kell is one of the most complex blood group systems, with a highly polymorphic genetic background. Extensive allelic variations in the KEL gene affect the encoded erythrocyte surface protein Kell. Genetic variants causing aberrant splicing, premature termination of protein translation, or specific amino acid exchanges lead to a variety of different phenotypes with altered Kell expression levels or changes in the antigenic properties of the Kell protein. Using an in silico structural model of the Kell protein, we analyzed the biophysical and structural context of all full-length Kell variants of known phenotype. The results provided insights regarding the 3D co-localization of antigenic Kell variants and led us to suggest several conformational epitopes on the Kell protein surface. We found a number of correlations between the properties of individual genetic variants in the Kell protein and their respective serological phenotypes, which we used as a search filter to predict potentially new immunogenic Kell variants from an in-house whole exome sequencing dataset of 19,772 exomes. Our analysis workflow and results aid blood group serologists in predicting whether a newly identified Kell genetic variant may result in a specific phenotype.

Study of gene expression of the Toll-like receptor system in the forebrain cortex of rat pups with prenatal alcohol exposure and pharmacologic correction with rifampicin

Ethanol causes changes in the toll-like receptor (TLR) system in the brain promoting activation of neuroinflammatory pathways. Alcohol consumption during pregnancy induces neuroinflammatory processes in the fetus, which can lead to the development of symptoms of fetal alcohol spectrum disorder (FASD). Modeling prenatal alcohol exposure in our experiment resulted in changes in the expression of TLR system genes (Tlr3, Tlr4, Hmgb1, Trif, cytokine genes) in the forebrain cortex of baby rats. The administration of rifampicin (from the first to the seventh day of neonatal development) normalized the altered expression level of the studied genes. This suggests that rifampicin may prevent the development of persistent neuroinflammatory phenomena in the forebrain cortex of baby rats.

O-Acetyl Bakuchiol exhibit Analgesic, Anti-inflammatory and Anti-arthritic effects: A combined in silico and in vivo experimental study.

In the present manuscript, we evaluated the analgesic, anti-inflammatory and anti-arthritic effects of bakuchiol derivative, O-Acetyl bakuchiol (BAc) at 5, 10 and 20 mg/kg p.o. dose in adult female Sprague Dawley rats.BAc at 20 mg/kg p.o. exhibited maximum analgesic (47.4%), anti-inflammatory (66.50%) and antiarthritic effects. Among the different parameters,BAc at 20 mg/kg increased the body weight (2.89%), decreased the paw thickness (72.46%)) and paw inflammation (48.59%) in FCA induced arthritic rats. In hematological/serum and biochemical parameters, BAc at 20 mg/kg brought the altered level of ESR, Hb, HCT, RBC, TLC and platelet count, HDL, cholesterol, triglycerides, CRP and RA factornear to the normal. Moreover, the spleen weight was also reduced in BAc treated rats at 20 mg/kg. Histopathological analysis further revealed that a reduction in paw inflammation was observed in paw ankle joints and no inflammation was observed in brain, liver, lungs and kidney in BAc treated rats at 20 mg/kg p.o. Molecular docking studies further revealed that BAc has better binding affinity for TNF-α (PDB ID: 7JRA) -7.19 kcal/mol comparable to standard methotrexate with binding affinity -9.56 kcal/mol. Therefore, the present investigation provided the basis for the development of BAc as potential candidate for the treatment of arthritis.

DNA and RNA Methylation in Periodontal and Peri-implant Diseases.

Periodontal and peri-implant diseases are primarily biofilm-induced pathologies in susceptible hosts affecting the periodontium and dental implants. Differences in disease susceptibility, severity, and patterns of progression have been attributed to immune regulatory mechanisms such as epigenetics. DNA methylation is an essential epigenetic mechanism governing gene expression that plays pivotal roles in genomic imprinting, chromosomal stability, apoptosis, and aging. Clinical studies have explored DNA methylation inhibitors for cancer treatment and predictive methylation profiles for disease progression. In periodontal health, DNA methylation has emerged as critical, evidenced by clinical studies unraveling its complex interplay with inflammatory genes and its regulatory role in periodontitis contributing to disease severity. Human studies have shown that methylation enzymes associated with gene reactivation (e.g., ten-eleven translocation-2) are elevated in periodontitis compared with gingivitis. Dysregulation of these genes can lead to the production of inflammatory cytokines and an altered initial response to bacteria via the toll-like receptor signaling pathway in periodontal diseases. In addition, in peri-implant diseases, this dysregulation can result in altered DNA methylation levels and enzymatic activity influenced by the properties of the titanium surface. Beyond traditional perspectives, recent evidence highlights the involvement of RNA methylation (e.g., N6-methyladenosine [m6A], N6,2'-0-dimethyladenosine [m6Am]) in periodontitis and peri-implantitis lesions, playing vital roles in the innate immune response, production of inflammatory cytokines, and activation of dendritic cells. Both DNA and RNA methylation can influence the gene expression, virulence, and bacterial behavior of well-known periodontal pathogens such as Porphyromonas gingivalis. Alterations in bacterial methylation patterns result in changes in the metabolism, drug resistance, and gene expression related to survival in the host, thereby promoting tissue degradation and chronic inflammatory responses. In summary, the present state-of-the-art review navigates the evolving landscape of DNA and RNA methylation in periodontal and peri-implant diseases, integrating recent developments and mechanisms to reshape the understanding of epigenetic dynamics in oral health.

Virtual reality-guided therapy on a stroke unit: a feasibility study

BackgroundVR (Virtual Reality) has emerged as a recent treatment approach in neurorehabilitation. The feasibility of VR-guided therapy in the acute phase after stroke has not been assessed.MethodsThis was a cohort study of consecutive patients with suspected stroke who were admitted to the Essen University Hospital Stroke Unit between March 2022 and May 2022. All patients who had an indication for physical or occupational therapy due to upper extremity sensorimotor, cognitive or perceptual deficits were included and considered for VR-guided treatment. We excluded patients with predominant deficits in lower extremity function, since these could not be targeted with our VR system. A multidimensional approach was used to assess the feasibility of VR-guided therapy, which included characterization of eligible patients, resource utilization as well as treatment acceptance. For this purpose, we analyzed baseline and clinical characteristics, causes for withholding the treatment as well as qualitative and quantitative treatment metrics in patients who received VR-guided therapy.ResultsOut of 326 patients admitted with suspected stroke, n = 172 were included in our final analysis. Of these, n = 37 (21.5%) received VR-guided therapy. The most common cause for withholding treatment were neuropsychological limitations (22.9%), followed by physical impairment, comorbidity and level of consciousness alterations (all 17.8%). Patients who received VR-guided therapy tended to have better functional status and less severe neurological deficits. VR-guided sessions had a median duration of 20 min (IQR 17–29) with additional 13 min (IQR 9–17) of preparation time. In the majority of patients who received VR-guided therapy, motivation was rated equal or higher as compared with conventional treatment (76%) and therapists considered VR-guided therapy well feasible (65%).ConclusionsDespite important treatment barriers, VR may provide additional opportunities to enhance functional recovery in the acute phase after stroke for selected patients. Our findings could aid in planning further randomized controlled trials which are required to refine approaches and assess the effectiveness of VR-guided therapy in the acute setting.

The RNA-dependent association of phosphatidylinositol 4,5-bisphosphate with intrinsically disordered proteins contribute to nuclear compartmentalization.

The RNA content is crucial for the formation of nuclear compartments, such as nuclear speckles and nucleoli. Phosphatidylinositol 4,5-bisphosphate (PIP2) is found in nuclear speckles, nucleoli, and nuclear lipid islets and is involved in RNA polymerase I/II transcription. Intriguingly, the nuclear localization of PIP2 was also shown to be RNA-dependent. We therefore investigated whether PIP2 and RNA cooperate in the establishment of nuclear architecture. In this study, we unveiled the RNA-dependent PIP2-associated (RDPA) nuclear proteome in human cells by mass spectrometry. We found that intrinsically disordered regions (IDRs) with polybasic PIP2-binding K/R motifs are prevalent features of RDPA proteins. Moreover, these IDRs of RDPA proteins exhibit enrichment for phosphorylation, acetylation, and ubiquitination sites. Our results show for the first time that the RDPA protein Bromodomain-containing protein 4 (BRD4) associates with PIP2 in the RNA-dependent manner via electrostatic interactions, and that altered PIP2 levels affect the number of nuclear foci of BRD4 protein. Thus, we propose that PIP2 spatiotemporally orchestrates nuclear processes through association with RNA and RDPA proteins and affects their ability to form foci presumably via phase separation. This suggests the pivotal role of PIP2 in the establishment of a functional nuclear architecture competent for gene expression.

Neurometabolite, myo-inositol, induces conformational distortion with enhanced aggregation of Carbonic Anhydrase: Implications for altered metabolite levels in Alzheimer's disease

Neurometabolite, myo-inositol, induces conformational distortion with enhanced aggregation of Carbonic Anhydrase: Implications for altered metabolite levels in Alzheimer's disease

Associations of per- and polyfluoroalkyl substances and alternatives with subclinical hypothyroidism in children: A cross-sectional study in China

There is growing experimental and epidemiological evidence linking perfluoroalkyl and polyfluoroalkyl substances (PFAS) exposure to thyroid dysfunction; however, the association between PFAS and their alternatives to subclinical hypothyroidism in children remains to be elucidated. This study investigated the association between 30 PFASs and thyroid function using serum samples from 194 children (aged 3–17 years) who participated in the Zhejiang Human Biomonitoring Program. Various thyroid function indicators, including free triiodothyronine, free thyroxine (FT4), and thyrotropin, were tested, and subclinical hypothyroidism was diagnosed. Linear regression was employed to examine the associations between individual PFASs and thyroid hormone levels, and logistic regression was applied to assess their associations with subclinical hypothyroidism. The quantile g-computation (qgcomp) method was used to examine the combined and individual effects of PFAS mixtures on thyroid function. Both PFASs and their alternatives were associated with altered thyroid hormone levels and subclinical hypothyroidism. A higher level of perfluorohexanoic acid (PFHpA) was associated with decreased FT4 with a reduction of −0.028 pmol/L (95 % confidence interval [95 % CI]: −0.047, −0.008) per unit increase as well as increased odds of subclinical hypothyroidism (odds ratio [OR] = 1.95; 95 % CI: 1.11, 3.53). Moreover, a higher PFAS mixture was associated with elevated odds of subclinical hypothyroidism (OR = 3.72; 95 % CI: 1.08, 12.85), in which PFHpA, in conjunction with 6:2 chlorinated perfluoroalkyl ether sulfonic acid, accounted for the greatest proportion of the variance. These findings augment our understanding of the adverse effects of PFASs and their alternatives on thyroid homeostasis, underscoring the need for further epidemiological research.

Unravelling neuronal and glial differences in ceramide composition, synthesis, and sensitivity to toxicity

Ceramides are lipids that play vital roles in complex lipid synthesis, membrane function, and cell signaling. Disrupted ceramide homeostasis is implicated in cell-death and several neurologic diseases. Ceramides are often analyzed in tissue, but this approach fails to resolve cell-type differences in ceramide homeostasis that are likely essential to understanding cell and non-cell autonomous contributions to neurodegeneration. We show that human iPSC-derived neurons and glia differ in their rate of ceramide synthesis, ceramide isoform composition, and responses to altered ceramide levels. RNA-sequencing of cells treated to increase or decrease ceramides revealed connections to inflammation, ER stress, and apoptosis. Moreover, introducing labeled sphinganine showed that glia readily synthesize ceramide de novo and that neurons are relatively more sensitive to ceramide toxicity. Our findings provide a framework for understanding neurologic diseases with sphingolipid alternations and insights into designing therapeutics that target ceramide for treating them.

Biological Markers in the Gingival Crevicular Fluid Associated with External Invasive Resorption: A Split-Mouth Cross-Sectional Study

IntroductionThis study aimed to investigate the levels of interleukin-1 receptor antagonist (IL-1RA), receptor activator of nuclear factor-κB ligand (RANKL), osteoprotegerin (OPG), interleukin-1β (IL-1β), osteopontin (OPN), and tissue necrotizing factor-α (TNF-α) in teeth with external invasive resorption (EIR) in comparison to the contralateral healthy tooth of the same patient. Materials and MethodsTwenty-nine patients with at least one tooth with EIR and a healthy tooth on the contralateral side (33 paired teeth) were included. Data on patient demographics and medical and dental history were collected. Gingival crevicular fluid was collected from the subject and control teeth. Clinical, radiographical, and cone-beam computed tomography examinations were performed. Wilcoxon signed-rank test was used to compare biomarker concentrations, RANKL/OPG, and IL-1RA/IL-1β ratios in the diseased and healthy teeth. Teeth pairs were grouped based on Heithersay and Patel’s classification, and the differences in biomarker concentrations between diseased and healthy teeth were compared using a Kruskal-Wallis test. ResultsTeeth with EIR had significantly lower concentrations of IL-1RA and OPG compared to their respective healthy control teeth (p<0.05). The RANKL/OPG ratio in teeth with EIR was significantly higher than in their paired healthy teeth (p<0.05). A history of herpes zoster infection (HZI) was associated with a higher IL-1RA concentration and RANKL/OPG ratio (p<0.05). Orthodontic treatment was significantly associated with lower OPG concentration (p<0.05). ConclusionsThere is a significant association between EIR and specific biological markers. A history of orthodontic treatment and HZI are significantly associated with altered levels of biomarkers in the GCF.

Identification of coilin interactors reveals coordinated control of Cajal body number and structure.

The cell nucleus contains distinct biomolecular condensates that form at specific genetic loci, organize chromosomes in 3D space, and regulate RNA processing. Among these, Cajal bodies (CBs) require key "scaffolding" proteins for their assembly, which is not fully understood. Here, we employ proximity biotinylation, mass spectrometry, and functional screening to comprehensively identify and test the functions of CB components. We document 144 protein interactors of coilin, of which 70 were newly detected, and establish 25 players needed for CB assembly and/or maintenance. Surprisingly, the depletion of nine coilin interactors-mostly constituents of the 60S ribosome (RPLs)-increased CB number and caused subdomains defined by coilin and the survival motor neuron protein (SMN) to merge. These phenotypes were traceable to altered nuclear levels of dimethylarginine. Our data implicate RPL24 and other players in the regulation of CBs by modulating posttranslational modifications. Moreover, the prevalence of transcription factors among the identified components highlights roles for gene activity in CB assembly and nuclear positioning.

Distinct therapeutic effects of auraptene and umbelliprenin on TNF-α and IL-17 levels in a murine model of chronic inflammation

ObjectiveTo compare the anti-arthritic potential of orally administered auraptene (AUR) and umbellliprenin (UMB) in chronic inflammation by exploring the differential effect on regulating TNF-α and IL-17. Methods & materialsSixty male rats were divided into ten groups, and after confirming chronic inflammation, the treatment groups received AUR or UMB orally for 9 days. On day 16, histopathological changes were evaluated. Altered serum levels of the inflammatory cytokines TNF-α and IL-17 were examined as the underlying mechanisms. ResultsAdministering AUR orally at 16 mM/kg caused a significant increase in body weight gain compared to the baseline (p < 0.05), while UMB at a dose of 64 mM/kg significantly reduced edema size (p < 0.01). TNF-α levels were significantly lower in all doses of AUR and UMB treatments compared to the arthritis control group (p < 0.05). Treatment with AUR at all relative doses resulted in a significant decrease in IL-17 levels compared to the arthritis control group (p < 0.05), whereas UMB treatment did not show a significant effect on IL-17 levels. ConclusionAUR and UMB regulate TNF-α and IL-17 differently; AUR inhibits both, showing broad therapeutic potential, while UMB specifically targets TNF-α, showing a specialized role.

Effects of heat stress on global DNA methylation and blood parameters of two strains of laying hens.

This study aimed to determine the global levels of DNA methylation and alterations in hematological and electrolytic parameters of two strains of laying hens subjected to heat stress and thermal comfort in climatic chambers. The experiment was conducted in two climate chambers with 192 laying hens of two strains: Dekalb White and Dekalb Brown. After the seven-day adaptation period, each climate chamber was programmed to a thermal condition for 28 consecutive days: Comfort (THI = 73.8) and Heat Stress (THI = 85.9). Blood samples were collected weekly. At each collection, a total of three milliliters of venous blood was collected from the ulnar wing or jugular vein. The experimental design was a randomized complete block design, with a 2 × 2 factorial scheme with split plots. Blood glucose, complete blood count, pH, ionized calcium, sodium, potassium, chloride, and global DNA methylation were evaluated. Stress increased chloride levels but did not affect the other evaluated blood parameters. At 28days of the experiment, the Dekalb Brown strain showed higher levels of leukocytes and hematocrit and lower concentrations of chloride and sodium compared to the Dekalb White strain. Leukocyte levels, plasma protein, sodium, and ionized calcium remained above reference values for both strains. There were no methylation differences between temperature treatments, but a significant difference was observed between strains at 28days of the experiment. Methylation patterns were independent of the evaluated blood parameters in this study but dependent on the bird strain, suggesting that strains respond with different biological mechanisms to heat adaptation. The absence of correlation does not completely exclude a causal relationship, and further studies are needed to investigate possible physiological and biological associations of blood and how strains respond to different heat adaptive mechanisms.

Prognostic Relevance of Copy Number Losses in Ovarian Cancer.

Aneuploidy is a prevalent cancer feature that occurs in many solid tumors. For example, high-grade serous ovarian cancer shows a high level of copy number alterations and genomic rearrangements. This makes genomic variants appealing as diagnostic or prognostic biomarkers, as well as for their easy detection. In this study, we focused on copy number (CN) losses shared by ovarian cancer stem cells (CSCs) to identify chromosomal regions that may be important for CSC features and, in turn, for patients' prognosis. Array-CGH and bioinformatic analyses on three CSCs subpopulations were performed. Pathway and gene ontology analyses on genes involved in copy number loss in all CSCs revealed a significant decrease in mRNA surveillance pathway, as well as miRNA-mediated gene silencing. Then, starting from these CN losses, we validated their potential prognostic relevance by analyzing the TCGA cohort. Notably, losses of 4q34.3-q35.2, 8p21.2-p21.1, and 18q12.2-q23 were linked to increased genomic instability. Loss of 18q12.2-q23 was also related to a higher tumor stage and poor prognosis. Finally, specific genes mapping in these regions, such as PPP2R2A and TPGS2A, emerged as potential biomarkers. Our findings highlight the importance of genomic alterations in ovarian cancer and their impact on tumor progression and patients' prognosis, offering advance in understanding of the application of numerical aberrations as prognostic ovarian cancer biomarkers.

Association between the variations in metabolic pathways and oral cancer risk: results from a Pakistani case-control study.

Oral cancer (OC) is a significant global health concern, with Pakistan ranking 5th worldwide in OC incidence. Given the poor prognosis, early detection of at-risk individuals is crucial. Genetic factors, particularly single nucleotide polymorphisms (SNPs) in metabolic genes, may influence OC susceptibility. This study investigated the association between SNPs in CYP1A1, COX2, SOD2, and HIF1a genes and OC risk in the Pakistani population. A prospective study was conducted from October 2019 to March 2022, enrolling 215 newly diagnosed OC patients and 410 controls. Genetic variations were analyzed using High-Resolution Melting (HRM)analysis and Sanger sequencing, with protein expression evaluated by ELISA. No significant associations were found between the studied SNPs and OC risk. However, a non-significant trend was observed for the SOD2 variant (rs4880), where the G allele was associated with a higher OC risk than the A allele (p = 0.20). Elevated COX2 and HIF1α levels (p-values of 0.014 and <0.001, respectively) and reduced SOD2 levels (p < 0.0001) were observed in OC patients, while CYP1A1 levels remained similar in both controls and cases. Although SNPs in CYP1A1, COX2, SOD2, and HIF1α were not significantly associated with OC risk in the Pakistani population, altered protein expression levels of COX2, HIF1α and SOD2 suggest additional regulatory mechanisms. Further investigation into post-transcriptional modifications and epigenetic factors could lead to novel biomarkers and therapeutic targets for OC in Pakistan.

Sex Differences in Sleep and Physical Activity Patterns in Autism Spectrum Disorder.

Physical activity (PA) programs have been found to result in improved sleep in males with autism spectrum disorder (ASD), but little is known about the female characteristics. The aim of this work was to assess sex differences in sleep and PA indices using an accelerometer over 7 days and 7 nights. Sleep and PA variables were measured with questionnaires and with accelerometry in twenty-four children with ASD (16 boys, 10.3 ± 2.8; 8 girls, 11.1 ± 3.9). Some significant differences were reported between girls and boys. The total time in bed and wake time after sleep onset (WASO) were significantly higher in girls compared to boys (p < 0.01), whereas sleep efficiency was significantly lower in girls (p < 0.01). The results obtained from the sleep questionnaire (CSHQ) show averages above the threshold of 41 in both groups (the threshold indicates the presence of sleep disorders or low sleep quality). The number of daily steps was significantly lower in the girls' group (p < 0.01), and the PA volume for vigorous and strong vigorous intensities was significantly higher in the boys' group (p < 0.01 and p < 0.05, respectively). Our results show major alterations in girls, with a low level of PA and sleep alteration. PA is a relevant non-pharmacological approach to improve sleep quality and achieve sufficient sleep duration. However, particularly for girls with ASD, more personalized approaches to improve sleep may be needed to manage specific associated disorders.