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BACKGROUND AND AIMS: The etiology of biliary atresia (BA) is not known and is likely multifactorial, including a genetic predisposition, a viral or environmental trigger, an aberrant autoimmune response targeting cholangiocytes, and unique susceptibilities of the neonatal bile ducts to injury. Damaged cholangiocytes may express neo self-antigens and elicit autoreactive T-cell-mediated inflammation and B-cell production of autoantibodies. The aim of this study was to discover autoantibodies in BA that correlated with outcomes. APPROACH AND RESULTS: An autoantigen microarray encompassing approximately 9,500 autoantigens was used to screen for serum immunoglobulin M (IgM) and immunoglobulin G (IgG) autoantibodies in patients with BA or other liver disease controls. Validation of candidate autoantibodies by enzyme-linked immunosorbent assay on a second cohort of subjects (6-12 months following Kasai portoenterostomy) and correlations of autoantibodies with outcomes were performed (serum bilirubin levels and need for liver transplant in first 2 years of life). Mean anti-chitinase 3-like 1 (CHI3L1), anti-delta-like ligand (DLL-4), and antisurfactant protein D (SFTPD) IgM autoantibodies in BA were significantly higher compared with controls, and IgM autoantibody levels positively correlated with worse outcomes. Immunofluorescence revealed cholangiocyte-predominant expression of CHI3L1, DLL-4, and SFTPD. The humoral autoantibody response was associated with C3d complement activation and T-cell autoimmunity, based on detection of cholangiocyte-predominant C3d co-staining and peripheral blood autoreactive T cells specific to CHI3L1, DLL-4 and SFTPD, respectively. CONCLUSIONS: BA is associated with cholangiocyte-predominant IgM autoantibodies in the first year after Kasai portoenterostomy. Anti-CHI3L1, anti-DLL-4, and anti-SFTPD IgM autoantibody correlations with worse outcomes and the detection of C3d on cholangioctyes and antigen-specific autoreactive T cells suggest that autoimmunity plays a role in the ongoing bile duct injury and progression of disease.
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Autoanticuerpos/inmunología , Conductos Biliares Extrahepáticos/inmunología , Atresia Biliar/inmunología , Inmunoglobulina M/inmunología , Conductos Biliares Extrahepáticos/citología , Atresia Biliar/cirugía , Línea Celular , Preescolar , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Técnica del Anticuerpo Fluorescente , Humanos , Lactante , Masculino , Portoenterostomía HepáticaRESUMEN
BACKGROUND: The role of the human microbiome in human health and disease has been studied in various body sites. However, compared to the gut microbiome, where most of the research focus is, the salivary microbiome still bears a vast amount of information that needs to be revealed. This study aims to characterize the salivary microbiome composition in the Qatari population, and to explore specific microbial signatures that can be associated with various lifestyles and different oral conditions. MATERIALS AND METHODS: We characterized the salivary microbiome of 997 Qatari adults using high-throughput sequencing of the V1-V3 region of the 16S rRNA gene. RESULTS: In this study, we have characterized the salivary microbiome of 997 Qatari participants. Our data show that Bacteroidetes, Firmicutes, Actinobacteria and Proteobacteria are the common phyla isolated from the saliva samples, with Bacteroidetes being the most predominant phylum. Bacteroidetes was also more predominant in males versus females in the study cohort, although differences in the microbial diversity were not statistically significant. We also show that, a lower diversity of the salivary microbiome is observed in the elderly participants, with Prevotella and Treponema being the most significant genera. In participants with oral conditions such as mouth ulcers, bleeding or painful gum, our data show that Prevotella and Capnocytophaga are the most dominant genera as compared to the controls. Similar patterns were observed in participants with various smoking habits as compared to the non-smoking participants. Our data show that Streptococcus and Neisseria are more dominant among denture users, as compared to the non-denture users. Our data also show that, abnormal oral conditions are associated with a reduced microbial diversity and microbial richness. Moreover, in this study we show that frequent coffee drinkers have higher microbial diversity compared to the non-drinkers, indicating that coffee may cause changes to the salivary microbiome. Furthermore, tea drinkers show higher microbial richness as compared to the non-tea drinkers. CONCLUSION: This is the first study to assess the salivary microbiome in an Arab population, and one of the largest population-based studies aiming to the characterize the salivary microbiome composition and its association with age, oral health, denture use, smoking and coffee-tea consumption.
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Microbiota , Adulto , Anciano , Bacterias/genética , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , ARN Ribosómico 16S/genética , SalivaRESUMEN
OBJECTIVES: Cytokines released by infiltrating T cells may promote mechanisms leading to fibrosis in scleroderma. The aim of this study was to investigate the role of the Th2 cytokine IL-31, and its receptor IL-31RA, in scleroderma skin and lung fibrosis. METHODS: IL-31 was measured by ELISA of plasma, and by immunochemistry of fibrotic skin and lung tissue of scleroderma patients. The receptor, IL-31RA, was assayed by qPCR of tissue resident cells. Next-generation sequencing was used to profile the responses of normal skin fibroblasts to IL-31. In wild-type Balb/c mice, IL-31 was administered by subcutaneous mini pump, with or without additional TGFß, and the fibrotic reaction measured by histology and ELISA of plasma. RESULTS: IL-31 was present at high levels in plasma and fibrotic skin and lung lesions in a subset of scleroderma patients, and the receptor overexpressed by downstream cells relevant to the disease process, including skin and lung fibroblasts, through loss of epigenetic regulation by miR326. In skin fibroblasts, IL-31 induced next generation sequencing profiles associated with cellular growth and proliferation, anaerobic metabolism and mineralization, and negatively associated with angiogenesis and vascular repair, as well as promoting phenotype changes including migration and collagen protein release via pSTAT3, resembling the activation state in the disease. In mice, IL-31 induced skin and lung fibrosis. No synergy was seen with TGFß, which supressed IL-31RA. CONCLUSION: IL-31/IL-31RA is confirmed as a candidate pro-fibrotic pathway, which may contribute to skin and lung fibrosis in a subset of scleroderma patients.
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Interleucinas/inmunología , Pulmón , Receptores de Interleucina/inmunología , Esclerodermia Sistémica , Piel , Animales , Epigénesis Genética/inmunología , Fibroblastos/metabolismo , Fibrosis/inmunología , Humanos , Pulmón/inmunología , Pulmón/patología , Ratones , Ratones Endogámicos BALB C , Esclerodermia Sistémica/inmunología , Esclerodermia Sistémica/patología , Piel/inmunologíaRESUMEN
INTRODUCTION: The increased consumption of sugar-sweetened beverages (SSBs) has been implicated in the increased incidence of obesity and metabolic syndrome Little of the research on sugar-sweetened beverage intake has examined the consumption patterns of sugared beverages by college students, despite the vulnerabilities of this population to weight gain. The current study sought to characterize sugar-sweetened beverage intake of undergraduate students who belong to high socio-economic strata and to study its correlation with presence of non-alcoholic fatty liver disease. MATERIAL AND METHODS: In a cross sectional, a self reported questionnaire based study about soft drink consumption (≥2/day, 1/day, <1/day). That included undergraduate medical students. Anthropometry and blood pressure were recorded and fasting glucose, insulin and lipid profile and abdominal ultrasonography for the presence of fatty liver was assessed. RESULTS: A total of 242 students were studied. The students in group 1 (≥2/day) had significantly higher BMI, waist circumference and diastolic blood pressure than students of other groups. They also had higher triglycerides, fasting insulin, HOMA-IR and significantly lower levels of HDL-cholesterol. Overall (40%) students had metabolic syndromes in group 1 compared to 8% and 3% in other groups while presence of NAFLD was observed in 75%, 16% and 4% in three groups respectively. Duration of soft drink consumption had positive correlation with presence of NAFLD. CONCLUSIONS: Substantial consumption of soft drinks is leading to increased obesity and cardio-metabolic risk factors in young adults. Artificially sweetened diet soft drinks have been posed as a healthier alternative due to their lack of calories but they do not guarantee protection against non-alcoholic fatty liver disease.
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Bebidas Gaseosas/estadística & datos numéricos , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Estudiantes de Medicina/estadística & datos numéricos , Adolescente , Adulto , Estudios Transversales , Ingestión de Líquidos , Femenino , Humanos , India/epidemiología , Masculino , Enfermedad del Hígado Graso no Alcohólico/diagnóstico por imagen , Prevalencia , Factores de Riesgo , Encuestas y Cuestionarios , Ultrasonografía , Adulto JovenRESUMEN
This research delves into the role of metal ions in enhancing the electronic properties of 5,5'-bis(mercaptomethyl)-2,2'-bipyridine (BPD) self-assembled monolayers (SAMs). It combines experimental techniques and numerical simulations to understand the impact of these ions on the structural, electronic, and transport properties of BPD SAMs. Key findings include the varied bonding preferences of metal ions and their significant role in modifying the electronic structure of BPD molecules, leading to enhanced electron delocalization and migration. The study highlights the potential of metal ions in advancing molecular electronics, particularly in the development of high-performance electronic and energy devices.
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[This corrects the article DOI: 10.1039/D4RA02950J.].
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INTRODUCTION: To date, only a limited number of case reports have documented the co-occurrence of PNS and melanocytic nevus in the medical literature. This study aims to report an exceptionally rare case of posterior chest wall PNS in conjunction with a melanocytic nevus. CASE PRESENTATION: A 46-year-old female presented with a long-standing black lesion on her left upper posterior chest wall, that had become painful in the two months prior to presentation. There was a painful, dark blue, non-erythematous, and non-tender nodule on the left upper posterior chest wall. Based on the patient's desire for cosmetic purposes, the lesion was excised totally with primary closure under local anaesthesia. Histopathological examination revealed intradermal melanocytic nevus with inflamed pilonidal sinus. DISCUSSION: The rarity of posterior chest wall PNS associated with nevi poses unique diagnostic and therapeutic challenges for clinicians. The distinct anatomical location, different from the conventional region, and the rare association between the two conditions may delay accurate diagnosis and result in mismanagement or inappropriate interventions. CONCLUSION: The posterior chest wall PNS is another type of atypical PNS that is extremely rare. The association between PNS and blue nevus is a fascinating medical finding that deserves further investigation.