Weight loss and brown adipose tissue reduction in rat model of sleep apnea

<p>Abstract</p> <p>Background -</p> <p>Obesity is related to obstructive sleep apnea-hypopnea syndrome (OSAHS), but its roles in OSAHS as cause or consequence are not fully clarified. Isocapnic intermittent hypoxia (IIH) is a model of OSAHS. We verified the effect of IIH on body weight and brown adipose tissue (BAT) of Wistar rats.</p> <p>Methods</p> <p>Nine-month-old male breeders Wistar rats of two groups were studied: 8 rats submitted to IIH and 5 control rats submitted to sham IIH. The rats were weighed at the baseline and at the end of three weeks, after being placed in the IIH apparatus seven days per week, eight hours a day, in the lights on period, simulating an apnea index of 30/hour. After experimental period, the animals were weighed and measured as well as the BAT, abdominal, perirenal, and epididymal fat, the heart, and the gastrocnemius muscle.</p> <p>Results</p> <p>Body weight of the hypoxia group decreased 17 ± 7 grams, significantly different from the variation observed in the control group (p = 0,001). The BAT was 15% lighter in the hypoxia group and reached marginally the alpha error probability (p = 0.054).</p> <p>Conclusion</p> <p>Our preliminary results justify a larger study for a longer time in order to confirm the effect of isocapnic intermittent hypoxia on body weight and BAT.</p

miR-203 drives breast cancer cell differentiation

Breast cancer; Cell differentiationCáncer de mama; Diferenciación celularCàncer de mama; Diferenciació cel·lularA hallmark of many malignant tumors is dedifferentiated (immature) cells bearing slight or no resemblance to the normal cells from which the cancer originated. Tumor dedifferentiated cells exhibit a higher capacity to survive to chemo and radiotherapies and have the ability to incite tumor relapse. Inducing cancer cell differentiation would abolish their self-renewal and invasive capacity and could be combined with the current standard of care, especially in poorly differentiated and aggressive tumors (with worst prognosis). However, differentiation therapy is still in its early stages and the intrinsic complexity of solid tumor heterogeneity demands innovative approaches in order to be efficiently translated into the clinic. We demonstrate here that microRNA 203, a potent driver of differentiation in pluripotent stem cells (ESCs and iPSCs), promotes the differentiation of mammary gland tumor cells. Combining mouse in vivo approaches and both mouse and human-derived tridimensional organoid cultures, we report that miR-203 influences the self-renewal capacity, plasticity and differentiation potential of breast cancer cells and prevents tumor cell growth in vivo. Our work sheds light on differentiation-based antitumor therapies and offers miR-203 as a promising tool for directly confronting the tumor-maintaining and regeneration capability of cancer cells.This work has been in part financed by the crowdfunding project “Match point against breast cancer” (PRECIPITA PR242, 2019; FECYT; Spanish Ministry of Science and Innovation, MICINN, led by MS-R) and donations to Asociación Española contra el Cáncer (AECC). The work has been funded also by the Comunidad de Madrid (Y2020/BIO-6519 and S2022/BMD-7437) to MM, the Spanish Ministry of Science and Innovation through CNS2022-135364 to MS-R and PID2021-128726 to MM and the Spanish Ministry of Economy and Competitiveness by Instituto de Salud Carlos III (ISC III) through PI20/00590 to CS and co-funded by the European Union. MS-R was supported by AECC (AIOA120833SALA and INVES18005SALA), a Juan de la Cierva Incorporación and a Ramón y Cajal contract (RYC2020-028929-I, from the MICINN, FSE/ Agencia Estatal de Investigación). NGM-I was supported by AECC (PRDMA19003GARC)

Metal-sensitive and thermostable trypsin from the crevalle jack (Caranx hippos) pyloric caeca: purification and characterization

Background: Over the past decades, the economic development and world population growth has led to increased for food demand. Increasing the fish production is considered one of the alternatives to meet the increased food demand, but the processing of fish leads to by-products such as skin, bones and viscera, a source of environmental contamination. Fish viscera have been reported as an important source of digestive proteases with interesting characteristics for biotechnological processes. Thus, the aim of this study was to purify and to characterize a trypsin from the processing by-products of crevalle jack (Caranx hippos) fish.Results: A 27.5 kDa trypsin with N-terminal amino acid sequence IVGGFECTPHVFAYQ was easily purified from the pyloric caeca of the crevalle jack. Its physicochemical and kinetic properties were evaluated using N-alpha-benzoyl-(DL)-arginine-p-nitroanilide (BApNA) as substrate. in addition, the effects of various metal ions and specific protease inhibitors on trypsin activity were determined. Optimum pH and temperature were 8.0 and 50 degrees C, respectively. After incubation at 50 degrees C for 30 min the enzyme lost only 20% of its activity. K-m, k(cat), and k(cat)/K-m values using BApNA as substrate were 0.689 mM, 6.9 s(-1), and 10 s(-1) mM(-1), respectively. High inhibition of trypsin activity was observed after incubation with Cd2+, Al3+, Zn2+, Cu2+, Pb2+, and Hg2+ at 1 mM, revealing high sensitivity of the enzyme to metal ions.Conclusions: Extraction of a thermostable trypsin from by-products of the fishery industry confirms the potential of these materials as an alternative source of these biomolecules. Furthermore, the results suggest that this trypsin-like enzyme presents interesting biotechnological properties for industrial applications.Financiadora de Estudos e Projetos (FINEP/RECARCINE)Petroleo do Brasil S/A (PETROBRAS)Secretaria Especial de Aquicultura e Pesca (SEAP/PR)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundacao de Apoio a Ciencia e Tecnologia do Estado de Pernambuco (FACEPE)Univ Fed Pernambuco, Lab Enzimol LABENZ, Dept Bioquim CCB, BR-50670910 Recife, PE, BrazilUniv Fed Pernambuco, LIKA, BR-50670910 Recife, PE, BrazilUniversidade Federal de São Paulo, Dept Biofis, Escola Paulista Med, BR-04044020 São Paulo, BrazilUniv Fed Pernambuco, Lab Glicoprot, Dept Bioquim CCB, BR-50670910 Recife, PE, BrazilUniversidade Federal de São Paulo, Dept Biofis, Escola Paulista Med, BR-04044020 São Paulo, BrazilWeb of Scienc

Early liver function improvement following successful treatment of chronic hepatitis C in patients with decompensated cirrhosis: a real-life study

OBJECTIVES: Despite higher rates of sustained virologic response (SVR), important concerns remain when patients with decompensated cirrhosis due to hepatitis C virus (HCV) are treated with direct-acting antiviral agents (DAA). Questions include efficacy, safety, and the magnitude of liver function improvement. Here, we aimed to evaluate HCV treatment data in this specific population in Brazil. METHODS: We included 85 patients with decompensated cirrhosis submitted to HCV therapy with DAA followed at two academic tertiary centers in the southeastern region of Brazil. RESULTS: Seventy-nine patients (92.9%) were Child-Pugh (CP) score B, and six (7.1%) were CP score C. The mean MELD score was 12.86. The most common treatment was sofosbuvir plus daclatasvir±ribavirin for 24 weeks. The overall intention-to-treat (ITT) SVR rate was 87.4% (74/85) and modified-ITT 96.1% (74/77). ITT SVR was associated with lower baseline INR values (p=0.029). Adverse events (AE) occurred in 57.9% (44/76) of patients. Serious AE were reported in 12.8% (10/78), and were related to the presence of hepatic encephalopathy (p=0.027). SVR was associated with improvement in CP (p&lt;0.0001) and MELD scores (p=0.021). Among baseline CP score B patients with SVR, 46% (29/63) regressed to CP score A. Ascites was independently associated with no improvement in liver function in patients who achieved SVR (p=0.001; OR:39.285; 95% CI:4.301-258.832). CONCLUSIONS: Patients with decompensated HCV cirrhosis showed a high SVR rate with interferon-free therapy. Early liver function improvement occurred after successful HCV eradication. However, long-term follow-up of these patients after SVR remains strongly advised. &nbsp

Implication of breast cancer phenotype for patients with leptomeningeal carcinomatosis

Abstract Background We aimed to study the implications of breast cancer (BC) subtypes for the development and prognosis of leptomeningeal carcinomatosis (LC). Patients and methods Data from the breast cancer patients diagnosed with LC between 2005 and 2010 were retrieved. Patients were classified in luminal A, B, HER2 positive and triple negative (TN) and their BC diagnosis, treatment, and outcome were analyzed according to each subtype. Pearson's chi-square and Fisher's exact test were used for categorical variables. Survival analyses were performed by Kaplan–Meier method and compared with the log-rank test. Results A total of 38 BC patients were identified, with a median age of 54.8 years (range 36–79). The proportion of luminal A, B, HER2 positive and TN was 18.4%, 31.6%, 26.3% and 23.7%, respectively. LC was the first evidence of metastatic disease in 5 BC patients. Twenty patients received the systemic chemotherapy, with 16 (80%) whole brain radiotherapy (WBRT). Nine patients received only WBRT. TN patients had the shorter interval between metastatic breast cancer diagnosis and the development of LC. Median survival after the diagnosis of LC (OSLC) was 2.6 months (range 1.2–6.4), and did not differ across breast cancer subtypes. In univariate analysis, performance status (ECOG = 0–2) and chemotherapy were prognostic for OSLC, but only the treatment stood as an independent prognostic factor in multivariate analysis. Conclusions Breast cancer subtype influences the timing of LC appearance, but not OSLC. Patients with LC from breast cancer should be offered systemic treatment, as it appears to associate with the improved outcome. New therapeutic strategy, including, targeted and intrathecal therapy are deserved for BC patients with LC

Early impact of abdominal compartment syndrome on liver, kidney and lung damage in a rodent model

Background: Abdominal compartment syndrome (ACS) sometimes occurs in critically ill patients following damage control surgery. The purpose of the present study was to develop a model of ACS and to evaluate its pathologic impact on liver, kidney, and lung morphology. Methods: Twenty Wistar rats (mass 300\u2013350 g) were randomly divided into four groups: 1) intra-abdominal hypertension (IAH): a laparotomy was performed and the abdomen packed with cotton until an intra-abdominal pressure (IAP) of 15 mm Hg was reached; 2) hypovolemia (HYPO): blood was withdrawn until a mean arterial pressure ~60 mm Hg was reached; 3) IAH + HYPO (to resemble clinical ACS); and 4) sham surgery. After 3 hours of protective mechanical ventilation, the animals were euthanized and the liver, kidney and lungs removed to examine the degree of tissue damage. Results: IAH resulted in the following: oedema and neutrophil infiltration in the kidney; necrosis, congestion, and microsteatosis in the liver; and alveolar collapse, haemorrhage, interstitial oedema, and neutrophil infiltration in the lungs. Furthermore, IAH was associated with greater cell apoptosis in the kidney, liver and lungs compared to sham surgery. HYPO led to oedema and neutrophil infiltration in the kidney. The combination of IAH and HYPO resulted in all the aforementioned changes in lung, kidney and liver tissue, as well as exacerbation of the inflammatory process in the kidney and liver and kidney cell necrosis and apoptosis. Conclusions: Intra-abdominal hypertension by itself is associated with kidney, liver and lung damage; when combined with hypovolemia, it leads to further impairment and organ damage

In vitro antileishmanial and antitrypanosomal activities of flavanones from Baccharis retusa DC. (Asteraceae)

Leishmaniasis and Chagas' are parasitic protozoan diseases that affect the poorest population in the world, causing a high mortality and morbidity. As a result of highly toxic and long-term treatments, novel, safe and more efficacious drugs are essential. in this work, the CH2Cl2 phase from MeOH extract from the leaves of Baccharis retusa DC. (Asteraceae) was fractioned to afford two flavonoids: naringenin (1) and sakuranetin (2). These compounds were in vitro tested against Leishmania spp. promastigotes and amastigotes and Ttypanosoma cruzi trypomastigotes and amastigotes. Compound 2 presented activity against Leishmania (L) amazonensis, Leishmania (V.) braziliensis, Leishmania (L) major, and Leishmania (L) chagasi with IC50 values in the range between 43 and 52 mu g/mL and against T. cruzi trypomastigotes (IC50= 20.17 mu g/mL). Despite of the chemical similarity, compound 1 did not show antiparasitic activity. Additionally, compound 2 was subjected to a methylation procedure to give sakuranetin-4'-methyl ether (3), which resulted in an inactive compound against both Leishmania spp. and T. cnizi. the obtained results indicated that the presence of one hydroxyl group at C-4' associated to one methoxyl group at C-7 is important to the antiparasitic activity. Further drug design studies aiming derivatives could be a promising tool for the development of new therapeutic agents for Leishmaniasis and Chagas' disease. (C) 2011 Elsevier Inc. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Pesquisa e DesenvolvimentoUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Diadema, SP, BrazilInst Adolfo Lutz Registro, Dept Parasitol, São Paulo, BrazilUniv Fed ABC, Ctr Ciencias Nat & Humanas, Santo Andre, SP, BrazilUniv Presbiteriana Mackenzie, Ctr Ciencias & Humanidades, São Paulo, BrazilUniversidade Federal de São Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Diadema, SP, BrazilFAPESP: 06/57626-5FAPESP: 08/11496-9Conselho Nacional de Pesquisa e Desenvolvimento: 473405/2008-3Conselho Nacional de Pesquisa e Desenvolvimento: 477422/2009-8Web of Scienc

Genome-wide signatures of complex introgression and adaptive evolution in the big cats.

The great cats of the genus Panthera comprise a recent radiation whose evolutionary history is poorly understood. Their rapid diversification poses challenges to resolving their phylogeny while offering opportunities to investigate the historical dynamics of adaptive divergence. We report the sequence, de novo assembly, and annotation of the jaguar (Panthera onca) genome, a novel genome sequence for the leopard (Panthera pardus), and comparative analyses encompassing all living Panthera species. Demographic reconstructions indicated that all of these species have experienced variable episodes of population decline during the Pleistocene, ultimately leading to small effective sizes in present-day genomes. We observed pervasive genealogical discordance across Panthera genomes, caused by both incomplete lineage sorting and complex patterns of historical interspecific hybridization. We identified multiple signatures of species-specific positive selection, affecting genes involved in craniofacial and limb development, protein metabolism, hypoxia, reproduction, pigmentation, and sensory perception. There was remarkable concordance in pathways enriched in genomic segments implicated in interspecies introgression and in positive selection, suggesting that these processes were connected. We tested this hypothesis by developing exome capture probes targeting ~19,000 Panthera genes and applying them to 30 wild-caught jaguars. We found at least two genes (DOCK3 and COL4A5, both related to optic nerve development) bearing significant signatures of interspecies introgression and within-species positive selection. These findings indicate that post-speciation admixture has contributed genetic material that facilitated the adaptive evolution of big cat lineages

Development and characterization of L-alanyl-L-glutamine containing pellets employing extrusion-spheronization method and drying process in fluidized bad equipment

No presente trabalho foram desenvolvidas e avaliadas cinco formulações de péletes, contendo L-alanil-L-glutamina (glutamina dipeptídeo), em diferentes concentrações: F1 (9,07%); F2 (17,70%); F3 (27,98%); F4 (37,74%) e F5 (47,53%). Os péletes foram preparados pelo método da extrusão-esferonização, seguido de secagem em equipamento de leito fluidizado. Os lotes obtidos foram submetidos aos ensaios de: granulometria, friabilidade, densidade verdadeira e análise morfológica. Dentre as cinco formulações avaliadas, os péletes resultantes de F3 apresentaram maior rendimento (75,80%), distribuição granulométrica mais uniforme (89,67% dos péletes com tamanho entre 0,80 e 1,18), densidade mais elevada (2,1634 g/mL) e melhor aspecto (1,0795 ± 0,0410). Devido às características obtidas a partir da F3 os péletes foram considerados adequados para posterior aplicação de revestimento polimérico,visando produzir sistema multiparticulado de liberação prolongada da substância ativa L-alanil-L-glutamina.In this work, five formulations of L-alanyl-L-glutamine (glutamine dipeptide) containing pellets with different drug concentration were developed and evaluated: F1 (9.07%); F2 (17.70%); F3 (27.98%); F4 (37.74%) e F5 (47.53%). Pellets were prepared by extrusion- spheronization method and, further, dried in fluidized bad equipment. The following assays were carried out with the batches obtained: granulometry, friability, true density and morphologic analysis. Between the five formulations evaluated, pellets obtained from F3 present best yield (75.80%), most uniform particle size distribution (89.67% of pellets with size in the range of 0.80 to 1.18), most high true density (2.1634 g/ml) and best aspect (1.0795 ± 0.0410). Due to these features, pellets obtained from F3 were considered adequate to further polymeric coating process in order to produce a multiparticulate system to prolong L-alanyl-L-glutamine release.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Multivariate Analysis Applied to Forestry Agricultural Sciences: The Model-Directed Study

This is a literature review that aimed to find articles that exemplify and describe the use of multivariate analysis in different fields of Forest Agricultural Sciences, considering effective practices using multivariate statistical techniques for the simultaneous processing of data. For data collection were selected for the meta-analysis of 70 technical articles of which 54 were employed in the study directed to the use of multivariate techniques applied in the areas of agricultural sciences. The results showed thatstudies directed to certain areas within the Forest Agricultural Sciences exhibit some regularity in the use of multivariate analysis, and most application analyzes were more usual as the Cluster Analysis (AA) and Principal Component Analysis (PCA). Thus the use of multivariate analysis studies and evaluations of experiments in Agricultural Sciences proved to great value to allow greater clarity and better interpretation of dealing with complex phenomena