Thermal treatment of superconductor thin film of the BSCCO system using domestic microwave oven

In this work, we report the preparation of a superconductor thin film of the BSCCO system using a good quality powder with nominal composition Bi_{1.8}Pb_{0.4}Sr_2CaCu_2O_x which was thermally treated using a domestic microwave oven (2.45 GHz, 800 W). This film was grew on a single crystal of LaAlO_3(100) substrate and exhibited a crystalline structure with the c-axis perpendicular to the plane of the substrate. An onset superconducting transition temperature was measured at 80 K.Comment: 4 pages, 5 figure

Diet-induced maternal obesity alters insulin signalling in male mice offspring rechallenged with a high-fat diet in adulthood

Modern lifestyle has resulted in an increase in the prevalence of obesity and its comorbidities in pregnant women and the young population. It has been well established that the consumption of a high-fat diet (HFD) has many direct effects on glucose metab118122FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO2011/22156-7; 2013/12003-

Hypothalamic Inhibition Of Acetyl-coa Carboxylase Stimulates Hepatic Counter-regulatory Response Independent Of Ampk Activation In Rats.

Hypothalamic AMPK acts as a cell energy sensor and can modulate food intake, glucose homeostasis, and fatty acid biosynthesis. Intrahypothalamic fatty acid injection is known to suppress liver glucose production, mainly by activation of hypothalamic ATP-sensitive potassium (K(ATP)) channels. Since all models employed seem to involve malonyl-CoA biosynthesis, we hypothesized that acetyl-CoA carboxylase can modulate the counter-regulatory response independent of nutrient availability. In this study employing immunoblot, real-time PCR, ELISA, and biochemical measurements, we showed that reduction of the hypothalamic expression of acetyl-CoA carboxylase by antisense oligonucleotide after intraventricular injection increased food intake and NPY mRNA, and diminished the expression of CART, CRH, and TRH mRNA. Additionally, as in fasted rats, in antisense oligonucleotide-treated rats, serum glucagon and ketone bodies increased, while the levels of serum insulin and hepatic glycogen diminished. The reduction of hypothalamic acetyl-CoA carboxylase also increased PEPCK expression, AMPK phosphorylation, and glucose production in the liver. Interestingly, these effects were observed without modification of hypothalamic AMPK phosphorylation. Hypothalamic ACC inhibition can activate hepatic counter-regulatory response independent of hypothalamic AMPK activation.8e6266

JAK2/STAT3 pathway is required for α7nAChR-dependent expression of POMC and AGRP neuropeptides in male mice

Cholinergic signalling mediated by the activation of muscarinic and nicotinic receptors has been described in the literature as a classic and important signalling pathway in the regulation of the inflammatory response. Recent research has investigated the role of acetylcholine, the physiological agonist of these receptors, in the control of energy homeostasis at the central level. Studies have shown that mice that do not express acetylcholine in brain regions regulating energy homeostasis present with excessive weight gain and hyperphagia. However, it has not yet been well-described in the literature which cholinergic receptor subunits are involved in this response; moreover, the signalling pathways responsible for the observed effects are not fully delineated. The hypothalamus is the regulating centre of energy homeostasis, and the α7 subunit of the nicotinic acetylcholine receptor (α7nAChR) is highly expressed in this region. When active, α7nAChR recruits proteins such as JAK2/STAT3 to mediate its signalling; the same intracellular components are required by leptin, an anorexigenic hormone. The aim of the present study was to evaluate the role of the hypothalamic α7nAChR in the control of energy homeostasis. Methods: The work was performed on Swiss male mice. Initially, using immunofluorescent staining on brain sections, the presence of α7nAChR in hypothalamic cells regulating energy homeostasis was evaluated. Animals were submitted to stereotaxis in the lateral ventricle and intracerebroventricular stimulation (ICV) was used for the administration of an agonist (PNU) or antagonist (α-bungarotoxin) of α7nAChR. Metabolic parameters were evaluated and the expression of neuropeptides was evaluated in the hypothalamus by real-time PCR and western blot. The expression of hypothalamic neuropeptides was evaluated in mice treated with siRNA or inhibitors of JAK2/STAT3 (AG490 and STATTIC) proteins. We also evaluated food intake in α7nAChR knockout animals (α7KO). Additionally, in mouse hypothalamic cell culture (the mypHoA-POMC/GFP lineage), we evaluated the expression of neuropeptides and pSTAT3 after stimulation with PNU. Results: Our results indicate co-localisation of α7nAChR with α-MSH, AgRP and NPY in hypothalamic cells. Pharmacological activation of α7nAChR reduced food intake and increased hypothalamic POMC expression and decreased NPY and AgRP mRNA levels and the protein content of pAMPK. Inhibition of α7nAChR with an antagonist increased the mRNA content of NPY and AgRP. Inhibition of α7nAChR with siRNA led to the suppression of POMC expression and an increase in AgRP mRNA levels. α7KO mice showed no changes in food intake. Inhibition of proteins involved in the JAK2/STAT3 signalling pathway reversed the effects observed after PNU stimulation. POMC-GFP cells, when treated with PNU, showed increased POMC expression and nuclear translocation of pSTAT3. Conclusion: Thus, selective activation of α7nAChR is able to modulate important markers of the response to food intake, suggesting that α7nAChR activation can suppress the expression of orexigenic markers and favour the expression of anorexics using the intracellular JAK2/STAT3 machinery534701712COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPNão tem16/23484-1; 18/01863-6This work was supported by grants from the Coordination for the Improvement of Higher Education Personnel (CAPES) and São Paulo Research Foundation (FAPESP) (grant # 16/23484-1 and # 18/01863-6). The authors Adriana Souza Torsoni, Leticia M. Ignacio-Souza, Marciane Milanski, and Marcio Alberto Torsoni are affiliated with the Obesity and Comorbidities Research Center (OCRC) of the Sao Paulo Research Foundation (FAPESP). Animal experiments conform to internationally accepted standards and have been approved by the appropriate institutional review body. Souza CM performed all the experiments of the article, analyzed the data as well as wrote the introduction, methodology, subtitles and summary of the article. Amaral CL, contributed to the cell culture experiment and the revision of the writing of the introduction and methodology and summary of the article. Costa SO and Souza ACP assisted in animal care and surgical procedures. Martins ICA and Contieri LS, assisted in the experiment with siRNA. Milanski M, Torsoni AS, and Ignacio-Souza LM participated in the textual revision of the article. Torsoni MA guided all the experiments and wrote the results and discussion of the article, as well as revised the entire manuscrip

Maternal consumption of a high-fat diet modulates the inflammatory response in their offspring, mediated by the M1 muscarinic receptor

IntroductionHigh-fat diet (HFD) consumption is associated with various metabolic disorders and diseases. Both pre-pregnancy and maternal obesity can have long-term consequences on offspring health. Furthermore, consuming an HFD in adulthood significantly increases the risk of obesity and metabolic disorders. However, an intriguing phenomenon known as the obesity paradox suggests that obesity may confer a protective effect on mortality outcomes in sepsis. In sepsis, activation of the cholinergic anti-inflammatory pathway (CAP) can help mitigate systemic inflammation. We employed a metabolic programming model to explore the relationship between maternal HFD consumption and offspring response to sepsis.MethodsWe fed female mice either a standard diet (SC) or an HFD during the pre-pregnancy, pregnancy, and lactation periods. Subsequently, we evaluated 28-day-old male offspring. ResultsNotably, we discovered that offspring from HFD-fed dams (HFD-O) exhibited a higher survival rate compared with offspring from SC-fed dams (SC-O). Importantly, inhibition of the m1 muscarinic acetylcholine receptor (m1mAChR), involved in the CAP, in the hypothalamus abolished this protection. The expression of m1mAChR in the hypothalamus was higher in HFD-O at different ages, peaking on day 28. Treatment with an m1mAChR agonist could modulate the inflammatory response in peripheral tissues. Specifically, CAP activation was greater in the liver of HFD-O following agonist treatment. Interestingly, lipopolysaccharide (LPS) challenge failed to induce a more inflammatory state in HFD-O, in contrast to SC-O, and agonist treatment had no additional effect. Analysis of spleen immune cells revealed a distinct phenotype in HFD-O, characterized by elevated levels of CD4+ lymphocytes rather than CD8+ lymphocytes. Moreover, basal Il17 messenger RNA (mRNA) levels were lower while Il22 mRNA levels were higher in HFD-O, and we observed the same pattern after LPS challenge. DiscussionFurther examination of myeloid cells isolated from bone marrow and allowed to differentiate showed that HFD-O macrophages displayed an anti-inflammatory phenotype. Additionally, treatment with the m1mAChR agonist contributed to reducing inflammatory marker levels in both groups. In summary, our findings demonstrate that HFD-O are protected against LPS-induced sepsis, and this protection is mediated by the central m1mAChR. Moreover, the inflammatory response in the liver, spleen, and bone marrow-differentiated macrophages is diminished. However, more extensive analysis is necessary to elucidate the specific mechanisms by which m1mAChR modulates the immune response during sepsis

Short-Term High-Fat Diet Consumption Reduces Hypothalamic Expression of the Nicotinic Acetylcholine Receptor α7 Subunit (α7nAChR) and Affects the Anti-inflammatory Response in a Mouse Model of Sepsis

Sepsis is one of the leading causes of death in hospitalized patients and the chronic and low-grade inflammation observed in obesity seems to worsen susceptibility and morbidity of infections. However, little is known with respect to a short-term high-fat diet (HFD) and its role in the development of sepsis. Here, we show for the first time, that short-term HFD consumption impairs early nicotinic acetylcholine receptor α7 subunit (α7nAChR)- mediated signaling, one of the major components of the cholinergic anti-inflammatory pathway, with a focus on hypothalamic inflammation and innate immune response. Mice were randomized to a HFD or standard chow (SC) for 3 days, and sepsis was subsequently induced by a lethal intraperitoneal (i.p.) injection of lipopolysaccharide (LPS) or by cecal ligation and puncture (CLP) surgery. In a separate experiment, both groups received LPS (i.p.) or LPS (i.p.) in conjunction with the selective α7nAChR agonist, PNU-282987 (i.p. or intracerebroventricular; i.c.v.), and were sacrificed 2 h after the challenge. Short-term HFD consumption significantly reduced the α7nAChR mRNA and protein levels in the hypothalamus and liver (p < 0.05). Immunofluorescence microscopy demonstrated lower cholinergic receptor nicotinic α7 subunit (α7nAChR)+ cells in the arcuate nucleus (ARC) (α7nAChR+ cells in SC = 216 and HFD = 84) and increased F4/80+ cells in the ARC (2.6-fold) and median eminence (ME) (1.6-fold), which can contribute to neuronal damage. Glial fibrillary acidic protein (GFAP)+ cells and neuronal nuclear antigen (NeuN)+ cells were also increased following consumption of HFD. The HFD-fed mice died quickly after a lethal dose of LPS or following CLP surgery (2-fold compared with SC). The LPS challenge raised most cytokine levels in both groups; however, higher levels of TNF-α (Spleen and liver), IL-1β and IL-6 (in all tissues evaluated) were observed in HFD-fed mice. Moreover, PNU-282987 administration (i.p. or i.c.v.) reduced the levels of inflammatory markers in the hypothalamus following LPS injection. Nevertheless, when the i.c.v. injection of PNU-282987 was performed the anti-inflammatory effect was much smaller in HFD-fed mice than SC-fed mice. Here, we provide evidence that a short-term HFD impairs early α7nAChR expression in central and peripheral tissues, contributing to a higher probability of death in sepsis

Nanoparticles In Treatment Of Thermal Injured Rats: Is It Safe?

The aim of this study was to assess whether thermal trauma induced oxidative stress altered the balance between oxidant and antioxidant systems in the blood of burn wound rats in the absence and presence of silver nanoparticles and S-nitrosoglutathione, GSNO. Free silver nanoparticles, free GSNO and silver nanoparticles + GSNO had no cytotoxic effects. Under anesthesia, the shaved dorsum of the rats was exposed to 90°C (burn group) water bath. Studied compounds were administered topically immediately and at 28 days after the burn injury, four times a day. Silver nanoparticles and silver nanoparticles + GSNO were no toxic in vitro and in vivo. There were no significant differences in the levels of urea, creatinine, aminotransferases and hematological parameters, in control-burn groups (free silver nanoparticles) and treated-burn groups (free GSNO or silver nanoparticles + GSNO). There were no differences in lipid peroxidation and in the levels of protein carbonyls and glutathione, used as oxidative stress markers. A little inflammatory cell response, papillary dermis vascularization, fibroblasts differentiated into contractile myofibroblasts and the presence of a large amount of extracellular matrix were evidenced in treated groups following skin injury. These results indicate that silver nanoparticles and GSNO may provide an effective action on wound healing.3041Tian, J., Wong, K.K.Y., Ho, C.M., Lok, C.N., Yu, W.Y., Che, C.M., Chiu, J.F., Tam, P.K.H., (2007) J. Chem. Med. Chem., 2, p. 129Teli, M.K., Mutalik, S., Rajanikant, G.K., (2010) Cur. Pharm. Design., 16, p. 1882Schaller, M., Laude, J., Bodewaldt, H., Hamm, G., Korting, H.C., (2004) Skin Pharmacol. Physiol., 17, p. 31Seabra, A.B., Da Silva, R., De Souza, G.F.P., De Oliveira, M.G., (2008) Artif. Organs, 32, p. 262Seabra, A.B., Pankotai, E., Fehér, M., Somlai, A., Kiss, L., Bíró, L., Szabó, C., Lacza, Z., (2007) Br. J. Dermatol., 156, p. 814Seabra, A.B., Martins, D., Simes, M.M.S.G., Da Silva, R., Brocchi, M., De Oliveira, M.G., (2010) Artif. Organs, 34, p. 204Durán, N., Marcato, P.D., Alves, O.L., De Souza, G.I.H., Esposito, E., (2005) J. Nanobiotechnol., 3, p. 1Durán, N., Marcato, P.D., De Souza, G.I.H., Alves, O.L., Esposito, E., (2007) J. Biomed. Nanotechnol., 3, p. 203Amadeu, T.P., Seabra, A.B., De Oliveira, M.G., Costa, A.M.A., (2007) J. Eur. Acad. Dermatol. Venereol., 21, p. 629Amadeu, T.P., Seabra, A.B., De Oliveira, M.G., Costa, A.M.A., (2008) J. Surg Res., 149, p. 84Correa, D.H.A., Melo, P.S., De Carvalho, C.A.A., De Azevedo, M.B.M., Durán, N., Haun, M., (2005) Eur. J. Pharmacol., 510, p. 17De Conti, R., Oliveira, D.A., Fernandes, A.M.A.P., Melo, P.S., Rodriguez, J.A., Haun, M., Castro, S.L., Durán, N., (1998) Vitro Mol. Toxicol, 11, p. 153Borefreund, E., Puerner, J.A., (1984) J. Tissue Cult. Methods, 9, p. 7Denizot, F., Lang, R., (1986) J. Immunol. Methods, 89, p. 271Michailidis, Y., Jamurta, A.Z., Nikolaidis, M.G., Fatouros, I.G., Koutedakis, Y., Papassotiriou, I., (2007) Med. Sci. Sport Exerc., 39, p. 1107Davis, T.A., Amare, M., Naik, S., Kovalchuk, A.L., Tadaki, D., (2007) Wound Repair Regen., 15, p. 57