Promotion of cardiac microtissue assembly within G-CSF-enriched collagen I-cardiogel hybrid hydrogel.

Tissue engineering as an interdisciplinary field of biomedical sciences has raised many hopes in the treatment of cardiovascular diseases as well as development of in vitro three-dimensional (3D) cardiac models. This study aimed to engineer a cardiac microtissue using a natural hybrid hydrogel enriched by granulocyte colony-stimulating factor (G-CSF), a bone marrow-derived growth factor. Cardiac ECM hydrogel (Cardiogel: CG) was mixed with collagen type I (ColI) to form the hybrid hydrogel, which was tested for mechanical and biological properties. Three cell types (cardiac progenitor cells, endothelial cells and cardiac fibroblasts) were co-cultured in the G-CSF-enriched hybrid hydrogel to form a 3D microtissue. ColI markedly improved the mechanical properties of CG in the hybrid form with a ratio of 1:1. The hybrid hydrogel demonstrated acceptable biocompatibility and improved retention of encapsulated human foreskin fibroblasts. Co-culture of three cell types in G-CSF enriched hybrid hydrogel, resulted in a faster 3D structure shaping and a well-cellularized microtissue with higher angiogenesis compared to growth factor-free hybrid hydrogel (control). Immunostaining confirmed the presence of CD31+ tube-like structures as well as vimentin+ cardiac fibroblasts and cTNT+ human pluripotent stem cells-derived cardiomyocytes. Bioinformatics analysis of signaling pathways related to the G-CSF receptor in cardiovascular lineage cells, identified target molecules. The in silico-identified STAT3, as one of the major molecules involved in G-CSF signaling of cardiac tissue, was upregulated in G-CSF compared to control. The G-CSF-enriched hybrid hydrogel could be a promising candidate for cardiac tissue engineering, as it facilitates tissue formation and angiogenesis.

Decoding common genetic alterations between Barrett's esophagus and esophageal adenocarcinoma: A bioinformatics analysis.

Background: Esophageal adenocarcinoma (EAC) is a common cancer with a poor prognosis in advanced stages. Therefore, early EAC diagnosis and treatment have gained attention in recent decades. It has been found that various pathological changes, particularly Barrett's Esophagus (BE), can occur in the esophageal tissue before the development of EAC. In this study, we aimed to identify the molecular contributor in BE to EAC progression by detecting the essential regulatory genes that are differentially expressed in both BE and EAC. Materials and methods: We conducted a comprehensive bioinformatics analysis to detect BE and EAC-associated genes. The common differentially expressed genes (DEGs) and common single nucleotide polymorphisms (SNPs) were detected using the GEO and DisGeNET databases, respectively. Then, hub genes and the top modules within the protein-protein interaction network were identified. Moreover, the co-expression network of the top module by the HIPPIE database was constructed. Additionally, the gene regulatory network was constructed based on miRNAs and circRNAs. Lastly, we inspected the DGIdb database for possible interacted drugs. Results: Our microarray dataset analysis identified 92 common DEGs between BE and EAC with significant enrichment in skin and epidermis development genes. The study also identified 22 common SNPs between BE and EAC. The top module of PPI network analysis included SCEL, KRT6A, SPRR1A, SPRR1B, SPRR3, PPL, SPRR2B, EVPL, and CSTA. We constructed a ceRNA network involving three specific mRNAs, 23 miRNAs, and 101 selected circRNAs. According to the results from the DGIdb database, TD101 was found to interact with the KRT6A gene. Conclusion: The present study provides novel potential candidate genes that may be involved in the molecular association between Esophageal adenocarcinoma and Barrett's Esophagus, resulting in developing the diagnostic tools and therapeutic targets to prevent progression of BE to EAC.

Translational Approach Using Advanced Therapy Medicinal Products for Huntington's Disease.

Current therapeutic approaches for Huntington's disease (HD) focus on symptomatic treatment. Therefore, the unavailability of efficient disease-modifying medicines is a significant challenge. Regarding the molecular etiology, targeting the mutant gene or advanced translational steps could be considered promising strategies. The evidence in gene therapy suggests various molecular techniques, including knocking down mHTT expression using antisense oligonucleotides and small interfering RNAs and gene editing with zinc finger proteins and CRISPR-Cas9-based techniques. Several post-transcriptional and post-translational modifications have also been proposed. However, the efficacy and long-term side effects of these modalities have yet to be verified. Currently, cell therapy can be employed in combination with conventional treatment and could be used for HD in which the structural and functional restoration of degenerated neurons can occur. Several animal models have been established recently to develop cell-based therapies using renewable cell sources such as embryonic stem cells, induced pluripotent stem cells, mesenchymal stromal cells, and neural stem cells. These models face numerous challenges in translation into clinics. Nevertheless, investigations in Advanced Therapy Medicinal Products (ATMPs) open a promising window for HD research and their clinical application. In this study, the ATMPs entry pathway in HD management was highlighted, and their advantages and disadvantages were discussed.

UBE2C: A pan-cancer diagnostic and prognostic biomarker revealed through bioinformatics analysis.

BACKGROUND: The diverse and complex attributes of cancer have made it a daunting challenge to overcome globally and remains to endanger human life. Detection of critical cancer-related gene alterations in solid tumor samples better defines patient diagnosis and prognosis, and indicates what targeted therapies must be administered to improve cancer patients' outcome. MATERIALS AND METHODS: To identify genes that have aberrant expression across different cancer types, differential expressed genes were detected within the TCGA datasets. Subsequently, the DEGs common to all pan cancers were determined. Furthermore, various methods were employed to gain genetic alterations, co-expression genes network and protein-protein interaction (PPI) network, pathway enrichment analysis of common genes. Finally, the gene regulatory network was constructed. RESULTS: Intersectional analysis identified UBE2C as a common DEG between all 28 types of studied cancers. Upregulated UBE2C expression was significantly correlated with OS and DFS of 10 and 9 types of cancer patients. Also, UBE2C can be a diagnostic factor in CESC, CHOL, GBM, and UCS with AUC = 100% and diagnose 19 cancer types with AUC ≥90%. A ceRNA network constructed including UBE2C, 41 TFs, 10 shared miRNAs, and 21 circRNAs and 128 lncRNAs. CONCLUSION: In summary, UBE2C can be a theranostic gene, which may serve as a reliable biomarker in diagnosing cancers, improving treatment responses and increasing the overall survival of cancer patients and can be a promising gene to be target by cancer drugs in the future.

Role of long noncoding RNAs in pathological cardiac remodeling after myocardial infarction: An emerging insight into molecular mechanisms and therapeutic potential.

Myocardial infarction (MI) is the leading cause of heart failure (HF), accounting for high mortality and morbidity worldwide. As a consequence of ischemia/reperfusion injury during MI, multiple cellular processes such as oxidative stress-induced damage, cardiomyocyte death, and inflammatory responses occur. In the next stage, the proliferation and activation of cardiac fibroblasts results in myocardial fibrosis and HF progression. Therefore, developing a novel therapeutic strategy is urgently warranted to restrict the progression of pathological cardiac remodeling. Recently, targeting long non-coding RNAs (lncRNAs) provided a novel insight into treating several disorders. In this regard, numerous investigations have indicated that several lncRNAs could participate in the pathogenesis of MI-induced cardiac remodeling, suggesting their potential therapeutic applications. In this review, we summarized lncRNAs displayed in the pathophysiology of cardiac remodeling after MI, emphasizing molecular mechanisms. Also, we highlighted the possible translational role of lncRNAs as therapeutic targets for this condition and discussed the potential role of exosomes in delivering the lncRNAs involved in post-MI cardiac remodeling.

Fragmented QRS, a strong predictor of mortality and major arrhythmic events in patients with nonischemic cardiomyopathy: A systematic review and meta-analysis.

Background and Aims: Fragmented QRS (fQRS), which is associated with rhythm disturbances, can predispose the heart to fatal ventricular arrhythmias. Recently, accumulating studies indicates that fQRS is associated with poor prognosis in various types of cardiomyopathies. Therefore, we assessed the association between fQRS with all-cause mortality and major arrhythmic events (MAEs) in patients with nonischemic cardiomyopathy, in this systematic review and meta-analysis study. Methods: We performed a comprehensive search in databases of PubMed/Medline, EMBASE, and Web of Science from the beginning to December 31, 2022. Published observational studies (cohorts, case-control, or analytical cross-sectional studies) were included that report the prognostic value of fQRS in patients with different types of nonischemic cardiomyopathies for MAEs (sudden cardiac death, sudden cardiac arrest, sustained ventricular tachycardia [VT], ventricular fibrillation [VF], and appropriate shock) and all-cause mortality. We pooled risk ratios (RRs) through raw data and adjusted hazard ratios (aHRs) using "Comprehensive Meta-Analysis" software, Version 2.0. Results: Nineteen cohort and three analytical cross-sectional studies were included in this meta-analysis involving a total of 4318 subjects with nonischemic cardiomyopathy (1279 with fQRS and 3039 without fQRS). FQRS was significantly associated with an increased risk of all-cause mortality in patients with nonischemic cardiomyopathy (pooled RR: 1.920; 95% confidence interval [CI]: 1.388-2.656, p < 0.0001/pooled HR: 1.729; 95% CI: 1.327-2.251, p < 0.0001). Also, the risk of developing MAEs in the presence of fQRS was significantly increased (pooled RR: 2.041; 95% CI: 1.644-2.533, p < 0.0001/pooled HR: 3.626; 95% CI: 2.119-6.204, p < 0.0001). In the subgroup analysis, the strongest association between fQRS presence and increased MAEs was observed in patients with hypertrophic cardiomyopathy (HCM) (pooled RR: 3.44; 95% CI: 2.07-5.71, p < 0.0001/pooled HR: 3.21; 95% CI: 2.04-5.06, p < 0.0001). Conclusion: Fragmented QRS could be a prognostic marker for all-cause mortality and MAEs in patients with various types of nonischemic cardiomyopathies, particularly HCM.

Factors Affecting Late Atrial Fibrillation and Its Association With Coronary Artery Bypass Outcomes.

BACKGROUND: Although predictors and outcomes of postoperative atrial fibrillation (POAF) are well studied, evidence is lacking concerning postdischarge late/recurrent atrial fibrillation (AF). This study evaluated factors affecting late/recurrent AF and its association with coronary artery bypass grafting (CABG) outcomes in a real-world setting. METHODS: From 2012 through 2016, 5175 patients were included. Independent factors associated with late/recurrent AF were identified in a competing risk setting. Cox proportional hazard regression was used to evaluate the association between late/recurrent AF and study outcomes, consisting of all-cause mortality, major adverse cardio-cerebrovascular events, acute coronary syndrome, cerebrovascular events, and heart failure admissions. RESULTS: During a median follow-up of 60 months (quartile 1-quartile 3, 59.3-60.7 months), late/recurrent AF developed in 85 patients (1.64%). Independent factors associated with late/recurrent AF were age (subdistribution hazard ratio [sHR], 1.04; 95% CI, 1.02-1.07), left-ventricular ejection fraction (sHR, 0.97; 95% CI, 0.95-0.99), length of stay (sHR, 1.02; 95% CI, 1.01-1.04), and POAF (sHR, 4.02; 95% CI, 2.50-6.45). Late/recurrent AF was not significantly associated with all-cause mortality and major adverse cardio-cerebrovascular events at unadjusted or adjusted levels (adjusted hazard ratio, 0.80 [95% CI, 0.50-1.28] and 0.74 [95% CI, 0.48-1.13], respectively). Nevertheless, it significantly increased the unadjusted risk of cerebrovascular events (hazard ratio, 2.28; 95% CI, 01.07-4.87), which disappeared after adjustments. CONCLUSIONS: Patients with advanced age, a lower left-ventricular ejection fraction, and POAF are more likely to have late/recurrent clinical AF. Albeit counterintuitive, late/recurrent AF was not independently associated with worse midterm post-CABG outcomes. These observations need to be further elucidated in larger-scale studies and interpreted in the context of a developing country with limited resources for late AF surveillance.

Recent Insights into the Angioregulatory Role of Long Non-coding RNAs and Circular RNAs in Gliomas: From Signaling Pathways to Clinical Aspects.

The most prevalent and severe malignancy of the central nervous system within the brain is glioma. Glioma is a vascularized cancer, and angiogenesis is necessary for glioma growth, invasion, and recurrence. It is also believed that this factor is this factor to be accountable for therapy resistance in many cancers, including glioma. The process of angiogenesis, which plays a crucial role in both health and disease situations such as cancer, involves the creation of new blood vessels from pre-existing ones. Non-coding RNAs (ncRNAs) are unique molecules that have been found to possess a wide range of abilities to modify the expression of various genes. They carry out their gene-modulating roles at a variety of distinct levels, including post-transcriptional and post-translational levels. Long ncRNAs (lncRNAs) and circular RNAs (circRNAs) are a group of ncRNA that have attracted particular attention and are involved in the angiogenesis mechanism in cancer. Understanding the regulatory mechanisms of these RNAs in the angiogenesis process in gliomas provides unique fundamental information about the process of tumor-associated neovascularization. On the other hand, due to developments in the characterisation of lncRNAs and circRNAs, these novel structures may potentially be used in clinics as possible biomarkers for treatment strategies that target tumor angiogenesis. Throughout the review, new knowledge and views about the angioregulatory function of circRNAs and lncRNAs in gliomas have been presented. Additionally, we talk about the novel idea of ncRNA-based therapeutics for gliomas in the future.

Predictive modeling for acute kidney injury after percutaneous coronary intervention in patients with acute coronary syndrome: a machine learning approach.

BACKGROUND: Acute kidney injury (AKI) is one of the preventable complications of percutaneous coronary intervention (PCI). This study aimed to develop machine learning (ML) models to predict AKI after PCI in patients with acute coronary syndrome (ACS). METHODS: This study was conducted at Tehran Heart Center from 2015 to 2020. Several variables were used to design five ML models: Naïve Bayes (NB), Logistic Regression (LR), CatBoost (CB), Multi-layer Perception (MLP), and Random Forest (RF). Feature importance was evaluated with the RF model, CB model, and LR coefficients while SHAP beeswarm plots based on the CB model were also used for deriving the importance of variables in the population using pre-procedural variables and all variables. Sensitivity, specificity, and the area under the receiver operating characteristics curve (ROC-AUC) were used as the evaluation measures. RESULTS: A total of 4592 patients were included, and 646 (14.1%) experienced AKI. The train data consisted of 3672 and the test data included 920 cases. The patient population had a mean age of 65.6 ± 11.2 years and 73.1% male predominance. Notably, left ventricular ejection fraction (LVEF) and fasting plasma glucose (FPG) had the highest feature importance when training the RF model on only pre-procedural features. SHAP plots for all features demonstrated LVEF and age as the top features. With pre-procedural variables only, CB had the highest AUC for the prediction of AKI (AUC 0.755, 95% CI 0.713 to 0.797), while RF had the highest sensitivity (75.9%) and MLP had the highest specificity (64.35%). However, when considering pre-procedural, procedural, and post-procedural features, RF outperformed other models (AUC: 0.775). In this analysis, CB achieved the highest sensitivity (82.95%) and NB had the highest specificity (82.93%). CONCLUSION: Our analyses showed that ML models can predict AKI with acceptable performance. This has potential clinical utility for assessing the individualized risk of AKI in ACS patients undergoing PCI. Additionally, the identified features in the models may aid in mitigating these risk factors.

New Insights into the Long Non-coding RNAs Dependent Modulation of Heart Failure and Cardiac Hypertrophy: From Molecular Function to Diagnosis and Treatment.

Heart failure (HF) is a public health issue that imposes high costs on healthcare systems. Despite the significant advances in therapies and prevention of HF, it remains a leading cause of morbidity and mortality worldwide. The current clinical diagnostic or prognostic biomarkers, as well as therapeutic strategies, have some limitations. Genetic and epigenetic factors have been identified to be central to the pathogenesis of HF. Therefore, they might provide promising novel diagnostic and therapeutic approaches for HF. Long non-coding RNAs (lncRNAs) belong to a group of RNAs that are produced by RNA polymerase II. These molecules play an important role in the functioning of different cell biological processes, such as transcription and regulation of gene expression. LncRNAs can affect different signaling pathways by targeting biological molecules or a variety of different cellular mechanisms. The alteration in their expression has been reported in different types of cardiovascular diseases, including HF, supporting the theory that they are important in the development and progression of heart diseases. Therefore, these molecules can be introduced as diagnostic, prognostic, and therapeutic biomarkers in HF. In this review, we summarize different lncRNAs as diagnostic, prognostic, and therapeutic biomarkers in HF. Moreover, we highlight various molecular mechanisms dysregulated by different lncRNAs in HF.

Non-coding RNAs in leukemia drug resistance: new perspectives on molecular mechanisms and signaling pathways.

Like almost all cancer types, timely diagnosis is needed for leukemias to be effectively cured. Drug efflux, attenuated drug uptake, altered drug metabolism, and epigenetic alterations are just several of the key mechanisms by which drug resistance develops. All of these mechanisms are orchestrated by up- and downregulators, in which non-coding RNAs (ncRNAs) do not encode specific proteins in most cases; albeit, some of them have been found to exhibit the potential for protein-coding. Notwithstanding, ncRNAs are chiefly known for their contribution to the regulation of physiological processes, as well as the pathological ones, such as cell proliferation, apoptosis, and immune responses. Specifically, in the case of leukemia chemo-resistance, ncRNAs have been recognized to be responsible for modulating the initiation and progression of drug resistance. Herein, we comprehensively reviewed the role of ncRNAs, specifically its effect on molecular mechanisms and signaling pathways, in the development of leukemia drug resistance.

Coronary Artery Bypass Graft Surgery After Primary Percutaneous Coronary Intervention in Patients With ST-Elevation Myocardial Infarction.

OBJECTIVE: To determine whether primary percutaneous coronary intervention (PPCI) is associated with adverse outcomes following coronary artery bypass graft (CABG) among patients with ST-elevation myocardial infarction (STEMI). METHODS: Patients presenting with acute STEMI who underwent CABG between September 2015 and November 2020 were included. Among 354 patients, 222 (62.7%) underwent PPCI prior to CABG (PPCI+CABG group) and were compared with the rest of the patients (CABG only group). The effects of PPCI on primary endpoints---including in-hospital mortality, length of stay (LOS), and bleeding events---were investigated using the stabilised inverse probability weighting method (S-IPW). Further, in-hospital mortality in various PPCI subgroups was analysed using univariable regression. RESULTS: Patients with and without PPCI were comparable regarding their baseline and surgical characteristics, except that those without PPCI were more likely to have left-main disease (29.5% vs 16.2%, p-value=0.003). Among the PPCI+CABG group, 3.6% mortality and 55.9% bleeding events occurred, and the LOS was 7 [5-10] days. The respective figures for the CABG only group were 4.5%, 50.8%, and 7 [6-10.5] days. Primary percutaneous coronary intervention, as a whole, was not significantly associated with either morality (S-IPW odds ratio (S-IPW OR) 0.61; p=0.393), LOS logarithm (S-IPW ß -0.050; p=0.403), or bleeding events (S-IPW OR 1.06; p=0.821). Nevertheless, the unadjusted mortality risk was significantly higher in complicated PPCIs compared with the CABG only group (OR 7.50, 95% CI 2.03-27.77); it was also higher among some other PPCI subgroups, albeit non-significantly. CONCLUSION: This study found that PPCI did not confer additional risk regarding in-hospital mortality, LOS, or bleeding among patients with acute STEMI who underwent CABG. However, some PPCI subgroups, especially those with complicated PPCI, were at increased risk.

Circular RNAs: novel actors of Wnt signaling pathway in lung cancer progression.

Circular RNAs (CircRNAs) are a class of regulatory RNA transcripts, which are ubiquitously expressed in eukaryotes. CircRNA dysregulation has been shown to disrupt the interaction of the Wnt/ß-catenin pathway, which regulates several biological processes involved in tumorigenesis, thereby contributing to the development and progression of cancer. Interactions of tumor-derived circRNAs with the Wnt/ß-catenin signaling pathway provide both clinical diagnostic biomarkers and promising therapeutic targets. In this review, we outlined current evidence on the roles of circRNAs associated with the Wnt/ß-catenin pathway in regulating lung cancer formation and development. We believe that our findings will assist in the advancement or establishment of circRNA-based lung cancer therapeutic approaches.

Melatonin as a regulator of apoptosis in leukaemia: molecular mechanism and therapeutic perspectives.

Leukaemia is a dangerous malignancy that causes thousands of deaths every year throughout the world. The rate of morbidity and mortality is significant despite many advancements in therapy strategies for affected individuals. Most antitumour medications used now in clinical oncology use apoptotic signalling pathways to induce cancer cell death. Accumulated data have shown a direct correlation between inducing apoptosis in cancer cells with higher tumour regression and survival. Until now, the efficacy of melatonin as a powerful antitumour agent has been firmly established. A change in melatonin concentrations has been reported in multiple tumours such as endometrial, hematopoietic, and breast cancers. Findings show that melatonin's anticancer properties, such as its prooxidation function and ability to promote apoptosis, indicate the possibility of utilizing this natural substance as a promising agent in innovative cancer therapy approaches. Melatonin stimulates cell apoptosis via the regulation of many apoptosis facilitators, including mitochondria, cytochrome c, Bcl-2, production of reactive oxygen species, and apoptosis receptors. This paper aimed to further assess the anticancer effects of melatonin through the apoptotic pathway, considering the role that cellular apoptosis plays in the pathogenesis of cancer. The effect of melatonin may mean that it is appropriate for use as an adjuvant, along with other therapeutic approaches such as radiotherapy and chemotherapy.

The prognostic role of the low and very low baseline LDL-C level in outcomes of patients with cardiac revascularization; comparative registry-based cohort design.

BACKGROUND: Although low-density lipoprotein-cholesterol (LDL-C) level is considered one of the main prognostic factors in patients with coronary artery bypass grafting (CABG), the question about "the lower the better" is still unanswered. We aimed to evaluate and compare the outcomes of patients with CABG and low or very low baseline LDL-C, regardless of statin usage. METHODS: In this registry-based cohort study, 10,218 patients with low/very low (70-100 and ≤ 70 mg/dL) baseline LDL-C who underwent isolated and the first-time CABG without known previous history of cardio-cerebrovascular events, were included and compared. The median follow-up was 73.33 (72.15-74.51) months. Primary outcomes were all-cause mortality and major adverse cardio-cerebrovascular events (MACCE) (consisted of all-cause mortality, acute coronary syndrome, stroke or transient ischemic attack, and the need for repeat revascularization [percutaneous coronary intervention or redo-CABG]). Cox regression analyses before and after the propensity score matching (PSM) model were applied to evaluate and compare outcomes. RESULTS: The mean age of the study population was 66.17 ± 9.98 years old and 2506 (24.5%) were women. Diabetes mellitus and a history of cigarette smoking were significantly higher in the very low LDL group (P-value ≤ 0.001). In Cox regression analyses before applying PSM model, both all-cause mortality (14.2% vs. 11.9%, P-value = 0.004 and MACCE (26.0% vs. 23.6%, P-value = 0.006) were significantly higher in the very low LDL group compared to low LDL. However, these results were no longer significant after applying the PSM model (all-cause mortality HR: 1.115 [95% CI: 0.986-1.262], P = 0.083 and MACCE HR: 1.077 [95%CI: 0.984-1.177], P = 0.095). The sensitivity analysis to remove the statin effect demonstrated that very low LDL-C level was correlated to higher risk of all-cause mortality in both unmatched and PSM analyses. CONCLUSION: Very low serum LDL-C levels (≤ 70 mg/dl) could increase long-term all-cause mortality and cardiovascular events in patients who have undergone isolated CABG.

The Significant Role of microRNAs in Gliomas Angiogenesis: A Particular Focus on Molecular Mechanisms and Opportunities for Clinical Application.

MicroRNAs (miRNAs) are non-coding RNAs with only 20-22 nucleic acids that inhibit gene transcription and translation by binding to mRNA. MiRNAs have a diverse set of target genes and can alter most physiological processes, including cell cycle checkpoints, cell survival, and cell death mechanisms, affecting the growth, development, and invasion of various cancers, including gliomas. So optimum management of miRNA expression is essential for preserving a normal biological environment. Due to their small size, stability, and capability of specifically targeting oncogenes, miRNAs have emerged as a promising marker and new biopharmaceutical targeted therapy for glioma patients. This review focuses on the most common miRNAs associated with gliomagenesis and development by controlling glioma-determining markers such as angiogenesis. We also summarized the recent research about miRNA effects on signaling pathways, their mechanistic role and cellular targets in the development of gliomas angiogenesis. Strategies for miRNA-based therapeutic targets, as well as limitations in clinical applications, are also discussed.

Anti-Mullerian hormone and cardiometabolic status: a systematic review.

BACKGROUND: To summarise the relationship between Anti-mullerian hormone (AMH) levels and cardiometabolic status in different populations. METHODS: PubMed, Scopus, and Embase were searched for retrieving observational studies published up to February 2022 investigating the relationship between AMH level and cardiometabolic status. RESULTS: Of 3,643 studies retrieved from databases, a total of 37 observational studies were included in this review. The majority of the included studies revealed an inverse association between AMH and lipid profiles, including triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), and a positive correlation with high-density lipoprotein (HDL). While some studies have revealed a significant inverse association between AMH and glycemic parameters, including fasting plasma glucose (FPG), fasting insulin, and HOMA-IR, others found no such relationships. There is also an inconsistency among studies regarding the association of AMH with adiposity indices and blood pressure. Evidence indicates a significant association between AMH and some vascular markers, such as intima-media thickness and coronary artery calcification. Of 3 studies evaluating the relationship between AMH and cardiovascular events, two studies showed an inverse relationship between AMH levels and cardiovascular (CVD), whereas another study showed no significant association. CONCLUSIONS: The results of this systematic review suggest that serum AMH levels can be associated with CVD risk. This may provide new insight into the use of AMH concentrations as a predictive marker for assessing the risk of cardiovascular disease, although more well-design longitudinal studies are still necessary for this area. Future studies on this topic will hopefully provide an opportunity to run a meta-analysis; it will increase the persuasiveness of this interpretation.

Impact of polyphenols on heart failure and cardiac hypertrophy: clinical effects and molecular mechanisms.

Polyphenols are abundant in regular diets and possess antioxidant, anti-inflammatory, anti-cancer, neuroprotective, and cardioprotective effects. Regarding the inadequacy of the current treatments in preventing cardiac remodeling following cardiovascular diseases, attention has been focused on improving cardiac function with potential alternatives such as polyphenols. The following online databases were searched for relevant orginial published from 2000 to 2023: EMBASE, MEDLINE, and Web of Science databases. The search strategy aimed to assess the effects of polyphenols on heart failure and keywords were "heart failure" and "polyphenols" and "cardiac hypertrophy" and "molecular mechanisms". Our results indicated polyphenols are repeatedly indicated to regulate various heart failure-related vital molecules and signaling pathways, such as inactivating fibrotic and hypertrophic factors, preventing mitochondrial dysfunction and free radical production, the underlying causes of apoptosis, and also improving lipid profile and cellular metabolism. In the current study, we aimed to review the most recent literature and investigations on the underlying mechanism of actions of different polyphenols subclasses in cardiac hypertrophy and heart failure to provide deep insight into novel mechanistic treatments and direct future studies in this context. Moreover, due to polyphenols' low bioavailability from conventional oral and intravenous administration routes, in this study, we have also investigated the currently accessible nano-drug delivery methods to optimize the treatment outcomes by providing sufficient drug delivery, targeted therapy, and less off-target effects, as desired by precision medicine standards.

The landscape of exosomal non-coding RNAs in breast cancer drug resistance, focusing on underlying molecular mechanisms.

Breast cancer (BC) is the most common malignancy among women worldwide. Like many other cancers, BC therapy is challenging and sometimes frustrating. In spite of the various therapeutic modalities applied to treat the cancer, drug resistance, also known as, chemoresistance, is very common in almost all BCs. Undesirably, a breast tumor might be resistant to different curative approaches (e.g., chemo- and immunotherapy) at the same period of time. Exosomes, as double membrane-bound extracellular vesicles 1) secreted from different cell species, can considerably transfer cell products and components through the bloodstream. In this context, non-coding RNAs (ncRNAs), including miRNAs, long ncRNAs (lncRNAs), and circular RNAs (circRNAs), are a chief group of exosomal constituents with amazing abilities to regulate the underlying pathogenic mechanisms of BC, such as cell proliferation, angiogenesis, invasion, metastasis, migration, and particularly drug resistance. Thereby, exosomal ncRNAs can be considered potential mediators of BC progression and drug resistance. Moreover, as the corresponding exosomal ncRNAs circulate in the bloodstream and are found in different body fluids, they can serve as foremost prognostic/diagnostic biomarkers. The current study aims to comprehensively review the most recent findings on BC-related molecular mechanisms and signaling pathways affected by exosomal miRNAs, lncRNAs, and circRNAs, with a focus on drug resistance. Also, the potential of the same exosomal ncRNAs in the diagnosis and prognosis of BC will be discussed in detail.

Evaluating the pure effect of weight on cardiac function in patients with cardiac syndrome X.

BACKGROUND: Obese patients have more coronary artery disease (CAD) risk factors that may affect myocardial function. We aimed to assess the ability of echocardiography-derived conventional parameters, left atrial strain, and global longitudinal strain to detect early diastolic and systolic dysfunction in obese individuals with almost no CAD risk factors. METHOD: We studied 100 participants with structurally normal hearts, ejection fractions above 50%, almost normal coronary arteries in coronary angiogram (syndrome X), and no cardiovascular risk factor except dyslipidemia. Participants were classified as normal-weight (BMI < 25.0 kg/m2 , n = 28) and high-weight (BMI ≥ 25.0 kg/m2 , n = 72). Conventional echocardiographic parameters and two-dimensional speckle tracking (2DSTE) were used to measure peak LA strain and global longitudinal strain to evaluate diastolic and systolic function, respectively. RESULT: There was no significant difference in the standard and conventional echocardiographic parameters between the two groups. 2DSTE echocardiographic parameters of the longitudinal deformation of the LV myocardium were not significantly different within the two groups. However, there were significant differences between the subjects with normal-weight and high-weight in terms of LA strain (34.51 ± 8.98% vs. 39.06 ± 8.62%, p = .021). The normal-weight group had lower LA strain, in compression with the high-weight group. All echocardiographic parameters were in the normal range. CONCLUSION: In the present study we demonstrated that global longitudinal subendocardial deformations, for the evaluation of systolic function, and conventional echocardiographic parameters, for the evaluation of diastolic function, were not significantly different between normal- and high-weight groups. Although LA strain was higher among overweight patients, it was not above the normal range of diastolic dysfunction.