Assessing azithromycin's ecological toll: Unveiling multifaceted impacts on Poecilia reticulata THROUGH biomarker analysis.

This study investigates the impact of environmentally relevant concentrations of azithromycin on Poecilia reticulata, through biomarkers at different levels. To this end, the somatic indexes of P. reticulata were evaluated, and liver and gill samples were collected and analyzed for biochemical and histopathological alterations.

The Role of Biomedical and Pharmaceutical Sciences in Pharmacy Education and Practice.

A current major topic of conversation in academic pharmacy is "curricular hoarding," the overloading of the curriculum due to the steady addition of required knowledge and skills without a concomitant subtraction of existing content. It can be tempting to consider addressing hoarding by just reducing content in the foundational biomedical and pharmaceutical sciences or by shifting some foundational content into prerequisites for admission into the Doctor of Pharmacy program. The health care education literature suggests that this approach would negatively impact the development of the critical and clinical thinking skills needed by a modern pharmacist.

The Enigma of Transcriptional Activation Domains.

Activation domains (ADs) of eukaryotic gene activators remain enigmatic for decades as short, extremely variable sequences which often are intrinsically disordered in structure and interact with an uncertain number of targets. The general absence of specificity increasingly complicates the utilization of the widely accepted mechanism of AD function by recruitment of coactivators. The long-standing enigma at the heart of molecular biology demands a fundamental rethinking of established concepts.

Time-efficient germ cell transplantation from goldfish () into adult common carp ().

Germ cell transplantation in fish is a promising technique for surrogate broodstock parents with broader application in aquaculture and conserving endangered and valuable genetic resources. Herein, we describe the establishment of an intrapapillary xenogeneic transplant of germ cells from sexually mature goldfish () males into common carp () males cytoablated with a thermochemical treatment (two doses of busulfan at 40 mg/kg at 35°C). To analyze the presence and development of donor germ cells in recipient testes, donor germ cells were labeled with PKH26, a fluorescent cell membrane dye, before transplantation.

Characterization and enrichment of spermatogonial stem cells of common carp (Cyprinus carpio).

Spermatogenesis is a systematically organized process that ensures uninterrupted sperm production in which the spermatogonial stem cells (SSCs) play a crucial role. However, the existing absence of teleost-specific molecular markers for SSCs presents a notable challenge. Herein we characterized phenotypically the spermatogonial stem cells using specific molecular markers and transmission electron microscopy.

Thyroid axis participates in high-temperature-induced male sex reversal through its activation by the stress response.

Environmental changes alter the sex fate in about 15% of vertebrate orders, mainly in ectotherms such as fish and reptiles. However, the effects of temperature changes on the endocrine and molecular processes controlling gonadal sex determination are not fully understood. Here, we provide evidence that thyroid hormones (THs) act as co-players in heat-induced masculinization through interactions with the stress axis to promote testicular development.

The First Anti-Snakebite and Hepatoprotective Characterization of a Trypsin Kunitz-like Inhibitor (EcTI) from the Plant A Case of Two Soul Mates Meeting.

Snake venom serine protease (SVSP) interferes with the regulation and control of important biological reactions in homeostasis and can be classified as an activator of the fibrinolytic system and platelet aggregation. Our group has recently isolated a new serine protease from total venom (Cdtsp-2). This protein exhibits edematogenic capacity and myotoxic activity.

In Silico Evaluation of Quercetin Methylated Derivatives on the Interaction with Secretory Phospholipases A2 from and .

Quercetin derivatives have already shown their anti-inflammatory potential, inhibiting essential enzymes involved in this process. Among diverse pro-inflammatory toxins from snake venoms, phospholipase A2 is one of the most abundant in some species, such as and from the Viperidae family. These enzymes can induce the inflammatory process through hydrolysis at the sn-2 position of glycerophospholipids.

Exploring functional and structural features of chemically related natural prenylated hydroquinone and benzoic acid from Piper crassinervium (Piperaceae) on bacterial peroxiredoxin inhibition.

Multiple drug resistance (MDR) bacterial strains are responsible by 1.2 million of human deaths all over the world. The pathogens possess efficient enzymes which are able to mitigate the toxicity of reactive oxygen species (ROS) produced by some antibiotics and the host immune cells.

Adenanthin Is an Efficient Inhibitor of Peroxiredoxins from Pathogens, Inhibits Bacterial Growth, and Potentiates Antibiotic Activities.

The emergence and re-emergence of bacterial strains resistant to multiple drugs represent a global health threat, and the search for novel biological targets is a worldwide concern. AhpC are enzymes involved in bacterial redox homeostasis by metabolizing diverse kinds of hydroperoxides. In pathogenic bacteria, AhpC are related to several functions, as some isoforms are characterized as virulence factors.

Gallic Acid as a Non-Selective Inhibitor of α/β-Hydrolase Fold Enzymes Involved in the Inflammatory Process: The Two Sides of the Same Coin.

(1) Background: Gallic acid (GA) has been characterized as an effective anti-inflammatory, antivenom, and promising drug for therapeutic use. (2/3) Methods and Results: GA was identified from ethanolic extract of fresh pitanga () leaves, which was identified using commercial GA. Commercial GA neutralized the enzymatic activity of secretory PLA2 (sPLA2) by inhibiting the active site and inducing changes in the secondary structure of the enzyme.

Developing an international industrial advanced pharmacy practice experience in Brazil.

Introduction: In this commentary, we advocate for implementing international industry-focused advanced pharmacy practice experiences (APPEs) that engage pharmacy students and schools with the pharmaceutical industry to develop products for the global market to broaden pharmacy student experiences in non-patient care electives.

Commentary: Our five-year experience suggests the following structural components are essential to the success of the APPE: (1) identification of suitable international industry partners through non-traditional methods, such as the local, United States (US) chamber of commerce; (2) commitment by the company and educational institutions to develop key personnel to work with international students in the host country; (3) development of a global regulatory affairs course and workshops that target the product development stage; (4) development of student experiences based on projects directly linked to a new product(s); (5) use of technology platforms to support weekly video conferencing and translation; (6) engagement of students in community service; (7) cooperative evaluation of students and the program. The aggregate of student projects led to the development of a line of dietary supplement products introduced to the US market.

Relevance of peroxiredoxins in pathogenic microorganisms.

The oxidative and nitrosative responses generated by animals and plants are important defenses against infection and establishment of pathogenic microorganisms such as bacteria, fungi, and protozoa. Among distinct oxidant species, hydroperoxides are a group of chemically diverse compounds that comprise small hydrophilic molecules, such as hydrogen peroxide and peroxynitrite, and bulky hydrophobic species, such as organic hydroperoxides. Peroxiredoxins (Prx) are ubiquitous enzymes that use a highly reactive cysteine residue to decompose hydroperoxides and can also perform other functions, like molecular chaperone and phospholipase activities, contributing to microbial protection against the host defenses.

Effects of Serine or Threonine in the Active Site of Typical 2-Cys Prx on Hyperoxidation Susceptibility and on Chaperone Activity.

Typical 2-Cys peroxiredoxins (2-Cys Prx) are ubiquitous Cys-based peroxidases, which are stable as decamers in the reduced state, and may dissociate into dimers upon disulfide bond formation. A peroxidatic Cys (C) takes part of a catalytic triad, together with a Thr/Ser and an Arg. Previously, we described that the presence of Ser (instead of Thr) in the active site stabilizes yeast 2-Cys Prx as decamers.

Expression patterns of peroxiredoxin genes in bronchial epithelial cells exposed to diesel exhaust particles.

Several mechanisms have been suggested to explain the adverse effects of air pollutants on airway cells. One such explanation is the presence of high concentrations of oxidants and pro-oxidants in environmental pollutants. All animal and plant cells have developed several mechanisms to prevent damage by oxidative molecules.

Molecular characterization and expression analysis of anti-Müllerian hormone in common carp (Cyprinus carpio) adult testes.

Anti-Müllerian hormone (Amh) is a member of the transforming growth factor-β (Tgf-β) superfamily required in the regression of Müllerian ducts during gonadal sex differentiation of higher vertebrates. Teleost fish lack Müllerian ducts, but identified Amh orthologs have been shown to exert crucial functions during sex determination and differentiation of several species of teleosts. However, the function of Amh during gametogenesis in adult fish remains poorly investigated.

Structural and functional diversity of asparaginases: Overview and recommendations for a revised nomenclature.

Asparaginases (ASNases) are a large and structurally diverse group of enzymes ubiquitous amongst archaea, bacteria and eukaryotes, that catalyze hydrolysis of asparagine to aspartate and ammonia. Bacterial ASNases are important biopharmaceuticals for the treatment of acute lymphoblastic leukemia, although some patients experience adverse allergic side effects during treatment with these protein therapeutics. ASNases are currently divided into three families: plant-type ASNases, Rhizobium etli-type ASNases and bacterial-type ASNases.

RADSex: A computational workflow to study sex determination using restriction site-associated DNA sequencing data.

The study of sex determination and sex chromosome organization in nonmodel species has long been technically challenging, but new sequencing methodologies now enable precise and high-throughput identification of sex-specific genomic sequences. In particular, restriction site-associated DNA sequencing (RAD-Seq) is being extensively applied to explore sex determination systems in many plant and animal species. However, software specifically designed to search for and visualize sex-biased markers using RAD-Seq data is lacking.

Influence of lysosomal protease sensitivity in the immunogenicity of the antitumor biopharmaceutical asparaginase.

L-asparaginase (ASNase) from Escherichia coli (EcAII) is used in the treatment of acute lymphoblastic leukaemia (ALL). EcAII activity in vivo has been described to be influenced by the human lysosomal proteases asparaginyl endopeptidase (AEP) and cathepsin B (CTSB); these hydrolases cleave and could expose epitopes associated with the immune response against EcAII. In this work, we show that ASNase resistance to CTSB and/or AEP influences the formation of anti-ASNase antibodies, one of the main causes of hypersensitivity reactions in patients.

The Human Pathogen Has a Unique 1-Cys Peroxiredoxin That Localizes Both Intracellularly and at the Cell Surface.

is a temperature-dependent dimorphic fungus that causes systemic paracoccidioidomycosis, a granulomatous disease. The massive production of reactive oxygen species (ROS) by the host's cellular immune response is an essential strategy to restrain the fungal growth. Among the ROS, the hydroperoxides are very toxic antimicrobial compounds and fungal peroxidases are part of the pathogen neutralizing antioxidant arsenal against the host's defense.

Heavy metal concentrations in Brazilian port areas and their relationships with microorganisms: can pollution in these areas change the microbial community?

The objectives of this study were to analyze the difference in ways in which metals polluting Brazilian port areas influence bacterial communities and the selection of resistant strains. The hypothesis tested was that port areas would have microbial communities significantly different from a pristine area, mainly due to a greater load of metals found in these areas. Sediment samples were collected in two port areas (Santos and São Sebastião) and one pristine area (Ubatuba).

Functional and structural evaluation of the antileukaemic enzyme L-asparaginase II expressed at low temperature by different Escherichia coli strains.

Acute lymphoblastic leukaemia (ALL) affects lymphoblastic cells and is the most common neoplasm during childhood. Among the pharmaceuticals used in the treatment protocols for ALL, Asparaginase (ASNase) from Escherichia coli (EcAII) is an essential biodrug. Meanwhile, the use of EcAII in neoplastic treatments causes several side effects, such as immunological reactions, hepatotoxicity, neurotoxicity, depression, and coagulation abnormalities.

Reduction of sulfenic acids by ascorbate in proteins, connecting thiol-dependent to alternative redox pathways.

Sulfenic acids are the primary product of thiol oxidation by hydrogen peroxide and other oxidants. Several aspects of sulfenic acid formation through thiol oxidation were established recently. In contrast, the reduction of sulfenic acids is still scarcely investigated.

Thiol Peroxidases as Major Regulators of Intracellular Levels of Peroxynitrite in Live Cells.

Thiol peroxidases (TP) are ubiquitous and abundant antioxidant proteins of the peroxiredoxin and glutathione peroxidase families that can catalytically and rapidly reduce biologically relevant peroxides, such as hydrogen peroxide and peroxynitrite. However, the TP catalytic cycle is complex, depending on multiple redox reactions and partners, and is subjected to branching and competition points that may limit their peroxide reductase activity in vivo. The goals of the present study were to demonstrate peroxynitrite reductase activity of TP members in live cells in real time and to evaluate its catalytic characteristics.