Diagnostic accuracy of circular RNA for diabetes Mellitus : a systematic review and diagnostic Meta-analysis

Acknowledgements: We thank all our staff at the Tehran University of medical sciences and at Kurdistan University of Medical sciences who helped us in this work. We also acknowledge the papers that we used and participants in those papers. Funding Information: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Publisher Copyright: © 2023, The Author(s).Peer reviewedPublisher PD

Catálogo Taxonômico da Fauna do Brasil: setting the baseline knowledge on the animal diversity in Brazil

The limited temporal completeness and taxonomic accuracy of species lists, made available in a traditional manner in scientific publications, has always represented a problem. These lists are invariably limited to a few taxonomic groups and do not represent up-to-date knowledge of all species and classifications. In this context, the Brazilian megadiverse fauna is no exception, and the Catálogo Taxonômico da Fauna do Brasil (CTFB) (http://fauna.jbrj.gov.br/), made public in 2015, represents a database on biodiversity anchored on a list of valid and expertly recognized scientific names of animals in Brazil. The CTFB is updated in near real time by a team of more than 800 specialists. By January 1, 2024, the CTFB compiled 133,691 nominal species, with 125,138 that were considered valid. Most of the valid species were arthropods (82.3%, with more than 102,000 species) and chordates (7.69%, with over 11,000 species). These taxa were followed by a cluster composed of Mollusca (3,567 species), Platyhelminthes (2,292 species), Annelida (1,833 species), and Nematoda (1,447 species). All remaining groups had less than 1,000 species reported in Brazil, with Cnidaria (831 species), Porifera (628 species), Rotifera (606 species), and Bryozoa (520 species) representing those with more than 500 species. Analysis of the CTFB database can facilitate and direct efforts towards the discovery of new species in Brazil, but it is also fundamental in providing the best available list of valid nominal species to users, including those in science, health, conservation efforts, and any initiative involving animals. The importance of the CTFB is evidenced by the elevated number of citations in the scientific literature in diverse areas of biology, law, anthropology, education, forensic science, and veterinary science, among others

Atrial natriuretic peptide 31-67: A novel therapeutic factor for cardiovascular diseases

The characterization of the cardiac hormone atrial natriuretic peptide (ANP 9 9 – 1 26 ), synthesized and secreted predominantly by atrial myocytes under stimulation by mechanical stretch, has established the heart as an endocrine organ with potent natriuretic, diuretic, and vasodilating actions. Three additional distinct polypeptides resulting from proteolytic cleavage of proANP have been identified in the circulation in humans. The mid-sequence proANP fragment 31–67 (also known as proANP 3 1 – 6 7 ) has unique potent and prolonged diuretic and natriuretic properties. In this review, we report the main effects of this circulating hormone in different tissues and organs, and its mechanisms of actions. We further highlight recent evidence on the cardiorenal protective actions of chronic supplementation of synthetic proANP 3 1 – 6 7 in preclinical models of cardiorenal disease. Finally, we evaluate the use of proANP 3 1 – 6 7 as a new therapeutic strategy to repair end-organ damage secondary to hypertension, diabetes mellitus, renal diseases, obesity, heart failure, and other morbidities that can lead to impaired cardiac function and structure

Identification of novel genetic variants associated with cardiorespiratory fitness

Introduction Low maximal oxygen uptake (VO2max) is a strong and independent risk factor for all-cause and cardiovascular disease (CVD) mortality. For other CVD risk factors, numerous genetic association studies have been performed, revealing promising risk markers and new therapeutic targets. However, large genomic association studies on VO2max are still lacking, despite the fact that VO2max has a large genetic component. Methods We performed a genetic association study on 123.545 single-nucleotide polymorphisms (SNPs) and directly measured VO2max in 3470 individuals (exploration cohort). Candidate SNPs from the exploration cohort were analyzed in a validation cohort of 718 individuals, in addition to 7 wild-card SNPs. Sub-analyses were performed for each gender. Validated SNPs were used to create a genetic score for VO2max. In silico analyses and genotype-phenotype databases were used to predict physiological function of the SNPs. Results In the exploration cohort, 41 SNPs were associated with VO2max (p < 5.0 ∗ 10−4). Six of the candidate SNPs were associated with VO2max also in the validation cohort, in addition to three wild-card SNPs (p < 0.05, in men, women or both). The cumulative number of high-VO2max-SNPs correlated negatively with CVD risk factors, e.g. waist-circumference, visceral fat, fat %, cholesterol levels and BMI. In silico analysis indicated that several of the VO2max-SNPs influence gene expression in adipose tissue, skeletal muscle and heart. Conclusion We discovered and validated new SNPs associated with VO2max and proposed possible links between VO2max and CVD. Studies combining several large cohorts with directly measured VO2max are needed to identify more SNPs associated with this phenotype

Identification of novel genetic variants associated with cardiorespiratory fitness

Introduction: Low maximal oxygen uptake (VO) is a strong and independent risk factor for all-cause and cardiovascular disease (CVD) mortality. For other CVD risk factors, numerous genetic association studies have been performed, revealing promising risk markers and new therapeutic targets. However, large genomic association studies on VO are still lacking, despite the fact that VO has a large genetic component. Methods: We performed a genetic association study on 123.545 single-nucleotide polymorphisms (SNPs) and directly measured VO in 3470 individuals (exploration cohort). Candidate SNPs from the exploration cohort were analyzed in a validation cohort of 718 individuals, in addition to 7 wild-card SNPs. Sub-analyses were performed for each gender. Validated SNPs were used to create a genetic score for VO. In silico analyses and genotype-phenotype databases were used to predict physiological function of the SNPs. Results: In the exploration cohort, 41 SNPs were associated with VO (p < 5.0 ∗ 10). Six of the candidate SNPs were associated with VO also in the validation cohort, in addition to three wild-card SNPs (p < 0.05, in men, women or both). The cumulative number of high-VO SNPs correlated negatively with CVD risk factors, e.g. waist-circumference, visceral fat, fat %, cholesterol levels and BMI. In silico analysis indicated that several of the VO-SNPs influence gene expression in adipose tissue, skeletal muscle and heart. Conclusion: We discovered and validated new SNPs associated with VO and proposed possible links between VO and CVD. Studies combining several large cohorts with directly measured VO are needed to identify more SNPs associated with this phenotype

Vibrational spectroscopy identifies myocardial chemical modifications in heart failure with preserved ejection fraction

Abstract Background Vibrational spectroscopy can be a valuable tool to monitor the markers of cardiovascular diseases. In the present work, we explored the vibrational spectroscopy characteristics of the cardiac tissue in an experimental model of heart failure with preserved ejection fraction (HFpEF). The goal was to detect early cardiac chemical modifications associated with the development of HFpEF. Methods We used the Fourier-transform infrared (FTIR) and Raman micro-spectroscopic techniques to provide complementary and objective tools for the histological assessment of heart tissues from an animal model of HFpEF. A new sampling technique was adopted (tissue print on a CaF2 disk) to characterize the extracellular matrix. Results Several spectroscopic markers (lipids, carbohydrates, and glutamate bands) were recognized in the cardiac ventricles due to the comorbidities associated with the pathology, such as obesity and diabetes. Besides, abnormal collagen cross-linking and a decrease in tryptophan content were observed and related to the stiffening of ventricles and to the inflammatory state which is a favourable condition for HFpEF. Conclusions By the analyses of tissues and tissue prints, FTIR and Raman techniques were shown to be highly sensitive and selective in detecting changes in the chemistry of the heart in experimental HFpEF and its related comorbidities. Vibrational spectroscopy is a new approach that can identify novel biomarkers for early detection of HFpEF

Circulating microRNAs May Serve as Biomarkers for Hypertensive Emergency End-Organ Injuries and Address Underlying Pathways in an Animal Model

There is an incomplete understanding of the underlying pathophysiology in hypertensive emergencies, where severely elevated blood pressure causes acute end-organ injuries, as opposed to the long-term manifestations of chronic hypertension. Furthermore, current biomarkers are unable to detect early end-organ injuries like hypertensive encephalopathy and renal thrombotic microangiopathy. We hypothesized that circulating microRNAs (c-miRs) could identify acute and chronic complications of severe hypertension, and that combinations of c-miRs could elucidate important pathways involved. We studied the diagnostic accuracy of 145 c-miRs in Dahl salt-sensitive rats fed either a low-salt (N = 20: 0.3% NaCl) or a high-salt (N = 60: 8% NaCl) diet. Subclinical hypertensive encephalopathy and thrombotic microangiopathy were diagnosed by histopathology. In addition, heart failure with preserved ejection fraction was evaluated with echocardiography and N-terminal pro-brain natriuretic peptide; and endothelial dysfunction was studied using acetylcholine-induced aorta ring relaxation. Systolic blood pressure increased severely in animals on a high-salt diet (high-salt 205 ± 20 mm Hg vs. low-salt 152 ± 18 mm Hg, p < 0.001). Partial least squares discriminant analysis revealed 68 c-miRs discriminating between animals with and without hypertensive emergency complications. Twenty-nine c-miRs were strongly associated with hypertensive encephalopathy, 24 c-miRs with thrombotic microangiopathy, 30 c-miRs with heart failure with preserved ejection fraction, and 28 c-miRs with endothelial dysfunction. Hypertensive encephalopathy, thrombotic microangiopathy and heart failure with preserved ejection fraction were associated with deviations in many of the same c-miRs, whereas endothelial dysfunction was associated with a different set of c-miRs. Several of these c-miRs demonstrated fair to good diagnostic accuracy for a composite outcome of hypertensive encephalopathy, thrombotic microangiopathy and heart failure with preserved ejection fraction in receiver-operating-curve analyses (area-under-curve 0.75–0.88). Target prediction revealed an enrichment of genes related to several pathways relevant for cardiovascular disease (e.g., mucin type O-glycan biosynthesis, MAPK, Wnt, Hippo, and TGF-beta signaling). C-miRs could potentially serve as biomarkers of severe hypertensive end-organ injuries and elucidate important pathways involved

Circulating microRNAs May Serve as Biomarkers for Hypertensive Emergency End-Organ Injuries and Address Underlying Pathways in an Animal Model

There is an incomplete understanding of the underlying pathophysiology in hypertensive emergencies, where severely elevated blood pressure causes acute end-organ injuries, as opposed to the long-term manifestations of chronic hypertension. Furthermore, current biomarkers are unable to detect early end-organ injuries like hypertensive encephalopathy and renal thrombotic microangiopathy. We hypothesized that circulating microRNAs (c-miRs) could identify acute and chronic complications of severe hypertension, and that combinations of c-miRs could elucidate important pathways involved. We studied the diagnostic accuracy of 145 c-miRs in Dahl salt-sensitive rats fed either a low-salt (N = 20: 0.3% NaCl) or a high-salt (N = 60: 8% NaCl) diet. Subclinical hypertensive encephalopathy and thrombotic microangiopathy were diagnosed by histopathology. In addition, heart failure with preserved ejection fraction was evaluated with echocardiography and N-terminal pro-brain natriuretic peptide; and endothelial dysfunction was studied using acetylcholine-induced aorta ring relaxation. Systolic blood pressure increased severely in animals on a high-salt diet (high-salt 205 ± 20 mm Hg vs. low-salt 152 ± 18 mm Hg, p < 0.001). Partial least squares discriminant analysis revealed 68 c-miRs discriminating between animals with and without hypertensive emergency complications. Twenty-nine c-miRs were strongly associated with hypertensive encephalopathy, 24 c-miRs with thrombotic microangiopathy, 30 c-miRs with heart failure with preserved ejection fraction, and 28 c-miRs with endothelial dysfunction. Hypertensive encephalopathy, thrombotic microangiopathy and heart failure with preserved ejection fraction were associated with deviations in many of the same c-miRs, whereas endothelial dysfunction was associated with a different set of c-miRs. Several of these c-miRs demonstrated fair to good diagnostic accuracy for a composite outcome of hypertensive encephalopathy, thrombotic microangiopathy and heart failure with preserved ejection fraction in receiver-operating-curve analyses (area-under-curve 0.75–0.88). Target prediction revealed an enrichment of genes related to several pathways relevant for cardiovascular disease (e.g., mucin type O-glycan biosynthesis, MAPK, Wnt, Hippo, and TGF-beta signaling). C-miRs could potentially serve as biomarkers of severe hypertensive end-organ injuries and elucidate important pathways involved

Exercise training reveals inflexibility of the diaphragm in an animal model of patients with obesity-driven heart failure with a preserved ejection fraction

Background Respiratory muscle weakness contributes to exercise intolerance in patients with heart failure with a preserved ejection fraction (HFpEF)—a condition characterized by multiple comorbidities with few proven treatments. We aimed, therefore, to provide novel insight into the underlying diaphragmatic alterations that occur in HFpEF by using an obese cardiometabolic rat model and further assessed whether exercise training performed only after the development of overt HFpEF could reverse impairments. Methods and Results Obese ZSF1 rats (n=12) were compared with their lean controls (n=8) at 20 weeks, with 3 additional groups of obese ZSF1 rats compared at 28 weeks following 8 weeks of either sedentary behavior (n=13), high‐intensity interval training (n=11), or moderate‐continuous training (n=11). Obese rats developed an obvious HFpEF phenotype at 20 and 28 weeks. In the diaphragm at 20 weeks, HFpEF induced a shift towards an oxidative phenotype and a fiber hypertrophy paralleled by a lower protein expression in MuRF1 and MuRF2, yet mitochondrial and contractile functional impairments were observed. At 28 weeks, neither the exercise training regimen of high‐intensity interval training or moderate‐continuous training reversed any of the diaphragm alterations induced by HFpEF. Conclusions This study, using a well‐characterized rat model of HFpEF underpinned by multiple comorbidities and exercise intolerance (ie, one that closely resembles the patient phenotype), provides evidence that diaphragm alterations and dysfunction induced in overt HFpEF are not reversed following 8 weeks of aerobic exercise training. As such, whether alternative therapeutic interventions are required to treat respiratory muscle weakness in HFpEF warrants further investigation

Differential regulation of cysteine oxidative post-translational modifications in high and low aerobic capacity

Given the association between high aerobic capacity and the prevention of metabolic diseases, elucidating the mechanisms by which high aerobic capacity regulates whole-body metabolic homeostasis is a major research challenge. Oxidative post-translational modifications (Ox-PTMs) of proteins can regulate cellular homeostasis in skeletal and cardiac muscles, but the relationship between Ox-PTMs and intrinsic components of oxidative energy metabolism is still unclear. Here, we evaluated the Ox-PTM profile in cardiac and skeletal muscles of rats bred for low (LCR) and high (HCR) intrinsic aerobic capacity. Redox proteomics screening revealed different cysteine (Cys) Ox-PTM profile between HCR and LCR rats. HCR showed a higher number of oxidized Cys residues in skeletal muscle compared to LCR, while the opposite was observed in the heart. Most proteins with differentially oxidized Cys residues in the skeletal muscle are important regulators of oxidative metabolism. The most oxidized protein in the skeletal muscle of HCR rats was malate dehydrogenase (MDH1). HCR showed higher MDH1 activity compared to LCR in skeletal, but not cardiac muscle. These novel findings indicate a clear association between Cys Ox-PTMs and aerobic capacity, leading to novel insights into the role of Ox-PTMs as an essential signal to maintain metabolic homeostasis