RAP1-GTPase immunostaining is altered in human precancerous and cancerous cervical lesions.

This study investigated RAP1 immunostaining variation in different cell types during CC progression. Paraffin-embedded cervical tissues from 101 patients were categorized into control, pre-neoplastic and neoplastic groups. RAP1 immunolocalization, HPV detection and genotyping were performed.

Synthesis and cytotoxic evaluation of heterocyclic compounds by vinylic substitution of ketene dithioacetals.

N-heterocyclic compounds are important molecular scaffolds in the search for new drugs, since most drugs contain heterocyclic moieties in their molecular structure, and some of these classes of heterocycles are able to provide ligands for two or more biological targets. Ketene dithioacetals are important building blocks in organic synthesis and are widely used in the synthesis of N-heterocyclic compounds. In this work, we used double vinylic substitution reactions on ketene dithioacetals to synthesize a small library of heterocyclic derivatives and evaluated their cytotoxic activity in breast and ovarian cancer cells, identifying two benzoxazoles with good potency and selectivity.

Applications of Mass Spectrometry in the Characterization, Screening, Diagnosis, and Prognosis of COVID-19.

Mass spectrometry (MS) is a powerful analytical technique that plays a central role in modern protein analysis and the study of proteostasis. In the field of advanced molecular technologies, MS-based proteomics has become a cornerstone that is making a significant impact in the post-genomic era and as precision medicine moves from the research laboratory to clinical practice. The global dissemination of COVID-19 has spurred collective efforts to develop effective diagnostics, vaccines, and therapeutic interventions.

Extreme lymphocytosis in a dog with T-zone lymphoma.

Background: Canine T-zone lymphoma (TZL) is recognized as an indolent CD45-T cell lymphoma, with low aggressiveness and high overall survival. The diagnosis is obtained by histopathology and immunohistochemistry, but also by cytological examination of the lymph node associated with immunophenotyping. Lymphocytosis is commonly identified as around 10,000 cells/µl and may reach 30,760 cells/µl.

Evaluation of acute toxicity and in vitro antitumor activity of a novel doxorubicin-loaded folate-coated pH-sensitive liposome.

Doxorubicin (DOX) loaded liposomes have been used and studied in the last decades due to the significant decrease in DOX induced cardiac and systemic toxicity relative to administration of free drug. Therefore, new strategies are sought to improve DOX delivery and antitumor activity, while avoiding side effects. Recently, folate-coated pH-sensitive liposomes (SpHL-Fol) have been studied as a tool to enhance cellular uptake and antitumor activity of paclitaxel and DOX in breast cancer cells expressing folate receptor (FR+).

Reduction in the number of neutrophils in the broncho-alveolar aspirate is associated with worse prognosis in elderly patients with severe COVID-19.

The blood levels of neutrophils are associated with the severity of COVID -19. However, their role in the pulmonary environment during COVID -19 severity is not clear. Here, we found a decrease in the neutrophil count in BAL (bronchoalveolar lavage) in non-survivors and in older patients (> 60 years).

Tocotrienols-enriched Self-nanoemulsifying Drug Delivery System Enhances the Antileukemic Activity of All-trans Retinoic Acid but not Electrocardiogram Alterations Evoked by Its Combination with Arsenic Trioxide.

All-trans retinoic acid and arsenic trioxide are the leading choices for the treatment of acute promyelocytic leukemia. Notwithstanding the impressive differentiative properties of all-trans retinoic acid and the apoptotic properties of arsenic trioxide, some problems still occur in acute promyelocytic leukemia treatment. These problems are due to patients' relapses, mainly related to changes in the ligand-binding domain of RARα (retinoic acid receptor α) and the cardiotoxic effects caused by arsenic trioxide.

Dysfunctional phenotype of systemic and pulmonary regulatory T cells associate with lethal COVID-19 cases.

Severe cases of COVID-19 present hyperinflammatory condition that can be fatal. Little is known about the role of regulatory responses in SARS-CoV-2 infection. In this study, we evaluated the phenotype of regulatory T cells in the blood (peripheral blood mononuclear cell) and the lungs (broncho-alveolar) of adult patients with severe COVID-19 under invasive mechanical ventilation.

SARS-CoV-2 Omicron BA.1, BA.2, and XAG identification during routine surveillance on a university campus in Belo Horizonte, Brazil, 2022.

We report SARS-CoV-2 genomic surveillance results between Belo Horizonte, Brazil's third and fourth case waves. Samples were obtained through a routine university monitoring COVID-19 program from the 9th to the 22nd epidemiological weeks (March and June 2022). We identified ten samples from the BA.

Recent advances in point of care testing for COVID-19 detection.

The World Health Organizations declaration of the COVID-19 pandemic was a milestone for the scientific community. The high transmission rate and the huge number of deaths, along with the lack of knowledge about the virus and the evolution of the disease, stimulated a relentless search for diagnostic tests, treatments, and vaccines. The main challenges were the differential diagnosis of COVID-19 and the development of specific, rapid, and sensitive tests that could reach all people.

microRNA miR-133a as a Biomarker for Doxorubicin-Induced Cardiotoxicity in Women with Breast Cancer: A Signaling Pathway Investigation.

Cardiovascular toxicity is the main adverse effect of Doxorubicin (DOX) in cancer patients. microRNAs (miRNAs) are promising biomarkers to identify cardiac injury induced by DOX in breast cancer patients during the subclinical phase. Using RT-qPCR, we compared the expression of circulating miR-208a5p, miR-133a, miR-499a5p, miR-15a, miR-133b, and miR-49a3p in serum samples from DOX-induced cardiotoxicity (case) compared to the non-cardiotoxicity group (control).

Cytotoxic Activity of Triterpenoids from Cheiloclinium cognatum Branches against Chronic and Acute Leukemia Cell Lines.

Cheiloclinium cognatum (Miers) A.C.Sm.

Novel self-nanoemulsifying drug-delivery system enhances antileukemic properties of all- retinoic acid.

All- retinoic acid (ATRA) shows erratic oral bioavailability when administered orally against leukemia, which can be solved through its incorporation in self-nanoemulsifying drug-delivery systems (SEDDS). The SEDDS developed contained a hydrophobic ion pair between benzathine (BZT) and ATRA and was enriched with tocotrienols by the input of a palm oil tocotrienol rich fraction (TRF) in its composition. SEDDS-TRF-ATRA-BZT allowed the formation of emulsions with nanometric size that retained ATRA within their core after dispersion.

Association among ACE, ESR1 polymorphisms and preeclampsia in Brazilian pregnant women.

Background: Genetic, immune and environmental factors are involved in preeclampsia (PE) etiopathogenesis. Considering that hypertension and poor placental perfusion are important features in PE, polymorphisms in the angiotensin-converting enzyme (ACE) and estrogen nuclear receptor 1 (ESR1) genes could be involved in the predisposition and/or development of the disease. The aim of this study was to evaluate if polymorphisms in ACE and ESR1 genes were associated with PE occurrence.

Troponin as a cardiotoxicity marker in breast cancer patients receiving anthracycline-based chemotherapy: A narrative review.

The approach to breast cancer has changed in recent decades due to significant advances in screening, early diagnosis, and treatment; however, the risk of cardiovascular injury induced by chemotherapy has remained similar. Anthracyclines are the most common agents used in breast cancer treatment and may lead to cardiotoxicity, which appears to have a direct relationship with accumulated dose and duration of treatment. Therefore, the use of cardiac biomarkers derived from those used in cardiac disease diagnosis has been applied to the early identification, evaluation, and cardiotoxicity monitoring during chemotherapy.

Toxicological study of a new doxorubicin-loaded pH-sensitive liposome: A preclinical approach.

Doxorubicin (DOX) is widely used in cancer treatment, however, the use of this drug is often limited due to its cardiotoxic side effects. In order to avoid these adverse effects, the encapsulation of DOX into nanosystems has been used in the last decades. In this context, pH-sensitive liposomes have been shown promising for delivering cytotoxic agents into tumor cells, however, the lack of information about in vivo toxicity of this nanocarrier has impaired translational studies.

Advances in chronic lymphocytic leukemia pharmacotherapy.

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease that affects B lymphocytes in most cases. Leukemic lymphocytes have prolonged longevity, defined by resistance to apoptosis. These cells can accumulate in peripheral blood, bone marrow, and solid lymphoid organs.

Peritoneal dialysis and inflammation.

Peritoneal dialysis (PD) is a kidney replacement therapy for end stage renal disease (ESRD) patients. Despite being a lifesaving treatment, the rate of mortality in patients under PD is elevated, mainly due to the chronic peritoneal dysfunction which is characterized by inflammation, peritoneal fibrosis and neoangiogenesis. The inflammatory process is trigged and modulated by the type of the peritoneal dialysis solutions (PDSs) used during PD.

Plasminogen activator inhibitor-1 4G/5G promoter polymorphism and PAI-1 plasma levels in young patients with ischemic stroke.

The 4G/5G polymorphism in the plasminogen activator inhibitor-1 (PAI-1) gene, has been associated with arterial disease. In this study, we investigated the association of IS in young patients with CRP and PAI-1 levels and frequency of insertion-deletion polymorphism of PAI-1 gene. The plasma levels of PAI-1 and CRP and the frequency of 4G/5G polymorphism were analyzed in 127 Brazilian young patients that presented IS and in 201 healthy and unrelated control subjects.

ApoB/ApoA-I ratio in young patients with ischemic cerebral stroke or peripheral arterial disease.

Although smoking and hypertension are classic risk factors for atherothrombotic diseases, the relationship of dyslipidemia and vascular diseases, other than myocardial infarction, is less clearly established, especially in young subjects. In the current study, a detailed analysis of the lipid and apolipoprotein profiles was conducted in young patients of ischemic cerebral stroke (IS) and peripheral arterial disease (PAD). Plasma levels of C-reactive protein (hs-CRP), total cholesterol (TC), high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), triglycerides (TG), and apolipoproteins A-I (ApoA-I) and apolipoproteins B (ApoB), which include the ApoB/ApoA-I ratio, were analyzed in a group of 81 patients who presented with IS (n = 46) or PAD (n = 35) as well as in 167 control subjects.

Increased Factor V Leiden frequency is associated with venous thrombotic events among young Brazilian patients.

Introduction: Of the inherited thrombophilias, the Factor V Leiden (FVL) and the prothrombin mutant (FII G20210A) are associated with increased risk of venous thromboembolism (VTE). The C677T mutation of the methylenetetrahydrofolate reductase gene, which may lead to hyperhomocysteinemia, is also considered a risk factor for VTE in some studies. However, the frequency of these genetic risk factors may vary significantly among different populations.

Factor V Leiden and increased risk for arterial thrombotic disease in young Brazilian patients.

The contribution of mutations in the prothrombin (FII G20210A), methylenetetrahydrofolate reductase (C677T) genes and factor V Leiden (FVL) to the pathogenesis of arterial thrombosis remains controversial. In this study, these polymorphisms were investigated by polymerase chain reaction-restriction fragment length polymorphism in a group of 53 patients that presented arterial thrombosis other than myocardial infarction as a first thrombotic event and 275 control subjects living in the state of Minas Gerais, Brazil. Odds ratio (OR) and chi tests were applied for statistical comparisons.