The Vibrio cholerae CBASS phage defence system modulates resistance and killing by antifolate antibiotics.

Toxic bacterial modules such as toxin-antitoxin systems hold antimicrobial potential, though successful applications are rare. Here we show that in Vibrio cholerae the cyclic-oligonucleotide-based anti-phage signalling system (CBASS), another example of a toxic module, increases sensitivity to antifolate antibiotics up to 10×, interferes with their synergy and ultimately enables bacterial lysis by these otherwise classic bacteriostatic antibiotics. Cyclic-oligonucleotide production by the CBASS nucleotidyltransferase DncV upon antifolate treatment confirms full CBASS activation under these conditions, and suggests that antifolates release DncV allosteric inhibition by folates.

Celastrol: A lead compound that inhibits SARS-CoV-2 replication, the activity of viral and human cysteine proteases, and virus-induced IL-6 secretion.

The global emergence of coronavirus disease 2019 (COVID-19) has caused substantial human casualties. Clinical manifestations of this disease vary from asymptomatic to lethal, and the symptomatic form can be associated with cytokine storm and hyperinflammation. In face of the urgent demand for effective drugs to treat COVID-19, we have searched for candidate compounds using in silico approach followed by experimental validation.

MG-: A Novel Galectin-3 Ligand with Antimelanoma Properties and Adjuvant Effects to Dacarbazine.

Melanoma is a highly metastatic and rapidly progressing cancer, a leading cause of mortality among skin cancers. The melanoma microenvironment, formed from the activity of malignant cells on the extracellular matrix and the recruitment of immune cells, plays an active role in the development of drug resistance and tumor recurrence, which are clinical challenges in cancer treatment. These tumoral metabolic processes are affected by proteins, including Galectin-3 (Gal-3), which is extensively involved in cancer development.

Ruthenium (II) complex cis-[Ru(ŋ-OCCHO)(dppm)]PF-hmxbato induces ROS-mediated apoptosis in lung tumor cells producing selective cytotoxicity.

Ruthenium complexes have been extensively explored as potential molecules for cancer treatment. Considering our previous findings on the remarkable cytotoxic activity exhibited by the ruthenium (II) complex 3-hydroxy-4-methoxybenzoate (hmxbato)-cis-[Ru(ŋ-OCCHO)(dppm)]PF against Leishmania promastigotes and also the similar metabolic characteristics between trypanosomatids and tumor cells, the present study aimed to analyze the anticancer potential of hmxbato against lung tumor cells, as well as the partial death mechanisms involved. Hmxbato demonstrated selective cytotoxicity against A549 lung tumor cells.

A Synthetic Snake-Venom-Based Tripeptide Protects PC12 Cells from the Neurotoxicity of Acrolein by Improving Axonal Plasticity and Bioenergetics.

The synthetic peptide p-BTX-I is based on the native peptide (formed by glutamic acid, valine and tryptophan) isolated from Bothrops atrox venom. We have previously demonstrated its neuroprotective and neurotrophic properties in PC12 cells treated with the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP+). Now, we have investigated the neuroprotective effects and mechanisms of p-BTX-I against the toxicity of acrolein in PC12 cells.

Time of copulation during estrus period on estrus duration and LH response in Boer goats.

The objectives of this investigation were to determine the effect of the time of copulation during the estrus period on estrus duration and luteinizing hormone (LH) response in goats. A controlled randomized study with two replicates (first = n = 12; second = n = 24), in which Boer does were divided at each replicate into three groups, was performed. Copulations at the beginning of estrus (two copulas within the first 4 h after estrus; COP-1; n = 12), copulations around the middle of estrus (two copulas around 16 h after estrus; COP-2; n = 12), and noncopulations (only mounts) throughout the estrus period (control group; CON; n = 12) were performed.

Effect of copulation on estrus duration, LH response, and ovulation in Boer goats.

The objectives of this investigation were to determine the effect of copulation on estrus duration, LH response and ovulation in Boer goats. A controlled randomized study, with two replicates, in which does were divided at each replicate in treatment (COP; n = 12) and control (CON; n = 12) groups was performed. All the does were pluriparous and estrus synchronized with CIDR (progesterone 300 mg) maintained in the vagina for seven days, and received 50 μg of GnRH at device insertion and 5 mg of natural prostaglandin F-2 im at CIDR removal.

Analysis of the effects of mesoporous silica particles SBA-15 and SBA-16 in Streptococcus pneumoniae transformation process.

Streptococcus pneumoniae are natural competent bacteria which requires the presence of a pheromone-like molecule to do the transformation process. This study verified the influence of mesoporous silica (SBA-15 and SBA-16) on the transformation process in S. pneumoniae using a donor DNA obtained from a mutant strain of this microorganism (Sp360∆luxS).

CR-LAAO causes genotoxic damage in HepG2 tumor cells by oxidative stress.

Snake venom L-amino acid oxidases (SV-LAAOs) are enzymes of great interest in research due to their many biological effects with therapeutic potential. CR-LAAO, an L-amino acid oxidase from Calloselasma rhodostoma snake venom, is a well described SV-LAAO with immunomodulatory, antiparasitic, microbicidal, and antitumor effects. In this study, we evaluated the genotoxic potential of this enzyme in human peripheral blood mononuclear cells (PBMC) and HepG2 tumor cells, as well as its interaction with these cells, its impact on the expression of DNA repair and antioxidant pathway genes, and reactive oxygen species (ROS)-induced intracellular production.

Pubertal Escape From Estradiol Negative Feedback in Ewe Lambs Is Not Accounted for by Decreased ESR1 mRNA or Protein in Kisspeptin Neurons.

In this study, we investigated whether decreased sensitivity to estradiol negative feedback is associated with reduced estrogen receptor α (ESR1) expression in kisspeptin neurons as ewe lambs approach puberty. Lambs were ovariectomized and received no implant (OVX) or an implant containing estradiol (OVX+E). In the middle arcuate nucleus (mARC), ESR1 messenger RNA (mRNA) was greater in OVX than OVX+E lambs but did not differ elsewhere.

Interaction of dietary energy source and body weight gain during the juvenile period on metabolic endocrine status and age at puberty in beef heifers.

Using a previously established model for nutritional acceleration of puberty, beef heifers ( = 48; 1/2 Angus × 1/4 Hereford × 1/4 Brahman) were used in a replicated 2 × 2 factorial design to examine the effects of diet type (high forage [HF] vs. high concentrate [HC]) and rate of BW gain (low gain [LG], 0.45 kg/d, vs.

Nutritional programming of accelerated puberty in heifers: alterations in DNA methylation in the arcuate nucleus.

High rates of body weight gain during the juvenile period appear to program molecular events within the hypothalamus, leading to advancement of puberty. Methylation of DNA, an epigenetic mechanism that controls gene expression, is associated with metabolic programming events and is proposed to play a role in the pubertal process. In this study, DNA methylation was assessed in genomic DNA obtained from the arcuate nucleus (ARC) of juvenile heifers fed to gain body weight at low (0.

Onset of luteolytic action of exogenous prostaglandinF-2α during estrous cycle in goats.

The objectives of these two experiments were to determine the day of onset of luteolysis after exogenous PGF-2α administration during the estrous cycle and the fertility of this synchronized estrus in goats. In the first experiment, during the breeding season, 48 Nubian does were estrous synchronized, using intravaginal sponges impregnated with a progestin, and estrus was detected by vasectomized bucks. The does were divided at random into three groups of 16 does each to be treated at days 2, 3, and 4 of the estrous cycle (estrus = day 0).

Evaluation of the influence of prenatal transportation stress on GnRH-stimulated luteinizing hormone and testosterone secretion in sexually mature Brahman bulls.

This study examined the relationship of prenatal transportation stress (PNS) with exogenous GnRH-induced LH and testosterone secretion in sexually mature Brahman bulls. Brahman cows (n = 96; 48 were stressed by transportation at 5 stages of gestation and 48 were controls) produced a calf crop of 85 calves. All bulls (n = 46) from this calf crop were electroejaculated every 2 wk beginning at a scrotal circumference of 24 cm until sexual maturity (SM; i.

Impurity profiling of l-asparagine monohydrate by ion pair chromatography applying low wavelength UV detection.

l-asparagine is a non-essential amino acid being used for a variety of pharmaceutical applications. The compound may be produced following synthetic or fermentative pathways leading to the formation of distinct impurities such as organic acids, other amino acids, dipeptides, or cyclic amino acid derivatives. Analysis of the respective analytes is challenging due to the lack of a chromophore, thus the monograph of the European Pharmacopoeia describes a thin layer chromatographic test for detection of other amino acids.

κ-Opioid Receptor Is Colocalized in GnRH and KNDy Cells in the Female Ovine and Rat Brain.

Kisspeptin-neurokinin B-dynorphin (KNDy) cells of the hypothalamus are a key component in the neuroendocrine regulation of GnRH secretion. Evidence in sheep and other species suggests that dynorphin released by KNDy cells inhibits pulsatile GnRH secretion by acting upon κ-opioid receptors (KOR). However, the precise anatomical location and neurochemical phenotype of KOR-expressing cells in sheep remain unknown.

Continuous presence of male on estrus onset, estrus duration, and ovulation in estrus-synchronized Boer goats.

The objectives of the present study were to assess the effect of permanent contact of teasers without copulation on the interval from controlled internal drug release (CIDR) removal to estrus onset, estrus duration, ovulation time, number of ovulations, and interval from CIDR removal to ovulation time on estrus-synchronized Boer goats. During the fall season, a controlled randomized design experiment with two groups, control (CON; n = 18) and treatment (TRE; n = 18), was performed. The TRE group was maintained permanently in a pen with an aproned buck immediately after CIDR removal.

Effect of copulation on estrus duration and ovulation time in goats.

The objective of the present study was to evaluate the effect of copulation on estrus duration and ovulation in goats. During the fall season, 14 multiparous Boer does were estrous synchronized with controlled internal drug release (300 mg), maintained in the vagina for 7 days, and received 50 μg of intramuscular GnRH device insertion and 5 mg of natural intramuscular PGF2α at device removal. The does were randomly divided into two equal groups: a treatment group (TRE; n = 7) and a control group (CON; n = 7).

Pathogen- and Host-Directed Antileishmanial Effects Mediated by Polyhexanide (PHMB).

Background: Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoan parasites of the genus Leishmania. CL causes enormous suffering in many countries worldwide. There is no licensed vaccine against CL, and the chemotherapy options show limited efficacy and high toxicity.

Nutritional Programming of Accelerated Puberty in Heifers: Involvement of Pro-Opiomelanocortin Neurones in the Arcuate Nucleus.

The timing of puberty and subsequent fertility in female mammals are dependent on the integration of metabolic signals by the hypothalamus. Pro-opiomelanocortin (POMC) neurones in the arcuate nucleus (ARC) comprise a critical metabolic-sensing pathway controlling the reproductive neuroendocrine axis. α-Melanocyte-stimulating hormone (αMSH), a product of the POMC gene, has excitatory effects on gonadotrophin-releasing hormone (GnRH) neurones and fibres containing αMSH project to GnRH and kisspeptin neurones.

Short communication: Insertion of an intravaginal progesterone device at the time of gonadotropin-releasing hormone (GnRH) injection affects neither GnRH-induced release of luteinizing hormone nor development of dominant follicle in early diestrus of lactating dairy cows.

Our objectives were to evaluate the acute effects of a controlled internal drug release (CIDR) insert containing 1.38 g of progesterone (P4) on the release of LH, follicular growth, and circulating concentrations of P4 in cows treated with GnRH at the time of CIDR insertion. Nonpregnant, lactating dairy cows (n=27) were blocked by parity, predicted 305-d mature-equivalent milk production, and body condition score and randomly assigned to 1 of 3 treatments: (1) CIDR insertion concurrent with an injection of 200 µg of GnRH (n=10; 2GP4); (2) CIDR insertion concurrent with an injection of 100 µg of GnRH (n=10; 1GP4); and (3) injection of 100 µg of GnRH (n=7; CON).

Elevated body weight gain during the juvenile period alters neuropeptide Y-gonadotropin-releasing hormone circuitry in prepubertal heifers.

Increased body weight (BW) gain during the juvenile period leads to early maturation of the reproductive neuroendocrine system. We investigated whether a nutritional regimen that advances the onset of puberty leads to alterations in the hypothalamic neuropeptide Y (NPY) circuitry that are permissive for enhanced gonadotropin-releasing hormone (GnRH) secretion. It was hypothesized that NPY mRNA and NPY projections to GnRH and kisspeptin neurons are reduced in heifers that gain BW at an accelerated rate, compared with a lower one, during the juvenile period.

Reciprocal changes in leptin and NPY during nutritional acceleration of puberty in heifers.

Feeding a high-concentrate diet to heifers during the juvenile period, resulting in increased body weight (BW) gain and adiposity, leads to early-onset puberty. In this study, we tested the hypothesis that the increase in GnRH/LH release during nutritional acceleration of puberty is accompanied by reciprocal changes in circulating leptin and central release of neuropeptide Y (NPY). The heifers were weaned at 3.

Temporal changes in histomorphology and gene expression in goat testes during postnatal development.

Testicular cell proliferation and differentiation is critical for development of normal testicular function and male reproductive maturity. The objective of the current study was to evaluate histoarchitecture and expression of genes marking specific cells and important functions as well as testosterone production of the developing goat testes. Testes were harvested from Alpine bucks at 0, 2, 4, 6, and 8 mo of age (n = 5/age group).

Reproduction Symposium: hypothalamic neuropeptides and the nutritional programming of puberty in heifers.

Nutrition during the juvenile period has a major impact on timing reproductive maturity in heifers. Restricted growth delays puberty, whereas elevated BW gain advances the onset of puberty. The initiation of high-frequency episodic release of GnRH and, consequently, LH during the peripubertal period is crucial for maturation of the reproductive axis and establishment of normal estrous cycles.