Antimicrobial peptides in livestock: a review with a one health approach.

Antimicrobial peptides (AMPs), often referred to as nature's antibiotics, are ubiquitous in living organisms, spanning from bacteria to humans. Their potency, versatility, and unique mechanisms of action have garnered significant research attention. Unlike conventional antibiotics, peptides are biodegradable, adding to their appeal as potential candidates to address bacterial resistance in livestock farming-a challenge that has been under scrutiny for decades. This issue is complex and multifactorial, influenced by a variety of components. The World Health Organization (WHO) has proposed a comprehensive approach known as One Health, emphasizing the interconnectedness of human-animal-environment relationships in tackling such challenges. This review explores the application of AMPs in livestock farming and how they can mitigate the impact of this practice within the One Health framework.

The role of ETFS amino acids on the stability and inhibition of p53-MDM2 complex of anticancer p53-derivatives peptides: Density functional theory and molecular docking studies.

Cancer is one of the leading causes of mortality in the world. Despite the existence of diverse antineoplastic treatments, these do not possess the expected efficacy in many cases. Knowledge of the molecular mechanisms involved in tumor processes allows the identification of a greater number of therapeutic targets employed in the study of new anticancer drugs. In the last decades, peptide-based therapy design using computational chemistry has gained importance in the field of oncology therapeutics. This work aims to evaluate the electronic structure, physicochemical properties, stability, and inhibition of ETFS amino acids and peptides derived from the p53-MDM2 binding domain with action in cancer cells; by means of chemical descriptors at the DFT-BHandHLYP level in an aqueous solution, and its intermolecular interactions through molecular docking studies. The results show that The ETFS fragment plays a critical role in the intermolecular interactions. Thus, the amino acids E17, T18 and S20 increase intermolecular interactions through hydrogen bonds and enhance structural stability. F19, W23 and V25 enhance the formation of the alpha-helix. The hydrogen bonds formed by the backbone atoms for PNC-27, PNC-27-B and PNC-28 stabilize the α-helices more than hydrogen bonds formed by the side chains atoms. Also, molecular docking indicated that the PNC27B-MDM2, PNC28B-MDM2, PNC27-MDM2 and PNC28A-MDM2 complexes show the best binding energy. Therefore, DFT and molecular docking studies showed that the proposed peptides: PNC-28B, PNC-27B and PNC-28A could inhibit the binding of MDM2 to the p53 protein, decreasing the translocation and degradation of p53 native protein.

Crystal polymorphism and spectroscopical properties of sulfonamides in solid state by means of First Principles calculations.

Sulfonamides are an important class of therapeutic agents. The increase in the number of new sulfonamide derivatives makes it necessary to study more rationally the chemical structure, because the solid forms often display different mechanical, thermal and physicochemical properties that can influence the bioavailability and stability of the drugs; consequently, the polymorphic structures are of great interest to the pharmaceutical industry because of their ability to modify the physical properties of the active pharmaceutical ingredient. The molecular interactions of these drugs in their crystal lattice are important for the stability of the crystals and polymorphism and for preparing composite complexes for optimizing the use of these drugs. In this work, the crystal structure of these drugs and crystal polymorphism is investigated. So, the crystal forms of antibiotics derivatives of the sulfonamides, sulfamethoxazole, sulfamethazine, sulfachloropyridazine, and sulfacetamide are studied at the molecular and supramolecular level by using computational modeling approach at quantum mechanical level. The spectroscopic properties of these systems are also studied explaining assignments of previous experimental data. The results of DFT calculations reproduce the crystal structures of sulfonamides determined experimentally and the polymorphism in these molecules have been clarified. Likewise, the main intermolecular interactions in all crystal forms of these sulfonamides are H-bonds among the sulfonic and amino groups and SNH groups, and also some π-π interactions. Also, these 3-D periodical models allow the exploration of the intermolecular interactions included in the crystal structures and some of these interactions can alter the vibration modes of the molecules. Therefore, the use of these models can be useful for experimental spectroscopy studies where use actual crystal solids.

In silico tools to study molecular targets of neglected diseases: inhibition of TcSir2rp3, an epigenetic enzyme of Trypanosoma cruzi.

There is a growing interest to study and address neglected tropical diseases (NTD). To this end, in silico methods can serve as the bridge that connects academy and industry, encouraging the development of future treatments against these diseases. This chapter discusses current challenges in the development of new therapies, available computational methods and successful cases in computer-aided design with particular focus on human trypanosomiasis. Novel targets are also discussed. As a case study, we identify amentoflavone as a potential inhibitor of TcSir2rp3 (sirtuine) from Trypanosoma cruzi (20.03 µM) with a workflow that integrates chemoinformatic approaches, molecular modeling, and theoretical affinity calculations, as well as in vitro assays.

Genetic structure analysis of Amblyomma mixtum populations in Veracruz State, Mexico.

Amblyomma mixtum Koch, 1844 parasitizes livestock, humans, and wildlife in Mexico. However, information on population genetics for this tick species in the country is missing. Tick samples were collected from livestock in ten regions across the state of Veracruz (22°28'N, 17°09'S, 93°36'E, 98°39'W) to analyze the genetic structure of A. mixtum populations. Ticks were morphologically identified using taxonomic keys. In order to test the intra-specific variability of A. mixtum fragments of the mitochondrial gene 16S-rRNA and cytochrome oxidase subunit 1 (COI) were amplified. Ninety-six sequences were amplified from the 50 specimens' analyzed (96% amplification success). Eleven haplotypes were detected in 16S-rRNA gene and 10 more for COI. Neutrality tests showed negative results in most of the locations analyzed, which is indicative of an excess of recently derived haplotypes. However, these results were not statistically significant. Minimal union network analysis revealed that there is no separation of populations by geography, and that there is an overlap of several haplotypes among diverse populations. Significant genetic differentiation was not detected in the A. mixtum populations sampled in the state of Veracruz, Mexico, this may be due to the frequent movement of livestock hosts. This is the first report on the genetic structure of A. mixtum populations in Mexico.

Computational study of substituent effects on the acidity, toxicity and chemical reactivity of bacteriostatic sulfonamides.

Relationships among physicochemical properties, the chemical structure and antibacterial activity of sulfonamides have not been completely explicated yet. Nevertheless, from a therapeutics and prodrugs design point of view, a substituent group can modify the electronic structure, the physicochemical features and chemical reactivity which are critical for the biological activity. In this work, we analyze the substituent effects on the physicochemical properties, toxicity, chemical reactivity and its relation with the bacteriostatic activity of selected sulfonamides by means of DFT-M06-2X calculations in aqueous solution, using quantum chemical and docking descriptors. A correlation between the theoretical acidity and the pKa experimental values has been found. The more active sulfonamides have a larger acidity. The acidity increases with electron-withdrawing substituents. The main reactivity takes place on N4 atoms linked to aromatic ring, and in the SO2NH moiety, which are influenced by substituents. Docking descriptors showed binding affinities between sulfonamides and target receptor, the dihydropteroate synthase (DHPS).

Seroepidemiology of Infection with Neospora Caninum, Leptospira, and Bovine Herpesvirus Type 1 in Water Buffaloes (Bubalus Bubalis) in Veracruz, Mexico.

We aimed to determine the seroprevalence of infection with Neospora caninum, Leptospira, and bovine herpesvirus type 1 and risk factors associated with these infections in water buffaloes in Veracruz State, Mexico. Through a cross-sectional study, 144 water buffaloes (Bubalus bubalis) raised in 5 ranches of Veracruz were examined for anti-N. caninum and anti-bovine herpesvirus type 1 antibodies by enzyme immunoassays, and anti-Leptospira interrogans antibodies by microscopic agglutination test. Of the 144 buffaloes studied, 35 (24.3%) were positive for N. caninum, 50 (34.7%) for Leptospira, and 83 (57.6%) for bovine herpes virus. The frequencies of leptospiral serovars in buffaloes were as follows: 18.7% for Muenchen (n = 27), 10.4% for Hardjo LT (n = 15), 9.0% for Pyrogenes (n = 13), and 4.8% for Icterohaemorrhagiae (n = 7). Seropositive buffaloes were found in all 5 ranches studied. Logistic regression showed that cohabitation of buffaloes with cows was associated with infection with Leptospira (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.04-4.5; P = 0.03) and bovine herpesvirus (OR, 12.0; 95% CI, 4.0-36.2; P < 0.01). This is the first study that provides serological evidence of N. caninum, Leptospira, and bovine herpesvirus type 1 infections in water buffaloes in Mexico. Our findings could be used to enhance preventive measures against these infections.

A Comprehensive Proteomic Study of the Skin Secretions of the Frog Lithobates spectabilis.

Disulfide C-terminal loop fragments derived from AMPs and the presence of peptidases have been previously reported in the skin secretions of different amphibians. However, there are only a few studies on the identification of enzymes in frog skin secretion based on the primary structure of these proteins. Similarly, little data exist regarding the identification of disulfide C-terminal loops at large scale. Therefore, a comprehensive study on this issue certainly could bring in much more information for understanding this molecular process and its biochemical consequences. Thus, the aim of this work was to characterize the presence of disulfide C-terminal loop fragments of AMPs and identify the proteins and probable enzymes present in the completely unknown secretion contents of the frog Lithobates spectabilis. For this purpose, high-resolution mass spectrometry was applied to analyze the skin secretions processed by two different protocols: (1) using a cocktail of enzymatic inhibitors and 2) without any protease inhibitors, maintaining the solution for 2 hours at 10°C. Results from procedure-1, revealed 122 molecular masses, whereas procedure-2 permitted 253 different molecular masses to be identified. Fifty-nine peptides including 22 disulfide C-terminal loop-containing peptides were obtained following procedure-2. Polyacrylamide gel electrophoresis separation, tryptic digestion and LCMS/ MS were used for "de novo" sequencing of 111 different peptides and the unequivocal identification of fifteen proteins including at least three different peptidases. Additionally, it was possible to fully sequence eight peptides, including a ranatuerin-related peptide identified here as Spectabilin, that was subsequently chemically synthesized and showed high antibacterial, antiparasitic and cytotoxic activities.

Predominant information quality scheme for the essential amino acids: an information-theoretical analysis.

In this work we undertake a pioneer information-theoretical analysis of 18 selected amino acids extracted from a natural protein, bacteriorhodopsin (1C3W). The conformational structures of each amino acid are analyzed by use of various quantum chemistry methodologies at high levels of theory: HF, M062X and CISD(Full). The Shannon entropy, Fisher information and disequilibrium are determined to grasp the spatial spreading features of delocalizability, order and uniformity of the optimized structures. These three entropic measures uniquely characterize all amino acids through a predominant information-theoretic quality scheme (PIQS), which gathers all chemical families by means of three major spreading features: delocalization, narrowness and uniformity. This scheme recognizes four major chemical families: aliphatic (delocalized), aromatic (delocalized), electro-attractive (narrowed) and tiny (uniform). All chemical families recognized by the existing energy-based classifications are embraced by this entropic scheme. Finally, novel chemical patterns are shown in the information planes associated with the PIQS entropic measures.

Electronic structure evaluation through quantum chemical descriptors of 17ß-aminoestrogens with an anticoagulant effect.

17ß-aminoestrogens have been experimentally studied due to their anticoagulant effect, shown both in in vitro and in vivo assays; this is a non-typical behavior for steroids. The anticoagulant effect of these aminoestrogens has been related to the aromaticity of the A-ring of the steroid molecule; as well as to the length of the amino-alcohol side-chain at C17, which might have an influence on the biological activity of these compounds. The study of the electronic structure of 17ß-aminoestrogens using quantum chemical descriptors could provide significant information and may contribute to a better understanding of structure-activity relationships in these molecules. In this work, we present a density functional theory (DFT) study at the B3LYP level of theory for selected 17ß-aminoestrogens compounds, with the main purpose of characterizing their electronic and physicochemical properties and relating them to their anticoagulant effect, using quantum chemical descriptors such as: atomic charges, bond order, electrostatic potential isosurface analysis, hardness, electrophilicity and aromaticity indexes. The results obtained from these quantum chemical descriptors, led us to characterize the physicochemical properties, reactive sites and substituent influence on electronic structure, as well as to identify additional quantum chemical descriptors that could be associated with the anticoagulant effect of 17ß-aminoestrogens.

[Survival of patients with malignant astrocytomas according to the expression of Ki67 antigen in a pediatric hospital]. / Sobrevida de los pacientes con astrocitoma de alto grado que expresan el antígeno Ki67, atendidos en un hospital de pediatría.

BACKGROUND: Pediatric patients with malignant gliomas and same histological diagnosis respond distinctly to treatment. It is thus necessary to determine other factors that may influence the response to treatment and survival. Over expression of the Ki67 protein has been associated with poor treatment response. The aim of this study was to determine if the expression of this antigen influences survival of patients treated for malignant gliomas in the CMN SXXI Pediatrics Hospital. METHODS: We included patients with anaplasic astrocitoma or glioblastoma multiforme seen at our hospital between 1995 and 2005. We determined the expression of Ki67 by immunohistochemistry and correlated the findings with tumor histology and patient survival. RESULTS: Of the 21 patients studied, 12 overexpressed antigen Ki67. There was no significant association between over expression of Ki67 and survival, although we observed a clinical association. Over expression of Ki67 correlated with more aggressive histology. Being under the age of 11 was a poor prognostic factor. Overall survival was 49% at 120 months. CONCLUSIONS: Being young (under 11 years) is a marker of poor prognosis among pediatric patients with anaplasic astrocytoma or glioblastoma multiforme. Overexpression expression of antigen Ki67 is associated with histology and may be associated with poor survival among patients treated in our hospital.

Sobrevida de los pacientes con astrocitoma de alto grado que expresan el antígeno Ki67, atendidos en un hospital de pediatría / Survival of patients with malignant astrocytomas according to the expression of Ki67 antigen in a pediatric hospital

Antecedentes: Los pacientes pediátricos con astrocitomas de alto grado con mismas histologías presentan respuestas diferentes a idéntico tratamiento. Es necesario identificar los factores que influyen en el pronóstico y respuesta al mismo. La sobreexpresión de la proteína Ki67 se ha asociado con respuestas poco favorables. El objetivo fue determinar si la expresión de este antígeno influye en la sobrevida de los pacientes con astrocitoma de alto grado del Hospital de Pediatría del Centro Médico Nacional Siglo XXI. Métodos: Se incluyeron pacientes con astrocitoma anaplásico o glioblastoma multiforme atendidos entre 1995 y 2005. Por inmunohistoquímica se determinó la expresión del antígeno Ki67 en las muestras de tejido tumoral y se correlacionó con la histología tumoral y la sobrevida de los pacientes. Resultados: De 21 pacientes, 12 sobreexpresaron el antígeno Ki67. No se encontró asociación estadísticamente significativa entre la sobreexpresión del antígeno Ki67 y la sobrevida, aunque sí clínica. Se encontró asociación estadísticamente significativa entre la sobreexpresión del Ag Ki67 y el grado de malignidad del tumor. La edad menor de 11 años resultó un factor de mal pronóstico. La sobrevida global fue de 49 % a 120 meses. Conclusiones: La edad menor de 11 años fue un factor de mal pronóstico en los pacientes estudiados con astrocitoma o glioblastoma multiforme. La sobreexpresión del antígeno Ki67 está asociada con la histología y pareciera tener relación con la sobrevida de los pacientes pediátricos con astrocitoma.

BACKGROUND: Pediatric patients with malignant gliomas and same histological diagnosis respond distinctly to treatment. It is thus necessary to determine other factors that may influence the response to treatment and survival. Over expression of the Ki67 protein has been associated with poor treatment response. The aim of this study was to determine if the expression of this antigen influences survival of patients treated for malignant gliomas in the CMN SXXI Pediatrics Hospital. METHODS: We included patients with anaplasic astrocitoma or glioblastoma multiforme seen at our hospital between 1995 and 2005. We determined the expression of Ki67 by immunohistochemistry and correlated the findings with tumor histology and patient survival. RESULTS: Of the 21 patients studied, 12 overexpressed antigen Ki67. There was no significant association between over expression of Ki67 and survival, although we observed a clinical association. Over expression of Ki67 correlated with more aggressive histology. Being under the age of 11 was a poor prognostic factor. Overall survival was 49% at 120 months. CONCLUSIONS: Being young (under 11 years) is a marker of poor prognosis among pediatric patients with anaplasic astrocytoma or glioblastoma multiforme. Overexpression expression of antigen Ki67 is associated with histology and may be associated with poor survival among patients treated in our hospital.

Computational study of the electronic structure characterization of a novel anti-inflammatory tripeptide derived from monocyte locomotion inhibitory factor (MLIF)-pentapeptide.

The structure and properties of molecules are determined by their charge-density distribution. Several works have shown that electron delocalization along the peptide backbone and side-chain modulates the physical and chemical features of peptides and protein properties. Research on Entamoeba histolytica-soluble factors led to the identification of the pentapeptide Met-Gln-Cys-Asn-Ser, with anti-inflammatory in vivo and in vitro effects. A synthetic pentapeptide, Met-Pro-Cys-Asn-Ser, maintained the same anti-inflammatory actions in experimental assays. A previous theoretical study allowed proposing the Cys-Asn-Ser tripeptide (CNS tripeptide) as the pharmacophore group of both molecules. This theoretical hypothesis was recently confirmed experimentally. The aim of this study was to characterize the electronic structure and physico-chemical properties of the CNS tripeptide through a theoretical study at the second-order Møller-Plesset perturbation theory (MP2) and density functional theory (DFT) theoretical levels. Our results in deprotonation energies show that the hydrogen atom (H2) of the serine-amide group possesses acidic characteristics. This result was confirmed by means of a study of bond order. Atomic charges, dipole moment, frontier molecular orbitals (Highest occupied molecular orbital [HOMO-1] and Lowest unoccupied molecular orbital [LUMO+1]), and electrostatic potential isosurface and its geometric parameters permitted to characterize its electronic structure and physico-chemical features and to identify some reactive sites that could be associated with this tripeptide's anti-inflammatory activity.

Electronic structure and physicochemical properties characterization of the amino acids 12-26 of TP53: a theoretical study.

PNC-27, a synthetic peptide, is derived from the TP53-HDM2 binding domain that include TP53 amino acids 12-26 linked with 17 amino acids from the antennapedia protein transference domain. This peptide induces membrane rupture in tumor cells through toroidal pores formation and has motivated several experimental studies; nonetheless, its mechanism of biological action remains unknown to date. Herein, we present a theoretical study at the Hartree-Fock and density functional theory (B3LYP) levels of theory of TP53 protein residues 12-26 (PPLSQETFSDLWKLL) in order to characterize its electronic structure and physicochemical properties. Our results for atomic and group charges, fitted to the electrostatic potential (ESP) show important reactive sites (L14, S15, T18, S20, L25, and L26), suggesting that these amino acids are exposed to nucleophilic and electrophilic attacks. Analysis of bond orders, intramolecular interactions and of several global reactivity descriptors, such as ionization potentials, hardness, electrophilicity index, dipole moments, total energies, frontier molecular orbitals (HOMO-LUMO), and electrostatic potential, led us to characterize active sites and the electronic structure and physiochemical features that taken together may be important in understanding the specific selectivity for this peptides type's cancer-cell membrane lysis properties.