Alterations In Levels Research Articles

Effects of Fasting on THP1 Macrophage Metabolism and Inflammatory Profile.

Fasting can affect the body's inflammatory response, and this has been linked to potential health benefits, including improvements for people with rheumatic diseases. In this work, we evaluated, in vitro, how changes in nutrient availability alter the inflammatory response of macrophages. Macrophage-differentiated THP1 cells were cultured, deprived of FCS or subjected to cycles of FCS deprivation and restoration to mimic intermittent fasting. Changes in the macrophage phenotype, the cells' response to inflammatory stimuli and the level of mitochondrial alteration were assessed. The results indicate that while periods of serum starvation are associated with a decrease in IL1β and TNFα expression, consistent with an anti-inflammatory response, intermittent serum starvation cycles promote a pro-inflammatory phenotype. Rapid changes in reducing capacity and mitochondrial response were also observed. Of note, while some changes, such as the production of oxygen free radicals, were reversed with refeeding, others, such as a decrease in reducing capacity, were maintained and even increased. This study shows that different fasting protocols can have diverging effects and highlights that time-limited nutrient changes can significantly affect macrophage functions in cell cultures. These findings help elucidate some of the mechanisms by which specific fasting dietary interventions could help control inflammatory diseases.

The effects of air and transportation noise pollution-related altered blood gene expression, DNA methylation, and protein abundance levels on gastrointestinal diseases risk

IntroductionAir pollution and transportation noise pollution has been linked to gastrointestinal (GI) diseases, but their relationship remains unclear. MethodsWe extracted the significantly modulated genes and CpG sites related to air pollution (PM2.5, PM10, and NOx) and transportation noise pollution (aircraft, railway, and traffic road noise) from previous published studies. Genome-wide methylation analysis and colocalization analysis with these CpG sites and GWAS data of GI diseases were performed to disentangle the relationship between pollution-related blood DNA methylation (DNAm) alterations and GI diseases risk. Summary-based Mendelian randomization (SMR) analysis assessed the impact of pollution-related genes on GI diseases risk across methylation, gene expression, and protein levels. Enrichment analysis investigated the implicated biological pathways and immune cell types. ResultsDNAm at cg00227781 [CD300A] (modulated by NOx exposure) and cg19215199 [ZMIZ1] (modulated by PM2.5 exposure) was significantly linked to increased noninfective enteritis and colitis risk, while cg08500171 [BAT2] (modulated by NOx exposure) is significantly associated with an increased gastroesophageal reflux disease (GERD) risk. Colocalization analysis provides strong evidence supporting a shared causal variant between these associations. Multi-omics levels SMR analysis revealed that pollution-modulated lower DNAm at 5 specific CpG sites were associated with increased expression of 4 genes (IL21R, EVPL, SYNGR1, and WDR46), subsequently increasing the risk of GERD, ulcerative colitis, and gastric ulcer. 7 circulating proteins coded by pollution-modulated genes were observed to be associated with 6 GI diseases risk. Enrichment analysis implicates immune and inflammatory responses, MAPK signaling, and telomere maintenance in these pollution-induced effects. ConclusionWe identified potential links between air and transportation noise pollution-related gene methylation, expression, and protein abundance with GI diseases risk, possibly revealing new therapeutic targets.

Morphology and taphonomy of the gastropod Terebralia palustris from an iron age site in the Arabian Peninsula

The Indo-Pacific gastropod Terebralia palustris is particularly suitable for comparing natural and anthropogenic induced taphonomic pathways due to its wide geographic distribution and common presence within archeological context. The present study aims to (1) correlate shell architecture and morphology with fragmentation pattern and preservation, (2) quantify taphonomic changes to differentiate between natural vs. anthropogenic preservation features, (3) provide a guideline for analyzing fragmented shell remains in archeological material. Shells and taphonomic features were studied from both recent mangrove environments from the Emirate of Sharjah, United Arab Emirates as well as archeological material within the Iron age II site (1000–600 BC) of Muweilah near the City of Sharjah. Techniques utilized include morphometry, thin sectioning, scanning electron microscopy (SEM) of recent specimens and a semi—quantitative taphonomic analysis of anthropogenic material. Thin sectioning shows a complex internal shell morphology with a tripartite subdivision of shell layers. The recent material shows better preserved features on both the exterior and internal shell surfaces than the highly fragmented material recovered from the archeological context, which shows a distinct size distribution as well as showing higher levels of surface abrasion, surface cracks and color alterations. These features are correlated to extraction techniques, cooking methods and waste disposal handling.

HSP70 promotes pancreatic cancer cell epithelial-mesenchymal transformation and growth via the NF-κB signaling pathway.

To study the effects of HSP70 on proliferation, migration, invasion, and epithelial-mesenchymal transformation (EMT) of pancreatic cancer cells and explore its underlying mechanisms. Pancreatic cancer cell models with either reduced HSP70 or increased HSP70 expression were established. RT-qPCR and Western blot assays were used to determine mRNA and protein levels of HSP70, IKK/IκBa/NF-κB signaling pathway-related genes, and EMT markers. The CCK-8 and cell cloning assays were used to evaluate cell proliferation and cloning abilities. Transwell and wound healing assays were used to assess the invasive and migratory properties of the cells. Effects of NF-κB signaling modulation were explored using an IKK inhibitor (BAY11-7082) and an IKK overexpression vector (pCMV-IKK). Electrophoretic mobility shift assay (EMSA) and luciferase reporter assays were conducted to analyze NF-κB's promoter binding and transcriptional activities. HSP70 knockdown inhibited p-p65 nuclear translocation and reduced the expression of p-p65, p-IKKα/β, p-IκBα, N-cadherin, Vimentin, and Twist. It also decreased NF-κB's promoter binding and transcriptional activities, increased E-cadherin levels, and suppressed pancreatic cancer cell proliferation, cloning, migration, and invasion. In contrast, HSP70 overexpression led to increased expression of p-p65, p-IKKα/β, p-IκBα, N-cadherin, Vimentin, and Twist, decreased E-cadherin levels, and enhanced cell proliferation, cloning, migration, and invasion capabilities. NF-κB signaling pathway modulation reversed EMT changes induced by altered HSP70 expression levels. rhHSP70 also increased p-IKKα/β and p-IκBα protein levels. HSP70 promotes the EMT and enhances pancreatic cancer cell proliferation, migration, and invasion by activating the NF-κB pathway.

Quantitative Susceptibility Mapping in Adults with Persistent-Post Concussion Symptoms after Mild Traumatic Brain Injury: An Exploratory Study.

It is estimated that 18-30% of concussion sufferers experience symptoms lasting more than 1 month, known as persistent post-concussion symptoms (PPCS). Symptoms can be debilitating, and include headache, dizziness, nausea, problems with memory and concentration, sleep and mood disruption, and exercise intolerance. Previous studies have used quantitative susceptibility mapping (QSM) to show altered tissue susceptibility levels in adults acutely following concussion, however this finding has yet to be investigated in participants with PPCS. In this exploratory case-controlled study, we measured tissue susceptibility using quantitative susceptibility mapping (QSM) in 24 participants with PPCS following mild traumatic brain injury (mTBI) and 23 healthy controls with no history of concussion. We compute tissue susceptibility for seven white matter tracts and three deep grey matter regions and compare tissue susceptibility between groups using ANCOVA models controlling for age and sex. We also assess the relationship between regional tissue susceptibility and symptoms. There were no significant differences between tissue susceptibility in participants with PPCS compared to control subjects in any of the evaluated regions. However, we show lower tissue susceptibility across four white matter tracts was generally associated with worse symptoms in the PPCS group. Specifically, we saw relationships between white matter susceptibility and headache (p=0.006), time since injury (p=0.03), depressive symptoms (p=0.021) and daytime fatigue (p=0.01) in participants with PPCS. These results provide evidence in support of persistent changes in the brain months-to-years following injury and highlight the need to further understand the pathophysiology of PPCS, to determine effective prevention and treatment options. ATR: Anterior Thalamic Radiation; Caud: Caudate; CCB: Corpus Callosum Body; CCG: Corpus Callosum Genus; CCS: Corpus Callosum Splenium; CH: Cingulum; DHI: Dizziness Handicap Inventory; ESS: Epworth Sleepiness Scale; FM: Forceps Minor; FSS: Fatigue Severity Scale; GAD: Generalized Anxiety Disorder; HIT-6: Headache Impact Test 6; IFOF: Inferior Fronto-Occipital Fasciculus; ILF: Inferior Longitudinal Fasciculus; mTBI: mild traumatic brain injury; Pal: Pallidum; PPCS: Persistent Post-Concussive Symptoms; PCSC: Postconcussional Syndrone Checklist; PHQ: Patient Health Questionnaire; Put: Putamen; RPQ: Rivermead Post Concussion Symptoms Questionnaire; SLF: Superior Longitudinal Fasciculus; QSM: Quantitative Susceptibility Mapping.

Triiodothyronine levels in athyreotic pediatric patients during levothyroxine therapy.

Levothyroxine (LT4) monotherapy is the current recommended approach for treating pediatric patients post-total thyroidectomy (TT) based on the assumption that peripheral conversion of thyroxine (T4) to triiodothyronine (T3) normalizes thyroid hormone levels. In adults, approximately 15% of post-TT patients on LT4 monotherapy have altered T4:T3 ratios with ongoing debate in regard to the clinical impact with respect to health-related quality of life (hrQOL). The ability to normalize T3 and T4 levels on LT4 monotherapy for pediatric patients' post-TT is important but not previously described. This study reports data on T3 levels in athyreotic pediatric patients to determine if a similar cohort of patients exists on LT4 monotherapy targeting normalization of TSH (LT4 replacement) or suppression (LT4 suppression). Thyroid function tests (TFTs) were retrospectively extracted from medical charts for patients <19 years old who underwent TT for definitive treatment of Graves' disease (GD) or differentiated thyroid cancer (DTC) between 2010-2021. LT4 dosing was selected to normalize the TSH in GD patients (LT4 replacement) or suppress TSH in DTC patients (LT4 suppression). Pre- and post-surgical TSH, T3 and T4 levels were compared. Of 108 patients on LT4 replacement (n=53) or LT4 suppression (n=55) therapy, 94% (102/108) of patients demonstrated T3 levels in the normal range post-TT. However, the majority of patients on LT4 replacement (44/53; 83%) and LT4 suppression (31/55; 56%) displayed post-TT T3 levels in the lower half of the normal range despite 50% (22/44) and 48% (15/31) of these patients, respectively, having post-TT fT4 levels above the upper limit of the normal range. A significant number of pediatric patients do not achieve similar T3 and T4:T3 levels pre- and post-TT. Future multi-center, prospective studies evaluating LT4 monotherapy in comparison to combined LT4/LT3 therapy are warranted to determine the potential clinical impact of altered T3 levels in athyreotic pediatric patients.

Trimethylamine N-oxide detection by electrochemical sensor based on screen printed electrode modified with molecularly imprinted polypyrrole-molybdenum(III) sulfide nanosheets

Trimethylamine N-oxide (TMAO) is a gut metabolite produced by dietary L-carnitine and choline metabolism. Its altered level in the serum has been implicated in human health and diseases such as colorectal cancer, chronic kidney diseases, cardiovascular diseases, etc. Early detection of TMAO in body fluids has been presumed to be significant in understanding the pathogenesis and treatment of many diseases. Hence, developing reliable and rapid technologies for its detection may augment our understanding of pathogenesis and diagnosis of diseases. Hence, in the present work, polypyrrole (Ppy)@molybdenum(III)sulfide (Mo2S3) nanosheets (NS) composite molecularly imprinted polymer (MIP) (Ppy@Mo2S3-MIP) based electrochemical sensor has been fabricated for the detection of TMAO. Polypyrrole (Ppy) and Mo2S3 NS have been synthesized by chemical oxidative polymerization and hydrothermal techniques, respectively. The synthesized nanocomposite has been validated using different techniques such as X-ray diffraction (XRD), Raman spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The fabricated Ppy@Mo2S3-MIP sensor showed a linear detection range from 30 µM to 210 µM, a sensitivity of 1.21 μA μM−1 cm−2 and a limit of detection as 1.4 μM for the detection of TMAO and found more robust and improved when compared with Ppy-MIP using identical parameters. The fabricated sensor is also highly selective towards TMAO. It can be further used to detect TMAO in human samples such as urine quickly.

Biomarkers as predictors of CBT responsiveness in major depressive disorder: The role of heart rate variability and inflammation

ObjectiveBiological risk factors for cardiovascular disease may relate to poor treatment responsiveness in major depressive disorder (MDD). These factors encompass low-grade inflammation and autonomic dysregulation, as indexed by decreased heart rate variability (HRV) and increased heart rate (HR). This secondary analysis examined whether higher levels of inflammatory markers or autonomic alterations relate to lower responsiveness to cognitive behavioral therapy (CBT) among individuals with MDD. MethodsEighty antidepressant-free patients with MDD were randomly assigned to 14 weeks of CBT or waitlist (WL). Potential biological moderators at study entry included HR and HRV (24-h, daytime, nighttime) and inflammatory markers such as C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-α. Forty non-clinical controls were involved to verify biological alterations in MDD at study entry. Depressive symptoms were assessed at baseline and at the end of treatment. ResultsIndividuals with MDD exhibited reduced total 24-h HRV (i.e., triangular index) and daytime HRV (i.e., triangular index, HF-HRV, LF-HRV, RMSSD), as well as increased levels of inflammatory markers. Patients who received CBT exhibited stronger reductions in self- and clinician-rated depressive symptoms, compared to WL. False discovery rate-adjusted moderation analyses did not show overall moderating effects of biological measures on treatment responsiveness. However, higher CRP levels were specifically associated with poorer improvement in somatic depressive symptoms. ConclusionsThere was no overall evidence for a moderating role of inflammation or autonomic features in CBT responsiveness in MDD. Higher levels of CRP might, however, specifically be associated with less improvement in somatic depressive symptoms during CBT.

Exposure to different cobalt chloride levels produces oxidative stress and lipidomic changes and affects the liver structure of Cyprinus carpio juveniles.

The present investigation was undertaken to evaluate the toxic effects of CoCl2-induced hepatotoxicity and fatty acid changes in juvenile Cyprinus carpio. Fish were divided into six experimental groups in duplicate. The first group served as controls. The second group received the lowest exposure dose at 2.5µg/L. In the third group, fish were exposed to 25µg/L of CoCl2. The fourth group was exposed to 50µg/L of CoCl2. The last two groups were exposed to the highest doses, 100 and 500µg/L of CoCl2. Total antioxidant activities were estimated using a colorimetric method. Liver fatty acid compositions were analyzed by high-performance gas chromatography (GC). Hepatopathy was identified through microscopic analysis. Exposure of C. carpio to CoCl2 resulted in hepatotoxicity, indicated by increased levels of malondialdehyde (MDA), hydrogen peroxide (H2O2), protein carbonyls (PCO), and alterations in the ferric reducing antioxidant power system (FRAP). Superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione peroxidase (GPx), reduced glutathione (GSH), metallothioneins (MTs), and low thiol levels (L-SH) significantly increased, particularly under exposure to the highest CoCl2 doses (100 and 500µg/L). Acetylcholinesterase activity decreased significantly in C. carpio exposed to graded CoCl2 doses. Additionally, there was a decrease in polyunsaturated fatty acids (PUFA), primarily n-3 PUFA, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA), while an increase in monounsaturated (MUFA) and saturated fatty acids (SFA), including palmitic (C16:0), stearic (C18:0), palmitoleic (C16:1), and oleic (C18:1) acids, was observed. Histopathological examination of the liver confirmed hepatopathy revealing characteristic tissue changes such as leucocyte infiltration, hepatic cell membrane degradation, vacuolization, and lipid inclusions. The study provided ethnophysiology insights into the responses of C. carpio to CoCl2-induced oxidative stress and lipidomic alteration, underscoring its potential as a bioindicator for assessing environmental impacts and metal contamination.

Delirium care burden of intensive care nurses caring for patients undergoing open-heart surgery: A mixed-method research.

Delirium is an acute confusional state characterized by inattention, cognitive dysfunction and an altered level of consciousness. Delirium causes negative outcomes in patients, and patients with delirium increase the workload of nurses. Therefore, it is important to recognize the challenges and burdens experienced by nurses caring for patients with delirium. To determine the subjective burden experienced by intensive care nurses caring for patients who have undergone open-heart surgery. A mixed-method sequential explanatory design. A non-probability purposive sampling method was used for the quantitative stage. Using OpenEpi, we employed the method of sample calculation with an unknown universe. The sample size of the quantitive study comprised 130 nurses. Quantitative data were collected with Google survey. For gathering qualitative data, online video interviews were conducted with 10 nurses, an interpretive phenomenological approach was used and content analysis was performed. In the quantitative phase, we found that the subjective burden was high. In the qualitative phase, five main themes emerged: difficulty in recognizing delirium, physical burden, emotional burden, burden in care management of patients with delirium and the effect of patients with delirium on other patients. The nurses experienced physical and emotional burden in delirium management and felt lonely while caring for patients with delirium. Because nurses play a key role in the care of patients with delirium, reducing the burden nurses experience when caring for patients with delirium should be considered important in ensuring that this patient population receives adequate care. Delirium patients create a care burden for intensive care nurses. To reduce this burden of care, in-service training in patient management and bedside teaching support should be provided to nurses. Furthermore, the use of a valid scale to diagnose delirium should be integrated into health policies. Nurses should not be left alone in the management of delirium. Managing delirium patients with a team including physicians, nurses and professionals from other health disciplines will ensure that patients receive high-quality care, thereby reducing the care burden of nurses.

Salivary 8-hydroxy-2′-deoxyguanosine levels in patients with oral cancer: a systematic review and meta-analysis

BackgroundDNA is an important target for oxidative attack and its modification may increase the risk of mutagenesis. The aim of this study was to evaluate and compare salivary levels of the oxidative stress biomarker 8-hydroxy-2′-deoxyguanosine (8-OHdG) in patients with oral cancer (OC) compared to the control group by a comprehensive search of the available literature.MethodsThe present systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and was registered in Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/X3YMR. Four electronic databases were used to identify studies for this systematic review: PubMed, Scopus, ScienceDirect, and Web of Science from January 15, 2005, to April 15, 2021. The Joanna Briggs Institute (JBI) tool was used to assess article quality.ResultsOf the 166 articles identified, 130 articles were excluded on the basis of title and abstract screening (duplicates, reviews, etc.). Thirty-six articles were evaluated at full text and 7 articles met the inclusion criteria. Of these, only 5 studies had compatible data for quantitative analysis. An increase in salivary 8-OHdG levels was found in patients with OC compared to healthy subjects, but without statistical significance. 8-OHdG: SMD = 2,72 (95%CI= -0.25–5.70); *p = 0.07.ConclusionsThis systematic review and meta-analysis suggests a clear trend of increased 8-OHdG levels in saliva of OC patients compared to the control group. However, further studies are required to clarify and understand the altered levels of this oxidative stress marker.

Transgenic Drosophila melanogaster Carrying a Human Full-Length DISC1 Construct (UAS-hflDISC1) Showing Effects on Social Interaction Networks.

Disrupted in Schizophrenia 1 (DISC1) is a scaffold protein implicated in major mental illnesses including schizophrenia, with a significant negative impact on social life. To investigate if DISC1 affects social interactions in Drosophila melanogaster, we created transgenic flies with second or third chromosome insertions of the human full-length DISC1 (hflDISC1) gene fused to a UAS promotor (UAS-hflDISC1). Initial characterization of the insertion lines showed unexpected endogenous expression of the DISC1 protein that led to various behavioral and neurochemical phenotypes. Social interaction network (SIN) analysis showed altered social dynamics and organizational structures. This was in agreement with the altered levels of the locomotor activity of individual flies monitored for 24 h. Together with a decreased ability to climb vertical surfaces, the observed phenotypes indicate altered motor functions that could be due to a change in the function of the motor neurons and/or central brain. The changes in social behavior and motor function suggest that the inserted hflDISC1 gene influences nervous system functioning that parallels symptoms of DISC1-related mental diseases in humans. Furthermore, neurochemical analyses of transgenic lines revealed increased levels of hydrogen peroxide and decreased levels of glutathione, indicating an impact of DISC1 on the dynamics of redox regulation, similar to that reported in transgenic mammals. Future studies are needed to address the localization of DISC1 expression and to address how the redox parameter changes correlate with the observed behavioral changes.

Orbital Observations Suggest Decoupled Olivine and Carbonate Enrichments in Jezero Crater

AbstractIt has been hypothesized that the olivine‐ and carbonate‐bearing units within Jezero crater are part of the broader olivine‐carbonate rock unit found in the Nili Fossae region. Further, it is commonly proposed that olivine and carbonate are closely associated with each other in Jezero crater based on visible/near‐infrared spectral data. In this work, we investigate the olivine‐ and carbonate‐rich units in Jezero crater using spectral, thermophysical, and morphological analyses to determine the relationship between olivine‐ and carbonate‐rich units. Thermal infrared spectral data indicate largely weak to absent olivine signatures in the marginal carbonates. Our analyses suggest a decoupled relationship between olivine and carbonate in Jezero. The distinct appearances of olivine and carbonate in Jezero crater compared to the regional olivine‐carbonate rocks in Nili Fossae may imply unique formation mechanisms for olivine and carbonate in Jezero or variable levels of olivine alteration across the broader region.

IL-33 prevents age-related bone loss and memory impairment by suppression of Th17 response: evidence in a d-galactose-induced aging mouse model.

Cytokines are the primary mediators of age-related disorders. The IL-17/IL-10 axis plays a crucial role in bone destruction and neuro-inflammation. Additionally, a new Th2 cytokine-IL-33-has gained attention for its potential implications in aging-associated conditions. However, the involvement of IL-33 in aging-mediated bone loss and memory impairment remains unclear and needs further investigation. This study reveals the impact of IL-33 on various aspects of the immune system, bone health, and neural functions. To induce senescence, we used d-galactose for its convenience and fewer side effects. The experimental design involved treating 20-week-old C57BL/6J mice with d-galactose subcutaneously for 10weeks to induce aging-like effects. Thereafter, IL-33 recombinant protein was administered intraperitoneally for 15days to evaluate its impact on various immune, skeletal, and neural parameters. The results demonstrated that d-galactose-induced aging led to bone loss and compromised osteogenic parameters, accompanied by increased oxidative stress and neurodegeneration in specific brain regions. Behavioral activities were also affected. However, supplementation with IL-33 mitigated these effects, elevating osteogenic parameters and reducing senescence markers in osteoblast cells in an aging mouse model and exerted neuroprotective potential. Notably d-galactose-induced aging was characterized by high bone turnover, reflected by altered serum levels of CTX, PTH, beta-galactosidase, and P1NP. IL-33 treatment attenuated these effects, suggesting its role in regulating bone metabolism. Furthermore, d-galactose-induced aging was associated with increased differentiation of Th17 cells and upregulation of associated markers, such as STAT-3 and ROR-γt, while downregulating Foxp3, which antagonizes Th17 cell differentiation. IL-33 treatment countered these effects by suppressing Th17 cell differentiation and promoting IL-10-producing T-regulatory cells. Overall, these findings provide insights into the potential therapeutic implications of IL-33 in addressing aging-induced bone loss and memory impairment.

APOD: A biomarker associated with oxidative stress in acute rejection of kidney transplants based on multiple machine learning algorithms and animal experimental validation

BackgroundOxidative stress is an unavoidable process in kidney transplantation and is closely related to the development of acute rejection after kidney transplantation. This study aimed to investigate the biomarkers associated with oxidative stress and their potential biological functions during acute rejection of kidney transplants. MethodsWe identified Hub genes using five machine learning algorithms based on differentially expressed genes (DEGs) in the kidney transplant acute rejection dataset GSE50058 and oxidative stress-related genes (OS) obtained from the MSigDB database, and validated them with the datasets GSE1563 and GSE9493, as well as with animal experiments; Subsequently, we explored the potential biological functions of Hub genes using single-gene GSEA enrichment analysis; The Cibersort algorithm was used to explore the altered levels of infiltration of 22 immune cells during acute rejection of renal transplantation, and a correlation analysis between Hub genes and immune cells was performed; Finally, we also explored transcription factors (TFs), miRNAs, and potential drugs that regulate Hub genes. ResultsWe obtained a total of 57 genes, which we defined as oxidative stress-associated differential genes (DEOSGs), after intersecting DEGs during acute rejection of kidney transplants with OSs obtained from the MSigDB database; The results of enrichment analysis revealed that DEOSGs were mainly enriched in response to oxidative stress, response to reactive oxygen species, and regulation of oxidative stress and reactive oxygen species; Subsequently, we identified one Hub gene as APOD using five machine learning algorithms, which were validated by validation sets and animal experiments; The results of single-gene GSEA enrichment analysis revealed that APOD was closely associated with the regulation of immune signaling pathways during acute rejection of kidney transplants; The Cibersort algorithm found that the infiltration levels of a total of 10 immune cells were altered in acute rejection, while APOD was found to correlate with the expression of multiple immune cells; Finally, we also identified 154 TFs, 12 miRNAs, and 12 drugs or compounds associated with APOD regulation. ConclusionIn this study, APOD was identified as a biomarker associated with oxidative stress during acute rejection of kidney transplants using multiple machine learning algorithms, which provides a potential therapeutic target for mitigating oxidative stress injury and reducing the incidence of acute rejection in kidney transplantation.

A single-cell transcriptomic census of mammalian olfactory epithelium aging.

Mammalian olfactory epithelium has the capacity of self-renewal throughout life. Aging is one of the major causes leading to the olfactory dysfunction. Here, we performed single-cell RNA sequencing (scRNA-seq) analysis on young and aged murine olfactory epithelium (OE) and identified aging-related differentially expressed genes (DEGs) throughout 21 cell types. Aging led to the presence of activated horizontal basal cells (HBCs) in the OE and promoted cellular interaction between HBCs and neutrophils. Aging enhanced the expression of Egr1 and Fos in sustentacular cell differentiation from multipotent progenitors, whereas Bcl11b was downregulated during the sensory neuronal homeostasis in the aged OE. Egr1 and Cebpb were predictive core regulatory factors of the transcriptional network in the OE. Overexpression of Egr1 in aged OE organoids promoted cell proliferation and neuronal differentiation. Moreover, aging altered expression levels and frequencies of olfactory receptors. These findings provide a cellular and molecular framework of OE aging at the single-cell resolution.

Clinical and laboratory characteristics and outcome predictors of cerebral venous sinus thrombosis in a referral neurology hospital in Bangladesh.

We aimed to describe clinical and laboratory characteristics and determine the predictors of outcome in patients with cerebral venous sinus thrombosis. This prospective study was conducted over 2 years among hospitalized patients with cerebral venous sinus thrombosis. Patient outcome was assessed using the Modified Rankin Scale (mRS) score at 3 months. Outcome predictors were identified using logistic regression analysis. Eighty-one patients were included in this study. The median mRS outcome at 3 months was 1 (interquartile range 1-3). Poor outcomes were observed in 27.2% of patients, and the mortality rate was 9.8%. Factors associated with poor outcomes were age >60 years (relative risk [RR] 5.1), hemiparesis (RR 5.4), altered level of consciousness (RR 7.1), and transverse sinus involvement (RR 1.1). In general, mRS scores were not associated with D-dimer levels (RR 2.4). However, older patients with elevated D-dimer levels showed a significant association with poor outcomes (1.6) according to mRS scores. Older age, hemiparesis, and altered consciousness levels were independent predictors of poor outcomes in patients with cerebral venous sinus thrombosis. High D-dimer level showed no association with functional disability, except in older patients.

Association between pulp stones and systemic diseases: A case-control study

Introduction: Pulp stones (PS) are calcifications commonly found in the pulp tissue that may be associated with systemic diseases. Objective: To evaluate the association between PS and systemic diseases. Methods: A case-control study with the inclusion of individuals from 18 to 65 years of age, of both sexes. Analysis was made of 1047 digital panoramic radiographs. The controls could not have any teeth with PS; the cases were the contrary. A questionnaire comprising demographic, habit, and general health (diabetes, problems with blood vessels, altered cholesterol level, heart attack, kidney or gallbladder stone, arthritis, or autoimmune disease, and for women, endometriosis, and ovarian cyst). Data were submitted to the Student's t-test to identify differences between groups about sex and age. The Chi-square test was applied to the cross-tabulation. The analyses were performed using SPSS®, version 25.0, with a 5% significance level. Results: 490 patients participated (242 cases and 248 controls). There was no difference between groups for the sex (p=0.966) and age (p=0.186). Only “kidney stone” was associated with the case group (p=0.001), being almost three times higher when compared to the control group. No significant differences were found in females about the presence or absence of PS (p&gt;0.05). Conclusion: In this research, it is suggested the existence of an association between kidney stones and the presence of pulp stones.

Hepatoprotective activity of Mentha rotundifolia aqueous extract against hepatocellular damage induced by CCL4 in rats

This study aims to assess hepatoprotective properties of M. rotundifolia. Decoction was used to prepare the aqueous extract. The preliminary cytotoxicity evaluated against Caco 2 and RAW 264 cells demonstrate no cytotoxic effect. The preventive impact of the extract against liver damage was evaluated by examining blood levels of AST, ALT, ALP, total proteins, and histological alterations in liver tissues. Thirty albino rats were separated into five groups: the first served as normal group, the second was injected by olive oil (3 ml/kg), and the third was injected by CCL4 (3 ml/kg). However, groups IV and V received daily doses of 250 and 500 mg extract/kg bw, respectively before CCL4 injection. The results showed that the administration of the extract led to a marked improvement in plasma biochemical markers and a reduction in symptoms of CCL4-induced liver damage. The extract exhibits hepatoprotective activity, which may be attributed to its phytochemical components.

Gut microbiota mediates the anti-inflammatory effects of supplemental infrared irradiation in mice.

In recent years, studies have shown that low-dose supplemental infrared (IR) irradiation exhibits systemic anti-inflammatory effects. The gut microbiota is increasingly recognized as a potential mediator of these effects due to its role in regulating host metabolism and inflammatory responses. To investigate the role of gut microbiota diversity and metabolite changes in the mechanism of light-emitting diodes (LED) infrared's anti-inflammatory action, we conducted IR irradiation on mice. Serum inflammatory cytokines were measured using ELISA, and fecal samples were subjected to metagenomic, untargeted, and targeted metabolomic analyses. Our results demonstrated a significant increase in the anti-inflammatory cytokine IL-10 in the IR group, accompanied by a declining trend in pro-inflammatory cytokines. Gut microbiome analysis revealed distinct alterations in composition and functional genes between the groups, including the enrichment of beneficial bacteria like various species of Parabacteroides and Akkermansia muciniphila in the IR group. Notably, the IR group exhibited enrichment in carbohydrate metabolism pathways and a reduction in DNA damage and repair pathways. Furthermore, targeted metabolomic analysis highlighted a notable increase in short-chain fatty acids (SCFAs), including butyric acid and isobutyric acid, which positively correlated with the abundance of several beneficial bacteria. These findings suggest a potential interplay between gut microbiota-derived SCFAs and the anti-inflammatory response. In conclusion, our study provides comprehensive insights into the changes in gut microbiota species and functions associated with IR irradiation. Moreover, we emphasize the significance of altered SCFAs levels in the IR group, which may contribute to the observed anti-inflammatory effects. Our findings contribute valuable evidence supporting the role of low-dose infrared light irradiation as an anti-inflammatory therapy.