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Chronic noncommunicable diseases are a global health problem causing increased rates of mortality and sick leaves, which can be reduced by controlling dyslipidemia and hyperglycemia. Experimental and clinical studies have demonstrated the antidiabetic, lipid-lowering, antiobesogenic, anti-inflammatory, and antihypertensive properties of cinnamon; therefore, its use in yogurt can help reverse the effects of these diseases. Our study aims to evaluate the effect of a microencapsulated aqueous extract of cinnamon (Cinnamomum zeylanicum) (MCE Cz) incorporated in a yogurt drink on metabolic syndrome (MS) in a rabbit (Oryctolagus cuniculus). Physicochemical, microbiological, and proximal chemical characterization; total phenol, flavonoid, and 2,2-diphenyl-1-picrylhydrazil activity quantification; intestinal bioaccessibility; sensory analysis; MS induction through diet; and treatment with 5, 10, and 20 mg/kg of flavonoids contained in the MCE Cz were performed to help evaluate morphological, biochemical, and lipid peroxidation measurements in the liver and heart. The results show that the addition of MCE Cz in the yogurt modified the yogurt texture, increased its adhesiveness and firmness, and imparted a characteristic cinnamon color and biological value by providing intestinally bioaccessible antioxidants with antioxidant potential by reducing lipoperoxidation in the liver and heart after treatment. MCE Cz reduced the weight of the animals by up to 38.5% and the abdominal circumference by 29%. Biochemically, it decreased glucose levels by 24.38%, total cholesterol levels by 69.2%, triglyceride levels by 72.69%, and low-density lipoprotein levels by 89.25%; it increased high-density lipoprotein levels by 67.08%. Therefore, adding MCE Cz in doses of 5 and 10 mg of flavonoids in drinkable yogurt can be an alternative to preparing functional foods with physicochemical attributes and biological properties that can be consumed at all stages of life without undesirable effects. Moreover, it can act as a potential adjuvant in the treatment of comorbidities related to MS.
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Cinnamomum zeylanicum , Síndrome Metabólica , Extratos Vegetais , Iogurte , Animais , Coelhos , Cinnamomum zeylanicum/química , Síndrome Metabólica/dietoterapia , Iogurte/análise , Extratos Vegetais/administração & dosagem , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Masculino , Alimentos Fortificados/análise , Flavonoides/análise , Flavonoides/administração & dosagem , Composição de Medicamentos , HumanosRESUMO
Recently, the use of nanotechnology in food has gained great interest. Iron nanoparticles with unique chemical, physical and structural properties allow their potential use mainly as iron fortifiers, colorants and antimicrobial agents. However, in the market we can find only supplements and food colorants based on iron nanoparticles. Their use in food fortification has so far been focused only on in vitro and in vivo experimental studies, since the toxicological evaluation of these studies has so far been the basis for the proposals of laws and regulations, which are still in an early stage of development. Therefore, the aim of this work was to summarize the use of the different forms of iron nanoparticles (oxides, oxyhydroxides, phosphates, pyrophosphates and sulfates) as food additives and supplements and to resume the perspectives of legislation regarding the use of these types of nanoparticles in the food industry.
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Metabolic syndrome (MetS) predisposes individuals to chronic non-communicable diseases (NCDs) like type 2 diabetes (T2D), non-alcoholic fatty liver disease, atherosclerosis, and cardiovascular disorders caused by systemic inflammation, intestinal dysbiosis, and diminished antioxidant ability, leading to oxidative stress and compromised insulin sensitivity across vital organs. NCDs present a global health challenge characterized by lengthy and costly pharmacological treatments. Complementary and alternative medicine using herbal therapies has gained popularity. Approximately 350,000 plant species are considered medicinal, with 80% of the world's population opting for traditional remedies; however, only 21,000 plants are scientifically confirmed by the WHO. The Rubiaceae family is promissory for preventing and treating MetS and associated NCDs due to its rich content of metabolites renowned for their antioxidative, anti-inflammatory, and metabolic regulatory properties. These compounds influence transcription factors and mitigate chronic low-grade inflammation, liver lipotoxicity, oxidative stress, and insulin resistance, making them a cost-effective non-pharmacological approach for MetS prevention and treatment. This review aims to collect and update data that validate the traditional uses of the Rubiaceae family for treating MetS and associated NCDs from experimental models and human subjects, highlighting the mechanisms through which their extracts and metabolites modulate glucose and lipid metabolism at the molecular, biochemical, and physiological levels.
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Diabetic nephropathy is a major complication in diabetic patients. Podocytes undergo loss and detachment from the basal membrane. Intra- and intercellular communication through exosomes are key processes for maintaining function, and the Rab3A/Rab27A system is an important counterpart. Previously, we observed significant changes in the Rab3A/Rab27A system in podocytes under glucose overload, demonstrating its important role in podocyte injury. We investigated the implication of silencing the Rab3A/Rab27A system in high glucose-treated podocytes and analysed the effect on differentiation, apoptosis, cytoskeletal organisation, vesicle distribution, and microRNA expression in cells and exosomes. For this, we subjected podocytes to high glucose and transfection through siRNAs, and we isolated extracellular vesicles and performed western blotting, transmission electron microscopy, RT-qPCR, immunofluorescence and flow cytometry assays. We found that silencing RAB3A and RAB27A generally leads to a decrease in podocyte differentiation and cytoskeleton organization and an increase in apoptosis. Moreover, CD63-positive vesicles experienced a pattern distribution change. Under high glucose, Rab3A/Rab27A silencing ameliorates some of these detrimental processes, suggesting a differential influence depending on the presence or absence of cellular stress. We also observed substantial expression changes in miRNAs that were relevant in diabetic nephropathy upon silencing and glucose treatment. Our findings highlight the Rab3A/Rab27A system as a key participant in podocyte injury and vesicular traffic regulation in diabetic nephropathy.
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BACKGROUND: Endothelial dysfunction is a forerunner of atherosclerosis, leading to cardiovascular disease, and albuminuria is a marker of endothelial dysfunction. Circulating levels of microRNAs are emerging as potential biomarkers for cardiovascular disease. Here we estimate the predictive value of a plasma microRNAs signature associated with albuminuria in the incidence of cardiovascular events. METHODS: Plasma microRNAs quantified in hypertensive patients by next generation sequencing were validated in a cohort of patients and controls by real-time quantitative PCR. The microRNAs found to be associated with albuminuria were analysed for their prognostic value in predicting cardiovascular events incidence on a retrospective, population-based study (Hortega Study), using Cox proportional hazard models. RESULTS: A plasma microRNA profile was identified in the discovery cohort (n = 48) associated with albuminuria and three microRNAs (miR-126-3p, miR-1260b and miR-374a-5p) were confirmed in the validation cohort (n = 98). The microRNA signature discriminates urinary albumin excretion at baseline (n = 1025), and predicts the incidence of cardiovascular events and coronary heart disease and stroke in a general population retrospective study within a 14-year follow-up (n = 926). High miR-126-3p levels were associated with a shorter time free of both cardiovascular events (HR=1.48, (1.36-1.62), p < 0.0001), as well as coronary artery disease and stroke combined (HR=2.49, (2.19-2.83), p < 0.0001). CONCLUSIONS: An increased plasma microRNAs profile was identified in hypertensive patients with albuminuria. Increased miR-126-3p suggest it may serve as a prognostic marker for cardiovascular events in a long-term general population. Further studies will assess the potential role of miR-126-3p as a guide for the status of endothelial dysfunction.
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Doenças Cardiovasculares , Hipertensão , MicroRNAs , Acidente Vascular Cerebral , Humanos , Estudos Retrospectivos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Albuminúria , MicroRNAs/genética , Biomarcadores , Hipertensão/epidemiologiaRESUMO
Despite considerable progress in our understanding of systemic lupus erythematosus (SLE) pathophysiology, patient diagnosis is often deficient and late, and this has an impact on disease progression. The aim of this study was to analyze non-coding RNA (ncRNA) packaged into exosomes by next-generation sequencing to assess the molecular profile associated with renal damage, one of the most serious complications of SLE, to identify new potential targets to improve disease diagnosis and management using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The plasma exosomes had a specific ncRNA profile associated with lupus nephritis (LN). The three ncRNA types with the highest number of differentially expressed transcripts were microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and piwi-interacting RNAs (piRNAs). We identified an exosomal 29-ncRNA molecular signature, of which 15 were associated only with LN presence; piRNAs were the most representative, followed by lncRNAs and miRNAs. The transcriptional regulatory network showed a significant role for four lncRNAs (LINC01015, LINC01986, AC087257.1 and AC022596.1) and two miRNAs (miR-16-5p and miR-101-3p) in network organization, targeting critical pathways implicated in inflammation, fibrosis, epithelial-mesenchymal transition and actin cytoskeleton. From these, a handful of potential targets, such as transforming growth factor-ß (TGF-ß) superfamily binding proteins (activin-A, TGFB receptors, etc.), WNT/ß-catenin and fibroblast growth factors (FGFs) have been identified for use as therapeutic targets of renal damage in SLE.
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Exossomos , Lúpus Eritematoso Sistêmico , Nefrite Lúpica , MicroRNAs , RNA Longo não Codificante , Humanos , Nefrite Lúpica/diagnóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Lúpus Eritematoso Sistêmico/genética , MicroRNAs/genética , Rim/metabolismo , Exossomos/genética , Exossomos/metabolismo , RNA de Interação com PiwiRESUMO
BACKGROUND: Preclinical and clinical evidence implies that destructive therapies in local and malignant tissue are frequently used on patients with head and neck cancer. Consequently, the microbiome of the treated and adjacent regions is affected. Disruption of the normal microbiome plays an important role not only in the disease progression but also in its emergence, therefore new therapies involving probiotics, prebiotics, and synbiotics have been developed to control or regulate this microbial disruption. OBJECTIVE: This review aims to describe the current and potential uses of probiotics at different stages of development of head and neck squamous cell carcinoma, as an adjuvant therapy to prevent common complications such as radiation-induced oral mucositis (RIOM) and its role in other areas. METHODS: Currently, there is no widely effective strategy to treat or prevent this kind of cancer. Surgery, radiation therapy, and chemotherapy are the three main treatments for head and neck cancer. Some therapies can also cause long-term health problems, or complications which might change the way you eat, talk, hear and breathe. RESULTS: The main uses for which probiotics have been studied are: Prevention and reduction of severity of RIOM, change in dental plaque to reduce dysbiosis, and reduction of complications in post-operated patients. Potential uses of probiotics include the reduction of disease initiation and progression by reducing local inflammation caused by bacteria and other organisms. CONCLUSION: The incidence and severity of RIOM may be lessened by probiotics. To establish its uses in additional clinical settings, though, more studies are necessary.
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Neoplasias de Cabeça e Pescoço , Probióticos , Estomatite , Simbióticos , Humanos , Probióticos/uso terapêutico , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/complicações , Prebióticos , Estomatite/etiologia , Estomatite/prevenção & controleRESUMO
Pamabrom is a diuretic that is effective in treating premenstrual syndrome and primary dysmenorrhea. The aim of this study was to examine the effect of metformin and modulators of the opioid receptor-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP)-K+ channel pathway on the local antinociception induced by pamabrom. The rat paw 1% formalin test was used to assess the effects. Rats were treated with local administration of pamabrom (200-800 µg/paw) or indomethacin (200-800 µg/paw). The antinociception of pamabrom or indomethacin was evaluated with and without the local pretreatment of the blockers. Local administration of pamabrom and indomethacin produced dose-dependent antinociception during the second phase of the test. Local pretreatment of the paws with naloxone (50 µg/paw), l-nitro-arginine methyl ester (10-100 µg/paw), or 1H-(1,2,4)-oxadiazolo[4,2-a]quinoxalin-1-one (10-100 µg/paw) reverted the antinociception induced by local pamabrom, but not of indomethacin. Similarly, the K+ channel blockers glibenclamide, glipizide, 4-aminopyridine, tetraethylammonium, charybdotoxin, or apamin reverted the pamabrom-induced antinociception, but not of indomethacin. Metformin significantly blocked the antinociception of pamabrom and indomethacin. Our data suggest that pamabrom could activate the opioid receptor-NO-cGMP-K+ channel pathway to produce its peripheral antinociception in the formalin test. Likewise, a biguanide-dependent mechanism could be activated by pamabrom and indomethacin to generate antinociception.
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Metformina , Naloxona , Feminino , Ratos , Animais , Naloxona/farmacologia , GMP Cíclico/metabolismo , Ratos Wistar , Óxido Nítrico/metabolismo , Diuréticos , Metformina/farmacologia , Indometacina , Receptores Opioides , Analgésicos/farmacologia , Bloqueadores dos Canais de Potássio/farmacologiaRESUMO
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is now considered the most common chronic liver disease worldwide. NAFLD is related to changes in lipid metabolism and is characterized by the increase or accumulation of fat in hepatocytes that may progress to nonalcoholic steatohepatitis (NASH), which leads to the appearance of inflammatory processes. Treatment consists of changes in diet, physical activity, and weight control; however, these disorders represent a health problem and require the development of novel alternatives to treatment and prevention. NAFLD/NASH are strongly associated with other disorders, such as metabolic syndrome (MetS); in fact, NAFLD is considered the hepatic manifestation of MetS. These disorders are related to other components of MetS, including dyslipidemia, which is characterized by an imbalance in blood cholesterol and triglyceride levels. Prebiotics and probiotics benefit from treating and preventing several ailments, including liver diseases. Specifically, in dyslipidemia, NAFLD, and NASH, probiotics play a fundamental role in conducting the biotransformation of primary bile acids into secondary bile acids, which generally have important activity as immunomodulators and metabolism regulators. The mechanisms of action of pre and probiotics involve the activity of bile acid receptors, such as FXR and TGR-5, and the events resulting from their activation. Therefore, prebiotics and probiotics may be reasonable options to prevent and treat metabolic- related liver diseases.
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Dislipidemias , Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Probióticos , Humanos , Hepatopatia Gordurosa não Alcoólica/terapia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Prebióticos , Fígado/metabolismo , Probióticos/uso terapêutico , Síndrome Metabólica/metabolismo , Dislipidemias/tratamento farmacológico , Dislipidemias/metabolismo , Ácidos e Sais Biliares/metabolismoRESUMO
OBJECTIVE: Primary dysmenorrhea has a high prevalence among the student population. The objective of this study was to determine the prevalence of dysmenorrhea, its severity and its impact on academic performance in Mexican university students. METHODS: Cross-sectional study. An anonymous multiple-choice questionnaire was applied in class hours in the classrooms. The visual pain scale (VAS) was used for the measurement of pain. A descriptive and inferential analysis of the variables studied was carried out using the program SPSS® IBM. RESULTS: A total of 2154 (n=2154) students were surveyed. The average age of the women was 20.4 ±1.9years. The general prevalence of dysmenorrhea was 78.9%, with psychology students having the highest value (83.7%). The VAS mean pain score was of 64.0. The severity of menstrual pain in students was reported as mild in 9.0%, and moderate-severe in 91.0%. The VAS mean pain scores and intensity of pain of gerontology students were significantly higher than those reported by dentistry and medicine students (P<.05). Limitation of daily activities was reported in 90.4% of women, with medical students reporting the highest percentage (93.3%). Women reported school absenteeism in 37.0%, with medical students presenting the highest percentage (41.4%). The severity of menstrual pain as a risk factor (independent variable) positively influenced various dependent variables involved in students' academic performance (P<.05), including: stop doing their activities due to pain in 1 to 6 menstruations a year, minor concentration, absenteeism, low school performance, and lower grades during dysmenorrhea. CONCLUSION: A high prevalence of dysmenorrhea was observed and it is concluded that the severity of the symptomatology significantly interferes with the academic performance of the participants.
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Desempenho Acadêmico , Estudantes de Medicina , Adolescente , Adulto , Estudos Transversais , Dismenorreia/epidemiologia , Dismenorreia/psicologia , Feminino , Humanos , Universidades , Adulto JovemRESUMO
The components of metabolic syndrome (MetS) and hepatogastrointestinal diseases are widespread worldwide, since many factors associated with lifestyle and diet influence their development and correlation. Due to these growing health problems, it is necessary to search for effective alternatives for prevention or adjuvants in treating them. The positive impact of regulated microbiota on health is known; however, states of dysbiosis are closely related to the development of the conditions mentioned above. Therefore, the role of prebiotics, probiotics, or symbiotic complexes has been extensively evaluated; the results are favorable, showing that they play a crucial role in the regulation of the immune system, the metabolism of carbohydrates and lipids, and the biotransformation of bile acids, as well as the modulation of their central receptors FXR and TGR-5, which also have essential immunomodulatory and metabolic activities. It has also been observed that they can benefit the host by displacing pathogenic species, improving the dysbiosis state in MetS. Current studies have reported that paraprobiotics (dead or inactive probiotics) or postbiotics (metabolites generated by active probiotics) also benefit hepatogastrointestinal health.
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Microbioma Gastrointestinal , Síndrome Metabólica , Probióticos , Disbiose/complicações , Disbiose/terapia , Humanos , Síndrome Metabólica/complicações , Síndrome Metabólica/terapia , Prebióticos , Probióticos/uso terapêuticoRESUMO
AIM: To determine through a systematic review and meta-analysis the level of knowledge about pain of nursing health professionals based on their scores on the Knowledge and Attitudes Survey Regarding Pain tool and its subdimensions in different settings. BACKGROUND: Adequate pain management is closely related to the degree of knowledge about pain of the healthcare personnel. Therefore, pedagogical programs on pain have been implemented in diverse health setting. However, several studies have found significant deficiencies in the knowledge of pain in health professionals, including nurses. DESIGN: Systematic review and meta-analysis. The study protocol was developed, registered and published in the international prospective register of systematic reviews (PROSPERO). DATA SOURCES: Scopus, PubMed, Embase, Web of Science, Cochrane Library and Google Scholar databases were searched up to June 2021. Studies from 2010 to 2021 were included in the analysis. METHODS: This study was conducted according to the Report Article for Systematic Reviews and Meta-analysis (PRISMA) guidelines and the quality evaluation was realized by the Mix Methods Appraisal Tool (MMAT). A random effects model analyzed the data, due on the heterogeneity among the studies. The I2 index and Cochran's Q test were employed to inspect the heterogeneity between the studies. For the Cochran's Q test, the P-value was set at 0.05. RESULTS: Eighteen studies with 7942 nurses were included in the systematic review and meta-analysis. The percentage of total pain knowledge was 52.9 % (95 % CI: 47.2-58.6). The highest and the lowest knowledge scores were for the spiritual/cultural dimension (69.9 %, 95 % CI: 63.4-76.0) and the intervention dimension (36.8 %, 95 % CI: 28.1-45.9), respectively. The score of total knowledge of the six domains in nurses in the area of oncology (58.6 %, 95 % CI: 45.3-71.2) was higher than that of nurses of the other areas. CONCLUSIONS: The knowledge of the nursing professionals about pain was lower that the suggested level of 80 %. Our study found that the pain knowledge is positively related to the prior pain training. Therefore, there is an urgent need to include continuing educational initiatives to improve the knowledge level about pain management in all the health personnel, including the nursing professionals.
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Competência Clínica , Enfermeiras e Enfermeiros , Atitude , Pessoal de Saúde/educação , Humanos , DorRESUMO
Non-coding RNA (ncRNA)-mediated targeting of various genes regulates the molecular mechanisms of the pathogenesis of hypertension (HTN). However, very few circulating long ncRNAs (lncRNAs) have been reported to be altered in essential HTN. The aim of our study was to identify a lncRNA profile in plasma and plasma exosomes associated with urinary albumin excretion in HTN by next-generation sequencing and to assess biological functions enriched in response to albuminuria using GO and KEGG analysis. Plasma exosomes showed higher diversity and fold change of lncRNAs than plasma, and low transcript overlapping was found between the two biofluids. Enrichment analysis identified different biological pathways regulated in plasma or exosome fraction, which were implicated in fatty acid metabolism, extracellular matrix, and mechanisms of sorting ncRNAs into exosomes, while plasma pathways were implicated in genome reorganization, interference with RNA polymerase, and as scaffolds for assembling transcriptional regulators. Our study found a biofluid specific lncRNA profile associated with albuminuria, with higher diversity in exosomal fraction, which identifies several potential targets that may be utilized to study mechanisms of albuminuria and cardiovascular damage.
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Exossomos , Hipertensão , MicroRNAs , RNA Longo não Codificante , Albuminúria/genética , Albuminúria/metabolismo , Exossomos/genética , Exossomos/metabolismo , Feminino , Humanos , Hipertensão/metabolismo , Masculino , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA não Traduzido/genéticaRESUMO
Autoimmune diseases (ADs) are characterized by the activation of the immune system against self-antigens. More common in women than in men and with an early onset, their incidence is increasing worldwide, and this, combined with their chronic nature, is contributing to an enlarged medical and economic burden. Conventional immunosuppressive agents are designed to alleviate symptoms but do not constitute an effective therapy, highlighting a need to develop new alternatives. In this regard, mesenchymal stem cells (MSCs) have demonstrated powerful immunosuppressive and regenerative effects. MSC-derived extracellular vesicles (MSC-EVs) have shown some advantages, such as less immunogenicity, and are proposed as novel therapies for ADs. In this review, we summarize current perspectives on therapeutic options for ADs based on MSCs and MSC-EVs, focusing particularly on their mechanism of action exerted through their non-coding RNA (ncRNA) cargo. A complete state-of-the-art review was performed, centralized on some of the most severe ADs (rheumatoid arthritis, autoimmune type 1 diabetes mellitus, and systemic lupus erythematosus), giving evidence that a promising field is evolving to overcome the current knowledge and provide new therapeutic possibilities centered on MSC-EVs and their role as ncRNA delivery vehicles for AD gene therapy.
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Pomegranate is a polyphenol-rich fruit. Studies have shown that extracts prepared from its juice or from different parts of the pomegranate plant have various biological activities including antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, cardioprotective, and antidiabetic. The therapeutic potential has been attributed to various phytochemicals, including ellagic acid, punicic acid, flavonoids, anthocyanidins, anthocyanins, flavonols, and flavones. This review focuses on the scientific evidence of pomegranate juice as hypoglycemic, emphasizing the chemical composition and the possible mechanisms of action associated with this effect. Studies were identified using the PubMed, Scopus, and ISI Web of Science databases to identify relevant articles focused on the hypoglycemic effect of pomegranate juice. The physiological responses to pomegranate juice are reported here, including a decrease of oxidative stress damage, an increase of insulin-dependent glucose uptake, maintenance of ß-cell integrity, inhibition of nonenzymatic protein glycation, an increase of insulin sensitivity, modulation of peroxisome proliferator-activated receptor-gamma, inhibition of α-amylase, inhibition of α-glucosidase and dipeptidyl peptidase-4, and decreases in inflammation. Overall, we found a significant hypoglycemic effect of pomegranate in in vitro and in vivo studies and we summarize the potential mechanisms of action.
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Non-coding RNA (ncRNA), released into circulation or packaged into exosomes, plays important roles in many biological processes in the kidney. The purpose of the present study is to identify a common ncRNA signature associated with early renal damage and its related molecular pathways. Three individual libraries (plasma and urinary exosomes, and total plasma) were prepared from each hypertensive patient (with or without albuminuria) for ncRNA sequencing analysis. Next, an RNA-based transcriptional regulatory network was constructed. The three RNA biotypes with the greatest number of differentially expressed transcripts were long-ncRNA (lncRNA), microRNA (miRNA) and piwi-interacting RNA (piRNAs). We identified a common 24 ncRNA molecular signature related to hypertension-associated urinary albumin excretion, of which lncRNAs were the most representative. In addition, the transcriptional regulatory network showed five lncRNAs (LINC02614, BAALC-AS1, FAM230B, LOC100505824 and LINC01484) and the miR-301a-3p to play a significant role in network organization and targeting critical pathways regulating filtration barrier integrity and tubule reabsorption. Our study found an ncRNA profile associated with albuminuria, independent of biofluid origin (urine or plasma, circulating or in exosomes) that identifies a handful of potential targets, which may be utilized to study mechanisms of albuminuria and cardiovascular damage.
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Albuminúria/etiologia , Ácidos Nucleicos Livres , Exossomos , Hipertensão/sangue , Hipertensão/complicações , RNA não Traduzido/genética , Transcriptoma , Albuminúria/diagnóstico , Biomarcadores , Pressão Sanguínea , Suscetibilidade a Doenças , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Hipertensão/diagnóstico , Hipertensão/etiologia , Biópsia Líquida/métodos , MasculinoRESUMO
The objective of the present study was to scrutinize the effect of nitric oxide (NO), cyclic GMP (cGMP), potassium channel blockers, and metformin on the citral-produced peripheral antinociception. The rat paw 1% formalin test was used to assess nociception and antinociception. Rats were treated with local peripheral administration of citral (10-100 µg/paw). The antinociception of citral (100 µg/paw) was evaluated with and without the local pretreatment of naloxone, NG-L-nitro-arginine methyl ester (L-NAME, a NO synthesis inhibitor), 1H-(1,2,4)-oxadiazolo(4,2-a)quinoxalin-1-one (ODQ, a soluble guanylyl cyclase inhibitor), metformin, opioid receptors antagonists, and K+ channel blockers. Injection of citral in the rat paw significantly decreased the nociceptive effect of formalin administration during the two phases of the test. Local pretreatment of the paws with L-NAME and ODQ did not reduced the citral-induced antinociception. Glipizide or glibenclamide (Kir6.1-2; ATP-sensitive K+ channel blockers), tetraethylammonium or 4-aminopyridine (KV; voltage-gated K+ channel blockers), charybdotoxin (KCa1.1; big conductance calcium-activated K+ channel blocker), apamin (KCa2.1-3; small conductance Ca2+-activated K+ channel antagonist), or metformin, but not the opioid antagonists, reduced the antinociception of citral. Citral produced peripheral antinociception during both phases of the formalin test. These effects were due to the activation of K+ channels and a biguanide-dependent mechanism.
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GMP Cíclico , Metformina , Monoterpenos Acíclicos , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Animais , GMP Cíclico/metabolismo , Metformina/farmacologia , Óxido Nítrico/metabolismo , Nociceptividade , Medição da Dor , Bloqueadores dos Canais de Potássio/farmacologia , Ratos , Ratos Wistar , Receptores Opioides/metabolismoRESUMO
Cereals have phytochemical compounds that can diminish the incidence of chronic diseases such as hypertension. The angiotensin-converting enzyme 2 (ACE2) participates in the modulation of blood pressure and is the principal receptor of the virus SARS-CoV-2. The inhibitors of the angiotensin-converting enzyme (ACE) and the block receptors of angiotensin II regulate the expression of ACE2; thus, they could be useful in the treatment of patients infected with SARS-CoV-2. The inferior peptides from 1 to 3 kDa and the hydrophobic amino acids are the best candidates to inhibit ACE, and these compounds are present in rice, corn, wheat, oats, sorghum, and barley. In addition, the vitamins C and E, phenolic acids, and flavonoids present in cereals show a reduction in the oxidative stress involved in the pathogenesis of hypertension. The influence of ACE on hypertension and COVID-19 has turned into a primary point of control and treatment from the nutritional perspective. The objective of this work was to describe the inhibitory effect of the angiotensin-converting enzyme that the bioactive compounds present in cereals possess in order to lower blood pressure and how their consumption could be associated with reducing the virulence of COVID-19.
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Artificial Intelligence is creating a paradigm shift in health care, with phenotyping patients through clustering techniques being one of the areas of interest. OBJECTIVE: To develop a predictive model to classify heart failure (HF) patients according to their left ventricular ejection fraction (LVEF), by using available data from Electronic Health Records (EHR). SUBJECTS AND METHODS: 2854 subjects over 25 years old with a diagnosis of HF and LVEF, measured by echocardiography, were selected to develop an algorithm to predict patients with reduced EF using supervised analysis. The performance of the developed algorithm was tested in heart failure patients from Primary Care. To select the most influentual variables, the LASSO algorithm setting was used, and to tackle the issue of one class exceeding the other one by a large amount, we used the Synthetic Minority Oversampling Technique (SMOTE). Finally, Random Forest (RF) and XGBoost models were constructed. RESULTS: The full XGBoost model obtained the maximum accuracy, a high negative predictive value, and the highest positive predictive value. Gender, age, unstable angina, atrial fibrillation and acute myocardial infarct are the variables that most influence EF value. Applied in the EHR dataset, with a total of 25,594 patients with an ICD-code of HF and no regular follow-up in cardiology clinics, 6170 (21.1%) were identified as pertaining to the reduced EF group. CONCLUSION: The obtained algorithm was able to identify a number of HF patients with reduced ejection fraction, who could benefit from a protocol with a strong possibility of success. Furthermore, the methodology can be used for studies using data extracted from the Electronic Health Records.
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Small Rab GTPases, the largest group of small monomeric GTPases, regulate vesicle trafficking in cells, which are integral to many cellular processes. Their role in neurological diseases, such as cancer and inflammation have been extensively studied, but their implication in kidney disease has not been researched in depth. Rab3a and its effector Rabphillin-3A (Rph3A) expression have been demonstrated to be present in the podocytes of normal kidneys of mice rats and humans, around vesicles contained in the foot processes, and they are overexpressed in diseases with proteinuria. In addition, the Rab3A knockout mice model induced profound cytoskeletal changes in podocytes of high glucose fed animals. Likewise, RphA interference in the Drosophila model produced structural and functional damage in nephrocytes with reduction in filtration capacities and nephrocyte number. Changes in the structure of cardiac fiber in the same RphA-interference model, open the question if Rab3A dysfunction would produce simultaneous damage in the heart and kidney cells, an attractive field that will require attention in the future.