Linderae radix ethanol extract attenuates alcoholic liver injury via attenuating inflammation and regulating gut microbiota in rats

This study aimed to explore the influence of gut microbiota alterations induced by Linderae radix ethanol extract (LREE) on alcoholic liver disease (ALD) in rats and to study the anti-inflammatory effect of LREE on ALD through the lipopolysaccharide (LPS) toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB) pathway. ALD rat models were established by intragastric liquor [50% (v/v) ethanol] administration at 10 mL/kg body weight for 20 days. Rats were divided into six groups: normal group (no treatment), model group (ALD rats), Essentiale group (ALD rats fed with Essentiale, 137 mg/kg), and LREE high/moderate/low dose groups (ALD rats fed with 4, 2, or 1 g LREE/kg). NF-κB and LPS levels were evaluated. Liver pathological changes and intestinal ultrastructure were examined by hematoxylin and eosin staining and transmission electron microscopy. The gut microbiota composition was evaluated by 16S rDNA sequencing. Expression levels of TLR4 and CD68 in liver tissue, and occludin and claudin-1 in intestinal tissue were measured. LREE treatment significantly reduced NF-κB and LPS levels, improved liver pathological changes, and ameliorated intestinal ultrastructure injury. Meanwhile, LREE-fed groups showed a higher abundance of Firmicutes and a lower abundance of Bacteroidetes than the rats in the model group. Administration of LREE suppressed TLR4 overexpression and promoted the expression of occludin and claudin-1 in intestine tissue. Thus, LREE could partly ameliorate microflora dysbiosis, suppress the inflammatory response, and attenuate liver injury in ALD rats. The protective effect of LREE might be related to the LPS-TLR4-NF-κB pathway.

Obese with higher FNDC5/Irisin levels have a better metabolic profile, lower lipopolysaccharide levels and type 2 diabetes risk

ABSTRACT Objective: Thus, the aim of this study was to compare if higher or smaller fibronectin type 3 domain-containing protein 5 (FNDC5)/irisin levels are associated with inflammatory and metabolic markers, caloric/macronutrient intake, physical fitness and type 2 diabetes mellitus (T2DM) risk in obese middle-aged men, and also to correlate all variables analyzed with FNDC5/irisin. Subjects and methods: On the basis of a cluster study, middle-aged obese men (IMC: 31.01 ± 1.64 kg/m2) were divided into groups of higher and smaller levels of FNDC5/irisin. The levels of leptin, resistin, adiponectin, tumor necrosis factor alpha (TNFα), interleukin 6 and 10 (IL6, IL10), lipopolysaccharide (LPS), glucose, insulin, glycated hemoglobin, insulin resistance and sensibility, lipid profile, risk of T2DM development, body composition, rest energy expenditure, caloric/macronutrient intake and physical fitness were measured. Results: The higher FNDC5/ irisin group presented improved insulin sensibility (homeostasis model assessment - sensibility (HOMA-S) (p = 0.01) and QUICKI index (p < 0.01)), insulin (p = 0.02) and triglyceride levels (p = 0.01), lower insulin resistance (homeostasis model assessment - insulin resistance (HOMA-IR) (p = 0.01), triglycerides/glucose (TYG index) (p = 0.02), neck circumference (p = 0.02), risk of T2DM development (p = 0.02), tendency to decrease serum resistin (p = 0.08) and significant lower LPS levels (p = 0.02). Inverse correlations between FNDC5/irisin and body weight (r −0.46, p = 0.04), neck circumference (r −0.51, p = 0.02), free fat mass (r −0.49, p = 0.02), triglycerides (r −0.43, p = 0.05) and risk of developing T2DM (r −0.61, p = 0.04) were observed. Conclusions: These results suggest that higher FNDC5/irisin levels in obese middle-aged men are related to a better metabolic profile and lower risk of T2DM development and serum LPS, a potential inducer of insulin resistance.

Immune development in HIV-exposed uninfected children born to HIV-infected women

ABSTRACT Immunological and clinical findings suggestive of some immune dysfunction have been reported among HIV-exposed uninfected (HEU) children and adolescents. Whether these defects are persistent or transitory is still unknown. HEU pediatric population at birth, 12 months, 6-12 years were evaluated in comparison to healthy age-matched HIV-unexposed controls. Plasma levels of LPS, sCD14, cytokines, lymphocyte immunophenotyping and T-cell receptor excision circles (TREC) were assessed. HEU and controls had similar LPS levels, which remained low from birth to 6-12 years; for plasma sCD14, IL-2, IL-6, IL-7, IL-10, IL-12p70, IL-13, IL-17, IFN-γ, TNF-α, G-CSF, GM-CSF and MCP-1, which increased from birth to 12 months and then decreased at 6-12 years; and for TREC/106 PBMC at birth in HEU and controls. By contrast, plasma MIP-1β levels were lower in HEU than in controls (p=0.009) at 12 months, and IL-4 levels were higher in HEU than controls (p=0.04) at 6-12 years. Immune activation was higher in HEU at 12 months and at 6-12 years than controls based on frequencies of CD38+HLA-DR+CD8+T cells (p=0.05) and of CD38+HLA-DR+CD4+T cells (p=0.006). Resting memory and activated mature B cells increased from birth to 6-12 years in both groups. The development of the immune system in vertically HEU individuals is comparable to the general population in most parameters, but subtle or transient differences exist. Their role in influencing clinical incidences in HEU is unknown.

Distress do paciente oncológico: prevalência e fatores associados na opinião de familiares / Distress of cancer patients: prevalence and associated factors in the opinion of family / Angustia de los pacientes con cáncer: prevalencia y factores asociados en la opinión de la familia

Este estudo verificou a prevalência e fatores associados ao distress de pacientes oncológicos, na opinião de familiares. Foram entrevistados 140 familiares responsáveis pelo cuidado de pacientes com câncer. O Termômetro de Distress foi adaptado para uso em familiares. Estes consideraram que 72,9% dos pacientes estavam com distress relacionado a preocupações (80,4%), nervosismo (78,4%), tristeza (74,5%), dor (67,6%), fadiga (67,6%) e problemas com alimentação (57,8%). Modelos de regressão logística hierárquica mostraram que, enquanto familiares do sexo masculino (OR=0,025) e idades mais avançadas (OR=0,006 a 0,059) tiveram menor risco de perceber o distress, indivíduos protestantes, comparados a católicos, tiveram chance 12,77 vezes maior de percebê-lo. Quanto aos fatores associados, nervosismo (OR=10,8) contribuiu significativamente mais com a percepção de distress pelos familiares quando comparado a fadiga (OR=3,38) ou ter plano de saúde privado (OR=2,55). Familiares podem ser grandes aliados na avaliação e acompanhamento do distress de pacientes com câncer.

The study aimed to verify the opinion of family members about distress on cancer patients and the factors associated with it. Interviews with 140 family members of cancer patients were conducted. The Distress Thermometer was adapted to be used with family members. Approximately 72.9% of patients were considered in distress, related to concern (80.4%), nervousness (78.4%), sadness (74.5%), pain (67.6%), fatigue (67.6%) and problems with eating (57.8%). The hierarchical logistic regression models showed that while male (OR=0.025) and older ages (OR=0.006 to 0.059) had lower risk of perceiving the distress, individuals Protestants, compared to Catholics, were 12.77 times more likely to perceive it. About the associated factors, nervousness (OR=10.8) contributed significantly more to the perception of distress for family members when compared to fatigue (OR=3.38) or have private health insurance (OR=2.55). Family can be great allies in the evaluation and monitoring of distress in patients with cancer.

Este estudio examinó la prevalencia y los factores asociados con el distress de los pacientes de cáncer, de acuerdo con los familiares. Fueran entrevistados 140 cuidadores familiares de pacientes con cáncer. El Termómetro de Distress fue adaptado para el uso en los familiares. Ellos encontraron que el 72,9% de los pacientes estaban con distress relacionado con preocupaciones (80,4%), nerviosismo (78,4%), tristeza (74,5%), dolor (67,6%), fatiga (67, 6%) y problemas con la alimentación (57,8%). Modelos de regresión logística jerárquica mostraran que, mientras los familiares de sexo masculino (OR=0,025) y de edades más avanzadas (OR=0,006 a 0,059) tuvieron un menor riesgo de percibir el distress, los individuos protestantes, comparados a los católicos, tuvieron oportunidad 12,77 veces mayor para percibirlo. En cuanto a los factores asociados, el nerviosismo (OR=10,8) contribuyó significativamente más a la percepción del distress de los familiares, en comparación con la fatiga (OR=3,38) o tener un seguro de salud privado (OR=2,55). Familiares pueden ser grandes aliados en la evaluación y el seguimiento de sufrimiento en los pacientes con cáncer.

Papel protector de las lipoproteínas de alta densidad en sepsis: aspectos básicos e implicancias clínicas / Protective role of high density lipoproteins in sepsis: basic issues and clinical implications

High density lipoproteins (HDL) are responsible of reverse cholesterol transport and play an important antiatherogenic role. In recent years, several studies suggest that HDL have additional functions, including a possible anti-inflammatory activity in infectious conditions. Furthermore, available evidence indicates that the presence of lipopolysaccharide (LPS) within the circulation during infectious states induced by gram-negative bacteria may be involved in the decrease in HDL cholesterol levels and changes in lipoprotein composition, which have been associated with a higher mortality due to sepsis in animal models and in humans. In this article, we review this subject and also discuss possible mechanisms that explain the positive impact achieved by native HDL, reconstituted HDL, or HDL apolipoprotein peptides on the inflammatory response and mortality in models of endotoxemia. In this regard, it has been proposed that one of the mechanisms by which HDL protect against sepsis may be mediated by its binding ability and/or neutralizing capacity on LPS, avoiding an excessive response of the immune system. Thus, increasing blood levels of HDL and/or parenteral HDL administration may represent a new anti-inflammatory tool for managing septic states in humans.

Las lipoproteínas de alta densidad (HDL) son responsables del transporte reverso de colesterol y ejercen un importante papel anti-aterogénico. En los últimos años, diversos estudios indican que las HDL también tendrían otras funciones críticas, incluyendo una posible actividad anti-inflamatoria durante estados infecciosos. Además, la evidencia disponible sugiere que la presencia de lipopolisacárido (LPS) en la circulación durante estados infecciosos inducidos por bacterias gramnegativas podría estar involucrado en la disminución del colesterol HDL y los cambios en composición de esta clase lipoproteínas, lo cual se asociaría con una mayor tasa de mortalidad por sepsis en modelos animales y en humanos. En este trabajo, se revisan los antecedentes mencionados y además se discuten posibles mecanismos que explican la disminución de la respuesta inflamatoria y de la mortalidad que se logran en modelos de endotoxemia tratados con HDL o preparaciones similares. En este sentido, se ha propuesto que uno de los mecanismos protectores de las HDL estaría mediado por su capacidad de unión y/o neutralización del LPS, evitando una respuesta exacerbada del sistema inmune. De esta manera, el aumento de los niveles sanguíneos de HDL y/o su administración parenteral podrían constituir nuevas herramientas anti-inflamatorias para el manejo de estados sépticos en humanos.

Identification of serological biomarkers of infection, disease progression and treatment efficacy for leprosy

Although leprosy is curable with drug treatment, the identification of biomarkers of infection, disease progression and treatment efficacy would greatly help to reduce the overall prevalence of the disease. Reliable biomarkers would also reduce the incidence of grade-2 disability by ensuring that those who are most at risk are diagnosed and treated early or offered repeated treatments in the case of relapse. In this study, we examined the reactivity of sera from lepromatous and tuberculoid leprosy patients (LPs) against a panel of 12 recombinant Mycobacterium leprae proteins and found that six proteins were strongly recognised by multibacillary (MB) patients, while only three were consistently recognised by paucibacillary patients. To better understand the dynamics of patient antibody responses during and after drug therapy, we measured antibody titres to four recombinant proteins, phenolic glycolipid-I and lipoarabinomannan at baseline and up to two years after diagnosis to investigate the temporal changes in the antibody titres. Reactivity patterns to individual antigens and decreases in antibody titres were patient-specific. Antibody titres to proteins declined more rapidly vs. those to carbohydrate and glycolipid antigens. Compared to baseline values, increases in antibody titres were observed during reactional episodes in one individual. Additionally, antibody responses against a subset of antigens that provided a good prognostic indicator of disease progression were analysed in 51 household contacts of MB index cases for up to two years. Although the majority of these contacts showed no change or exhibited decreases in antibody titres, seven individuals developed higher titres towards one or more of these antigens and one individual with progressively higher titres was diagnosed with borderline lepromatous leprosy 19 months after enrolment. The results of this study indicate that antibody titres to specific M. leprae antigens can be used to monitor treatment efficacy in LPs and assess disease progression in those most at risk for developing this disease.