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On Earth, there are significant variations in terms of exposure to naturally occurring radiation among different areas. Radon, a naturally-occurring radioactive gas that is the primary cause of lung cancer in nonsmokers and the second most prevalent cause among smokers, poses a considerable risk. Indoor radon, in particular, constitutes the most substantial source of natural radiation to which individuals are exposed. This study assessed the immune status of a population chronically exposed to high indoor radon concentration in Indonesia. Fifty-seven subjects from the Tande-Tande sub-village (high indoor radon concentration area) were compared to fifty-three participants living in the Topoyo village (low concentration area). We contrasted the immunological conditions of these two populations by measuring levels of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-4 (IL-4), and IL-10 in serum. Moreover, we also measured levels of the nuclear factor kappa B (NF-κB), superoxide dismutase (SOD), glutathione peroxidase (GPX), and protein kinase B in its phosphorylated (pAkt) and non-phosphorylated form (Akt) in peripheral blood mononuclear cells (PBMCs) of a subset of participants (31 from each population). TNF-α, IFN-γ, and IL-4 levels in Tande-Tande sub-village inhabitants were significantly lower than those in the control group living in the Topoyo village (p = 0.001, p = 0.017, and p = 0.002). The concentration of IL-10 also tended to be lower in people living in the high indoor radon concentration area, but it did not differ significantly between Tande-Tande sub-village inhabitants and Topoyo inhabitants (p = 0.106). Protein levels of NF-κB, pAkt, and Akt in Tande-Tande sub-village inhabitants also did not differ significantly between Tande-Tande sub-village inhabitants and Topoyo inhabitants (p = 0.234, p = 0.210, and p = 0.657). Similarly, activities of SOD and GPX did not differ significantly between the two populations (p = 0.569 and p = 0.949). Overall, despite their chronic exposure to high indoor radon concentrations, our study revealed no increase in the levels of TNF-α, IFN-γ, IL-10, IL-4, SOD, and GPX in the inhabitants of Tande-Tande sub-village compared with people living in the Topoyo village. Furthermore, our study demonstrated no activation in the Akt pathway, as indicated by the pAkt/Akt ratio observed in PBMC lysates of individuals residing in the Tande-Tande sub-village.
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Poluentes Radioativos do Ar , Poluição do Ar em Ambientes Fechados , Radônio , Humanos , Radônio/análise , Interleucina-10 , Proteínas Proto-Oncogênicas c-akt , Leucócitos Mononucleares , Interleucina-4 , NF-kappa B , Indonésia , Fator de Necrose Tumoral alfa , Poluição do Ar em Ambientes Fechados/análise , Poluentes Radioativos do Ar/análise , Superóxido DismutaseRESUMO
Background and Objectives: Non-alcoholic Fatty Liver Disease (NAFLD) can occur as a result of micronutrient deficiencies. Hibiscus sabdarifa, a plant used in traditional medicine, contains ingredients that can help prevent this process. This study looked at the potency of Hibiscus sabdariffa Ethanol Extract (HSE) to prevent homocysteine-induced liver damage in animals that were deficient in vitamin B12. Materials and Methods: A comparative study of the effects of roselle extract is presented in an experimental design. Thirty Sprague-Dawley rats were divided into six groups using randomization. To demonstrate the absence of liver damage in the experimental animals under normal conditions, a control group was fed a normal diet without HSE. For the induction of liver damage in the experimental animals, the vitamin B12-restricted group was administered a vitamin B12-restricted diet. To test the effect of HSE on liver damage, the treatment group was given HSE along with a vitamin B12-restricted diet. Each group was given two treatment periods of eight and sixteen weeks. These results were compared with the results of the parameter examination between the vitamin B12 restriction group, with and without HSE, using an ANOVA statistic. The data were analyzed with licensed SPSS 20.0 software. Results: HSE significantly increased the blood levels of vitamin B12 while lowering homocysteine levels. The administration of HSE reduced liver damage based on the activity of liver function enzymes in the plasma due to a limitation of vitamin B12. HSE decreased Sterol Regulatory Element-Binding Protein-1c (SREBP1c) and Nuclear Factor Kappa B (NFkB) protein expressions in the liver tissue, but did not decrease Glucose-Regulated Protein 78 (GRP78) protein expression. Significantly, the levels of Tumor Necrosis Factor alpha (TNF-a) and IL-6 in the liver tissue were lower, while the levels of IL-10 and Nuclear factor-erythroid-2 Related Factor 2 (NRF2) were higher with HSE administration. HSE produced a better histopathological profile of the Hematoxylin and Eosin (H&E)-Masson tricrome for inflammation, fat and fibrosis in the liver. Conclusions: In this study, HSE was found to slow the development of liver damage in experimental animals that were given a vitamin B12-deficient diet.
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Hibiscus , Hepatopatia Gordurosa não Alcoólica , Deficiência de Vitamina B 12 , Ratos , Animais , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Extratos Vegetais/metabolismo , Ratos Sprague-Dawley , Fígado , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Etanol/farmacologia , Deficiência de Vitamina B 12/complicações , Deficiência de Vitamina B 12/tratamento farmacológico , Vitamina B 12 , FloresRESUMO
In cross-sectional studies, chronic helminth infections have been associated with immunological hyporesponsiveness that can affect responses to unrelated antigens. To study the immunological effects of deworming, we conducted a cluster-randomized, double-blind, placebo-controlled trial in Indonesia and assigned 954 households to receive albendazole or placebo once every 3 mo for 2 y. Helminth-specific and nonspecific whole-blood cytokine responses were assessed in 1,059 subjects of all ages, whereas phenotyping of regulatory molecules was undertaken in 121 school-aged children. All measurements were performed before and at 9 and 21 mo after initiation of treatment. Anthelmintic treatment resulted in significant increases in proinflammatory cytokine responses to Plasmodium falciparum-infected red blood cells (PfRBCs) and mitogen, with the largest effect on TNF responses to PfRBCs at 9 mo-estimate [95% confidence interval], 0.37 [0.21-0.53], P value over time (Ptime) < 0.0001. Although the frequency of regulatory T cells did not change after treatment, there was a significant decline in the expression of the inhibitory molecule cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) on CD4+ T cells of albendazole-treated individuals, -0.060 [-0.107 to -0.013] and -0.057 [-0.105 to -0.008] at 9 and 21 mo, respectively; Ptime = 0.017. This trial shows the capacity of helminths to up-regulate inhibitory molecules and to suppress proinflammatory immune responses in humans. This could help to explain the inferior immunological responses to vaccines and lower prevalence of inflammatory diseases in low- compared with high-income countries.
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Albendazol/uso terapêutico , Infecções Comunitárias Adquiridas/prevenção & controle , Helmintíase/tratamento farmacológico , Helmintos/efeitos dos fármacos , Adolescente , Adulto , Animais , Anti-Helmínticos/uso terapêutico , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Antígeno CTLA-4/imunologia , Antígeno CTLA-4/metabolismo , Criança , Infecções Comunitárias Adquiridas/imunologia , Infecções Comunitárias Adquiridas/parasitologia , Estudos Transversais , Citocinas/sangue , Citocinas/imunologia , Método Duplo-Cego , Feminino , Helmintíase/epidemiologia , Helmintíase/imunologia , Helmintos/imunologia , Interações Hospedeiro-Parasita/efeitos dos fármacos , Interações Hospedeiro-Parasita/imunologia , Humanos , Indonésia/epidemiologia , Masculino , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/imunologia , Prevalência , Resultado do Tratamento , Adulto JovemRESUMO
Introduction: Nasopharyngeal cancer (NPC) is a complex cancer due to its unique genomic features and association with the Epstein-Barr virus (EBV). Despite therapeutic advancements, NPC prognosis remains poor, necessitating a deeper understanding of its genomics. Here, we present a comprehensive whole genome sequencing (WGS) view of NPC genomics and its correlation with the phenotype. Methods: This study involved WGS of a clinical NPC biopsy specimen. Sequencing was carried out using a long read sequencer from Oxford Nanopore. Analysis of the variants involved correlation with the phenotype of NPC. Results: A loss of genes within chromosome 6 from copy number variation (CNV) was found. The lost genes included HLA-A, HLA-B, and HLA-C, which work in the antigen presentation process. This loss of the major histocompatibility complex (MHC) apparatus resulted in the tumour's ability to evade immune recognition. The tumour exhibited an immunologically "cold" phenotype, with mild tumour-infiltrating lymphocytes, supporting the possible etiology of loss of antigen presentation capability. Furthermore, the driver mutation PIK3CA gene was identified along with various other gene variants affecting numerous signaling pathways. Discussion: Comprehensive WGS was able to detect various mutations and genomic losses, which could explain tumour progression and immune evasion ability. Furthermore, the study identified the loss of other genes related to cancer and immune pathways, emphasizing the complexity of NPC genomics. In conclusion, this study underscores the significance of MHC class I gene loss and its probable correlation with the cold tumour phenotype observed in NPC.
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Purpose: Large animal models are still used in many studies because of their likeness to humans. It has not been documented that regular-sized conventional farm-breed pigs, generally bred for meat production, can be used to generate hepatocellular carcinoma (HCC) animal models. The goal of this study was to investigate how N-diethylnitrosamine (DENA) and phenobarbital (PB) together can generate HCC in ordinary farmed pigs. Materials and Methods: Conventional domestic swine (Sus scrofa domesticus) were used. DENA 15 mg/kg was intraperitoneally injected weekly for 12 weeks, while PB tablets (4 mg/kg) were also administered through food for 16 weeks. Blood testing and ultrasonography evaluation were performed to monitor the progress. Subsequently, computed tomography was conducted in cases with suspected nodules, followed by histopathological examination to confirm the diagnosis. Results: Ten swine (seven males, three females; age: 2 months; weight: 9-15 kg) were included in the study and followed up for 25 months; nine were experimental, and one was control for ethical considerations. The maximum weight of animals during this study reached 162-228 kg. The weight gain seen in the intervention swine was predominantly lower than that documented in the control. The laboratory analysis revealed no notable abnormalities in liver function markers but did demonstrate statistically significant changes in urea (p = 0.028) and creatinine (p = 0.003) levels. Ultrasonography and computed tomography showed multiple liver nodules with characteristics resembling HCC. Serial imaging screening and more extended observations revealed that all animals eventually developed tumors. Histopathological confirmation at 15-22 weeks post-induction revealed that all intervened swine developed multiple nodules of well-differentiated HCC and some with hepatic angiosarcoma. Conclusion: This study successfully generated HCC in conventional domestic swine with a DENA and PB combination. This investigation required at least 15 months to develop tumors. This model will be beneficial for future investigations of HCC in large animals.
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Altered body composition and cytokine production due to SARS-CoV-2 antigens may affect homeostasis model assessment for insulin resistance (HOMA-IR) after SARS-CoV-2 infection. To elucidate this phenomenon, we conducted a longitudinal study involving 47 COVID-19 patients, who were followed up for 12 months. During recruitment, body composition and glucose indices were measured, and heparin blood samples were collected for measuring cytokine production. HOMA-IR was considered an elevated or non-elevated group based on the ratio between HOMA-IR at 12 months and 1 month of convalescence. Those with elevated HOMA-IR had a significantly higher body mass index, body fat percentage, and visceral fat rating and had a lower lean mass and lean/fat mass ratio than their counterparts. During the convalescent period, the elevated HOMA-IR group had lower TNFα, IFNγ, IL-2, IL-10, and granzyme B expression levels but had higher TNFα/IL-10, IFNγ/IL-10, IL-2/IL-10, and granzyme B/IL-10 ratios than the other group. The reduced cytokine production and pro-/anti-inflammatory imbalance in patients with elevated HOMA-IR may suggest immune cell dysfunction toward SARS-CoV-2. Patients with elevated HOMA-IR after SARS-CoV-2 infection may experience an increase in BMI and body fat percentage, leading to increased immune dysfunction and chronic inflammatory condition. A nutritional approach and promotion of physical activity may help reduce HOMA-IR and ameliorate glucose indices in these patients.
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Coronavirus disease 2019 (COVID-19) has been extensively researched, particularly with regard to COVID-19 vaccines. However, issues with logistics and availability might cause delays in vaccination programs. Thus, the efficacy and safety of half-dose heterologous mRNA should be explored. This was an open-label observational study to evaluate the immunogenicity and safety of half-dose mRNA-1273 as a booster vaccine among adults aged >18 years who underwent a complete primary SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination regimen with CoronaVac® and ChAdOx1-S. Adverse events (AEs), seropositivity rate, seroconversion, geometric mean titer (GMT) of SARS-CoV-2 antibodies, neutralizing antibodies, and T cells (CD4+ and CD8+) specific for SARS-CoV-2 were analyzed. Two hundred subjects were included in the final analysis, with 100 subjects in each priming vaccine group. Most of the AEs were mild, with systemic manifestations occurring between 1 and 7 days following vaccination. A significant difference was observed in the GMT and seropositivity rate following booster dose administration between the two groups. CD8+/CD3+, IFN (interferon)-producing CD8+, and TNF (tumor necrosis factor)-producing CD8+ cells showed significant increases in both groups. The administration of the half-dose mRNA-1273 booster is safe and effective in increasing protection against SARS-CoV-2 infection.
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Introduction Dry eye disease affects a substantial number of individuals globally and significantly impacts their quality of life and productivity. Understanding the underlying mechanisms and managing dry eye disease poses substantial challenges. Recent research has highlighted the involvement of various inflammatory mediators in the pathogenesis of dry eye disease, including the cytokines interferon (IFN)-γ and interleukin (IL)-17. Activation of stress signaling pathways and residential immune cells on the ocular epithelial surface ignites epithelial changes, destabilizes tear film, amplifies inflammation and creates an endless loop. Lutein is a ß-carotenoid antioxidant which has been proven to be beneficial in many ocular diseases due to its protective and anti-inflammatory effect induced by various stimulators. Lutein also acts as a direct and indirect antioxidant agent, suppressing oxidative stress and mitigating oxidative damage. The purpose of this research is to investigate the potential therapeutic effects of lutein in a mouse model of dry eye, aiming to elucidate its impact on ocular manifestation, goblet cells count, IFN-γ and IL-17 level. Methods Desiccating stress was induced in C57BL/6 mice. In a separate group, lutein was administered subcutaneously on a daily basis throughout the experimental period. Clinical manifestations of dry eye, including ocular surface changes, were documented photographically. Goblet cell concentration was assessed through Periodic Acid-Schiff (PAS) staining, and the levels of IFN-γ and IL-17 were measured using enzyme-linked immunosorbent assay (ELISA). Data obtained from these assessments were compared between the experimental groups to determine the potential effects of lutein on dry eye pathology and cytokine levels. Results Significant differences were observed in clinical observations and goblet cell concentrations among the groups; however, no statistically significant differences were found in the levels of IFN-γ and IL-17 between the groups. The untreated group exhibited significantly higher opacities and irregularities compared to the lutein-treated group, whereas the mean goblet cell count was highest in the lutein-treated group. Conclusion Lutein administration improves clinical observations and goblet cell concentrations in a mouse model of dry eye. The treated group exhibited improved ocular surface integrity, but no significant differences in the tested cytokine levels were observed. These findings suggest that lutein supplementation could be a promising therapeutic option for managing dry eye disease. Further research is needed to understand the underlying mechanisms and long-term effects of lutein in dry eye management.
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The frequencies of unstable and stable chromosome aberrations and micronuclei were examined in peripheral blood samples from 10 individuals living in elevated radon concentration areas (Takandeang Village, Mamuju, Indonesia). Blood samples from 10 people living in Topoyo Village were used as a control group. For unstable chromosome aberration analysis, a dicentric chromosome assay was conducted using conventional Giemsa staining. Chromosomal painting of chromosomes 1 and 4 using the fluorescence in situ hybridisation technique was also applied to four subjects to assess the stable chromosome aberration. Our study showed no significant increases across all groups in dicentric and other unstable chromosome aberrations, such as rings and acentric fragments. Translocations were found in one person from Takandeang Village and two Topoyo Village inhabitants. The translocations found in the subjects from Takandeang Village were due more to aging factors than to radon exposure. The number of micronuclei per 1000 binucleus cells in Takandeang Village inhabitants was not significantly different than that in the control group (p = 0.943). A more comprehensive analysis should be conducted in a subsequent study by increasing the number of study donors and the number of metaphases to be analysed in both dicentric chromosome assay and fluorescence in situ hybridisation assays. Such research could provide valid information on the cytogenetic effects of elevated indoor radon exposure.
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Aberrações Cromossômicas , Radônio , Animais , Testes para Micronúcleos , Cor , Translocação Genética , Corantes Azur , Linfócitos , Peixes , Radônio/efeitos adversosRESUMO
OBJECTIVE: This study investigated several inflammatory markers' gene and protein expression in status epilepticus (SE) and their correlation with diazepam resistance. MATERIALS AND METHODS: Peripheral blood samples were collected from 18 adult patients with SE in Cipto Mangunkusumo Central Hospital, consisting of 12 diazepam-responsive and six diazepam-resistant samples, within 72 hours of the onset of the seizure. We collected baseline demographic and clinical data from each subject. Peripheral blood mononuclear cells (PBMCs) were isolated, cultured, stimulated with lipopolysaccharide (LPS) 1 mg/ml, and harvested for RNA isolation. The RNA was used to determine the expression of Human Mobility Group Box 1 (HMGB1), Interleukin- 6 (IL-6), IL-10, Toll-like Receptor 4 (TLR4), and Glial fibrillary acidic protein (GFAP). In addition, we performed serum protein assay of HMGB1, IL-6, IL-10, TLR4, and GFAP to compare with gene expression. RESULTS: We found a significant difference between the responsive and resistant groups for serum HMGB1 and IL-6 concentration. The mRNA expression of HMGB1 and IL-6 was significantly higher in LPS-stimulated samples in the responsive but not in the resistant groups. The ratio of IL-6 to IL-10 showed a significant difference between LPS and control in the responsive group. Diazepam response was significantly correlated with seizure duration and serum protein concentration of HMGB1. CONCLUSION: HMGB1 was highly expressed in the resistant group and strongly correlated with diazepam response, and there was a significant increase in HMGB1 mRNA expression in response to LPS stimulation. These findings suggest that targeting HMGB1 may be a promising therapeutic strategy and that HMGB1 levels could be a valuable biomarker for predicting diazepam resistance in SE.
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Proteína HMGB1 , Estado Epiléptico , Adulto , Humanos , Diazepam/farmacologia , Diazepam/uso terapêutico , Interleucina-10 , Receptor 4 Toll-Like , Interleucina-6 , Leucócitos Mononucleares , Lipopolissacarídeos , Estado Epiléptico/tratamento farmacológico , Convulsões , Proteínas Sanguíneas , RNA , RNA MensageiroRESUMO
PURPOSE: To deepen our knowledge on the effects of high levels of indoor radon exposure, we assessed the frequencies of unstable and stable chromosome aberrations and micronucleus (MN), as well as the concentration of an endogenous antioxidant (catalase, CAT), in blood samples of individuals chronically exposed to high indoor radon concentrations in Indonesia (Tande-Tande sub-village, Mamuju, West Sulawesi). Moreover, we also investigated the occurrence of a radio-adaptive response (RAR) in Tande-Tande sub-village inhabitants using the G2 MN assay. MATERIALS AND METHODS: The frequencies of dicentric (DC), acentric (AF), ring (R), and translocation (Tr) chromosomes in Tande-Tande inhabitants were compared to those in people living in a reference area with low levels of indoor radon levels (Topoyo village, Indonesia). The number of MN per 1000 binucleated cells (BNC) and CAT concentration per total protein was quantified and compared between groups. Lastly, we irradiated (2 Gy) phytohemagglutinin-stimulated samples in vitro and measured the frequency of MN to verify the occurrence of a RAR in Tande-Tande sub-village inhabitants. RESULTS AND CONCLUSION: The frequencies of DC, AF, and Tr did not differ between Tande-Tande inhabitants and control subjects (p = 0.350, 0.521, 0.597). The frequency of MN in Tande-Tande inhabitants was significantly lower than that in the control group (p = 0.006). Similarly, CAT concentration in Tande-Tande inhabitants was also significantly lower than that in the control population (p < 0.001). Significant negative correlations were identified for MN number and CAT concentration versus indoor radon concentration, annual effective dose, or cumulative dose both within groups and when all data were analyzed together. Our findings indicate that, despite the high indoor radon levels, Tande-Tande inhabitants are not under oxidative stress, since this group had lower CAT concentration and MN frequency than those in the control group. The negative correlation between MN frequency and indoor radon concentration, annual effective dose, and cumulative dose suggests the occurrence of an RAR phenomenon in Tande-Tande sub-village inhabitants. This interpretation is also supported by the results of the G2 MN assay, which revealed lower MN frequencies after in vitro irradiation of samples from Tande-Tande sub-village inhabitants than those in samples from the control group (p = 0.0069, for cumulative MN frequency; p = 0.0146, for radiation-induced MN only).
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Catalase , Aberrações Cromossômicas , Micronúcleos com Defeito Cromossômico , Radônio , Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Indonésia , Aberrações Cromossômicas/efeitos da radiação , Aberrações Cromossômicas/estatística & dados numéricos , Micronúcleos com Defeito Cromossômico/estatística & dados numéricos , Catalase/sangue , Radônio/análise , Radônio/toxicidade , Doses de Radiação , Adaptação Fisiológica/efeitos da radiaçãoRESUMO
The heterogeneity of the lung microbiome and its alteration are prevalently seen among chronic lung diseases patients. However, studies to date have primarily focused on the bacterial microbiome in the lung rather than fungal composition, which might play an essential role in the mechanisms of several chronic lung diseases. It is now well established that Aspergillus spp. colonies may induce various unfavorable inflammatory responses. Furthermore, bacterial microbiomes such as Pseudomonas aeruginosa provide several mechanisms that inhibit or stimulate Aspergillus spp. life cycles. In this review, we highlighted fungal and bacterial microbiome interactions in the respiratory tract, with a focus on Aspergillus spp.
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Background: Prediabetes is a condition of intermediate hyperglycemia that may progress to type 2 diabetes. Vitamin D deficiency has been frequently linked to insulin resistance and diabetes. The study aimed to investigate the role of D supplementation and its possible mechanism of action on insulin resistance in prediabetic rats. Method: The study was conducted on 24 male Wistar rats that were randomly divided into 6 rats as healthy controls and 18 prediabetic rats. Prediabetic rats were induced with a high-fat and high-glucose diet (HFD-G) combined with a low dose of streptozotocin. Rats with the prediabetic condition were then randomized into three groups of 12-week treatment: one group that received no treatment, one that received vitamin D3 at 100 IU/kg BW, and one group that received vitamin D3 at 1000 IU/kg BW. The high-fat and high-glucose diets were continuously given throughout the twelve weeks of treatment. At the end of the supplementation period, glucose control parameters, inflammatory markers, and the expressions of IRS1, PPARγ, NF-κB, and IRS1 were measured. Results: Vitamin D3 dose-dependently improves glucose control parameters, as shown by the reduction of fasting blood glucose (FBG), oral glucose tolerance test (OGTT), glycated albumin, insulin levels, and markers of insulin resistance (HOMA-IR). Upon histological analysis, vitamin D supplementation resulted in a reduction of the islet of Langerhans degeneration. Vitamin D also enhanced the ratio of IL-6/IL-10, reduced IRS1 phosphorylation at Ser307, increased expression of PPAR gamma, and reduced phosphorylation of NF-KB p65 at Ser536. Conclusion: Vitamin D supplementation reduces insulin resistance in prediabetic rats. The reduction might be due to the effects of vitamin D on IRS, PPARγ, and NF-κB expression.
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Diabetes Mellitus Tipo 2 , Resistência à Insulina , Estado Pré-Diabético , Ratos , Masculino , Animais , Estado Pré-Diabético/tratamento farmacológico , Estado Pré-Diabético/metabolismo , NF-kappa B , PPAR gama , Diabetes Mellitus Tipo 2/metabolismo , Glicemia/análise , Suplementos Nutricionais/análise , Ratos Wistar , Vitamina D , Vitaminas/farmacologia , Vitaminas/uso terapêutico , Colecalciferol/farmacologiaRESUMO
The kinetics of hexogen coating with polyurethane-based hydroxyl-terminated polybutadiene (HTPB) using infrared spectrometry was investigated. The kinetics model was evaluated through reaction steps: (1) hydroxyl and isocyanate to produce urethane, (2) urethane and isocyanate to produce allophanate, and (3) nitro and isocyanate to produce diazene oxide and carbon dioxide. HTPB, ethyl acetate, TDI (toluene diisocyanate), and hexogen were mixed for 60 min at 40 °C. The sample was withdrawn and analyzed with infrared spectroscopy every ten minutes at reference wavelengths of 2270 (the specific absorption for isocyanate groups) and 1768 cm-1 (the specific absorption for N=N groups). The solvent was vaporized; then, the coated hexogen was cured in the oven for 7 days at 60 °C. The effect of temperature on the coating kinetics was studied by adjusting the reaction temperature at 40, 50, and 60 °C. This procedure was repeated with IPDI (isophorone diisocyanate) as a curing agent. The reaction rate constant, k3, was calculated from an independent graphic based on increasing diazene oxide concentration every ten minutes. The reaction rate constants, k1 and k2, were numerically calculated using the Newton-Raphson and Runge-Kutta methods based on decreasing isocyanate concentrations. The activation energy of those steps was 1178, 1021, and 912 kJ mole-1. The reaction rate of hexogen coating with IPDI was slightly faster than with TDI.
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BACKGROUND: Critically ill COVID-19 pneumonia is one of the main causes of extubation failure and mortality. Understanding clinical characteristics, laboratory profiles and bronchoalveolar lavage fluid (BALF) immunopathology may help improve outcomes in critically ill COVID-19 pneumonia. We aimed to describe clinical characteristics, laboratory profiles and BALF immunopathology based on lung severity in critically ill COVID-19 pneumonia patients. MATERIALS AND METHODS: Forty critically ill severe pneumonia patients requiring invasive mechanical ventilation in Cipto Mangunkusumo General (National Tertiary Referral Hospital), Indonesia within November 2020-January 2021 were enrolled in this study. Early BALF collection was performed after patients' intubation. Clinical characteristics, laboratory profiles and BALF biomarkers (sTREM-1, alveolar macrophage amount and function, IL-6, IL-17, CD4 T-cells, Tregs, SP-A and Caspase-3) were observed and analysed. Outcomes were measured based on extubation failure (within 19 days) and 28-days mortality. Univariate and bivariate analyses were performed. RESULTS: Early bronchoscopy was performed in an average of 4 h (SD = 0.82) after patients' intubation. Twenty-three and twenty-two patients had extubation failure (within 19 days) and 28-days mortality, respectively. In the baseline clinical characteristics of critically ill COVID-19 patients, we found no significant differences in the extubation and mortality status groups. In the laboratory profiles of critically ill COVID-19 patients, we found no significant differences in the extubation status groups. In critically ill COVID-19 pneumonia patients, there was a significant high D-dimer levels in survived group (p = .027), a significant low BALF CD4 T-cells count in the right lung (p = .001) and a significant low BALF CD4 T-cells count (p = .010 and p = .018) in severely affected lung with extubation failure and mortality. CONCLUSIONS: BALF CD4 T-cells count evaluation of severely affected lung is associated with early extubation failure and mortality in critically ill COVID-19 pneumonia patients. KEY MESSAGEFew studies have been conducted during the peak COVID-19 period analysing combined bronchoalveolar lavage fluid (BALF) immunopathology biomarkers within four hours of intubation to assess extubation failure and mortality. In this study, we reported eight BALF immunopathology biomarkers (sTREM-1, alveolar macrophage, IL-6, IL-17, CD4 T-cells, Tregs, SP-A and Caspase-3).We found significantly low BALF CD4 T-cells count in the right lung, and low BALF CD4 T-cells count in severely affected lung of critically ill COVID-19 pneumonia patients in extubation failure and mortality.
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Extubação , COVID-19 , Biomarcadores , Líquido da Lavagem Broncoalveolar , Linfócitos T CD4-Positivos , Caspase 3 , Estado Terminal , Humanos , Interleucina-17 , Interleucina-6RESUMO
Cryptic species of Aspergillus have rapidly increased in the last few decades. Chronic pulmonary aspergillosis (CPA) is a debilitating fungal infection frequently affecting patients with previous TB. The identification and antifungal susceptibility profiles of different species of Aspergillus are important to support the management of CPA. The aim of this study was to describe the molecular and susceptibility profiles of Aspergillus isolated from CPA patients. The species identity of isolates was determined by combined DNA analyses of internal transcribed space (ITS), partial ß-tubulin genes, and part of the calmodulin gene. We revealed a high (27%) prevalence of cryptic species among previous tuberculosis patients with persistent symptoms. Twenty-nine (49%) patients met the criteria for diagnosis of CPA with 24% containing Aspergillus cryptic species. This is the first report of five cryptic Aspergillus species from clinical isolates in Indonesia: A. aculea tus, A. neoniger, A. brunneoviolacues, A. welwitschiae, and A. tubingensis. Significantly, there was decreased sensitivity against itraconazole in the CPA group (66% susceptible to itraconazole) compared to the non-CPA group (90% susceptible to itraconazole) (p = 0.003). The species-level characterisation of Aspergillus and its antifungal susceptibility tests demands greater attention to better the management of CPA patients.
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BACKGROUND: The prevalence of asthma and atopic disease has been reported to be low in low income countries, however helminth infections are likely to be high among these communities. The question of whether helminth infections play a role in allergic diseases can best be addressed by intervention studies. None of the studies so far have been based on a large scale placebo-controlled trial. METHOD/DESIGN: This study was designed to assess how intestinal helminth infections can influence the immune response and atopic and allergic disorders in children in Indonesia. The relations between allergic outcomes and infection and lifestyle factors will be addressed. This study was set up among school-age children in semi urban and rural areas, located in Ende District of Flores Island, Indonesia. A randomized placebo-controlled anthelmintic treatment trial to elucidate the impact of helminth infections on the prevalence of skin prick test (SPT) reactivity and symptoms of allergic diseases will be performed. The children living in these semi-urban and rural areas will be assessed for SPT to allergens before and after 1 and 2 years of treatment as the primary outcome of the study; the secondary outcome is symptoms (asthma and atopic dermatitis); while the tertiary outcome is immune responses (both antibody levels to allergens and cellular immune responses). DISCUSSION: The study will provide information on the influence of helminth infections and anthelmintic treatment on immune response, atopy and allergic disorders. TRIAL REGISTRATION: Current Controlled Trials ISRCTN: ISRCTN83830814.
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Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Asma/epidemiologia , Dermatite Atópica/epidemiologia , Helmintíase/epidemiologia , Enteropatias Parasitárias/epidemiologia , Alérgenos/imunologia , Animais , Asma/complicações , Asma/imunologia , Criança , Pré-Escolar , Dermatite Atópica/complicações , Dermatite Atópica/imunologia , Método Duplo-Cego , Feminino , Helmintíase/tratamento farmacológico , Helmintíase/imunologia , Helmintíase/parasitologia , Helmintos/classificação , Helmintos/genética , Helmintos/imunologia , Helmintos/isolamento & purificação , Humanos , Hipersensibilidade Imediata/complicações , Hipersensibilidade Imediata/imunologia , Indonésia/epidemiologia , Enteropatias Parasitárias/tratamento farmacológico , Enteropatias Parasitárias/imunologia , Enteropatias Parasitárias/parasitologia , Estudos Longitudinais , Masculino , Prevalência , População Rural , Testes Cutâneos , Resultado do Tratamento , População UrbanaRESUMO
Type 2 diabetes mellitus (T2DM) is associated with chronic low-grade inflammation, which is marked by the dysregulation of innate and adaptive immune responses. Therefore, reducing inflammation, possibly through an immunoregulatory agent, may play a role in T2DM treatment. Butyrate is the most potent short-chain fatty acid (SCFA), and it exerts anti-inflammatory properties by inhibiting histone deacetylase activity. As an immunoregulatory agent, sodium butyrate can inhibit nuclear factor kB (NF-kB) activation and reduce the production of pro-inflammatory cytokines in immune cells. The aim of the study was to measure the level of plasma butyrate in poorly controlled T2DM and normoglycemic participants and to compare the response of peripheral blood mononuclear cells (PBMCs) to sodium butyrate treatment between the groups by measuring production of the following cytokines: tumor necrosis factor (TNF)-α, interleukin (IL)-6, interferon (IFN)-γ, IL-13, and IL-10. The in vitro study examined the PBMCs of 15 participants with poorly controlled T2DM and 15 normoglycemic participants. PBMCs were cultured with the following stimulations for two days at a temperature of 37°C and 5% CO2: 100 ng/mL lipopolysaccharide (LPS), 1 mM sodium butyrate, or a combination of 100 ng/mL LPS and 1 mM sodium butyrate. Plasma butyrate was measured using gas chromatography-mass spectrometry, and cytokines from culture supernatant were analyzed using magnetic beads multiplex assay. Plasma butyrate levels in participants with poorly controlled T2DM did not significantly differ from those in normoglycemic participants (p = 0.105). Compared to treatment with an LPS-stimulated PBMC culture, treatment with 1 mM sodium butyrate reduced the levels of TNF-α (p < 0.039) and IFN-γ (p < 0.038) in normoglycemic participants. The same general trend was seen in PBMC from participants with poorly controlled T2DM, but higher variability appeared to preclude statistical significance. These data suggest that butyrate may modulate inflammatory cytokine production in human PBMCs, but more research is needed to determine if butyrate is anti-inflammatory in poorly controlled T2DM.
Assuntos
Ácido Butírico/farmacologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/imunologia , Leucócitos Mononucleares/citologia , Lipopolissacarídeos/química , Adulto , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Inflamação , Interferon gama/metabolismo , Interleucina-10/metabolismo , Interleucina-13/metabolismo , Interleucina-6/metabolismo , Leucócitos Mononucleares/efeitos dos fármacos , Lipopolissacarídeos/metabolismo , Masculino , Pessoa de Meia-Idade , Subunidade p50 de NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The objective of this study was to assess the effect of radon exposure on the modulation of endogenous antioxidants in a population chronically exposed to high levels of radon indoors. To do so, we measured the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPX) in peripheral blood mononuclear cells (PBMCs) of people living in an area with high indoor radon concentration (Tande-Tande sub-village, Indonesia). The activities of SOD and GPX in Tande-Tande inhabitants were compared with those in subjects living in the Topoyo village (Indonesia), an area with low indoor radon levels. The activities of SOD and GPX in Tande-Tande sub-village inhabitants did not differ from those in people living in the Topoyo village (0.37 ± 0.021 versus 0.28 ± 0.018 U/mg protein and 8.46 ± 1.48 versus 8.34 ± 1.65 U/mg protein, p > .05). For both populations, there was a significant positive correlation between SOD and GPX activities (p < .001). No significant effects of gender, age, smoking habit, and body mass index on SOD and GPX activities were found for both groups. Although no significant modulation of SOD and GPX activities in PBMCs was detected, further studies should expand the sample size and also assess antioxidant levels in the serum. This study provides a first picture of endogenous antioxidant systems in Tande-Tande sub-village inhabitants, but a more comprehensive analysis, including the measurement of catalase (CAT) activity, might provide additional insight into the effects of chronic exposure to high indoor radon concentrations.
Assuntos
Antioxidantes , Radônio , Catalase , Glutationa Peroxidase , Humanos , Leucócitos Mononucleares , Radônio/efeitos adversos , Superóxido DismutaseRESUMO
The detection of Aspergillus antibody has a key role in the diagnosis of chronic pulmonary aspergillosis. Western blot (WB) and immunochromatography (ICT) lateral flow detection of Aspergillus antibody can be used as confirmatory and screening assays but their comparative performance in TB patients is not known. This study investigated the performance of these assays among 88 post-tuberculosis patients with suspected CPA. Sensitivity, specificity, receiver operating curve (ROC), area under-curve (AUC) and the agreement between two assays were evaluated. Both WB and ICT showed good sensitivity (80% and 85%, respectively) for detection of Aspergillus antibodies. Substantial agreement (0.716) between these assays was also obtained. The highest AUC result (0.804) was achieved with the combination of WB and ICT. The global intensity of WB correlated with the severity of symptoms in CPA group (p = 0.001). The combination of WB and ICT may increase specificity in CPA diagnosis.