Trp53 Deletion Promotes Exacerbated Colitis, Facilitates Lgr5+ Cancer Stem Cell Expansion, and Fuels Tumorigenesis in AOM/DSS-Induced Colorectal Cancer.

Colorectal cancer CRC remains one of the leading causes of cancer-related deaths worldwide, with chronic intestinal inflammation identified as a major risk factor. Notably, the tumor suppressor undergoes mutation at higher rates and earlier stages during human inflammation-driven colon tumorigenesis than in sporadic cases. We investigated whether deleting affects inflammation-induced tumor growth and the expression of Lgr5+ cancer stem cells in mice.

Contrasting Phenotypes of Neutrophils During Asymptomatic Versus Symptomatic Leishmania braziliensis Infection.

Background: The mechanisms that mediate immune protection in individuals with subclinical (SC) or asymptomatic infection with Leishmania braziliensis are largely unknown. Neutrophils (polymorphonuclear leukocytes [PMNs]) have been implicated in progressive symptomatic cutaneous leishmaniasis (CL), but their potential participation in maintenance of subclinical infection is unexplored. The aim of this study was to compare the phenotypic and functional profiles of PMNs in individuals with SC infection versus patients with symptomatic CL due to L braziliensis.

Synthesis of hydrazinyl-thiazole ester derivatives, trypanocidal and leishmanicidal activities.

To synthesize novel more potent trypanocidal and leishmanicidal agents. Hantzsch's synthetic strategy was used to synthesize 1,3-thiazole-4-carboxylates and their -benzylated derivatives. 28 new thiazole-carboxylates and their -benzylated derivatives were established to test their trypanocidal and leishmanicidal activities.

Endophytic fungus from Handroanthus impetiginosus immobilized on electrospun nanofibrous membrane for bioremoval of bisphenol A.

The current industrial and human activities scenario has accelerated the widespread use of endocrine-disrupting compounds (EDCs), which can be found in everyday products, including plastic containers, bottles, toys, cosmetics, etc., but can pose a severe risk to human health and the environment. In this regard, fungal bioremediation appears as a green and cost-effective approach to removing pollutants from water resources.

Structural design, synthesis, and anti-Trypanosomatidae profile of new Pyridyl-thiazolidinones.

The present work reports the synthesis of a novel series of pyridine-thiazolidinones with anti-Trypanosoma cruzi and leishmanicidal activities (compounds 10-27), derived from 2 or 4-pyridine thiosemicarbazones (1-9). The in vitro assays were performed with Trypanosoma cruzi trypomastigotes and amastigotes, as well as with Leishmania amazonensis promastigotes and amastigotes. The cytotoxicity profile was evaluated using the cell line RAW 264.

Identification of Novel Zika Virus Inhibitors: A Screening using Thiosemicarbazones and Thiazoles Templates.

Background: Zika virus (ZIKV) remains an important cause of congenital infection, fetal microcephaly, and Guillain-Barré syndrome in the population. In 2016, WHO declared a cluster of microcephaly cases and other neurological disorders reported as a global public health emergency in Brazil. There is still no specific treatment for Zika virus fever, only palliative care.

Outlining the Molecules Tested for Chagas Disease, Malaria, and Schistosomiasis Over the Last Six Years - A Literature Review Focused on New Synthetic Drug Identities and Repurposing Strategies.

Background: COVID-19 disrupted NTD programs in 60% of countries, impairing public health goals. Thus, boosting NTD's research knowledge is demanding, and in vivo screening of candidates allows for the prospect of promising options based on their overall profile.

Objective: In this work, we highlighted the relevant research done between 2015-2021 in the fields of synthetic and repurposed drugs that were tested in vivo for Chagas disease, malaria, and schistosomiasis.

Neglected tropical diseases and systemic racism especially in Brazil: from socio-economic aspects to the development of new drugs.

Neglected tropical diseases (NTDs) are highly prevalent communicable diseases in tropical and subtropical countries, generally not economically attractive for drug development and related to poverty. In Brazil, more specifically, socioeconomic inequalities and health indicators are strongly influenced by skin color, race, and ethnicity, due to the historical process of slavery. In this context, it is important to understand the concept of systemic racism: a form of indirect racial discrimination present in many institutions, which determines the process of illness and death of the black population, the ethnic group most affected by these diseases.

[Maternal mortality trend in the state of Rio de Janeiro, Brazil, 2006-2018, according to the ICD-MM classification].

The study aimed to analyze the trend in the maternal mortality ratio (MMR) according to the ICD classification for maternal mortality (ICD-MM) classification in the state of Rio de Janeiro, Brazil, from 2006 to 2018. This was a time trend study of MMR in Rio de Janeiro according to type of death (direct or indirect) and groups of causes in the World Health Organization (WHO) ICD-MM. MMR was calculated with data from Brazilian Mortality Information System (SIM) and Brazilian Information System on Live Births (SINASC).

Breast Cancer Management During the COVID-19 Pandemic: The Senologic International Society Survey.

Objective: In early 2020, the spread of coronavirus disease-2019 (COVID-19) led the World Health Organization to declare this disease a pandemic. Initial epidemiological data showed that patients with cancer were at high risk of developing severe forms of COVID-19. National scientific societies published recommendations modifying the patients' breast cancer (BC) management to preserve, in theory, quality oncologic care, avoiding the increased risk of contamination.

Stigma structure and receptivity in papaya (Carica papaya L.).

The objective of this study was to evaluate the stigma morphoanatomy and receptivity in ten promising papaya accessions, to expand knowledge useful for genetic improvement of the culture. The morphoanatomy was analyzed by light and scanning electron microscopy, and the stigma receptivity was investigated by application of hydrogen peroxide and α-naphthyl-acetate with fast blue B salt, in pre-anthesis, anthesis and post-anthesis. The papaya accessions presented dry stigma surface, presence of one to six erect stigmatic lobes, with structures joined to the upper base of the style and covered with numerous elongated unicellular tubular papillae, distributed on both faces of the epidermis.

Hypoglycemic episodes in hospitalized people with diabetes in Portugal: the HIPOS-WARD study.

Background: We intended to estimate the proportion hypoglycemic/hyperglycemic emergency episodes in treated diabetes mellitus (DM) patients admitted to a hospital ward, and calculate the prevalence of risk factors for hypoglycemia and diabetic complications.

Methods: In this cross-sectional, multicentered study, the observational data was collected by physicians from patient's hospitalization to discharge/death. Statistical tests were 2-tailed considering 5% significance level.

An Overview of the Compounds Tested In Vivo for Leishmania spp. of the Last 5 Years.

Background: Leishmaniasis, a still important public health problem, exhibits environmental risk factors such as massive migrations, urbanization, and deforestation. WHO research for Leishmaniasis is mainly focused on the development of new tools, such as diagnostic tests, drugs, and vaccines. During the drug development strategy, only a few compounds were promising and call for further study after the in vitro and in vivo preclinical tests.

Dual Parasiticidal Activities of Phthalimides: Synthesis and Biological Profile against Trypanosoma cruzi and Plasmodium falciparum.

Chagas disease and malaria are two neglected tropical diseases (NTDs) that prevail in tropical and subtropical regions in 149 countries. Chagas is also present in Europe, the US and Australia due to immigration of asymptomatic infected individuals. In the absence of an effective vaccine, the control of both diseases relies on chemotherapy.

Measuring mosquito control: adult-mosquito catches vs egg-trap data as endpoints of a cluster-randomized controlled trial of mosquito-disseminated pyriproxyfen.

Background: Aedes aegypti and Culex quinquefasciatus are the main urban vectors of arthropod-borne viruses causing human disease, including dengue, Zika, or West Nile. Although key to disease prevention, urban-mosquito control has met only limited success. Alternative vector-control tactics are therefore being developed and tested, often using entomological endpoints to measure impact.

Hospitalization Costs Due to Hypoglycemia in Patients with Diabetes: A Microcosting Approach.

Introduction: Hypoglycemia leading to hospitalization is associated with adverse economic outcomes, although the real burden is unknown. The HIPOS-WARD (Hypoglycemia In Portugal Observational Study-Ward) aimed to characterize ward admissions due to hypoglycemia episodes in treated patients with diabetes and assess their economic impact to the National Health System.

Methods: Observational, cross-sectional study, conducted in 16 Portuguese centers for 22 months.

Pyromellitic dianhydride crosslinked soluble cyclodextrin polymers: Synthesis, lopinavir release from sub-micron sized particles and anti-HIV-1 activity.

We report the synthesis of water soluble cyclodextrin (CD) polymers prepared by crosslinking pyromellitic dianhydride (PMDA) with two CD derivatives (methyl-β-CD - MβCD and (2-hydroxy)propyl-β-CD - HPβCD) and their evaluation as functional sub-micron sized carriers in the development of antiretroviral drug delivery systems. Using the protease inhibitor lopinavir (LPV) as model drug, LPV loaded CD polymers (pHPβCD and pMβCD) were prepared and fully characterized. The physicochemical characterization and in vitro drug release confirmed the successful synthesis of pHPβCD and pMβCD, the formation of sub-micron sized particles and a 12-14 fold increase in LPV solubility.

Orodispersible Carbamazepine/Hydroxypropyl-β-Cyclodextrin Tablets Obtained by Direct Compression with Five-in-One Co-processed Excipients.

The development of orodispersible tablets (ODTs) for poorly soluble and poorly flowable drugs via direct compression is still a challenge. This work aimed to develop ODTs of poorly soluble drugs by combining cyclodextrins that form inclusion complexes to improve wetting and release properties, and directly compressible co-processed excipients able to promote rapid disintegration and solve the poor flowability typical of inclusion complexes. Carbamazepine (CBZ) and hydroxypropyl-β-cyclodextrin (HPβCD) were used, respectively, as a model of a poorly soluble drug with poor flowability and as a solubilizing agent.

Phenolic Compound Biotransformation by Trametes versicolor ATCC 200801 and Molecular Docking Studies.

The filamentous fungus Trametes versicolor is a rich source of laccase (Tvlac). Laccases catalyze reactions that convert substituted phenol substrates into diverse derivatives through aromatic oxidation. We investigated methyl p-coumarate, methyl ferulate, and methyl caffeate biotransformation by Trametes versicolor ATCC 200801.

Cyclodextrin solubilization and complexation of antiretroviral drug lopinavir: In silico prediction; Effects of derivatization, molar ratio and preparation method.

Lopinavir (LPV) is currently used in combination with ritonavir for the clinical management of HIV infections due to its limited oral bioavailability. Herein, we report the application of an in silico method to study cyclodextrin (CyD) host-guest molecular interaction with LPV for the rational selection of the best CyD for developing a CyD based LPV delivery system. The predicted CyD, a (2-hydroxy)propyl-gamma derivative with high degree of substitution (HP17-γ-CyD) was synthesized and comparatively evaluated with γ-CyD and the commercially available HP-γ-CyD.

Genetic variants in 17q12-21 locus and childhood asthma in Brazil: Interaction with Varicella zoster virus seropositivity.

Background: Asthma is a complex disease with worldwide public health relevance, is related to environmental causes and a genetic predisposition. The chromosomal 17q12-21 locus has been consistently demonstrated to be associated with asthma risk. The effects of variants in the 17q12-21 locus on childhood asthma were first identified in a genome wide- association study.

Effects of chronic treatment with botulinum toxin type A in salivary glands of rats: Histological and immunohistochemical analyses.

Background: The intraglandular application of botulinum neurotoxin type A (BoNT-A) is used in patients with neuromotor disorders to control the escape of saliva. The aim of this study was to analyze the impact of repeated treatment with BoNT-A on the submandibular-sublingual complex of rats.

Methods: A total of 35 Wistar rats were divided into three groups: control group (C), in which animals were not treated; group B, treated with 2.

New species of Grubeulepis Pettibone, 1969 (Eulepethidae, Annelida) from northern Brazil.

Eulepethidae is one of the least diverse families of scale polychaetes, with only 23 species described thus far. In this study we describe an additional species of Grubeulepis from unconsolidated substrata from Maranhão, tropical Brazil (ca. 2°S).