Abstract Background Oncostatin M (OSM) is a pleiotropic cytokine which, after arterial injury, has proven to be to be rapidly expressed. Objectives To correlate the serum levels of OSM, soluble OSM receptor (sOSMR), and soluble fraction of glycoprotein 130 (sgp130) in patients with coronary artery disease (CAD) with clinical parameters. Methods Levels of sOSMR and sgp130 were evaluated by ELISA and OSM by Western Blot, in patients with CCS (n=100), patients with ACS (n=70), and 64 control volunteers without clinical manifestations of the disease. P-values < 0.05 were considered to be statistically significant. Results CAD patients exhibited significantly lower levels of sOSMR and sgp130 and higher levels of OSM when compared to the controls (both p < 0.0001). Clinical analysis displayed, lower levels of sOSMR in men ([OR] = 2.05, p = 0.026), youth (OR = 1.68, p = 0.0272), hypertensives (OR = 2.19, p = 0.041), smokers (OR = 2.19, p = 0.017), patients that did not present dyslipidemia (OR = 2.32, p = 0.013), patients with Acute Myocardial Infarction [AMI] (OR = 3.01, p = 0.001) and patients not treated with statin (OR = 1.95, p = 0.031), antiplatelet agent (OR = 2.46, p = 0.005), inhibitors of calcium channels (OR = 3.15, p = 0.028), and antidiabetic drugs (OR = 2.97, p = 0.005). The levels of sOSMR were also correlated with gender, age, hypertension, and use of medications in multivariate analysis. Conclusions Our data suggest that the enhanced serum levels of OSM, and decreased levels of sOSMR and sGP130 in patients with cardiac injury may play an important role in the pathophysiological mechanism of the disease. Furthermore, lower levels of sOSMR were associated with gender, age, hypertension, and the use of medications. (OSM which expressed sOSMR, , (sOSMR) 13 sgp (sgp130 (CAD parameters sgp13 Blot n=100, n100 n n=100 100 (n=100) n=70, n70 n=70 70 (n=70) 6 Pvalues P values 005 0 05 0.0 significant both 0.0001. 00001 0.0001 . 0001 0.0001) displayed OR ([OR 205 2 2.05 0.026, 0026 0.026 026 0.026) 168 1 68 1.68 0.0272, 00272 0.0272 0272 0.0272) 219 19 2.19 0.041, 0041 0.041 041 0.041) 0.017, 0017 0.017 017 0.017) 232 32 2.32 0.013, 0013 0.013 013 0.013) AMI [AMI 301 3 01 3.01 0.001 001 195 95 1.95 0.031, 0031 0.031 031 0.031) 246 46 2.46 0.005, 0005 0.005 0.005) 315 15 3.15 0.028, 0028 0.028 028 0.028) 297 97 2.97 0.005. gender age hypertension sGP sGP13 Furthermore (sOSMR (sgp13 sgp1 n10 n=10 10 (n=100 n7 n=7 7 (n=70 00 0. 0000 0.000 000 20 2.0 002 0.02 02 16 1.6 0027 0.027 027 21 2.1 004 0.04 04 0.01 23 2.3 30 3.0 0.00 9 1.9 003 0.03 03 24 4 2.4 31 3.1 29 2.9 sGP1 (sgp1 n1 n=1 (n=10 n= (n=7 2. 1. 3. (sgp (n=1 (n= (n

Resumo Fundamento A oncostatina M (OSM) é uma citocina pleiotrópica que, após lesão arterial, demonstra ser expressa rapidamente. Objetivos Correlacionar os níveis séricos da OSM, do receptor solúvel de oncostatina M (sOSMR) e da fração solúvel de glicoproteína 130 (sgp130) em pacientes com doença arterial coronariana (DAC) a parâmetros clínicos. Métodos Os níveis de sOSMR e sgp130 foram avaliados por ELISA, enquanto os de OSM foram avaliados por Western Blot, em pacientes com SCC (n=100), pacientes com SCA (n=70) e 64 voluntários do grupo de controle sem manifestações clínicas da doença. Valores de p <0,05 foram considerados estatisticamente significativos. Resultados Pacientes com DAC exibiram níveis significativamente mais baixos de sOSMR e sgp130 e níveis mais altos de OSM em comparação ao grupo de controle (ambos p <0,0001). A análise clínica mostrou níveis mais baixos de sOSMR em homens ([OR] = 2,05, p = 0,026), jovens (OR = 1,68, p = 0,0272), hipertensos (OR = 2,19, p = 0,041), fumantes (OR = 2,19, p = 0,017), pacientes que não apresentavam dislipidemia (OR = 2,32, p = 0,013), pacientes com infarto agudo do miocárdio [IAM] (OR = 3,01, p = 0,001) e pacientes não tratados com estatina (OR = 1,95, p = 0,031), antiplaquetário (OR = 2,46, p = 0,005), inibidores dos canais de cálcio (OR = 3,15, p = 0,028) e antidiabéticos (OR = 2,97, p = 0,005). Os níveis de sOSMR também foram correlacionados a sexo, idade, hipertensão e uso de medicamentos na análise multivariada. Conclusões Nossos dados sugerem que o aumento dos níveis séricos de OSM e a diminuição dos níveis de sOSMR e sGP130 em pacientes com injúria cardíaca podem desempenhar um papel importante no mecanismo fisiopatológico da doença. Além disso, níveis mais baixos de sOSMR foram associados a sexo, idade, hipertensão e uso de medicamentos. (OSM rapidamente (sOSMR 13 sgp (sgp130 (DAC clínicos sgp13 ELISA Blot n=100, n100 n n=100 , 100 (n=100) n=70 n70 70 (n=70 6 005 0 05 <0,0 significativos ambos <0,0001. 00001 <0,0001 . 0001 <0,0001) OR ([OR 205 2 2,05 0,026, 0026 0,026 026 0,026) 168 1 68 1,68 0,0272, 00272 0,0272 0272 0,0272) 219 19 2,19 0,041, 0041 0,041 041 0,041) 0,017, 0017 0,017 017 0,017) 232 32 2,32 0,013, 0013 0,013 013 0,013) IAM [IAM 301 3 01 3,01 0,001 001 195 95 1,95 0,031, 0031 0,031 031 0,031) 246 46 2,46 0,005, 0005 0,005 0,005) 315 15 3,15 0,028 0028 028 297 97 2,97 0,005. sexo idade multivariada sGP sGP13 disso (sgp13 sgp1 n10 n=10 10 (n=100 n=7 n7 7 (n=7 00 <0, 0000 <0,000 000 20 2,0 002 0,02 02 16 1,6 0027 0,027 027 21 2,1 004 0,04 04 0,01 23 2,3 30 3,0 0,00 9 1,9 003 0,03 03 24 4 2,4 31 3,1 29 2,9 sGP1 (sgp1 n1 n=1 (n=10 n= (n= <0 <0,00 2, 0,0 1, 3, (sgp (n=1 (n < 0,

Abstract Oxazolidine derivatives (OxD) have been described as third-line antibiotics and antitumoral agents. The inclusion complexes based on cyclodextrin could improve the solubility and bioavailability of these compounds. A novel synthetic OxD was used, and its inclusion complexes were based on 2-hydroxy-beta-cyclodextrin (2-HPβCD). We conducted an in silico study to evaluate the interaction capacity between OxD and 2-HPβCD. Characterization studies were performed through scanning electron microscopy (SEM), Fourier-transformed infrared (FTIR), nuclear magnetic resonance spectroscopy (1H-NMR), X-ray diffraction (XRD), and thermal analyses. A kinetic study of the OxD was performed, including a cytotoxicity assay using peripheral blood mononuclear cells (PBMCs). The maximum increment of solubility was obtained at 70 mM OxD using 400 mM 2-HPβCD. SEM analyses and FTIR spectra indicated the formation of inclusion complexes. 1H-NMR presented chemical shifts that indicated 1:1 stoichiometry. Different thermal behaviors were obtained. The pharmacokinetic profile showed a short release time. Pure OxD and its inclusion complex did not exhibit cytotoxicity in PBMCs. In silico studies provided a foremost insight into the interactions between OxD and 2-HPβCD, including a higher solubility in water and an average releasing profile without toxicity in normal cells. (OxD thirdline third line agents compounds used 2hydroxybetacyclodextrin hydroxybetacyclodextrin 2 hydroxy beta 2HPβCD. 2HPβCD HPβCD . (2-HPβCD) HPβCD. 2-HPβCD SEM, , (SEM) Fouriertransformed Fourier transformed FTIR, (FTIR) 1HNMR, 1HNMR HNMR 1H NMR H (1H-NMR) Xray X ray XRD, XRD (XRD) PBMCs (PBMCs) 7 40 11 1 1: stoichiometry time 2HPβCD, HPβCD, (2-HPβCD (SEM (FTIR (1H-NMR (XRD (PBMCs 4

Abstract Osteoarthritis (OA) encompasses degeneration of articular cartilage, subchondral bone erosions and sclerosis. Chondrocyte apoptosis and an oxygen-deprived microenvironment are essential factors in OA pathogenesis. PAR-4 (Prostate apoptosis response-4) is a pro-apoptotic protein implicated in many pathologies as well as in chondrocyte cell death mechanism. Vitamin D supplementation has been identified as a therapeutic tool for a variety of inflammatory pathologies. In the present manuscript, we investigated whether first, PAR-4 expression is influenced by chondrocytes in a model of OA, in vitro, and second, whether vitamin D modulates PAR-4 expression in the same model. To test our hypothesis, we used the primary culture of murine chondrocytes isolated from the femoral and tibial condyles of wistar rats. The expression of the pro-inflammatory effect interleukin IL-1β was evaluated in the presence and absence of vitamin D. Western blot and immunofluorescence analysis confirmed protein expression. In the normoxia condition, the chondrocytes expressed PAR-4 in the cell nucleus, and in the hypoxic condition, PAR-4 was expressed in the cell cytoplasm. We disclosed that the treatment with Vitamin D decreased PAR-4 (p= 0.0137) and caspase-3 (p= 0.0007) expression. Thus, the results suggested that PAR-4 and caspase-3 proteins could be potential targets for OA.However, we believe that research is needed to identify the mechanisms implicated in the regulation of PAR-4 in OA.

Abstract INTRODUCTION Herein, the authors describe a simple enhancement to a commercial rapid DNA extraction kit based on simple viral lysis for detecting COVID-19 via RT-qPCR. METHODS After testing several different modifications, the adapted protocol with the best results in preliminary experiments was statistically evaluated in comparison with an automated robotic protocol. RESULTS Processing and testing of 119 nasopharyngeal samples ultimately yielded near-perfect agreement with the automated protocol (κ = 0.981 [95% confidence interval 0.943-1.000]). CONCLUSIONS The low cost and rapidity of the enhanced protocol makes it suitable for adoption in laboratories diagnosing COVID-19, especially those with high demand for examinations.

Allergic asthma is a chronic, complex inflammatory disease of the airway. Despite extensive studies on the immunomodulation of T helper (Th) cell pathways (i.e., Th1 and Th2) in asthma, little is known about the effects of Th17 pathway modulation, particularly that involving peroxisome proliferator-activated receptors (PPARs). In response, two new thiazolidinedione derivatives-namely, LPSF-GQ-147 and LPSF-CR-35 were synthesized and evaluated for their immunomodulatory effects on Th17-related cytokines, including interferon γ (IFNγ), interleukin IL-6, IL-17, and IL-22 in the peripheral blood mononuclear cells of asthmatic children. Both compounds were nontoxic even at high concentrations (i.e., 100 µM). The LPSF-CR-35 compound significantly reduced the levels of IL-17A (p = .039) and IFNγ (p = .032) at 10 µM. For IL-22 and IL-6, significant reduction occurred at 100 µM (p = .039 and p = .02, respectively). Conversely, LPSF-GQ-147 did not significantly inhibit the production of the tested cytokines, the levels of all of which were more efficiently reduced by LPSF-CR-35 than methylprednisolone, the standard compound. Real-time polymerase chain reaction assay confirmed that LPSF-GQ-147 has significant PPARγ modulatory activity. Such data indicate that both LPSF-CR-35 and LPSF-GQ-147 are promising candidates as drugs for treating inflammation and asthma.

ABSTRACT Introduction: Schistosomiasis is an infectious parasitic disease caused by trematodes of the genus Schistosoma, which threatens at least 258 million people worldwide and its control is dependent on a single drug, praziquantel. The aim of this study was to evaluate the anti-Schistosoma mansoni activity in vitro of novel imidazolidine derivatives. Material and methods: We synthesized two novel imidazolidine derivatives: (LPSF/PTS10) (Z)-1-(2-chloro-6-fluorobenzyl)-4-(4-dimethylaminobenzylidene)-5-thioxoimidazolidin-2-one and (LPSF/PTS23) (Z)-1-(2-chloro-6-fluoro-benzyl)-5-thioxo-4-(2,4,6-trimethoxy-benzylidene)-imidazolidin-2-one. The structures of two compounds were determined by spectroscopic methods. During the biological assays, parameters such as motility, oviposition, mortality and analysis by Scanning Electron Microscopy were performed. Results: LPSF/PTS10 and LPSF/PTS23 were considered to be active in the separation of coupled pairs, mortality and to decrease the motor activity. In addition, LPSF/PTS23 induced ultrastructural alterations in worms, after 24 h of contact, causing extensive erosion over the entire body of the worms. Conclusion: The imidazolidine derivatives containing the trimetoxy and benzylidene halogens showed promising in vitro schistosomicidal activity.

A melhoria dos procedimentos diagnósticos que levam a uma identificação prematura do câncer de mama tem elevado a incidência de casos, mas também vêm reduzindo sofrimentos e óbitos em decorrência da doença. Dados da Organização Mundial de Saúde mostram que todo ano, são quase 13 milhões de casos novos de câncer no mundo e 7,5 milhões de mortes por causa da doença. Nas mulheres o câncer mais prevalente é o de mama, no Brasil as taxas de mortalidade continuam elevadas, muito provavelmente porque a doença é diagnosticada em estágios avançados. Neste estudo é feito um levantamento dos exames mais comuns para o diagnóstico do câncer de mama, baseado nos pontos positivos e negativos de cada método e sua efetividade no diagnóstico precoce. Pretende-se assim, identificar os propulsores para inovar nessa área e os métodos mais novos que chegaram ao mercado. Nas análises dos resultados foram observados: que os métodos de diagnósticos mais utilizados são: mamografia, ultrassonografia e ressonância magnética, o mais usado para o rastreamento e diagnóstico precoce é a mamografia, contudo a mesma apresenta-se defasada e ineficaz na diminuição dos óbitos por câncer de mama. Ademais, o acesso ao exame está longe de ser o ideal e a técnica em si depende de uma serie de fatores, tornando-se um procedimento limitado. Concluímos que existe um campo bastante amplo para inovação no diagnóstico em câncer de mama, buscando sempre por técnicas rápidas, práticas, com valores que se encaixem em todos os níveis econômicos e cheguem ate onde os antigos métodos não conseguiram. Os novos métodos são bastante promissores e mostram-se eficazes, se devidamente distribuídos e direcionados.

Improving diagnostic procedures that lead to premature identification of breast cancer has increased the incidence of cases, but have also reducing suffering and deaths from the disease. World Health Organization data show that each year, are nearly 13 million new cases of cancer worldwide and 7.5 million deaths from the disease. In women, the most prevalent cancer is breast cancer, in Brazil mortality rates remain high, most likely because the disease is diagnosed in advanced stages. In this study data is made a survey of the most common tests for the diagnosis of breast cancer, based on the strengths and weaknesses of each method and its effectiveness in the early diagnosis. This is intended to identify the drivers for innovation in this area and the newest methods that hechead the market. in the analyzes of results were observed: the most used diagnostic methods are: mammography, ultrasound and magnetic resonance imaging, the most widely used for screening and early diagnosis is mammography. However it presents itself outdated and ineffective in decreasing deaths breast cancer. in addition, access to the exam is far from ideal and the technique itself depends on a number of factors, making it a flawed procedure. We conclude that there is a very broad field for innovation in the diagnosis of breast cancer, always looking for quick techniques, practices, values that fit all economic levels and to come up to where the old methods have failed. The new methods are very promising and have proven effective if properly distributed and targeted.

Introdução: Lesões do cólon são predominantes em pacientes com esquistossomose, entretanto alterações dos carboidratos no cólon com esquistossomose permanecem desconhecidas. Ligantes de lectinas permitem a identificação das mudanças no padrão dos carboidratos celulares. Métodos: Biópsias do cólon descendente e sigmóide dos pacientes foram submetidas a histoquímica com as lectinas WGA e Con A. Resultados: WGA marcou o estroma dos tecidos das células glandulares do cólon descendente e sigmóide com um padrão citoplasmático intenso e granular em espécimes com esquistossomose diferindo do controle normal e da Con A, a qual não reconheceu nenhum tecido estudado. Cólon sem esquistossomose não apresentou marcação. Conclusões: ligantes de WGA são diferentemente expressos em pacientes com esquistossomose hepatoesplênica sem evidência de sistema ovo-granuloma.

Introduction: Colonic lesions are predominant in patients with schistosomiasis. However, carbohydrate alterations in colonic schistosomiasis remain unclear. Lectin-ligands allow us to identify changes in the saccharide patterns of cells. Methods: Biopsies of descending and rectosigmoid colon of patients were submitted to WGA and Con A lectin histochemistry. Results: WGA stained stroma and gland cells of descending colon and rectosigmoid tissues in a granular strong cytoplasmatic pattern in schistosomiasis specimens differing from normal control and Con A failing to recognize all samples analyzed. Conclusions: WGA ligands are expressed differently in patients with hepatosplenic schistosomiasis and no evidence of egg-granuloma system.

A hipóxia vem sendo bastante estudada nos tumores sólidos, principalmente nos de mama, os quais são frequentemente responsáveis pela resistência a quimioterapia e radioterapia. O hypoxia inducible factor (HIF)-1α é o principal responsável pela hipóxia no microambiente tumoral e seus mecanismos moleculares têm sido descritos, além de estratégias terapêuticas desenhadas para essa molécula. Porém, poucos estudos na literatura tratam do papel do microambiente hipóxico no momento do diagnóstico para colaborar com a conduta dos oncologistas. Este artigo alerta os pesquisadores em patologia e oncologia para que eles observem a importância da avaliação da extensão da área, bem como dos biomarcadores específicos para esse ambiente, já que moléculas responsivas à hipóxia podem ser indicativas de resposta à terapia antiangiogênica. A extensão das áreas hipóxicas pode mudar a decisão do oncologista na escolha da conduta terapêutica, visto que alguns tratamentos antiangiogênicos podem piorar consideravelmente a evolução clínica do paciente por criar um ambiente hipóxico.

Hypoxia has been extensively studied in solid tumors mainly in breast cancers and it is commonly associated with chemotherapy and radiotherapy resistance. Hypoxia inducible factor (HIF)-1α is responsible for hypoxia in the tumor microenvironment and its molecular mechanisms as well as its therapeutic strategies have been described. However, a few investigations in the literature deal with its role in the hypoxic environment at diagnosis with the aim to guide therapeutic approaches. This study alerts researchers in pathology and oncology to the importance of assessing area extension as well as specific biomarkers, inasmuch as molecules reactive to hypoxia may indicate response to antiangiogenic therapy. The extension of hypoxic areas may alter the choice of therapeutic approach, insofar as some antiangiogenic treatments may considerably aggravate patient's clinical course since they create a hypoxic environment.