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1.
Nutrients ; 16(11)2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38892493

RESUMEN

This study aimed to compare and relate the body composition (obtained through anthropometry with the pentacompartmental model and the tricompartmental model by DXA) with bone mineral density and biochemical and nutritional parameters in Chilean adults with overweight/obesity and normal weight from La Araucanía region, Chile. A case-control study was conducted with 116 adults and volunteers from the PURE cohort, collecting sociodemographic data, BMI assessment, waist-to-hip ratio (WHR), and body composition using the pentacompartmental model (5CM) and tricompartmental model (3CM) by DXA, as well as bone mineral density (BMD). Blood biochemical parameters (fasting glucose and lipid profile), physical activity (PA) measured by GPAQ, and average dietary habits (R24h) were measured. In the overweight/obesity group, the 5CM and 3CM adipose mass were indirectly and moderately correlated with PA (p < 0.05), except in the male 5CM group. In the overweight/obesity group, muscle and fat-free mass (FFM) of the 5CM and 3CM correlated directly and moderately with blood fasting glucose (BFG) and BMD (p < 0.05), except in females, where FFM was not related to BMD but was related to residual mass (p < 0.01). Independent of gender and BMI, bone mineral content was positively and highly correlated with BMD (p < 0.0000). In the male overweight/obesity group, bone, skin, and residual mass were correlated with BFG (p < 0.05). In conclusion, for the assessment of non-athletic adult populations, more routine use of the 5CM in clinical practice is recommended.


Asunto(s)
Composición Corporal , Densidad Ósea , Obesidad , Sobrepeso , Humanos , Masculino , Femenino , Chile , Adulto , Obesidad/sangre , Estudios de Casos y Controles , Persona de Mediana Edad , Sobrepeso/sangre , Estado Nutricional , Absorciometría de Fotón , Glucemia/metabolismo , Índice de Masa Corporal , Ejercicio Físico/fisiología
2.
Artículo en Inglés | MEDLINE | ID: mdl-38847831

RESUMEN

Cancer remains a global health challenge, prompting a search for effective treatments with fewer side effects. Thymol, a natural monoterpenoid phenol derived primarily from thyme (Thymus vulgaris) and other plants in the Lamiaceae family, is known for its diverse biological activities. It emerges as a promising candidate in cancer prevention and therapy. This study aims to consolidate current research on thymol's anticancer effects, elucidating its mechanisms and potential to enhance standard chemotherapy, and to identify gaps for future research. A comprehensive review was conducted using databases like PubMed/MedLine, Google Scholar, and ScienceDirect, focusing on studies from the last 6 years. All cancer types were included, assessing thymol's impact in both cell-based (in vitro) and animal (in vivo) studies. Thymol has been shown to induce programmed cell death (apoptosis), halt the cell division cycle (cell cycle arrest), and inhibit cancer spread (metastasis) through modulation of critical signaling pathways, including phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), extracellular signal-regulated kinase (ERK), mechanistic target of rapamycin (mTOR), and Wnt/ß-catenin. It also enhances the efficacy of 5-fluorouracil (5-FU) in colorectal cancer treatments. Thymol's broad-spectrum anticancer activities and non-toxic profile to normal cells underscore its potential as an adjunct in cancer therapy. Further clinical trials are essential to fully understand its therapeutic benefits and integration into existing treatment protocols.

3.
Int J Mol Sci ; 25(4)2024 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-38396672

RESUMEN

Cardiovascular diseases are the leading cause of death worldwide, and arterial hypertension is a recognized cardiovascular risk factor that is responsible for high morbidity and mortality. Arterial hypertension is the result of an inflammatory process that results in the remodeling and thickening of the vascular walls, which is associated with an immunological response. Previous studies have attempted to demonstrate the relationship between oral disease, inflammation, and the development of systemic diseases. Currently, the existence of an association between periodontitis and hypertension is a controversial issue because the underlying pathophysiological processes and inflammatory mechanisms common to both diseases are unknown. This is due to the fact that periodontitis is a chronic inflammatory disease that affects the interface of teeth and surrounding tissues. However, the most likely explanation for understanding this association is related to low-grade chronic inflammation. An initial path in the study of the relationship between the mentioned pathologies is the possibility of an epigenetic influence, mediated by noncoding RNAs as microRNAs. Thus, in the present review we describe the role of microRNAs related to arterial hypertension and/or periodontitis. In addition, we identified 13 common microRNAs between periodontitis and hypertension. According to the predictions of the DIANA-mirPath program, they can regulate genes involved in 52 signaling pathways.


Asunto(s)
Enfermedades Cardiovasculares , Hipertensión , MicroARNs , Periodontitis , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Periodontitis/complicaciones , Periodontitis/genética , Hipertensión/complicaciones , Hipertensión/genética , Inflamación , Enfermedades Cardiovasculares/complicaciones
4.
Int J Sport Nutr Exerc Metab ; 34(1): 11-19, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37875254

RESUMEN

Resistance exercise training (RET) can be applied effectively to increase muscle mass and function in older adults (65-75 years). However, it has been speculated that older adults above 85 years are less responsive to the benefits of RET. This study compares the impact of RET on muscle mass and function in healthy older adults 65-75 years versus older adults above 85 years. We subjected 17 healthy older adults 65-75 years (OLDER 65-75, n = 13/4 [female/male]; 68 ± 2 years; 26.9 ± 2.3 kg/m2) and 12 healthy older adults above 85 years (OLDER 85+, n = 7/5 [female/male]; 87 ± 3 years; 26.0 ± 3.6 kg/m2) to 12 weeks of whole-body RET (three times per week). Prior to, and after 6 and 12 weeks of training, quadriceps and lumbar spine vertebra 3 muscle cross-sectional area (computed tomography scan), whole-body lean mass (dual-energy X-ray absorptiometry scan), strength (one-repetition maximum test), and physical performance (timed up and go and short physical performance battery) were assessed. Twelve weeks of RET resulted in a 10% ± 4% and 11% ± 5% increase in quadriceps cross-sectional area (from 46.5 ± 10.7 to 51.1 ± 12.1 cm2, and from 38.9 ± 6.1 to 43.1 ± 8.0 cm2, respectively; p < .001; η2 = .67); a 2% ± 3% and 2% ± 3% increase in whole-body lean mass (p = .001; η2 = .22); and a 38% ± 20% and 46% ± 14% increase in one-repetition maximum leg extension strength (p < .001; η2 = .77) in the OLDER 65-75 and OLDER 85+ groups, respectively. No differences in the responses to RET were observed between groups (Time × Group, all p > .60; all η2 ≤ .012). Physical performance on the short physical performance battery and timed up and go improved (both p < .01; η2 ≥ .22), with no differences between groups (Time × Group, p > .015; η2 ≤ .07). Prolonged RET increases muscle mass, strength, and physical performance in the aging population, with no differences between 65-75 years and 85+ years older adults.


Asunto(s)
Fuerza Muscular , Entrenamiento de Fuerza , Humanos , Masculino , Femenino , Anciano , Fuerza Muscular/fisiología , Entrenamiento de Fuerza/métodos , Músculo Cuádriceps , Ejercicio Físico/fisiología , Composición Corporal , Músculo Esquelético/fisiología
5.
Front Pharmacol ; 14: 1275238, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38089043

RESUMEN

Introduction: The standard treatment for head and neck squamous cell carcinoma (HNSCC) is cisplatin chemoradiotherapy. One of the main treatment adverse reactions is nephrotoxicity, for which there is currently no adequate specific and sensitive biomarker. Thus, this study aimed to evaluate the use of microRNAs (miRNAs) as renal biomarker candidates. Methods: This was a retrospective cohort study. Nephrotoxicity was assessed through blood samples collected before and 5 days (D5) after chemotherapy. MiRNAs were extracted from urine samples collected at baseline and D5, and RNA sequencing identified miRNAs differentially expressed between participants with and without cisplatin-induced nephrotoxicity. Results: A total of 49 participants were included (n = 49). A significant difference was seen between the two groups for traditional renal markers (serum creatinine and creatinine clearance) and for the acute kidney injury (AKI) categories. Among the six miRNAs evaluated as biomarkers, four were upregulated (hsa-miR-6729-5p, hsa-miR-1238-5p, hsa-miR-4706, and hsa-miR-4322) and two were downregulated (hsa-miR-6805-5p and hsa-miR-21-5p), but only hsa-miR-6805-5p had a significant difference (p < 0.0001). Its receiver operating characteristic curve revealed excellent specificity (0.920) for its expression fluctuation assessment, while its absolute expression in D5 showed greater sensitivity (0.792). Conclusion: So, the integrated use of these two parameters seems to be an interesting approach for AKI.

6.
Front Cardiovasc Med ; 10: 1252542, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38075980

RESUMEN

Background: Temuco is a city in Southern Chile with elevated levels of air pollution (AP), mainly due to using wood as combustion throughout the cold season. The study aimed to assess the differences in cardiometabolic risk factors, estimated cardiovascular risk, and blood level of inflammatory markers between high AP (HAP) and low AP (LAP) periods. Methods: A prospective panel study was conducted between January to September 2018. Air pollution was assessed by PM2.5 concentration. Ninety individuals from the general population were included in the study. Measurements were performed in the HAP and LAP, including medical history and lifestyle, physical activity assessment, physical exam, and fasting blood samples for glucose, lipids, and circulatory inflammatory mediators. Results: In the high air pollution period, systolic blood pressure was 3 mmHg higher (p = 0.05). HDL-cholesterol was 14.2 mg/dl lower (p < 0.001), Framingham risk score increased from 14.5 to 18.0 (p < 0.001), and highly significant lower levels of interleukins, MCP1, MMP1, MMP2, sICAM, and svCAM were observed. Conclusions: HAP was associated with increased cardiometabolic risk factors and estimated cardiovascular risk. However, a lower level of circulating acute inflammatory molecules was observed. Inflammatory molecules blood levels were not associated with changes in cardiometabolic risk factors.

7.
Toxics ; 11(10)2023 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-37888695

RESUMEN

Exposure to polycyclic aromatic hydrocarbons (PAHs) present in air pollution increases cardiovascular risk. On the contrary, physical exercise is a widely used therapeutic approach to mitigate cardiovascular risk, but its efficacy in an environment of air pollution, particularly with PAHs, remains unclear. This study investigates the effects of exercise on inflammation, endothelial dysfunction, and REDOX imbalance due to PAH exposure using a mouse model. Twenty male BALB/c mice were subjected to a mixture of PAHs (phenanthrene, fluoranthene, pyrene) in conjunction with aerobic exercise. The investigation evaluated serum levels of inflammatory cytokines, gene expression linked to inflammatory markers, endothelial dysfunction, and REDOX imbalance in aortic tissues. Furthermore, the study evaluated the expression of the ICAM-1 and VCAM-1 proteins. Exercise led to notable changes in serum inflammatory cytokines, as well as the modulation of genes associated with endothelial dysfunction and REDOX imbalance in aortic tissue. In turn, exercise produced a modulation in the protein expression of ICAM-1 and VCAM-1. The findings implicate the potential of exercise to counter PAH-induced damage, as demonstrated by changes in markers. In conclusion, exercise could mitigate the adverse effects related to exposure to PAHs present in air pollution, as evidenced by changes in inflammatory markers, endothelial dysfunction, and REDOX imbalance.

8.
Front Physiol ; 14: 1223069, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37829114

RESUMEN

Introduction: Whether high-intensity interval training (HIIT) can improve lean mass, strength, and power of the lower limbs in young and older people is still under discussion. This study aimed to determine the effect of HIIT on lean mass, maximal strength, rate of force development (RFD), and muscle power of both lower limbs in healthy young and older adults. Secondarily, to compare the effects of HIIT between dominant vs. non-dominant lower limbs of each group. Materials and methods: Healthy older (n = 9; 66 ± 6 years; BMI 27.1 ± 3.1 kg m-2) and young (n = 9; 21 ± 1 years; BMI 26.2 ± 2.8 kg m-2) men underwent 12 weeks of HIIT (3x/week) on a stationary bicycle. The evaluations were made before and after the HIIT program by dual energy X-ray absorptiometry (DEXA), anthropometry, force transducer and, Sit-to-Stand test. The outcomes analyzed were limb lean mass, thigh circumference, maximal voluntary isometric strength, RFD (Time intervals: 0-50, 50-100, 100-200, and 0-200 ms), and muscle power in both lower limbs. Results: After 12 weeks of HIIT, non-dominant limb (NDL) showed increase in limb lean mass (p < 0.05) but without interaction (time*group). HIIT showed a gain in absolute maximal strength and also when adjusted for thigh circumference in the dominant lower limb (DL) in both groups. The RFD0-200 ms showed differences between groups but without interaction. The RFD0-50 ms of the NDL showed post-training improvements (p < 0.05) in both groups. Only the older group showed differences between DL vs. NDL in most of the RFD obtained post-intervention. In addition, post-HIIT muscle power gain was observed in both groups (p < 0.05), but mainly in older adults. Conclusion: HIIT promotes increases in lean mass, maximal strength, early RFD, and lower limb muscle power in healthy older and young individuals. The differences shown between the DL and the NDL must be analyzed in future studies.

9.
Int J Mol Sci ; 24(19)2023 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-37834215

RESUMEN

Osteoarthritis is a multifactorial joint disease characterized by degeneration, and aging stands as a significant risk factor. Autophagy, a crucial cellular homeostasis mechanism, is influenced by aging and closely linked to cartilage health. This correlation between autophagy, cell death, and OA underscores its relevance in disease progression. MicroRNAs have emerged as autophagy regulators, with miRNA-based interventions showing promise in preclinical models. Remarkably, the ethanolic extract of propolis exhibits positive effects on autophagy-related proteins and healthy cartilage markers in an in vitro osteoarthritis model. The aim of this brief report was to evaluate through in silico analysis and postulate five microRNAs that could regulate autophagy proteins (AKT1, ATG5, and LC3) and assess whether the ethanolic extract of propolis could regulate the expression of these microRNAs. Among the examined miRNAs (miR-19a, miR-125b, miR-181a, miR-185, and miR-335), the ethanolic extract of propolis induced significant changes in four of them. Specifically, miR-125b responded to EEP by counteracting IL-1ß-induced effects, while miR-181a, miR-185, and miR-335 exhibited distinct patterns of expression under EEP treatment. These findings unveil a potential link between miRNAs, EEP, and autophagy modulation in OA, offering promising therapeutic insights. Nevertheless, further validation and clinical translation are warranted to substantiate these promising observations.


Asunto(s)
MicroARNs , Osteoartritis , Própolis , Humanos , MicroARNs/metabolismo , Própolis/farmacología , Própolis/metabolismo , Condrocitos/metabolismo , Osteoartritis/tratamiento farmacológico , Osteoartritis/genética , Osteoartritis/metabolismo , Etanol/farmacología , Autofagia
10.
Exp Gerontol ; 181: 112280, 2023 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-37659743

RESUMEN

Neutrophil extracellular trap formation (NETosis) is a mechanism used by neutrophils to capture pathogens with their own DNA. However, the exacerbation of this immune response is related to serious inflammatory diseases. Aging is known to lead to an excessive increase in NETosis associated with various diseases. Under this scenario, the search for strategies that regulate the release of NETosis in older people becomes relevant. High-intensity interval training (HIIT) involves repeated bouts of relatively intense exercise with alternating short recovery periods. This training has shown beneficial effects on health parameters during aging and disease. However, little is known about the potential role of HIIT in the regulation of NETosis in healthy older people. The aim of this study was to evaluate the induction of NETosis by serum from healthy young and older men, before and after 12 weeks of HIIT using healthy neutrophils as a biosensor. HIIT was performed 3 times per week for 12 weeks in young (YOUNG; 21 ± 1 years, BMI 26.01 ± 2.64 kg⋅m-2, n = 10) and older men (OLDER; 66 ± 5 years, BMI 27.43 ± 3.11 kg⋅m-2, n = 10). Serum samples were taken before and after the HIIT program and NETosis was measured with live cell imaging in donated neutrophils cultured with serum from the participants for 30 h. Our results showed that serum from older men at baseline induced greater baseline NETosis than younger men (p < 0.05; effect size, ≥0.8), and 12 weeks of HIIT significantly reduced (Interaction Effect, p < 0.05; effect size, 0.134) the induction of NETosis in older men. In conclusion, HIIT is a feasible non-invasive training strategy modulating NETosis induction. Additionally, the use of neutrophils as a biosensor is an effective method for the quantification of NETosis induction in real time.


Asunto(s)
Técnicas Biosensibles , Trampas Extracelulares , Entrenamiento de Intervalos de Alta Intensidad , Masculino , Humanos , Anciano , Neutrófilos , Envejecimiento
11.
Int J Mol Sci ; 24(18)2023 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-37762574

RESUMEN

Aging is intricately linked to chronic low-grade systemic inflammation, which plays a significant role in various age-related conditions, including osteoarthritis (OA). The aging process significantly influences the development of OA due to alterations in cartilage composition, reduced proteoglycan content, dysregulation of growth factor signaling, and heightened oxidative stress. Propolis, a natural product renowned for its potent antioxidant and anti-inflammatory properties, has the potential to mitigate age-induced changes in cartilage. The primary objective of this study was to rigorously assess the impact of in vivo propolis treatment on the histopathological characteristics of knee articular cartilage in senescent rats. This study involved a cohort of twenty male Sprague-Dawley rats, randomly allocated into four distinct groups for comparative analysis: YR (control group consisting of young rats), SR (senescent rats), SR-EEP (senescent rats treated with an ethanolic extract of propolis, EEP), and SR-V (senescent rats administered with a control vehicle). This study employed comprehensive histological and stereological analyses of knee articular cartilage. Propolis treatment exhibited a significant capacity to alleviate the severity of osteoarthritis, enhance the structural integrity of cartilage, and augment chondrocyte density. These promising findings underscore the potential of propolis as a compelling therapeutic agent to counteract age-related alterations in cartilage and, importantly, to potentially forestall the onset of osteoarthritis.


Asunto(s)
Ascomicetos , Cartílago Articular , Osteoartritis , Própolis , Humanos , Masculino , Animales , Ratas , Ratas Sprague-Dawley , Própolis/farmacología , Própolis/uso terapéutico , Condrocitos , Inflamación , Osteoartritis/tratamiento farmacológico
12.
Acta Parasitol ; 68(3): 535-547, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37330945

RESUMEN

PURPOSE: Fasciola hepatica is a globally distributed trematode that causes significant economic losses. Triclabendazole is the primary pharmacological treatment for this parasite. However, the increasing resistance to triclabendazole limits its efficacy. Previous pharmacodynamics studies suggested that triclabendazole acts by interacting mainly with the ß monomer of tubulin. METHODS: We used a high-quality method to model the six isotypes of F. hepatica ß-tubulin in the absence of three-dimensional structures. Molecular dockings were conducted to evaluate the destabilization regions in the molecule against the ligands triclabendazole, triclabendazole sulphoxide and triclabendazole sulphone. RESULTS: The nucleotide binding site demonstrates higher affinity than the binding sites of colchicine, albendazole, the T7 loop and pßVII (p < 0.05). We suggest that the binding of the ligands to the polymerization site of ß-tubulin can lead a microtubule disruption. Furthermore, we found that triclabendazole sulphone exhibited significantly higher binding affinity than other ligands (p < 0.05) across all isotypes of ß-tubulin. CONCLUSIONS: Our investigation has yielded new insight on the mechanism of action of triclabendazole and its sulphometabolites on F. hepatica ß-tubulin through computational tools. These findings have significant implications for ongoing scientific research ongoing towards the discovery of novel therapeutics to treat F. hepatica infections.


Asunto(s)
Antihelmínticos , Fasciola hepatica , Fascioliasis , Animales , Triclabendazol/farmacología , Triclabendazol/metabolismo , Triclabendazol/uso terapéutico , Tubulina (Proteína)/genética , Simulación del Acoplamiento Molecular , Bencimidazoles/farmacología , Bencimidazoles/química , Bencimidazoles/metabolismo , Ligandos , Sulfonas/metabolismo , Sulfonas/uso terapéutico , Antihelmínticos/farmacología , Antihelmínticos/uso terapéutico , Fascioliasis/parasitología
13.
Int J Mol Sci ; 24(8)2023 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-37108373

RESUMEN

Cholesterol metabolism is important at the physiological level as well as in several diseases, with small RNA being an element to consider in terms of its epigenetic control. Thus, the aim of this study was to identify differences between bacterial small RNAs present at the gut level in hypercholesterolemic and normocholesterolemic individuals. Twenty stool samples were collected from hypercholesterolemic and normocholesterolemic subjects. RNA extraction and small RNA sequencing were performed, followed by bioinformatics analyses with BrumiR, Bowtie 2, BLASTn, DESeq2, and IntaRNA, after the filtering of the reads with fastp. In addition, the prediction of secondary structures was obtained with RNAfold WebServer. Most of the small RNAs were of bacterial origin and presented a greater number of readings in normocholesterolemic participants. The upregulation of small RNA ID 2909606 associated with Coprococcus eutactus (family Lachnospiraceae) was presented in hypercholesterolemic subjects. In addition, a positive correlation was established between small RNA ID 2149569 from the species Blautia wexlerae and hypercholesterolemic subjects. Other bacterial and archaeal small RNAs that interacted with the LDL receptor (LDLR) were identified. For these sequences, the prediction of secondary structures was also obtained. There were significant differences in bacterial small RNAs associated with cholesterol metabolism in hypercholesterolemic and normocholesterolemic participants.


Asunto(s)
Hipercolesterolemia , Humanos , Hipercolesterolemia/metabolismo , ARN Bacteriano/genética , Colesterol/metabolismo
14.
Biomedicines ; 11(3)2023 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-36979720

RESUMEN

Statins are currently the treatment of choice for hypercholesterolemia. However, wide interindividual variability has been observed in the response to treatment. Recent studies have reported the role of lncRNAs in the metabolism of lipids; nevertheless, there are few studies to date that show their role in the response to treatment with statins. Thus, the aim of this study was to assess the levels of expression of three lncRNAs (RP1-13D10.2; MANTIS; lncHR1) associated with genes involved in cholesterol homeostasis in leukocyte cells of hypercholesterolemic patients after treatment with atorvastatin and compare them with levels in subjects with normal cholesterol levels. A secondary aim was to assess the levels of expression in monocytic THP-1 cells differentiated to macrophages. The study included 20 subjects with normal cholesterol (NC) levels and 20 individuals with hypercholesterolemia (HC). The HC patients were treated with atorvastatin (20 mg/day/4 weeks). THP-1 cells were differentiated to macrophages with PMA and treated with different doses of atorvastatin for 24 h. Expression of lncRNAs was determined by RT-qPCR. The lncRNAs RP1-13D10.2 (p < 0.0001), MANTIS (p = 0.0013) and lncHR1 (p < 0.0001) presented increased expression in HC subjects compared with NC subjects. Furthermore, atorvastatin had a negative regulatory effect on the expression of lncHR1 (p < 0.0001) in HC subjects after treatment. In vitro, all the lncRNAs showed significant differences in expression after atorvastatin treatment. Our findings show that the lncRNAs tested present differential expression in HC patients and play a role in the variability reported in the response to atorvastatin treatment. Further research is needed to clarify the biological impact of these lncRNAs on cholesterol homeostasis and treatment with statins.

15.
Int J Mol Sci ; 24(4)2023 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-36834484

RESUMEN

Neuroinflammation is a common event in degenerative diseases of the central and peripheral nervous system, triggered by alterations in the immune system or inflammatory cascade. The pathophysiology of these disorders is multifactorial, whereby the therapy available has low clinical efficacy. This review propounds the relationship between the deregulation of T helper cells and hypoxia, mainly Th17 and HIF-1α molecular pathways, events that are involved in the occurrence of the neuroinflammation. The clinical expression of neuroinflammation is included in prevalent pathologies such as multiple sclerosis, Guillain-Barré syndrome, and Alzheimer's disease, among others. In addition, therapeutic targets are analyzed in relation to the pathways that induced neuroinflammation.


Asunto(s)
Síndrome de Guillain-Barré , Enfermedades Neuroinflamatorias , Humanos , Síndrome de Guillain-Barré/patología , Hipoxia/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia , Células Th17
16.
Front Cell Infect Microbiol ; 12: 943609, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36523636

RESUMEN

Introduction: In recent years, several studies have evidenced the importance of the microbiome to host physiology as metabolism regulator, along with its potential role in triggering various diseases. In this study, we analyzed the gut microbiota in hypercholesterolemic (cases) and normocholesterolemic (controls) individuals to identify characteristic microbial signature for each condition. Methods: Stool samples were obtained from 57 adult volunteers (27 hypercholesterolemic and 30 controls). The taxonomic profiling of microbial communities was performed using high-throughput sequencing of 16S rRNA V3-V4 amplicons, followed by data analysis using Quantitative Insights Into Microbial Ecology 2 (QIIME2) and linear discriminant analysis (LDA) effect size (LEfSe). Results: Significant differences were observed in weight, height, body mass index (BMI) and serum levels of triglycerides, total cholesterol and low-density lipoprotein cholesterol (LDL-C) between the groups (p<0.05). LEfSe showed differentially abundant prokaryotic taxa (α=0.05, LDA score > 2.0) in the group of hypercholesterolemic individuals (Methanosphaera, Rothia, Chromatiales, Clostridiales, Bacillaceae and Coriobacteriaceae) and controls (Faecalibacterium, Victivallis and Selenomonas) at various taxonomic levels. In addition, through the application of Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2 (PICRUSt2), the predominance of pathways related to biosynthesis in hypercholesterolemic patients was established, compared to controls in which degradation pathways were predominant. Finally, in the analysis of co-occurrence networks, it was possible to identify associations between the microorganisms present in both studied groups. Conclusion: Our results point out to unique microbial signatures, which likely play a role on the cholesterol metabolism in the studied population.


Asunto(s)
Microbioma Gastrointestinal , Microbiota , Adulto , Humanos , Microbioma Gastrointestinal/genética , ARN Ribosómico 16S/genética , Filogenia , Colesterol
17.
Biomolecules ; 12(10)2022 09 24.
Artículo en Inglés | MEDLINE | ID: mdl-36291573

RESUMEN

Cisplatin (CDDP) is the drug of choice against different types of cancer. However, tumor cells can acquire resistance to the damage caused by cisplatin, generating genetic and epigenetic changes that lead to the generation of resistance and the activation of intrinsic resistance mechanisms in cancer cells. Among them, we can find mutations, alternative splicing, epigenetic-driven expression changes, and even post-translational modifications of proteins. However, the molecular mechanisms by which CDDP resistance develops are not clear but are believed to be multi-factorial. This article highlights a description of cisplatin, which includes action mechanism, resistance, and epigenetic factors involved in cisplatin resistance.


Asunto(s)
Antineoplásicos , Cisplatino , Cisplatino/farmacología , Resistencia a Antineoplásicos/genética , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Línea Celular Tumoral , Epigénesis Genética
18.
Front Cardiovasc Med ; 9: 964721, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36176980

RESUMEN

Circulating endothelial progenitor cells (EPCs) play an important role in the repair processes of damaged vessels, favoring re-endothelization of stented vessels to minimize restenosis. EPCs number and function is diminished in patients with type 2 diabetes, a known risk factor for restenosis. Considering the impact of EPCs in vascular injury repair, we conducted a meta-analysis of microarray to assess the transcriptomic profile and determine target genes during the differentiation process of EPCs into mature ECs. Five microarray datasets, including 13 EPC and 12 EC samples were analyzed, using the online tool ExpressAnalyst. Differentially expressed genes (DEGs) analysis was done by Limma method, with an | log2FC| > 1 and FDR < 0.05. Combined p-value by Fisher exact method was computed for the intersection of datasets. There were 3,267 DEGs, 1,539 up-regulated and 1,728 down-regulated in EPCs, with 407 common DEGs in at least four datasets. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed enrichment for terms related to "AGE-RAGE signaling pathway in diabetic complications." Intersection of common DEGs, KEGG pathways genes and genes in protein-protein interaction network (PPI) identified four key genes, two up-regulated (IL1B and STAT5A) and two down-regulated (IL6 and MAPK11). MicroRNA enrichment analysis of common DEGs depicted five hub microRNA targeting 175 DEGs, including STAT5A, IL6 and MAPK11, with hsa-miR-124 as common regulator. This group of genes and microRNAs could serve as biomarkers of EPCs differentiation during coronary stenting as well as potential therapeutic targets to improve stent re-endothelization, especially in diabetic patients.

19.
Biomolecules ; 12(9)2022 08 31.
Artículo en Inglés | MEDLINE | ID: mdl-36139046

RESUMEN

Cisplatin (cis-diamminedichloroplatinum (II), DDP) is an antineoplastic agent widely used in the treatment of solid tumors because of its extensive cytotoxic activity. However, the main limiting side effect of DDP use is nephrotoxicity, a rapid deterioration in kidney function due to toxic chemicals. Several studies have shown that epigenetic processes are involved in DDP-induced nephrotoxicity. Noncoding RNAs (ncRNAs), a class of epigenetic processes, are molecules that regulate gene expression under physiological and pathological conditions. MicroRNAs (miRNAs) are the most characterized class of ncRNAs and are engaged in many cellular processes. In this review, we describe how different miRNAs regulate some pathways leading to cell death by apoptosis, specifically the intrinsic apoptosis pathway. Accordingly, many classes of natural products have been tested for their ability to prevent DDP-induced apoptosis. The study of epigenetic regulation for underlying cell death is still being studied, which will allow new strategies for the diagnosis and therapy of this unwanted disease, which is presented as a side effect of antineoplastic treatment.


Asunto(s)
Antineoplásicos , Productos Biológicos , MicroARNs , Antineoplásicos/efectos adversos , Apoptosis , Productos Biológicos/farmacología , Cisplatino/efectos adversos , Epigénesis Genética , MicroARNs/genética
20.
Toxics ; 10(9)2022 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-36136462

RESUMEN

The particulate matter present in air pollution is a complex mixture of solid and liquid particles that vary in size, origin, and composition, among which are polycyclic aromatic hydrocarbons (PAHs). Although exposure to PAHs has become an important risk factor for cardiovascular disease, the mechanisms by which these compounds contribute to increased cardiovascular risk have not been fully explored. The aim of the present study was to evaluate the effects of PAH exposure on systemic pro-inflammatory cytokines and markers of endothelial dysfunction. An intervention was designed using a murine model composed of twenty BALB/c male mice separated into controls and three groups exposed to a mixture of phenanthrene, fluoranthene, and pyrene using three different concentrations. The serum levels of the inflammatory cytokines and gene expression of adhesion molecules located on endothelial cells along with inflammatory markers related to PAH exposure in aortic tissue were determined. Furthermore, the expression of the ICAM-1 and VCAM-1 proteins was evaluated. The data showed significant differences in IL-6 and IFN-γ in the serum. In the gene expression, significant differences for ICAM-1, VCAM-1, and E-Selectin were observed. The results suggest that phenanthrene, fluoranthene, and pyrene, present in air pollution, stimulate the increase in serum inflammatory cytokines and the expression of markers of endothelial dysfunction in the murine model studied, both relevant characteristics associated with the onset of disease atherosclerosis and cardiovascular disease.

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