Variations in liver histology and P-gp expression among fish species in Doce River Basin, Brazil: implications for pollution sensitivity.

Fish may have different sensitivity to pollutants present in the water. We analyzed the liver histology, and P-gp expression in six species of fish from the Doce River basin. Fish were caught at six different points in the Doce River, and liver samples were taken for histological analysis.

In Vitro Antitumor and Antimetastatic Activity of a New Lapachol Derivative against Metastatic Breast Carcinoma.

Objective: Breast cancer represents the most prevalent type of tumor throughout the world. Considering the side effects caused by the available treatments, the resistance acquired by cells to cytotoxic agents, and metastasis, it is necessary to search for new sources of antitumor and antimetastatic therapies. Given the numerous antitumor studies involving the synthesis of substances derived from the naphthoquinone lapachol, we investigated the antineoplastic potential of a new synthetic substance (APO-3) derived from lapachol, alone and in combination with the chemotherapeutic agent paclitaxel (PTX), against 4T1 cells, a murine breast cancer cell line.

Ticks (Acari: Ixodidae) and tick-borne agents associated with domestic dogs in an environmental protection area in Brazil, with molecular evidence of Rhipicephalus linnaei (Audouin, 1826).

Wild animals and domestic dogs living in human dwellings near forested areas can share ectoparasites, including ticks. In this study, we surveyed ticks associated with dogs which tutors living in the Palmares Environmental Protection Area (EPA Palmares). Dogs were classified into three categories, domiciled, semi-domiciled and wandering dogs according to dog care/ type of dwelling.

Mineralocorticoid receptor activates postnatal adiposity in zebrafish lacking proopiomelanocortin.

The proopiomelanocortin (Pomc)-derived peptides, including adrenocorticotropic hormone and α-melanocyte stimulating hormone (α-Msh), play both a central and a peripheral role in modulating the stress response. The central role is predominantly associated with nutrient homeostasis, while peripherally they play an important role in the synthesis of glucocorticoids (GCs) in response to stress. Pomc mutations are a major risk factor in the development of early-onset childhood obesity in humans.

Toxicological effect of acetaminophen, metamizole, and nimesulide cocktail on early development of zebrafish.

Background: Several countries' most incorrectly discarded medicines are acetaminophen (ACM), metamizole (MTZ), and nimesulide (NMS). These xenobiotics easily reach the aquatic environment; such contamination is very important for the health of humans and other species, yet little explored.

Objectives: To evaluate the cocktail effect of ACM, MTZ, and NMS during zebrafish's initial development.

S-Se oxidative addition to auranofin derivatives: a DFT study.

Oxidative addition of the S-Se bond to Au(I) complexes is discussed for a series of 26 auranofin (AF) derivatives. AF and its analogues are Au(I) complexes with recognized anticancer activity that act by binding and inhibiting the thioredoxin reductase (TrxR) enzyme. Generally, the oxidative addition to Au(I) is a sluggish reaction under mild conditions (, a high activation barrier - Δ), which is also verified here for AF, Δ = 33.

Tapirira guianensis is Selectively Cytotoxic, Induces Apoptosis to the Glioblastoma and Decreases Tumor Growth and Angiogenesis in vivo.

Glioblastoma is the most frequent primary malignant brain tumor without effective treatment, which makes this work extremely relevant. The study of the bioactive compounds from medicinal plants plays an important role in the discovery of new drugs.This research investigated the constituents of and its antitumor potential ( and in glioblastoma.

Quantum chemical investigation of predominant conformation of the antibiotic azithromycin in water and DMSO solutions: thermodynamic and NMR analysis.

Azithromycin (AZM) is a macrolide-type antibiotic used to prevent and treat serious infections (mycobacteria or MAC) that significantly inhibit bacterial growth. Knowledge of the predominant conformation in solution is of fundamental importance for advancing our understanding of the intermolecular interactions of AZM with biological targets. We report an extensive density functional theory (DFT) study of plausible AZM structures in solution considering implicit and explicit solvent effects.

Translocation Processes of Pt(II)-Based Drugs through Human Breast Cancer Cell Membrane: Experiments.

Breast cancer is one of the most frequent modalities of cancer worldwide, with notable mortality. The medication based on platinum drugs (cisplatin (cddp), carboplatin (cpx), and oxaliplatin (oxa)) is a conventional chemotherapy despite severe side effects and the development of drug resistance. In order to provide a deeper molecular description of the influx and efflux processes of platinum drugs through breast cancer tissues, this study focuses on molecular dynamics (MD) simulations of the passive translocation process through a realistic plasma membrane prototype of human breast cancer cell (c_memb).

Modeling the Cellular Uptake of Functionalized Carbon Nanohorns Loaded with Cisplatin through a Breast Cancer Cell Membrane.

The cisplatin encapsulation into carbon nanohorns (CNH) is a promising nanoformulation to circumvent the drug dissipation and to specifically accumulate it in tumor sites. Herein, biased molecular dynamics simulations were used to analyze the transmembrane transport of the CNH loaded with cisplatin through a breast cancer cell membrane prototype. The simulations revealed a four-stage mechanism: approach, insertion, permeation, and internalization.

Toxicological effects of hydroxychloroquine sulfate and chloroquine diphosphate substances on the early-life stages of fish in the COVID-19 pandemic context.

Hydroxychloroquine sulfate (HCQ) and chloroquine diphosphate (CQ) have been used at increased rates to treat COVID-19 but can constitute a potential environmental risk. The objective was to evaluate the toxicity of sublethal concentrations of HCQ and CQ in zebrafish embryos/larvae. The 50% lethal concentrations (LC) of HCQ and CQ at 96 h post-fertilization (hpf) were calculated by testing various concentrations on 2,160 embryos.

Abamectin promotes behavior changes and liver injury in zebrafish.

The indiscriminate use of pesticides is a worldwide concern due to the environment contamination since it can cause deleterious effects to non-target organisms including the fishes. The effects of abamectin, a pesticide from the avermectin family, were evaluated in adult zebrafish (Danio rerio) after exposure to a commercial formula commonly used in Brazil. The animals were submitted to acute (96 h) and to a short-term chronic exposure (15 days) of distinct concentrations of abamectin.

An investigation of the predominant structure of antibiotic azithromycin in chloroform solution through NMR and thermodynamic analysis.

Azithromycin (AZM) is a well-known macrolide-type antibiotic that has been used in the treatment of infections and inflammations. Knowledge of the predominant molecular structure in solution is a prerequisite for an understanding of the interactions of the drug in biological media. Experimental structural determination can be carried out for samples in solid-state (X-ray diffraction technique) and gas phase (electron diffraction experiment).

The role of tridentate ligands on the redox stability of anticancer gold(III) complexes.

Gold(III) complexes are promising compounds for cancer chemotherapy, whose action depends on their redox stability. In this context, the choice of ligands is crucial to adjust their reactivity and biological response. The present study addressed the effect of the gold coordination sphere on the reduction potential (E) for ten gold(III) complexes containing five or six-membered rings tridentate ligands - [Au(trident)Cl] (trident = N^N^N, C^N^N, C^C^N, C^N^C, and N^C^N).

Computational Prediction of Tc-99 NMR Chemical Shifts in Technetium Complexes with Radiopharmaceutical Applications.

The Tc-99m nucleus is the most used nuclide in radiopharmaceuticals designed for imaging diagnosis. The metal can exist in nine distinct oxidation states and forms distinct coordination complexes with a variety of chelating agents and geometries. These complexes are usually characterized through Tc-99 NMR that is very sensitive to the Tc coordination sphere.

Solvent Dependent Competitive Mechanisms for the Ugi Multicomponent Reaction: A Joint Theoretical and Experimental Study in the α-Acyl Aminocarboxamides vs α-Amino Amidines Formation.

A synthetic protocol for the preparation of α-acyl aminocarboxamides and α-amino amidines is proposed. The selectivity toward each of these two possible products was tuned by simple modifications of the reaction conditions. A broad scope is presented, allowing access to the desired products in up to 87% (Ugi adduct) and 93% (α-amino amidine).

Analysis of Pleurotin binding to human thioredoxin reductase using docking and molecular dynamics simulation.

Thioredoxin reductase (TrxR) has been considered a potential target for cancer chemotherapy. It acts by controlling the redox homeostasis of human cells and, therefore, interfering in its function may trigger apoptosis, which is a crucial tumor suppression mechanism. Despite the great effort in the search for TrxR inhibitors, none was approved for human therapy.

Unveiling the Releasing Processes of Pt(II)-Based Anticancer Drugs from Oxidized Carbon Nanohorn: An In Silico Study.

About half of all cancer chemotherapies currently applied involve medication with the three worldwide approved Pt(II)-based drugs, cisplatin (cddp), carboplatin (cpx), and oxaliplatin (oxa), due to their notable antitumor activity for several cancers. However, this wide application is accompanied by severe side effects, such as nephrotoxicity, myelosuppression, and neurotoxicity, as a result of their low bioavailability and selectivity for cancer cells. To mitigate these drawbacks, the use of chemically functionalized carbon nanohorns (CNH) as nanocarriers represents a potential formulation since CNH has been noted for their biodegradability, biocompatibility, low toxicity, and cavities dimensionally compatible with small drugs.

Records and altitudinal assessment of Amblyomma aureolatum and Amblyomma ovale (Acari: Ixodidae) in the State of Rio de Janeiro, southeast Brazil.

Information on the altitudinal distribution of the hard ticks Amblyomma aureolatum and Amblyomma ovale in Brazil is scarce and mainly limited to occasional records. In this study we report our evaluation of records on the altitudinal distribution of A. aureolatum and A.

Effect of Fe on Na,K-ATPase: Unexpected activation of ATP hydrolysis.

Iron is a key element in cell function; however, its excess in iron overload conditions can be harmful through the generation of reactive oxygen species (ROS) and cell oxidative stress. Activity of Na,K-ATPase has been shown to be implicated in cellular iron uptake and iron modulates the Na,K-ATPase function from different tissues. In this study, we determined the effect of iron overload on Na,K-ATPase activity and established the role that isoforms and conformational states of this enzyme has on this effect.

Vibrational frequencies and intramolecular force constants for cisplatin: assessing the role of the platinum basis set and relativistic effects.

The role of platinum basis set (PTBS) and relativistic effects for predicting the vibrational frequencies and intramolecular force constants for cisplatin are discussed. Nonrelativistic and relativistic computational protocols were built at B3LYP/PTBS/jorge-DZP/C-PCM and B3LYP-DKH2/PTBS/jorge-DZP-DKH/C-PCM levels, respectively, where 19 distinct PTBS were tested. As expected, the structural parameters were not very sensitive to the PTBS, however, the inclusion of relativistic effects improves the description of the cisplatin structure.

Origin of Enantioselectivity in Chiral Phosphoric-Acid-Catalyzed Azlactone Dynamic Kinetic Resolution.

Theoretical calculations, associated with control experiments, were carried out to gain insights into the mechanism and origin of enantioselectivity in the phosphoric-acid-catalyzed dynamic kinetic resolution of azlactones. The results revealed a Münchnone intermediate as the key species involved in the isomerization of azlactone rings. The developed model was successfully employed in the comprehension and prediction of enantioselectivity under diverse of reaction conditions, including alcoholysis and aminolysis protocols.