Nitroaromatic-based triazene prodrugs to target the hypoxic microenvironment in glioblastoma.

Hypoxia is a hallmark of the glioblastoma multiforme microenvironment and represents a promising therapeutic target for cancer treatment. Herein, we report nitroaromatic-based triazene prodrugs designed for selective activation by tumoral endogenous reductases and release of the cytotoxic methyldiazonium ion a self-immolative mechanism. While compounds bearing a 2-nitrofuran bioreductive group were more efficiently activated by nitroreductases, 4-nitrobenzyl prodrugs 1b, 1d and 1e elicited a more pronounced cytotoxic effect against LN-229 and U-87 MG glioblastoma cell lines under hypoxic conditions when compared to temozolomide (TMZ), the golden standard for glioblastoma treatment.

Numerous rRNA molecules form the apicomplexan mitoribosome via repurposed protein and RNA elements.

Mitochondrial ribosomes (mitoribosomes) are essential, and their function of synthesising mitochondrial proteins is universal. The core of almost all mitoribosomes is formed from a small number of long and self-folding rRNA molecules. In contrast, the mitoribosome of the apicomplexan parasite Toxoplasma gondii assembles from over 50 extremely short rRNA molecules.

Cellular metabolism and hormone signalling: connecting growth and defence.

Plants, as sessile organisms, have developed mechanisms to balance growth and defence strategies against biotic and abiotic stresses. Two recent studies by Hong et al. and Lu et al.

Guard cells and mesophyll: a delicate metabolic relationship.

Understanding cell type-specific metabolism, especially under unfavorable conditions, is paramount. Recent discoveries by Shi et al. and Auler et al.

Functional analysis of the extraplastidial TRX system in germination and early stages of development of Arabidopsis thaliana.

A series of processes occur during seed formation, including remarkable metabolic changes that extend from early seed development to seedling establishment. The changes associated with processes initiated mainly after seed imbibition are usually characterized by extensive modification in the redox state of seed storage proteins and of pivotal enzymes for reserve mobilization and usage. Such changes in the redox state are often mediated by thioredoxins (TRXs), oxidoreductase capable of catalyzing the reduction of disulfide bonds in target proteins to regulate its structure and function.

Leukoreduction as a control measure in transfusion transmission of visceral leishmaniasis.

Background: Asymptomatic visceral leishmaniasis (VL) infection is a risk for transfusion safety. Leukoreduction has been an alternative for the prevention of some blood-borne diseases, including VL. This study aimed to evaluate the role of leukoreduction of cellular blood components as a control measure for transfusional VL transmission.

Role of TLR2/MyD88 in the production of specific IgM and IgG antibodies during the immunization of mice against Neospora caninum.

Neospora caninum is a parasite relevant to the veterinary field. Innate and adaptive responses against N. caninum induce effector mechanisms that limit parasite replication, but little is known about their role in humoral response.

Quercetin Liposomal Nanoformulation for Ischemia and Reperfusion Injury Treatment.

Ischemia and reperfusion injury (IRI) is a common complication caused by inflammation and oxidative stress resulting from liver surgery. Current therapeutic strategies do not present the desirable efficacy, and severe side effects can occur. To overcome these drawbacks, new therapeutic alternatives are necessary.

Antagonist G-targeted liposomes for improved delivery of anticancer drugs in small cell lung carcinoma.

Ligand-mediated targeted liposomes have the potential to increase therapeutic efficacy of anticancer drugs. This work aimed to evaluate the ability of antagonist G, a peptide targeting agent capable of blocking the action of multiple neuropeptides, to selectivity improve targeting and internalization of liposomal formulations (long circulating liposomes, LCL, and stabilized antisense lipid particles containing ionizable amino lipid, SALP) to H69 and H82 small cell lung carcinoma (SCLC) cell lines. Antagonist G-targeted LCL and SALP were prepared by two different methods (either by direct covalent linkage at activated PEG grafted onto the liposomal surface or by post-insertion of DSPE-PEG-antagonist-G-conjugates into pre-formed liposomes).

ASP-Enzymosomes with Asparaginase II Expressed in : Formulation Design and In Vitro Studies of a Potential Antileukemic Drug.

The bacterial enzyme asparaginase is the main treatment option for acute lymphoblastic leukemia. However, it causes side effects, such as immunological reactions, and presents undesirable glutaminase activity. As an alternative, we have been studying asparaginase II from , coded by gene, which was cloned and expressed in The recombinant asparaginase (ASP) presented antileukemic activity and a glutaminase activity 100 times lower in comparison to its asparaginase activity.

Liposomal Nanosystems in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease that affects the joints and results in reduced patient quality of life due to its chronic nature and several comorbidities. RA is also associated with a high socioeconomic burden. Currently, several available therapies minimize symptoms and prevent disease progression.

Drug delivery nanosystems targeted to hepatic ischemia and reperfusion injury.

Hepatic ischemia and reperfusion injury (IRI) is an acute inflammatory process that results from surgical interventions, such as liver resection surgery or transplantation, or hemorrhagic shock. This pathology has become a severe clinical issue, due to the increasing incidence of hepatic cancer and the high number of liver transplants. So far, an effective treatment has not been implemented in the clinic.

Identification of in blood donors from endemic regions for visceral leishmaniasis.

Visceral leishmaniasis is an endemic protozoonosis observed in over 60 countries, with over 500 000 new cases recorded annually. Although the diagnostic procedure of its symptomatic forms is well established, for asymptomatic patients, who represent about 85% of those infected, there is no consensus on the best method for its identification. Recent studies have presented molecular techniques as viable identification methods, with good sensitivity and specificity indices in asymptomatic individuals.

Chagas disease: Performance analysis of immunodiagnostic tests anti-Trypanosoma cruzi in blood donors with inconclusive screening results.

Background: The screening ofTrypanosoma cruzi-infected blood donors using two serological techniques frequently leads to conflicting results. This fact prompted us to evaluate the diagnostic performance of four "in-house" immunodiagnostic tests and two commercially available enzyme-linked immunosorbent assays (ELISAs).

Material And Methods: One hundred and seventy-nine blood donors, whose screening for Chagas disease was doubtful, underwent three in-house ELISAs, one in-house immunoblotting test (TESA-blot), and two commercial ELISAs (bioMérieux and Wiener) in an attempt to define the presence or absence of infection.

The ongoing COVID-19 epidemic in Minas Gerais, Brazil: insights from epidemiological data and SARS-CoV-2 whole genome sequencing.

The recent emergence of a coronavirus (SARS-CoV-2), first identified in the Chinese city of Wuhan in December 2019, has had major public health and economic consequences. Although 61,888 confirmed cases were reported in Brazil by 28 April 2020, little is known about the SARS-CoV-2 epidemic in this country. To better understand the recent epidemic in the second most populous state in southeast Brazil - Minas Gerais (MG) - we sequenced 40 complete SARS-CoV-2 genomes from MG cases and examined epidemiological data from three Brazilian states.

Targeting Cancer Resistance via Multifunctional Gold Nanoparticles.

Resistance to chemotherapy is a major problem facing current cancer therapy, which is continuously aiming at the development of new compounds that are capable of tackling tumors that developed resistance toward common chemotherapeutic agents, such as doxorubicin (DOX). Alongside the development of new generations of compounds, nanotechnology-based delivery strategies can significantly improve the in vivo drug stability and target specificity for overcoming drug resistance. In this study, multifunctional gold nanoparticles (AuNP) have been used as a nanoplatform for the targeted delivery of an original anticancer agent, a Zn(II) coordination compound [Zn(DION)2]Cl2 (ZnD), toward better efficacy against DOX-resistant colorectal carcinoma cells (HCT116 DR).

Socio-epidemiological characterisation of blood donors with asymptomatic Leishmania infantum infection from three Brazilian endemic regions and analysis of the transfusional transmission risk of visceral leishmaniasis.

Objectives: This study assessed the prevalence of visceral leishmaniasis in blood donors from three endemic regions in Brazil and evaluated the risk of transmission by transfusion.

Background: Despite strong evidence of the transmission of visceral leishmaniasis through blood transfusion, the real risk, an essential condition for taking effective measures to control this serious disease, has not been determined.

Methods: A multicentre study was performed in highly endemic areas.

Complete Genome Sequence of Staphylococcus aureus FCFHV36, a Methicillin-Resistant Strain Heterogeneously Resistant to Vancomycin.

We report here the sequence of the entire chromosome of Staphylococcus aureus strain FCFHV36, a methicillin-resistant strain heterogeneously intermediate to vancomycin, bearing a type II staphylococcal chromosome cassette mec element (SCCmec), belonging to multilocus sequence type (MLST) 105, and isolated from a vertebra of a patient with osteomyelitis.

Length and caliber of the rectosigmoid colon among patients with Chagas disease and controls from areas at different altitudes.

Introduction: In this study, we investigated radiological changes in the sigmoid colon in chagasic patients by comparing their colon lengths and caliber with those of non-chagasic living in the same region and non-chagasic living at high altitudes.

Methods: A total of 317 individuals were evaluated using clinical, serological and radiological methods and divided into three groups: 1) one hundred and nine non-chagasic individuals from Uberaba, Brazil; 2) sixty-one non-chagasic from Puno, Peru; 3) one hundred forty-seven chagasics examined in Uberaba, being 62 without megacolon (3A), 72 with megacolon (3B) and 13 with doubtful diagnosis of megacolon (3C).

Results: In group 2, the sigmoid colon had a significantly larger caliber (p=0.

A general latent class model for performance evaluation of diagnostic tests in the absence of a gold standard: an application to Chagas disease.

We propose a new general Bayesian latent class model for evaluation of the performance of multiple diagnostic tests in situations in which no gold standard test exists based on a computationally intensive approach. The modeling represents an interesting and suitable alternative to models with complex structures that involve the general case of several conditionally independent diagnostic tests, covariates, and strata with different disease prevalences. The technique of stratifying the population according to different disease prevalence rates does not add further marked complexity to the modeling, but it makes the model more flexible and interpretable.

[Control of transfusional transmission].

The high prevalence of chagasic blood donors in blood centers in Brazil (6.9%) and in Latin America (6.5%) in the 60's and 70's, together with the combat to the vector since the 70's have made transfusion Chagas disease the main mechanism of the disease transmission in the 80's.

Socioepidemiological screening of serologically ineligible blood donors due to Chagas disease for the definition of inconclusive cases.

Epidemiological screening combined with serological tests has become an important tool at blood banks for the characterization of donors with or without Trypanosoma cruzi infection. Thus, the objective of the present study was to describe the sociodemographic and epidemiological characteristics of blood donors with non-negative serology for T. cruzito determine possible risk factors associated with serological ineligibility.

Bioinvasion in a Brazilian bay: filling gaps in the knowledge of southwestern Atlantic biota.

Background: Biological invasions are a major cause of global species change. Nevertheless, knowledge about the distribution and ecology of introduced species is regionally biased, and many gaps in knowledge exist for most developing countries.

Methodology/principal Findings: To study the zoobenthos on the hard substratum of the Ilha Grande Bay, a survey was conducted on both natural and artificial substrata at three depths and seven sites.