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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.

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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.

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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.

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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.

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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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Grape pomace is a source of anthocyanins, which can prevent cardiovascular diseases due to their antioxidant properties. Anthocyanin activity is associated with the ability to regulate oxidative stress through the transcription factor Nrf2. Thus, the present study aimed to evaluate if the anthocyanins found in Pinot noir pomace extract can affect the target genes related to the Nrf2 signalling pathway in endothelial cells. Our results highlight that the predominant anthocyanin in the Pinot noir pomace extract was malvidin-3-glucoside (3.7 ± 2.7 Eq. Malv-3-glu/kg). Molecular docking indicated that cyanidin-3-glucoside (-6.9 kcal/mol), malvidin-3-glucoside (-6.6 kcal/mol) and peonidin-3-glucoside (-6.6 kcal/mol) showed the highest affinities for the binding sites of the BTB domains in Keap1, suggesting that these components may modify the interaction of this protein with Nrf2. In addition, when HUVEC cells were exposed to different concentrations of Pinot noir pomace extract (100 µg/mL, 200 µg/mL, and 400 µg/mL), no changes in Nrf2 gene expression were observed. However, the gene expression of HO-1 and NQO1, which are in the signalling pathway of this transcription factor, increased according the concentrations of the extract (p = 0.0004 and p = 0.0084, respectively). In summary, our results show that anthocyanins play a very important role in Nrf2 activation and release, while at the same time not promoting its transcription. These preliminary results strongly suggest that the Pinot noir pomace extract can serve as a potent bioactive component source that protects cells against oxidative stress.

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The treatment of hypercholesterolemia is mainly based on statins. However, the response to pharmacological therapy shows high inter-individual variability, resulting in variable effects in both lipid lowering and risk reduction. Thus, a better understanding of the lipid-lowering mechanisms and response variability at the molecular level is required. Previously, we demonstrated a deregulation of the microRNA expression profile in HepG2 cells treated for 24 h with atorvastatin, using a microarray platform. In the present study, we evaluated the expression of hsa-miR-17-5p, hsa-miR-20a-5p and hsa-miR-106a-5p in hypercholesterolemic patients before and after atorvastatin treatment and in HepG2 cells treated for 24 h with atorvastatin The miRNA hsa-mir-20a-5p was repressed after atorvastatin treatment in hypercholesteremic subjects and in HepG2 cells in culture. Repression of hsa-mir-20a-5p increased LDLR gene and protein expression in HepG2 cells, while hsa-mir-20a-5p overexpression reduced LDLR gene and protein expression.

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Cisplatin (DDP) is a well-known anticancer drug used for the treatment of numerous human cancers in solid organs, including bladder, breast, cervical, head and neck squamous cell, ovarian, among others. Its most important mode of action is the DNA-platinum adducts formation, inducing DNA damage response, silencing or activating several genes to induce apoptosis; these mechanisms result in genetics and epigenetics modifications. The ability of DDP to induce tumor cell death is often challenged by the presence of anti-apoptotic regulators, leading to chemoresistance, wherein many patients who have or will develop DDP-resistance. Cancer cells resist the apoptotic effect of chemotherapy, being a problem that severely restricts the successful results of treatment for many human cancers. In the last 30 years, researchers have discovered there are several types of RNAs, and among the most important are non-coding RNAs (ncRNAs), a class of RNAs that are not involved in protein production, but they are implicated in gene expression regulation, and representing the 98% of the human genome non-translated. Some ncRNAs of great interest are long ncRNAs, circular RNAs, and microRNAs (miRs). Accumulating studies reveal that aberrant miRs expression can affect the development of chemotherapy drug resistance, by modulating the expression of relevant target proteins. Thus, identifying molecular mechanisms underlying chemoresistance development is fundamental for setting strategies to improve the prognosis of patients with different types of cancer. Therefore, this review aimed to identify and summarize miRs that modulate chemoresistance in DDP-resistant in the top five deadliest cancer, both in vitro and in vivo human models.

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The purpose of this systematic review was to map out and summarize scientific evidence on dysregulated microRNAs (miRNAs) that can be possible biomarkers or therapeutic targets for cisplatin nephrotoxicity and have already been tested in humans, animals, or cells. In addition, an in silico analysis of the two miRNAs found to be dysregulated in the majority of studies was performed. A literature search was performed using eight databases for studies published up to 4 July 2021. Two independent reviewers selected the studies and extracted the data; disagreements were resolved by a third and fourth reviewers. A total of 1002 records were identified, of which 30 met the eligibility criteria. All studies were published in English and reported between 2010 and 2021. The main findings were as follows: (a) miR-34a and miR-21 were the main miRNAs identified by the studies as possible biomarkers and therapeutic targets of cisplatin nephrotoxicity; (b) the in silico analysis revealed 124 and 131 different strongly validated targets for miR-34a and miR-21, respectively; and (c) studies in humans remain scarce.

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Aim: miRNAs are potential biomarkers of several diseases. This review aimed to identify the miRNAs that could serve as biomarkers of COVID-19. Materials & methods: A literature search of nine databases was carried out for studies published before 13 June 2021 that described dysregulated miRNAs in cells or animals infected by SARS-CoV-2 or in patients with COVID-19. Two independent reviewers selected the studies and extracted data; disagreements were resolved by a third reviewer. Results: Twenty studies were included in this scoping review; results suggested that miR-21-5p, miR-146a, miR-126-3p, miR-144 and miR-155 are the most important dysregulated miRNAs that could serve as biomarkers for diagnosing and indicating the severity of COVID-19. miRNAs appear to play key roles in viral replication, proliferation of infected cells, immune response, inflammation and cardiovascular dysfunction. Conclusion: This review provides insights into the role of miRNAs as biomarkers in COVID-19 and the current status and future directions for research in this field.

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