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1.
An Acad Bras Cienc ; 96(3): e20230680, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38985030

RESUMEN

Sahelanthropus tchadensis has raised much debate since its initial discovery in Chad in 2001, given its controversial classification as the earliest representative of the hominin lineage. This debate extends beyond the phylogenetic position of the species, and includes several aspects of its habitual behavior, especially in what regards its locomotion. The combination of ancestral and derived traits observed in the fossils associated with the species has been used to defend different hypotheses related to its relationship to hominins. Here, the cranial morphology of Sahelanthropus tchadensis was assessed through 16 linear craniometric measurements, and compared to great apes and hominins through Principal Component Analysis based on size and shape and shape information alone. The results show that S. tchadensis share stronger morphological affinities with hominins than with apes for both the analysis that include size information and the one that evaluates shape alone. Since TM 266-01-060-1 shows a strong morphological affinity with the remaining hominins represented in the analysis, our results support the initial interpretations that S. tchadensis represents an early specimen of our lineage or a stem basal lineage more closely related to hominins than to Panini.


Asunto(s)
Cefalometría , Fósiles , Hominidae , Cráneo , Animales , Hominidae/anatomía & histología , Hominidae/clasificación , Fósiles/anatomía & histología , Cráneo/anatomía & histología , Análisis de Componente Principal , Filogenia
2.
Nutrients ; 16(12)2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38931299

RESUMEN

Carpal tunnel syndrome (CTS) is the most common cause of peripheral compressive neuropathy and consists of compression of the median nerve in the wrist. Although there are several etiologies, idiopathic is the most prevalent origin, and among the forms of treatment for CTS, conservative is the most indicated. However, despite the high prevalence in and impact of this syndrome on the healthcare system, there are still controversies regarding the best therapeutic approach for patients. Therefore, noting that some studies point to vitamin D deficiency as an independent risk factor, which increases the symptoms of the syndrome, this study evaluated the role of vitamin D supplementation and its influence on pain control, physical examination and response electroneuromyography to conservative treatment of carpal tunnel syndrome. For this, the sample consisted of 14 patients diagnosed with CTS and hypovitaminosis D, who were allocated into two groups. The control group received corticosteroid treatment, while the experimental group received corticosteroid treatment associated with vitamin D. Thus, from this study, it can be concluded that patients who received vitamin D, when compared to those who did not receive it, showed improvement in the degree of pain intensity, a reduction in symptom severity and an improvement in some electroneuromyographic parameters.


Asunto(s)
Síndrome del Túnel Carpiano , Electromiografía , Deficiencia de Vitamina D , Vitamina D , Humanos , Síndrome del Túnel Carpiano/tratamiento farmacológico , Vitamina D/uso terapéutico , Femenino , Deficiencia de Vitamina D/tratamiento farmacológico , Deficiencia de Vitamina D/complicaciones , Masculino , Persona de Mediana Edad , Adulto , Resultado del Tratamiento , Suplementos Dietéticos , Corticoesteroides/administración & dosificación , Nervio Mediano/fisiopatología , Anciano
3.
J Med Chem ; 67(12): 10025-10034, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38848103

RESUMEN

Low-affinity protein-ligand interactions are important for many biological processes, including cell communication, signal transduction, and immune responses. Structural characterization of these complexes is also critical for the development of new drugs through fragment-based drug discovery (FBDD), but it is challenging due to the low affinity of fragments for the binding site. Saturation transfer difference (STD) NMR spectroscopy has revolutionized the study of low-affinity receptor-ligand interactions enabling binding detection and structural characterization. Comparison of relaxation and exchange matrix calculations with 1H STD NMR experimental data is essential for the validation of 3D structures of protein-ligand complexes. In this work, we present a new approach based on the calculation of a reduced relaxation matrix, in combination with funnel metadynamics MD simulations, that allows a very fast generation of experimentally STD-NMR-validated 3D structures of low-affinity protein-ligand complexes.


Asunto(s)
Proteínas , Ligandos , Proteínas/química , Proteínas/metabolismo , Simulación de Dinámica Molecular , Modelos Moleculares , Espectroscopía de Resonancia Magnética/métodos , Resonancia Magnética Nuclear Biomolecular/métodos , Conformación Proteica , Humanos , Unión Proteica , Sitios de Unión , Descubrimiento de Drogas
4.
Microbiol Resour Announc ; 13(7): e0042224, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-38832805

RESUMEN

Here, we report 27 metagenome-assembled bacterial genomes (MAGs) from litter samples of a secondary forest located in Brazil over an Amazonian Dark Earth pool. The data set includes members from the phyla Pseudomonadata (14 MAGs), Actinomycetota (7 MAGs), Bacteroidota (4 MAGs), Bacillota (1 MAG), and Bdellovibrionota (1 MAG).

5.
Heliyon ; 10(9): e30546, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38726133

RESUMEN

This study involved the synthesis and characterization of graphene oxide (GO) from mineral coke and bituminous coal. HCl treated and non-HCl treated ultrafine powder obtained from both precursors were treated with H2SO4, followed by thermal treatment, and oxidation with ozone and ultra-sonication for GO production. The synthesized materials were characterized using Fourier transform infrared spectroscopy (FTIR), zeta potential (ZP), particle size distribution (PSD), transmission electron microscopy (TEM), X-ray diffraction (XRD) and Raman spectroscopy. The results confirmed the exfoliation of the material primarily at the edges of its structure and the formation of multilayer graphene oxide (GO) from mineral coke and bituminous coal. Furthermore, it was found that carbonaceous materials with graphitic morphology are easier to exfoliate and oxidize, leading to the production of higher quality graphene oxide. Therefore, the GO synthesized from mineral coke exhibited the best quality in this study. The methodology used proposes an innovative approach, offering a faster, more economical, and environmentally friendly synthesis compared to the traditional Hummers' method, thereby adding value to other raw materials that can be utilized in this process, such as Brazilian coke and coal.

6.
Sci Rep ; 14(1): 11885, 2024 05 24.
Artículo en Inglés | MEDLINE | ID: mdl-38789563

RESUMEN

This study investigated the effects of supplemental nucleotides, autolyzed yeast (Saccharomyces cerevisiae), and sodium butyrate in diets for nursery pigs on growth performance, diarrhea incidence, blood profile, intestinal morphology, mRNA expression of nutrient transporters, inflammatory markers, antioxidant profile, and tight junction proteins in the small intestine. One hundred eighty 21-day-old pigs (5.17 ± 0.57 kg) were assigned in a randomized block design to 1 of 4 dietary treatments: (1) CON: control, basal diet, (2) NUC: CON + nucleotides, (3) YSC: CON + lysed yeast S. cerevisiae, (4) ASB: CON + acidifier sodium butyrate. Pigs were fed for 24 days, phase 1 (21-32 days) and 2 (32-45 days). During phase 1, YSC and ASB improved average daily gain (ADG) and feed conversion (FC) compared with CON. At the overall period, ASB improved ADG and YSC improved FC compared with CON. The NUC diet did not affect growth performance. The ASB increased ileal villus height compared to CON. The YSC and ASB reduced the number of Peyer's patches in the ileum compared with CON. The YSC increased mRNA expression of nutrient transporters (SMCT2, MCT1, and PepT1), tight junction proteins (OCL and ZO-1), antioxidants (GPX), and IL1-ß in the jejunum compared with CON. The ASB increased mRNA expression of nutrient transporters (SGLT1 and MCT1), tight junction proteins (OCL and ZO-1), and antioxidants (GPX and SOD) compared with CON. In conclusion, autolyzed yeast and sodium butyrate promoted growth performance by improving the integrity of the intestinal barrier, the mRNA expression of nutrient transporters, and antioxidant enzymes in the jejunum of nursery pigs whereas supplementation of nucleotides did not show such effects.


Asunto(s)
Alimentación Animal , Ácido Butírico , Suplementos Dietéticos , Saccharomyces cerevisiae , Destete , Animales , Porcinos/crecimiento & desarrollo , Ácido Butírico/farmacología , Ácido Butírico/administración & dosificación , Saccharomyces cerevisiae/metabolismo , Alimentación Animal/análisis , Proteínas de Uniones Estrechas/metabolismo , Proteínas de Uniones Estrechas/genética , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Antioxidantes/metabolismo , Intestinos/efectos de los fármacos
7.
World J Clin Oncol ; 15(4): 496-522, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38689629

RESUMEN

Endometriosis is an estrogen-dependent inflammatory disease, defined by the presence of functional endometrial tissue outside of the uterine cavity. This disease is one of the main gynecological diseases, affecting around 10%-15% women and girls of reproductive age, being a common gynecologic disorder. Although endometriosis is a benign disease, it shares several characteristics with invasive cancer. Studies support that it has been linked with an increased chance of developing endometrial ovarian cancer, representing an earlier stage of neoplastic processes. This is particularly true for women with clear cell carcinoma, low-grade serous carcinoma and endometrioid. However, the carcinogenic pathways between both pathologies remain poorly understood. Current studies suggest a connection between endometriosis and endometriosis-associated ovarian cancers (EAOCs) via pathways associated with oxidative stress, inflammation, and hyperestrogenism. This article aims to review current data on the molecular events linked to the development of EAOCs from endometriosis, specifically focusing on the complex relationship between the immune response to endometriosis and cancer, including the molecular mechanisms and their ramifications. Examining recent developments in immunotherapy and their potential to boost the effectiveness of future treatments.

8.
Infect Genet Evol ; 121: 105598, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38653335

RESUMEN

Klebsiella pneumoniae is an opportunistic pathogen that can colonize the gastrointestinal tract (GIT) of humans. The mechanisms underlying the successful translocation of this pathogen to cause extra-intestinal infections remain unknown, although virulence and antimicrobial resistance traits likely play significant roles in the establishment of infections. We investigated K. pneumoniae strains isolated from GIT colonization (strains Kp_FZcol-1, Kp_FZcol-2 and Kp_FZcro-1) and from a fatal bloodstream infection (strain Kp_HM-1) in a leukemia patient. All strains belonged to ST307, carried a transferable IncF plasmid containing the blaCTX-M-15 gene (pKPN3-307 TypeA-like plasmid) and showed a multidrug-resistance phenotype. Phylogenetic analysis demonstrated that Kp_HM-1 was more closely related to Kp_FZcro-1 than to the other colonizing strains. The Kp_FZcol-2 genome showed 81 % coverage with the Kp_HM-1 246,730 bp plasmid (pKp_HM-1), lacking most of its putative virulence genes. Searching public genomes with similar coverage, we observed the occurrence of this deletion in K. pneumoniae ST307 strains recovered from human colonization and infection in different countries. Our findings suggest that strains lacking the putative virulence genes found in the pKPN3-307 TypeA plasmid are still able to colonize and infect humans, highlighting the need to further investigate the role of these genes for the adaptation of K. pneumoniae ST307 in distinct human body sites.


Asunto(s)
Tracto Gastrointestinal , Infecciones por Klebsiella , Klebsiella pneumoniae , Leucemia , Filogenia , beta-Lactamasas , Humanos , Masculino , Antibacterianos/farmacología , Bacteriemia/microbiología , beta-Lactamasas/genética , beta-Lactamasas/metabolismo , Farmacorresistencia Bacteriana Múltiple/genética , Tracto Gastrointestinal/microbiología , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/patogenicidad , Klebsiella pneumoniae/efectos de los fármacos , Leucemia/microbiología , Leucemia/complicaciones , Pruebas de Sensibilidad Microbiana , Plásmidos/genética , Virulencia/genética , Factores de Virulencia/genética , Persona de Mediana Edad
9.
World J Gastrointest Oncol ; 16(4): 1134-1153, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38660642

RESUMEN

Pancreatic cancer (PC) is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases worldwide. However, due to its complexity, it ranks 7th in the list of the most lethal cancers worldwide. The pathogenesis of PC involves several complex processes, including familial genetic factors associated with risk factors such as obesity, diabetes mellitus, chronic pancreatitis, and smoking. Mutations in genes such as KRAS, TP53, and SMAD4 are linked to the appearance of malignant cells that generate pancreatic lesions and, consequently, cancer. In this context, some therapies are used for PC, one of which is immunotherapy, which is extremely promising in various other types of cancer but has shown little response in the treatment of PC due to various resistance mechanisms that contribute to a drop in immunotherapy efficiency. It is therefore clear that the tumor microenvironment (TME) has a huge impact on the resistance process, since cellular and non-cellular elements create an immunosuppressive environment, characterized by a dense desmoplastic stroma with cancer-associated fibroblasts, pancreatic stellate cells, extracellular matrix, and immunosuppressive cells. Linked to this are genetic mutations in TP53 and immunosuppressive factors that act on T cells, resulting in a shortage of CD8+ T cells and limited expression of activation markers such as interferon-gamma. In this way, finding new strategies that make it possible to manipulate resistance mechanisms is necessary. Thus, techniques such as the use of TME modulators that block receptors and stromal molecules that generate resistance, the use of genetic manipulation in specific regions, such as microRNAs, the modulation of extrinsic and intrinsic factors associated with T cells, and, above all, therapeutic models that combine these modulation techniques constitute the promising future of PC therapy. Thus, this study aims to elucidate the main mechanisms of resistance to immunotherapy in PC and new ways of manipulating this process, resulting in a more efficient therapy for cancer patients and, consequently, a reduction in the lethality of this aggressive cancer.

10.
Entropy (Basel) ; 26(3)2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38539701

RESUMEN

Relativistic dissipative fluid dynamics finds widespread applications in high-energy nuclear physics and astrophysics. However, formulating a causal and stable theory of relativistic dissipative fluid dynamics is far from trivial; efforts to accomplish this reach back more than 50 years. In this review, we give an overview of the field and attempt a comparative assessment of (at least most of) the theories for relativistic dissipative fluid dynamics proposed until today and used in applications.

11.
3 Biotech ; 14(4): 102, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38464613

RESUMEN

A drug that is widely used in the treatment of psychiatric disorder is lithium (Li) salts. The people who make therapeutic use of this drug develop a series of side effects. Through metataxonomic data, this study assessed the impacts of lithium, as Li carbonate or Li-enriched mushrooms, on the microbial composition of the ileum, colon, and feces of piglets. Employing Bray-Curtis metric, no differences were observed among the treatments evaluated. Nevertheless, the alpha diversity indices showed differences in the Simpson, Shannon, and Chao-1 indices in the colon and Chao-1 in the feces in the diets with Li compared with the diets without Li. The taxa with the highest relative abundance varied among the ileum, colon, and feces, with a predominance of the phyla Firmicutes, Bacteroidota, and Proteobacteria in diets with Li. Many groups of microorganisms that are important for the health of the host (e.g., Lactobacillus, Ruminococcaceae, Enterorhabdus, Muribaculaceae, and Coprococcus) had their relative abundance increased in animals that received diets with the recommended dose of lithium. Furthermore, there was an increase in the abundance of Prevotellaceae and Bacteroidales (in the diet with Li-enriched mushroom) and Clostridia, Ruminococcus, Burkholderia, and Bacteroidales (diets with Li carbonate) at the recommended dosages. This is the first study to show the effects of Li carbonate and Li-enriched mushrooms on the intestinal microbiota of piglets. Thus, the effects of lithium on the body may be related to its ability to change the composition of the intestinal microbiota. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03938-3.

12.
World J Gastroenterol ; 30(6): 579-598, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38463019

RESUMEN

BACKGROUND: Helicobacter pylori (H. pylori) infection has been well-established as a significant risk factor for several gastrointestinal disorders. The urea breath test (UBT) has emerged as a leading non-invasive method for detecting H. pylori. Despite numerous studies confirming its substantial accuracy, the reliability of UBT results is often compromised by inherent limitations. These findings underscore the need for a rigorous statistical synthesis to clarify and reconcile the diagnostic accuracy of the UBT for the diagnosis of H. pylori infection. AIM: To determine and compare the diagnostic accuracy of 13C-UBT and 14C-UBT for H. pylori infection in adult patients with dyspepsia. METHODS: We conducted an independent search of the PubMed/MEDLINE, EMBASE, and Cochrane Central databases until April 2022. Our search included diagnostic accuracy studies that evaluated at least one of the index tests (13C-UBT or 14C-UBT) against a reference standard. We used the QUADAS-2 tool to assess the methodological quality of the studies. We utilized the bivariate random-effects model to calculate sensitivity, specificity, positive and negative test likelihood ratios (LR+ and LR-), as well as the diagnostic odds ratio (DOR), and their 95% confidence intervals. We conducted subgroup analyses based on urea dosing, time after urea administration, and assessment technique. To investigate a possible threshold effect, we conducted Spearman correlation analysis, and we generated summary receiver operating characteristic (SROC) curves to assess heterogeneity. Finally, we visually inspected a funnel plot and used Egger's test to evaluate publication bias. RESULTS: The titles and abstracts of 4621 studies were screened; 79 articles were retrieved and selected for full-text reading. Finally, 60 studies were included in the diagnostic test accuracy meta-analysis. Our analysis demonstrates superior diagnostic accuracy of 13C-UBT over 14C-UBT, indicated by higher sensitivity (96.60% vs 96.15%), specificity (96.93% vs 89.84%), likelihood ratios (LR+ 22.00 vs 10.10; LR- 0.05 vs 0.06), and area under the curve (AUC; 0.979 vs 0.968). Notably, 13C-UBT's DOR (586.47) significantly outperforms 14C-UBT (DOR 226.50), making it the preferred diagnostic tool for dyspeptic individuals with H. pylori infection. Correlation analysis revealed no threshold effect (13C-UBT: r = 0.48; 14C-UBT: r = -0.01), and SROC curves showed consistent accuracy. Both 13C-UBT and 14C-UBT showed high AUC values (13C-UBT 0.979; 14C-UBT 0.968) near 1.00, reinforcing their excellent accuracy and endorsing both as reliable diagnostic tools in clinical practice. CONCLUSION: In summary, our study has demonstrated that 13C-UBT has been found to outperform the 14C-UBT, making it the preferred diagnostic approach. Additionally, our results emphasize the significance of carefully considering urea dosage, assessment timing, and measurement techniques for both tests to enhance diagnostic precision. Nevertheless, it is crucial for researchers and clinicians to evaluate the strengths and limitations of our findings before implementing them in practice.


Asunto(s)
Infecciones por Helicobacter , Helicobacter pylori , Adulto , Humanos , Infecciones por Helicobacter/diagnóstico , Urea , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Pruebas Respiratorias/métodos , Pruebas Diagnósticas de Rutina
13.
J Chem Neuroanat ; 137: 102415, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38521203

RESUMEN

Over time, the body undergoes a natural, multifactorial, and ongoing process named senescence, which induces changes at the molecular, cellular, and micro-anatomical levels in many body systems. The brain, being a highly complex organ, is particularly affected by this process, potentially impairing its numerous functions. The brain relies on chemical messengers known as neurotransmitters to function properly, with dopamine being one of the most crucial. This catecholamine is responsible for a broad range of critical roles in the central nervous system, including movement, learning, cognition, motivation, emotion, reward, hormonal release, memory consolidation, visual performance, sexual drive, modulation of circadian rhythms, and brain development. In the present review, we thoroughly examine the impact of senescence on the dopaminergic system, with a primary focus on the classic delimitations of the dopaminergic nuclei from A8 to A17. We provide in-depth information about their anatomy and function, particularly addressing how senescence affects each of these nuclei.


Asunto(s)
Envejecimiento , Dopamina , Neuronas Dopaminérgicas , Humanos , Animales , Envejecimiento/metabolismo , Envejecimiento/fisiología , Dopamina/metabolismo , Neuronas Dopaminérgicas/metabolismo , Encéfalo/metabolismo
14.
Int J Dev Neurosci ; 84(3): 163-176, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38488315

RESUMEN

INTRODUCTION: Recent research indicates that some brain structures show alterations in conditions such as Autism Spectrum Disorder (ASD). Among them, are the basal ganglia that are involved in motor, cognitive and behavioral neural circuits. OBJECTIVE: Review the literature that describes possible volumetric alterations in the basal ganglia of individuals with ASD and the impacts that these changes have on the severity of the condition. METHODOLOGY: This systematic review was registered in the design and reported according to the PRISMA Items and registered in PROSPERO (CRD42023394787). The study analyzed data from published clinical, case-contemplate, and cohort trials. The following databases were consulted: PubMed, Embase, Scopus, and Cochrane Central Register of Controlled Trials, using the Medical Subject Titles (MeSH) "Autism Spectrum Disorder" and "Basal Ganglia". The last search was carried out on February 28, 2023. RESULTS: Thirty-five eligible articles were collected, analyzed, and grouped according to the levels of alterations. CONCLUSION: The present study showed important volumetric alterations in the basal ganglia in ASD. However, the examined studies have methodological weaknesses that do not allow generalization and correlation with ASD manifestations.


Asunto(s)
Trastorno del Espectro Autista , Ganglios Basales , Humanos , Trastorno del Espectro Autista/diagnóstico por imagen , Trastorno del Espectro Autista/patología , Trastorno del Espectro Autista/fisiopatología , Ganglios Basales/patología , Ganglios Basales/diagnóstico por imagen
15.
Animals (Basel) ; 14(2)2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38254395

RESUMEN

This review aimed to clarify the mechanisms through which exogenous enzymes (carbohydrases and phytase) influence intestinal health, as well as their effects on the nutrients and energy matrix in diets fed to poultry and pigs reared under sanitary challenging conditions. Enzyme supplementation can positively affect intestinal microbiota, immune system, and enhance antioxidant status. Although enzymes have been shown to save energy and nutrients, their responses under sanitary challenging conditions are poorly documented. Immune system activation alters nutrient partitioning, which can affect the matrix values for exogenous enzymes on commercial farms. Notably, the carbohydrases and phytase supplementation under sanitary challenging conditions align with energy and nutritional valorization matrices. Studies conducted under commercial conditions have shown that matrices containing carbohydrases and phytase can maintain growth performance and health in poultry and pigs. However, these studies have predominantly focused on assessing a single level of reduction in energy and/or available phosphorus and total calcium, limiting our ability to quantify potential energy and nutrient savings in the diet. Future research should delve deeper into determining the extent of energy and nutrient savings and understanding the effects of alone or blended enzymes supplementation to achieve more specific insights.

16.
Anal Chem ; 96(2): 615-619, 2024 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-38165272

RESUMEN

STD NMR spectroscopy is a powerful ligand-observed NMR tool for screening and characterizing the interactions of small molecules and low molecular weight fragments with a given macromolecule, identifying the main intermolecular contacts in the bound state. It is also a powerful analytical technique for the accurate determination of protein-ligand dissociation constants (KD) of medium-to-weak affinity, of interest in the pharmaceutical industry. However, accurate KD determination and epitope mapping requires a long series of experiments at increasing saturation times to carry out a full analysis using the so-called STD NMR build-up curve approach and apply the "initial slopes approximation". Here, we have developed a new protocol to bypass this important limitation, which allows us to obtain initial slopes by using just two saturation times and, hence, to very quickly determine precise protein-ligand dissociation constants by STD NMR.


Asunto(s)
Imagen por Resonancia Magnética , Proteínas , Ligandos , Proteínas/química , Espectroscopía de Resonancia Magnética/métodos , Mapeo Epitopo , Unión Proteica
17.
Cancer Manag Res ; 15: 1351-1367, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38058537

RESUMEN

Fighting cancer remains one of the greatest challenges for science in the 21st century. Advances in immunotherapy against different types of cancer have greatly contributed to the treatment, remission, and cure of patients. In this context, knowledge of epigenetic phenomena, their relationship with tumor cells and how the immune system can be epigenetically modulated represent some of the greatest advances in the development of anticancer therapies. Epigenetics is a rapidly growing field that studies how environmental factors can affect gene expression without altering DNA sequence. Epigenomic changes include DNA methylation, histone modifications, and non-coding RNA regulation, which impact cellular function. Epigenetics has shown promise in developing cancer therapies, such as immunotherapy, which aims to stimulate the immune system to attack cancer cells. For example, PD-1 and PD-L1 are biomarkers that regulate the immune response to cancer cells and recent studies have shown that epigenetic modifications can affect their expression, potentially influencing the efficacy of immunotherapy. New therapies targeting epigenetic modifications, such as histone deacetylases and DNA methyltransferases, are being developed for cancer treatment, and some have shown promise in preclinical studies and clinical trials. With growing understanding of epigenetic regulation, we can expect more personalized and effective cancer immunotherapies in the future. This review highlights key advances in the use of epigenetic and epigenomic tools and modern immuno-oncology strategies to treat several types of tumors.

18.
Curr Microbiol ; 81(1): 40, 2023 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-38103072

RESUMEN

Nosocomial infections caused by multidrug-resistant enterobacteria have become a major challenge in global public health. Previous studies have indicated that use of antibiotics in livestock production chains is linked to the rising threat of antibiotic resistance in humans. In this study, we aimed to evaluate the distribution of genes encoding resistance to tetracycline, ß-lactams, and colistin in multidrug-resistant enterobacteria isolated from feces of weaned pigs. Ninety-four enterobacteria isolates were submitted to antibiotic susceptibility test by minimum inhibitory concentration (MIC). In addition, we performed conjugation experiments to verify if plasmid-bearing isolates containing the mcr-1 gene could transfer their resistance determinant to a colistin-sensitive recipient strain. Our results demonstrated a positive association between the detection of antibiotic resistance genes in enterobacteria and the phenotypic resistance profiles of the bacterial isolates. At least one of the extended-spectrum ß-lactamases (ESBL) genes (blaCTX-M, blaTEM, or bla SHV) and tetA was found among most bacterial genera analyzed. In addition, results revealed that the mcr-1 gene can be transferred from E. coli UFV-627 isolate to an F- recipient (Escherichia coli K12) by conjugation. Our findings support the hypothesis that swine represents an important reservoir of antibiotic resistance genes and suggest that horizontal transfer mechanisms (e.g., conjugation) may mediate the spread of these genes in the swine gastrointestinal tract.


Asunto(s)
Infecciones por Escherichia coli , Proteínas de Escherichia coli , Humanos , Animales , Porcinos , Escherichia coli/genética , Antibacterianos/farmacología , Colistina/farmacología , Proteínas de Escherichia coli/genética , Infecciones por Escherichia coli/microbiología , Enterobacteriaceae/genética , Farmacorresistencia Bacteriana , beta-Lactamasas/genética , Plásmidos/genética , Heces/microbiología
19.
Front Vet Sci ; 10: 1243357, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38098993

RESUMEN

This study investigated the effect of crude protein (CP) and non-essential amino acid (NEAA) supplementation on the growth performance, blood profile, intestinal morphology, mRNA relative abundance of inflammatory and antioxidant markers, and tight junction proteins in piglets over the first 2 weeks after weaning. Ninety 21-day-old piglets (7.55 ± 0.72 kg) were assigned in a randomized block design to one of three dietary treatments: (1) high CP, a diet with 24% CP; (2) low CP, a diet with 18% CP; and (3) low CP + NEAA, a diet with 18% CP supplemented with 5 g/kg Arg (L-arginine; purity >99%) and 10 g/kg Glu + Gln (minimum 10% L-glutamine and minimum 10% L-glutamate). Piglets were fed with corn-soybean meal basal diets in a 14-day trial. There was an improvement (p < 0.05) in the feed conversion ratio of piglets fed the high-CP diet compared to treatments with low CP or low CP + NEAA. Serum urea nitrogen was higher (p < 0.05) in piglets fed high CP compared to other dietary treatments. In the duodenum, the villus height of animals fed the low-CP + NEAA diets was greater (p < 0.05) than those fed with the high- and low-CP diets. The goblet cell proportion of piglets fed low CP + NEAA or high CP was higher (p < 0.05) compared to low CP. In the jejunum, the crypt depth of the piglets with the high-CP dietary treatment was greater (p < 0.05) in comparison with low CP + NEAA. In the jejunum, IFN-γ mRNA expression was higher (p < 0.05) in animals fed the high-CP diets compared to other dietary treatments. However, superoxide dismutase and occludin mRNA expression were higher (p < 0.05) in animals fed low CP + NEAA than in piglets on the high-CP diets. In the ileum, the number of Peyer's patches in piglets fed high CP was higher (p < 0.05) compared to other dietary treatments. In conclusion, the high-CP diet (24% CP) improves the feed conversion of piglets in the first 2 weeks after weaning compared to the low-CP diet (18% CP) supplemented or not with NEAA. However, the low-CP diet supplemented with NEAA (Arg, Gln, and Glu) improves intestinal health in piglets by promoting greater villus height and proportion of goblet cells in the duodenum, reducing jejunal crypt depth, and reducing Peyer's number patches in the ileum. In addition, piglets that received the low-CP + NEAA diet showed an increase in superoxide dismutase and occludin and a lower expression of IFN-γ mRNA.

20.
J Anim Sci ; 1012023 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-37843846

RESUMEN

This study aimed to investigate the effects of diets with and without antibiotics supplementation and diets with 18.5% and 13.0% crude protein (CP) on growth performance, carcass characteristics, disease incidence, fecal microbiota, immune response, and antioxidant capacity of growing pigs. One hundred and eighty pigs (59-day-old; 18.5 ±â€…2.5 kg) were distributed in a randomized complete block design in a 2 × 2 factorial arrangement, nine replicates, and five pigs per pen. The factors were CP (18.5% or 13.0%) and antibiotics (none or 100 mg/kg tiamulin + 506 mg/kg oxytetracycline). Medicated diets were fed from days 59 to 73. After that, all pigs were fed their respective CP diets from 73 to 87 days. Data were analyzed using the Mixed procedure in SAS version 9.4. From days 59 to 73, pigs fed antibiotics diets had higher (P < 0.05) average daily feed intake (ADFI), average daily weight gain (ADG), gain to feed ratio (G:F), compared to the diets without antibiotics. From days 73 to 87 (postmedicated period), any previous supplementation of antibiotics did not affect pig growth performance. Overall (days 59 to 87), pigs-fed antibiotics diets had higher (P < 0.05) G:F compared to pigs-fed diets without antibiotics. In all periods evaluated, pigs fed 18.5% CP diets had higher (P < 0.05) ADG and G:F compared to pigs fed 13.0% CP. Pigs fed the 13.0% CP diets had lower (P < 0.05) fecal score and diarrhea incidence than those fed 18.5% CP. Pigs fed 18.5% CP diets had improved (P < 0.05) loin area compared to pigs-fed diets with 13.0% CP. At 66 days of age, pigs-fed antibiotics diets had lower (P < 0.05) alpha diversity estimated with Shannon and Simpson compared to the pig-fed diets without antibiotics. At family level, pigs fed 18.5% CP diets had higher (P < 0.05) relative abundance of Streptococcaceae, and lower (P < 0.05) relative abundance of Clostridiaceae at days 66 and 87 compared with pigs fed 13.0% CP. Pigs-fed antibiotics diets had lower (P < 0.05) immunoglobulin G and protein carbonyl concentrations at day 66 compared to the pigs-fed diets without antibiotics. The reduction of dietary CP from 18.5% to 13.0% reduced the growth performance and loin muscle area of growing pigs, although it was effective to reduce diarrhea incidence. Antibiotics improved growth performance, lowered diarrhea incidence, improved components of the humoral immune response, and reduced microbiota diversity. However, in the postmedicated period, we found no residual effect on the general health of the animals, and considering the overall period, only G:F was improved by the use of antibiotics.


Dietary antibiotics have been used in pig farming practices to avoid health problems and improve animal growth performance. However, their use in production animals is considered a global health challenge, due to its association with selection of resistance in zoonotic bacteria. Another negative impact of pig farming that has gained attention is related to environmental pollution due to the excretion of nitrogenous compounds. Reducing dietary crude protein content has become a goal in the pig feed industry due to the limited availability and high cost of dietary protein sources, as well as the aim of enhancing gut health in pigs. Thus, the aim of this study was to investigate the effects of diets with and without antibiotics supplementation and diets with 18.5% and 13.0% crude protein for pigs. The reduction of dietary crude protein in this study reduced growth performance, although it was effective to reduce diarrhea incidence. Antibiotics improved growth performance, positively affected the overall health of animals, and reduced microbiota diversity. However, during the postmedicated period, we found no residual effect on the general health of the animals, and considering the overall period, only gain to feed ratio was improved by the use of antibiotics.


Asunto(s)
Antibacterianos , Dieta , Porcinos , Animales , Antibacterianos/farmacología , Dieta/veterinaria , Dieta con Restricción de Proteínas/veterinaria , Heces , Aumento de Peso , Diarrea/prevención & control , Diarrea/veterinaria , Inmunidad , Alimentación Animal/análisis , Suplementos Dietéticos
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