Oral Angiotensin-(1–7) prevented obesity and hepatic inflammation by inhibition of resistin/TLR4/MAPK/NF-κB in rats fed with high-fat diet

AbstractObesity is characterized by a pro-inflammatory state commonly associated with type 2 diabetes and fat-liver disease. In the last few years, different studies pointed out the role of Angiotensin (Ang)-(1–7) in the metabolic regulation. The aim of the present study was to evaluate the effect of oral-administration of Ang-(1–7) in metabolism and inflammatory state of high-fat feed rats. Twenty-four male Sprague Dawley rats were randomized into three groups: High Fat Diet (HFD); Standard Diet (ST); High Fat Diet+Angiotensin-(1–7) [HFD+Ang-(1–7)]. Glycemic profile was evaluated by glucose tolerance and insulin sensitivity tests, plasmatic glucose and insulin. Cholesterol, HDL and triglycerides analyses presented lipidic profile. RT-PCR evaluated mRNA expression to ACE, ACE2, resistin, TLR4, IL-6, TNF-α and NF-κB genes. The main results showed that oral Ang-(1–7) decreased body weight and abdominal fat-mass. In addition, HFD+Ang-(1–7) treated rats presented enhanced glucose tolerance, insulin-sensitivity and decreased plasma-insulin levels, as well as a significant decrease in circulating lipid levels. These alterations were accompanied by a marked decreased expression of resistin, TLR4, ACE and increased ACE2 expression in liver. Furthermore, Ang-(1–7) decreases phosphorylation of MAPK and increases NF-κB expression. These alterations diminished expression of interleukin-6 and TNF-α, ameliorate inflammatory state in liver. In summary, the present study showed that oral-treatment with Ang-(1–7) in high-fat feed rats improved metabolism down-regulating resistin/TLR4/NF-κB-pathway

Smoking-induced aggravation of experimental arthritis is dependent of aryl hydrocarbon receptor activation in Th17 cells.

Background: Epidemiologic studies have highlighted the association of environmental factors with the development and progression of autoimmune and chronic inflammatory diseases. Among the environmental factors, smoking has been associated with increased susceptibility and poor prognosis in rheumatoid arthritis (RA). However, the immune and molecular mechanism of smoking-induced arthritis aggravation remains unclear. The transcription factor aryl hydrocarbon receptor (AHR) regulates the generation of Th17 cells, CD4 T cells linked the development of autoimmune diseases. AHR is activated by organic compounds including polycyclic aromatic hydrocarbons (PAHs), which are environmental pollutants that are also present in cigarette smoke. In this study, we investigated the role of AHR activation in the aggravation of experiment arthritis induced by exposure to cigarette smoke. Methods: Mice were exposed to cigarette smoke during the developmental phase of antigen-induced arthritis and collagen-induced arthritis to evaluate the effects of smoking on disease development. Aggravation of articular inflammation was assessed by measuring neutrophil migration to the joints, increase in articular hyperalgesia and changes in the frequencies of Th17 cells. In vitro studies were performed to evaluate the direct effects of cigarette smoke and PAH on Th17 differentiation. We also used mice genetically deficient for AHR (Ahr KO) and IL-17Ra (Il17ra KO) to determine the in vivo mechanism of smoking-induced arthritis aggravation. Results: We found that smoking induces arthritis aggravation and increase in the frequencies of Th17 cells. The absence of IL-17 signaling (Il17ra KO) conferred protection to smoking-induced arthritis aggravation. Moreover, in vitro experiments showed that cigarette smoke can directly increase Th17 differentiation of T cells by inducing AHR activation. Indeed, Ahr KO mice were protected from cigarette smoke-induced arthritis aggravation and did not display increase in TH17 frequencies, suggesting that AHR activation is an important mechanism for cigarette smoke effects on arthritis. Finally, we demonstrate that PAHs are also able to induce arthritis aggravation. Conclusions: Our data demonstrate that the disease-exacerbating effects of cigarette smoking are AHR dependent and environmental pollutants with AHR agonist activity can induce arthritis aggravation by directly enhancing Th17 cell development

Electrochemical atomic layer epitaxy deposition of ultrathin SnTe films.

Tin telluride (SnTe) ultrathin films were deposited electrochemically on polycrystalline and monocrystalline gold substrates using the electrochemical atomic layer epitaxy (ECALE) method. The electrochemical behaviors of Sn and Te were studied systematically by means of cyclic voltammetry. Cyclic voltammetry curves for Sn displayed a broad peak in the region between -0.15 V and -0.35 V, which was related to the under-potential deposition (UPD), while the curves for Te displayed a peak at 0.3 V for Te UPD. X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), Raman spectroscopy, and scanning electron microscopy (SEM) were employed for the characterization of the ultrathin SnTe films. XRD and Raman spectroscopy confirmed the deposition of a single SnTe phase, while SEM revealed that the deposits were composed of nanocrystallites

Alternative Biodefensive based on the Essential Oil from Allium sativum Encapsulated in PCL/Gelatin Nanoparticles

The goal of this paper was to develop a biodegradable system containing the essential oil from Allium sativum bulbs encapsulated in PCL/gelatin-based nanoparticles, as well as evaluate its efficiency to control Aedes aegypti Linn. larvae and Cerataphis lataniae Bois. aphids. The essential oil was analyzed by GC-FID and GC-MS, and six compounds were identified, representing 93.1% of the total oil. The major compounds were diallyl trisulfide (51.8%), diallyl disulfide (23.2%) and allyl methyl trisulfide (13.6%). The PCL/gelatin-based nanoparticles containing this essential oil exhibited encapsulation efficiency higher than 94%, average particle diameter around 200 nm and zeta potential values about -36 mV. The essential oil presented no antioxidant nor enzymatic activities, so its effectiveness might be explained by the presence of sulfur compounds. The release kinetics of the encapsulated essential oil confirmed the release mechanism by the Fick's Law. About 50% of the encapsulated essential oil was released after 1 h, and about 90% was released after 50 h. This behavior is interesting from the technological point of view since the nanoparticles released as much oil as possible in a short period of time and then the lethal dosages were maintained along the time. Nanoparticles containing the encapsulated essential oil was submitted to in vitro bioassays against A. aegypti and C. lataniae and showed 100% of mortality against larvae and aphids up to 24 h. In conclusion, the essential oil from A. sativum presented effectiveness to be applied in sustainable management of pests in greenhouses, as well as for larvicidal control

Análise da superfície e osseointegração de implantes dentários com superfícies biomiméticas contedo Ca, Mg e F

Os tratamentos das superfícies dos implantes dentários osseointegráveis sofreram modificações significativas com o objetivo de melhorar a estabilidade primária e secundária. Entre as modificações destaca-se a deposição de íons, como flúor, cálcio e magnésio. Estes íons possuem baixa taxa de degradação no meio corpóreo e ótima interação biológica com as células e com os tecidos ósseos. No presente trabalho, para avaliar os efeitos do F, Ca e do Mg na osseointegração foram realizados ensaios in vitro e in vivo. Implantes foram inseridos em tíbias de coelhos e determinou-se os torques de inserção e remoção após 2, 4 e 8 semanas. Os ensaios in vivo foram complementados pela medida da rugosidade, molhabilidade e análise da superfície em microscopia eletrônica de varredura. Os resultados foram comparados com os obtidos com implantes com a superfície tratada com ácido (superfície Porous) e com deposição de flúor (superfície Porous Nano). Os resultados obtidos mostraram que o torque para remover os implantes Porous 8 semanas após a cirurgia foi de 16,96 + 1,32 N.cm, o tratado com flúor apresentou melhores resultados (17,93 ± 4,47 N.cm) e a superfície com Ca e Mg foi a que apresentou a interface osso-implante com menor resistência (10,83 + 1,20 N.cm). O maior torque indica que a adição de flúor facilita os mecanismos envolvidos na osseointegração dos implantes e permite o carregamento da prótese em tempos menores

Multiplex qPCR Discriminates Variants of Concern to Enhance Global Surveillance of SARS-CoV-2

With the emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants that may increase transmissibility and/or cause escape from immune responses, there is an urgent need for the targeted surveillance of circulating lineages. It was found that the B.1.1.7 (also 501Y.V1) variant, first detected in the United Kingdom, could be serendipitously detected by the Thermo Fisher TaqPath COVID-19 PCR assay because a key deletion in these viruses, spike Δ69-70, would cause a spike gene target failure (SGTF) result. However, a SGTF result is not definitive for B.1.1.7, and this assay cannot detect other variants of concern (VOC) that lack spike Δ69-70, such as B.1.351 (also 501Y.V2), detected in South Africa, and P.1 (also 501Y.V3), recently detected in Brazil. We identified a deletion in the ORF1a gene (ORF1a Δ3675-3677) in all 3 variants, which has not yet been widely detected in other SARS-CoV-2 lineages. Using ORF1a Δ3675-3677 as the primary target and spike Δ69-70 to differentiate, we designed and validated an open-source PCR assay to detect SARS-CoV-2 VOC. Our assay can be rapidly deployed in laboratories around the world to enhance surveillance for the local emergence and spread of B.1.1.7, B.1.351, and P.1

SARS-CoV-2 uses CD4 to infect T helper lymphocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS-CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.</p

SARS-CoV-2 uses CD4 to infect T helper lymphocytes

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS-CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.</p