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SEEBF1, целевой ген множественных склерозов и сердечно-сосудистых заболеваний: основан на исследовании менделии случайности.

Исследования показывают, что у людей с множественным склерозом (МС) больше шансов на сердечно-сосудистые осложнения. Однако точные механизмы, лежащие в основе этой ассоциации, остаются неясными. В этом исследовании изучалась причинно-следственная связь между MS и сердечно-сосудистым заболеванием (CHD) с использованием методов менделиановой случайности (MR) для уточнения прямого воздействия и выявления соответствующих целевых генов. МЕТОДЫ: Мы провели различные методы, включая двухвыборный метод MR, обратный и многовариантный анализ MR, для изучения причинно-следственной связи между MS и CHD. Э

Совпадение в аннотации оригинала
BACKGROUND AND PURPOSE: Research shows that people with multiple sclerosis (MS) are more likely to experience cardiovascular complications. … of CHD, with an IVW-MR analysis yielding an odds ratio of 1.091 (95% CI: 1.030, 1.155, P = 0.0029). Mediation analysis revealed that frailty mediated 20.2% of the effect of MS on CHD (P = 0.026), suggesting that frailty is a critical pathway in this relationship. Additionally, low-density lipoprotein (LDL) is associated with an increased risk of developing both MS a …

Social Support and Tinnitus Distress: The Importance of Developing Positive Psychological Qualities in Patients with Chronic Tinnitus.

INTRODUCTION: The role of social support in the relief of tinnitus distress and related mechanisms remains unclear. This study aimed to confirm a hypothesis that the influence of social support on tinnitus distress is mediated by resilience and self-esteem. METHODS: The Social Support Rating Scale, Connor-Davidson Resilience Scale, Positive Version of Rosenberg Self-Esteem Scale, and Tinnitus Handicap Inventory were used to assess 296 patients who experience chronic subjective tinnitus. The collected data were subjected to correlational analysis, mediating effect testing, and structural equat

UEV1A attenuates MDA5-mediated antiviral immune response by reducing its ubiquitination and aggregation.

Ubiquitin-conjugating enzyme variant 1A (UEV1A) is an E2 ubiquitin-conjugating enzyme and participates in several physiological processes. However, its role in teleost antiviral innate immune response remains unknown. In this study, we identified and characterized a black carp UEV1A homolog (bcUEV1A) as a novel regulator of black carp MDA5 (bcMDA5)-mediated antiviral signaling. bcUEV1A is composed of 164 amino acids containing a conserved ubiquitin-conjugation enzyme catalytic (UBCc) domain spanning residues 31-163. Quantitative real-time PCR (qRT-PCR) analysis showed that bcUEV1A gene transcr

Evaluating customer engagement with AI-driven chatbot affordances in e-commerce: A multi-method analysis.

With technological advancements worldwide, developing effective and efficient chatbots for e-commerce platforms is essential. This study focused on how e-commerce platforms can develop well-functioning AI-driven chatbots using three different affordances: information association, visibility, and interactivity, based on affordance theory. This study also examines the mediating effects of customer satisfaction and trust in the relationship between the three AI-driven chatbot affordances and customer engagement. Further, this study analyzed how these variables are important, their performance, an

Genetically predicted serum Pimelylcarnitine mediates the association between CD39+ secreting Treg cells and intervertebral disc degeneration.

Investigating the causal relationship between CD39+ secreting Treg cells and intervertebral disc degeneration (IVDD) and identifying and quantifying the role of pimelylcarnitine (C7-DC) as a potential mediator. Using summary-level data from a genome-wide association study, a two-sample Mendelian randomization (MR) analysis of genetically predicted CD39+ secreting Treg (N = 3045) and IVDD (41,669 cases, 294,770 controls) was performed. Furthermore, two-step MR was used to quantitate the proportion of the effect of C7-DC protein-mediated RA on IVDD. MR analysis identified higher genetically pred

Dissecting Causal Links Between Gut Microbiota, Inflammatory Cytokines, and Parkinson's Disease: A Mendelian Randomization Study.

BACKGROUND: The association between gut microbiota (GM) and Parkinson's disease (PD) has been well established, but whether there is a causal relationship between the two and whether inflammatory cytokines (ICs) act as mediators remain unclear. METHODS: We utilized the summary databases of large-scale genome-wide association studies (GWAS) conducting Mendelian randomization (MR) analyses to investigate the causal relationships between GM, ICs, and PD. The inverse-variance weighted (IVW) method was primarily used to identify GM and ICs associated with PD and to examine the mediating role of IC

The Impact of Non-alcohol Fatty Liver Disease on Bone Mineral Density is Mediated by Sclerostin by Mendelian Randomization Study.

Non-alcoholic fatty liver disease (NAFLD) has been found to be associated with osteoporosis (OP) in observational studies. However, the precise causal relationship between NAFLD and OP remains unclear. Here, we used Mendelian randomization (MR) to explore the causal relationship. We selected NAFLD-related single-nucleotide polymorphisms from a genome-wide meta-analysis (8434 cases and 434,770 controls) as instrumental variants. We used inverse variance weighted analysis for the primary MR analysis. Furthermore, we used similar methodologies in parallel investigations of other chronic liver dis

Integrated genomics identifies convergence of ankylosing spondylitis with global immune mediated disease pathways.

Ankylosing spondylitis(AS), a highly heritable complex inflammatory arthritis. Although, a handful of non-HLA risk loci have been identified, capturing the unexplained genetic contribution to AS pathogenesis remains a challenge attributed to additive, pleiotropic and epistatic-interactions at the molecular level. Here, we developed multiple integrated genomic approaches to quantify molecular convergence of non-HLA loci with global immune mediated diseases. We show that non-HLA genes are significantly sensitive to deleterious mutation accumulation in the general population compared with toleran

Altered regulatory T cell-mediated Natural Killer cells suppression may lead to generalized vitiligo.

Generalized vitiligo (GV) is characterized by white patches due to autoimmune loss of melanocytes. Regulatory T cells (Tregs) maintain immune homeostasis, while NK cells eliminate pathogens and tumors. Increased NK cell frequency and reduced Treg frequency and suppressive capacity are observed in vitiligo patients. However, studies assessing Treg-mediated suppression of NK cell functions in GV are lacking. Therefore, our study aimed to assess in vitro Treg-mediated suppression of NK cells function over K562 and SK-Mel-28 cells in 31 GV patients and 30 controls using the BrdU-cell proliferation

Application of Restrictive Fluid Resuscitation in Emergency Traumatic Hemorrhagic Shock and Impact on Blood Gas Indicators.

BACKGROUND: The study aimed to observe the application of restrictive fluid resuscitation in emergency traumatic hemorrhagic shock (THS) and impact on blood gas indicators. METHODS: THS patients (n = 80) were divided into two groups: 40 cases in the active group received active fluid resuscitation, and 40 cases in the restricted group received restrictive fluid resuscitation. Blood gas indicators (blood lactate, partial pressure of arterial blood carbon dioxide, and partial pressure of arterial blood oxygen), coagulation parameters (activated partial thromboplastin time, prothrombin time, and

Physiological Stress Response Reactivity Mediates the Link Between Emotional Abuse and Youth Internalizing Problems.

Youth who are raised in emotionally abusive families are more likely to have poor mental health outcomes such as depression and anxiety. However, the mechanisms of this association are unclear. The present study utilized a longitudinal sample of low-SES youth (N = 101, MageT1 = 10.24) to examine stress response reactivity (i.e. vagal withdrawal, sympathetic activation, and hypothalamic-pituitary-adrenal [HPA] axis activation) as mediators between emotional abuse and prospective youth internalizing symptoms. Results indicated that blunted HPA reactivity to a laboratory social stress task mediat

Impact of the Aortic Graft on Arterial Stiffness and Inflammatory Biomarkers after Endovascular Aortic Repair or Open Surgical Repair in Abdominal Aortic Aneurysm Disease.

BACKGROUND: Abdominal aortic aneurysm (AAA) is an important cardiovascular (CV)-related disease that requires surgical treatment to prevent rupture. The elevation of arterial stiffness (AS) is an increasingly recognized independent determinant of CV morbidity and mortality and plays a special role in atherosclerosis. The importance of the surgical technique used for AAA repair in the long-term outcomes still needs to be clarified, and whether endovascular aortic repair (EVAR) or open surgical repair (OSR) confers high AS measurements and thus worse prognosis in terms of CV morbidity needs furt

Mecp2 regulates tnfa during zebrafish embryonic development and acute inflammation.

Mutations in MECP2 cause Rett syndrome, a severe neurological disorder with autism-like features. Duplication of MECP2 also causes severe neuropathology. Both diseases display immunological abnormalities that suggest a role for MECP2 in controlling immune and inflammatory responses. Here, we used mecp2-null zebrafish to study the potential function of Mecp2 as an immunological regulator. Mecp2 deficiency resulted in an increase in neutrophil infiltration and upregulated expression of the pro- and anti-inflammatory cytokines Il1b and Il10 as a secondary response to disturbances in tissue homeos

Intrinsic self-DNA triggers inflammatory disease dependent on STING.

Inflammatory diseases such as Aicardi-Goutières syndrome and severe systemic lupus erythematosus are generally lethal disorders that have been traced to defects in the exonuclease TREX1 (DNase III). Mice lacking TREX1 similarly die at an early age through comparable symptoms, including inflammatory myocarditis, through chronic activation of the stimulator of IFN genes (STING) pathway. In this study, we demonstrate that phagocytes rather than myocytes are predominantly responsible for causing inflammation, an outcome that could be alleviated following adoptive transfer of normal bone marrow int

Prevention of influenza by targeting host receptors using engineered proteins.

There is a need for new approaches for the control of influenza given the burden caused by annual seasonal outbreaks, the emergence of viruses with pandemic potential, and the development of resistance to current antiviral drugs. We show that multivalent biologics, engineered using carbohydrate-binding modules specific for sialic acid, mask the cell-surface receptor recognized by the influenza virus and protect mice from a lethal challenge with 2009 pandemic H1N1 influenza virus. The most promising biologic protects mice when given as a single 1-μg intranasal dose 7 d in advance of viral chall

Cutting edge: AIM2 and endosomal TLRs differentially regulate arthritis and autoantibody production in DNase II-deficient mice.

Innate immune pattern recognition receptors sense nucleic acids from microbes and orchestrate cytokine production to resolve infection. Inappropriate recognition of host nucleic acids also results in autoimmune disease. In this study, we use a model of inflammation resulting from accrual of self DNA (DNase II(-/-) type I IFN receptor [Ifnar](-/-)) to understand the role of pattern recognition receptor-sensing pathways in arthritis and autoantibody production. Using triple knockout (TKO) mice deficient in DNase II/IFNaR together with deficiency in either stimulator of IFN genes (STING) or absen

RNA released from necrotic keratinocytes upregulates intercellular adhesion molecule-1 expression in melanocytes.

Intercellular adhesion molecule-1 (ICAM-1) expression has been detected in melanocytes around active vitiligo patches as well as in surgically transplanted melanocytes. However, it is unclear whether and how skin injury induces the inappropriate expression of ICAM-1 and other proinflammatory genes in melanocytes. We previously reported that human melanocytes expressed TLR3. We hypothesized that the TLR3 expressed in melanocytes may recognize skin injury by binding to the endogenous ligands secreted by the damaged keratinocytes. Here we showed that RNA released from necrotic keratinocytes induc

Chronological evaluation of inflammatory mediators during peritoneal adhesion formation using a rat model.

PURPOSE: The inflammatory response to peritoneal injury is considered to be of particular importance in adhesion formation. The aim of this study was to investigate the dynamics of inflammatory mediators in peritoneal adhesions. METHODS: In 60 male rats, a peritoneal defect was performed using a standardized cecal abrasion model. On days 3, 5, 14, 30, 60, and 90, ten animals were sacrificed. The expression of five integral mediators for the cellular immune response (macrophages, T lymphocytes), inflammation (COX-2), cell differentiation, and proliferation (ß-catenin, c-myc) in visceral and pa

Cognitive-behavioral therapy for sleep disturbance decreases inflammatory cytokines and oxidative stress in hemodialysis patients.

Sleep disturbance is common in dialysis patients and is associated with the development of enhanced inflammatory responses. Cognitive-behavioral therapy is effective for sleep disturbance and reduces inflammation experienced by peritoneal dialysis patients; however, this has not been studied in hemodialysis patients. To determine whether alleviation of sleep disturbance in hemodialysis patients also leads to less inflammation, we conducted a randomized controlled interventional study of 72 sleep-disturbed hemodialysis patients. Within this patient cohort, 37 received tri-weekly cognitive-behav

Identification of novel single nucleotide polymorphisms in inflammatory genes as risk factors associated with trachomatous trichiasis.

BACKGROUND: Trachoma is the leading preventable cause of global blindness. A balanced Th1/Th2/Th3 immune response is critical for resolving Chlamydia trachomatis infection, the primary cause of trachoma. Despite control programs that include mass antibiotic treatment, reinfection and recurrence of trachoma are common after treatment cessation. Furthermore, a subset of infected individuals develop inflammation and are at greater risk for developing the severe sequela of trachoma known as trachomatous trichiasis (TT). While there are a number of environmental and behavioral risk factors for trac