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The inhibition of dipeptidyl- peptidase 4 (DPP-4) is an essential therapy for controlling hyperglycemia in patients with type 2 diabetes (T2DM). However, the role of DPP-4 in cancer is not yet clear, with some studies suggesting that it may either promote or suppress tumors. This makes it crucial to have personalized treatment for diabetic women with cancer to effectively manage their diabetes whilst and preventing cancer mortality. To address this issue, we conducted an integrative in-silico analysis and systematic review of the literature to comprehensively examine the relationship between DPP-4 expression and the effects of its inhibitors on prevalent female malignancies. We specifically chose studies that examined the effects of DPP-4 expression and DPP-4 inhibition (DPP-4i) on prevalent cancers in women, such as breast cancer (BC), ovarian cancer (OV), cervical cancer (CC), and endometrial cancer (EC). These studies comprised those conducted both in vivo and in vitro. The review of the literature indicated that DPP-4i may worsen aggressive traits such as metastasis, Epithelial-to-mesenchymal transition (EMT), and chemotherapy resistance in BC cells. However, cohort studies on diabetic and BC patients did not confirm these findings. In vitro studies indicate that on OV, DPP-4 upregulation has been shown to prevent metastasis, while CCappears to be influenced by DPP-4 expression in terms of cell migration. sitagliptin, a pharmaceutical inhibitor of DPP-4, had a significant impact on reducing adhesion in CC cells in vitro. Overexpression of DPP-4 increased cell migration and proliferation in CC and EC cells, and hence the application of sitagliptin is expected to prevent this effect. On the other hand, the result of in-silico data confirmed that a significant correlation exists between DPP-4 expression and immune cell infiltration in breast, ovarian, cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) as well as downregulated in these cancers compared to their normal tissue samples. Furthermore, a significant (p < 0.05) effect on OS of BC and CESC patients has been reported due to the elevation of DPP-4 methylation on a specific CPG Island. These findings could aid in creating specialized treatments for diabetic women with specific malignancies, but caution should be exercised when considering the patient's medical history and cancer type., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The evolution of novel Severe Acute Respiratory Syndrome-related Coronavirus 2 (SARS-CoV-2) strains with greater degrees of infectivity, resistance to vaccine-induced acquired immunity, and more severe morbidity have contributed to the recent spread of COVID-19. In light of this, novel therapeutic alternatives with improved effectiveness and fewer side effects have become a necessity. Despite many new or repurposed antiviral agents recommended for Coronavirus disease (COVID-19) therapy, this objective remains unfulfilled. Under these circumstances, the scientific community holds the significant responsibility to develop classes of novel therapeutic modalities to combat SARS-CoV-2 with the least harmful side effects., Objective: Antisense Oligonucleotides (ASOs) are short single-stranded oligonucleotides that allow the specific targeting of RNA, leading to its degradation. They may also prevent cellular factors or machinery from binding to the target RNA. It is possible to improve the pharmacokinetics and pharmacodynamics of ASOs by chemical modification or bioconjugation, which may provide conditions for customization of a particular clinical target. This study aimed to outline the potential use of ASOs in the treatment of COVID-19 disease, along with the use of antisense stabilization and transfer methods, as well as future challenges and limitations., Methods: We have reviewed the structure and properties of ASOs containing nucleobase, sugar, or backbone modifications, and provided an overview of the therapeutic potential, delivery challenges, and strategies of ASOs in the treatment of COVID-19., Results: The first-line therapy for COVID-19-infected individuals, as well as the development of oligonucleotide-based drugs, warrants further investigation. Chemical changes in the oligonucleotide structure can affect the biological processes. These chemical alterations may lead to enhanced potency, while changing the pharmacokinetics and pharmacodynamics., Conclusion: ASOs can be designed to target both coding and non-coding regions of the viral genome to disrupt or completely degrade the genomic RNA and thereby eliminate SARS-CoV-2. They may be very effective in areas, where vaccine distribution is challenging, and they may be helpful for future coronavirus pandemics., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Males and females exhibit intrinsic differences in the structure and function of the heart, while the prevalence and severity of cardiovascular disease vary in the two sexes. However, the mechanisms of this sex-based dimorphism are yet to be elucidated. Sex chromosomes and sex hormones are the main contributors to sex-based differences in cardiac physiology and pathophysiology. In recent years, the advances in induced pluripotent stem cell-derived cardiac models and multi-omic approaches have enabled a more comprehensive understanding of the sex-specific differences in the human heart. Here, we provide an overview of the roles of these two factors throughout cardiac development and explore the sex hormone signaling pathways involved. We will also discuss how the employment of stem cell-based cardiac models and single-cell RNA sequencing help us further investigate sex differences in healthy and diseased hearts.

Type 1 Diabetes mellitus (T1DM) is a chronic metabolic disorder characterized by pancreatic β-cells destruction. Despite substantial advances in T1DM treatment, lifelong exogenous insulin administration is the mainstay of treatments, and constant control of glucose levels is still a challenge. Endogenous insulin production by replacing insulin-producing cells is an alternative, but the lack of suitable donors is accounted as one of the main obstacles to its widespread application. The research and trials overview demonstrates that endogenous production of insulin has started to go beyond the deceased-derived to stem cells-derived insulin-producing cells. Several protocols have been developed over the past couple of years for generating insulin-producing cells (IPCs) from various stem cell types and reprogramming fully differentiated cells. A straightforward and quick method for achieving this goal is to investigate and apply the β-cell specific transcription factors as a direct strategy for IPCs generation. In this review, we emphasize the significance of transcription factors in IPCs development from different non-beta cell sources, and pertinent research underlies the marked progress in the methods for generating insulin-producing cells and application for Type 1 Diabetes treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Aims: Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease. Insertable cardiac monitors (ICMs) are increasingly used in this population to provide closer monitoring, with the potential for notification systems. However, little is known regarding the psychological impact this information may have on patients. The Abbott Confirm Rx™ ICM has the capability of connecting to the patient's smartphone to enable active participation in their care, as well as two-way communication between the patient and their care providers. This study aimed to explore individuals' experiences of having a smartphone-enabled ICM to monitor for arrhythmias in HCM., Methods and Results: Semi-structured interviews were conducted with 10 participants. Utilizing a grounded theory approach, the interview guide was modified based on emerging themes throughout the study. Reflexive thematic analysis was applied to categorize interview data into codes and overacting themes, with each interview independently coded by two study members. Analysis revealed three key themes: (i) psychological impact, (ii) educational needs, and (iii) technology expectations. Participants reported that receiving feedback from ICM transmissions resulted in improved symptom clarity, providing reassurance, and aiding implantable cardioverter defibrillator decision-making. Some participants reported uncertainty regarding when to send manual transmissions. Lastly, participants reported the app interface did not meet expectations with regard to the amount of data available for patients., Conclusion: Overall, utilizing a smartphone app to facilitate two-way communication of ICM transmissions was well accepted. Future directions include addressing gaps in educational needs and improvements in the patient interface with increased access to data., Competing Interests: Conflict of interest: J.F. reports receiving honorarium from Medtronic. M.W.D. reports receiving honoraria from Abbott. The other authors have no conflicts of interest to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose of Review: Cardiovascular diseases remain the leading causes of morbidity and mortality globally. Single-cell RNA sequencing has the potential to improve diagnostics, risk stratification, and provide novel therapeutic targets that have the potential to improve patient outcomes., Recent Findings: Here, we provide an overview of the basic processes underlying single-cell RNA sequencing, including library preparation, data processing, and downstream analyses. We briefly discuss how the technique has been adapted to related medical disciplines, including hematology and oncology, with short term translational impact. We discuss potential applications of this technology within cardiology as well as recent innovative research within the field. We also discuss future directions to translate this technology to other high impact clinical areas., Summary: The use of single-cell RNA sequencing technology has made significant advancements in the field of cardiology, with ongoing growth in terms of applications and uptake. Most of the current research has focused on structural or atherosclerotic heart disease. Future areas that stand to benefit from this technology include cardiac electrophysiology and cardio-oncology., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction : Sensorineural hearing loss (SNHL) is a prevalent sensory deficit presenting commonly as age-related hearing loss. Other forms of SNHL include noise-induced and sudden SNHL. Recent evidence has pointed to oxidative stress as a common pathogenic pathway in most subtypes of acquired SNHL. MicroRNAs (miRNAs) are small non-coding RNA sequences that suppress target mRNA expression and affect downstream processes. Many studies have shown that miRNAs are integral biomolecules in hypoxia-adaptive responses. They also promote apoptosis in response to oxidative stress resulting in SNHL. Our hypothesis is that miRNAs are involved in the pathophysiological responses to hypoxia and oxidative stress that result in SNHL. This study reviews the evidence for hypoxia-adaptive miRNAs (hypoxamiRs) in different types of acquired SNHL and focuses on miRNAs involved in hypoxia driven SNHL. Methods : Electronic bibliographic databases PubMed, Ovid MEDLINE, Ovid EMBASE, and Web of Science Core Collection were searched independently by two investigators for articles published in English from the inception of individual databases to the end of July 2020. The text word or medical subject heading searches of all fields, titles, abstracts, or subject headings depending on the database were undertaken with combinations of the words "microRNAs", "hypoxia", "hypoxamiRs", "oxidative stress", "ischemia" and "hearing loss". The reference lists of studies meeting the inclusion criteria were searched to identify additional relevant studies. The inclusion criteria included relevant clinical studies with human subjects, animals, and in vitro experiments. The risk of bias was assessed using the Cochrane risk of bias assessment tool for human studies and the Systematic Review Center for Laboratory animal Experimentation (SYRCLE) a risk of bias assessment tool for animal model and in vitro studies. Results : A total of 15 primary articles were selected for full text screening after excluding duplicates, reviews, retracted articles, and articles not published in English. All nine articles meeting the study inclusion criteria were from animal or in vitro model studies and were assessed to be at low risk of bias. miRNAs miR-34a and miR-29b were reported to be involved in SNHL in inner ear cell models exposed to oxidative stress. Signaling pathways Sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator-1-alpha (SIRT1/PGC-1α), SIRT1/p53, and SIRT1/hypoxia-inducible factor 1-alpha (HIF-1α) were identified as underlying pathways involved in acquired SNHL. Conclusion : There is evidence that miR-34a and -29b are involved in hypoxia-driven and other causes of oxidative stress-related acquired SNHL. Further studies are required to determine if these findings are clinically applicable., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Safabakhsh, Wijesinghe, Nunez and Nunez.)

Heart failure with preserved ejection fraction (HFpEF) is an increasingly recognized disorder. Many clinical trials have failed to demonstrate benefit in patients with HFpEF but have recognized alarming rates of sudden cardiac death (SCD). Genetic testing has become standard in the workup of patients with otherwise unexplained cardiac arrest, but the genetic architecture of HFpEF, and the overlap of a genetic predisposition to HFpEF and arrhythmias, is poorly understood. An understanding of the genetics of HFpEF and related SCD has the potential to redefine and generate novel diagnostic, prognostic, and therapeutic tools. In this review, we examine recent pathophysiological and clinical advancements in our understanding of HFpEF, which reinforce the heterogeneity of the condition. We also discuss data describing SCD events in patients with HFpEF and review the current literature on genetic underpinnings of HFpEF. Mechanisms of arrhythmogenesis which may lead to SCD in this population are also explored. Lastly, we outline several areas of promise for experimentation and clinical trials that have the potential to further advance our understanding of and contribute to improved clinical care of this patient population., (© 2022 The Authors.)

Heart disease is the leading cause of global morbidity and mortality. This is in part because, despite an abundance of animal and in vitro models, it has been a challenge to date to study human heart tissue with sufficient depth and resolution to develop disease-modifying therapies for common cardiac conditions. Single-nucleus RNA sequencing (snRNA-seq) has emerged as a powerful tool capable of analyzing cellular function and signaling in health and disease, and has already contributed to significant advances in areas such as oncology and hematology. Employing snRNA-seq technology on flash-frozen human tissue has the potential to unlock novel disease mechanisms and pathways in any organ. Studying the human heart using snRNA-seq is a key priority for the field of cardiovascular sciences; however, progress to date has been slowed by numerous barriers. One key challenge is the fact that the human heart is very resistant to shearing and stress, making tissue dissociation and nuclear isolation difficult. Here, we describe a tissue dissociation method allowing the efficient and cost-effective isolation of high-quality nuclei from flash-frozen human heart tissue collected in surgical operating rooms. Our protocol addresses the challenge of nuclear isolation from human hearts, enables snRNA-seq of the human heart, and paves the way for an improved understanding of the human heart in health and disease. Ultimately, this will be key to uncovering signaling pathways and networks amenable to therapeutic intervention and the development of novel biomarkers and disease-modifying therapies. © 2022 Wiley Periodicals LLC. Basic Protocol: Human heart tissue dissociation and nuclear isolation for snRNA-seq., (© 2022 Wiley Periodicals LLC.)

Atrial fibrillation (AF) is the most common arrhythmia worldwide. It is associated with significant increases in morbidity in the form of stroke and heart failure, and a doubling in all-cause mortality. The pathophysiology of AF is incompletely understood, and this has contributed to a lack of effective treatments and disease-modifying therapies. An important cellular process that may explain how risk factors give rise to AF includes post-translational modification of proteins. As the most commonly occurring post-translational modification, protein phosphorylation is especially relevant. Although many methods exist for studying protein phosphorylation, a common and highly resolute technique is mass spectrometry (MS). This review will discuss recent evidence surrounding the role of protein phosphorylation in the pathogenesis of AF. MS-based technology to study phosphorylation and uses of MS in other areas of medicine such as oncology will also be presented. Based on these data, future goals and experiments will be outlined that utilize MS technology to better understand the role of phosphorylation in AF and elucidate its role in AF pathophysiology. This may ultimately allow for the development of more effective AF therapies., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: Sudden cardiac death (SCD) risk stratification in hypertrophic cardiomyopathy (HCM) currently relies on arrhythmic burden quantification by 24 or 48-hour Holter monitoring. Whether this approach adequately captures arrhythmic burden, compared with longer-term continuous monitoring, is unclear. We sought to assess the long-term incidence of nonsustained ventricular tachycardia (NSVT) in HCM patients at low or moderate SCD risk, using implantable cardiac monitors (ICMs) paired with a novel Bluetooth-enabled 2-way communication platform., Methods: This prospective, single-arm, observational study enrolled 33 HCM patients. Patients were implanted with an Abbott (Chicago, IL) Confirm Rx ICM and monitored using a protocolized care pathway., Results: A total of 20 patients (60.6%) had ≥ 1 episode of NSVT recorded on the ICM, the majority of whom had previous Holter monitors that did not identify NSVT (60%, n = 12). A total of 71 episodes of NSVT were detected. Median time to first NSVT detection was 76.5 days (range: 0-553 days). A total of 19 patients underwent primary prevention implantable cardioverter defibrillator implantation during an average follow-up of 544 days (range: 42-925 days). A total of 172,112 automatic transmissions were received, and 65 (0.04%) required clinical follow-up. A total of 325 manual transmissions were received and managed. A total of 14 manual transmissions (4.3%) required follow-up, whereas 311 (95.7%) were managed solely with a text message., Conclusions: Surveillance and reporting systems utilizing 2-way communication enabled by novel ICMs are feasible and allow remote management of patients with HCM. Prolonged monitoring with ICMs identified more patients with nonsustained arrythmias than did standard Holter monitoring. In many cases, this information impacted both SCD risk stratification and patient management., (© 2021 The Authors.)

Aims/hypothesis: Variants in CREBRF (rs12513649 and rs373863828) have been strongly associated with increased BMI and decreased risk of type 2 diabetes in Polynesian populations; the A allele at rs373863828 is common in Polynesians but rare in most other global populations. The aim of the present study was to assess the association of CREBRF variants with obesity and diabetes in Pacific Islander (largely Marianas and Micronesian) populations from Guam and Saipan., Methods: CREBRF rs12513649 and rs373863828 were genotyped in 2022 participants in a community-based cross-sectional study designed to identify determinants of diabetes and end-stage renal disease (ESRD). Associations were analysed with adjustment for age, sex, ESRD and the first four genetic principal components from a genome-wide association study (to account for population stratification); a genomic control procedure was used to account for residual stratification., Results: The G allele at rs12513649 had an overall frequency of 7.7%, which varied from 2.2% to 20.7% across different Marianas and Micronesian populations; overall frequency of the A allele at rs373863828 was 4.2% (range: 1.1-5.4%). The G allele at rs12513649 was associated with higher BMI (β = 1.55 kg/m 2 per copy; p = 0.0026) as was the A allele at rs373863828 (β = 1.48 kg/m 2 , p = 0.033). The same alleles were associated with lower risk of diabetes (OR per copy: 0.63 [p = 0.0063] and 0.49 [p = 0.0022], respectively). Meta-analyses combining the current results with previous results in Polynesians showed a strong association between the A allele at rs373863828 and BMI (β = 1.38 kg/m 2 ; p = 2.5 × 10 -29 ) and diabetes (OR 0.65, p = 1.5 × 10 -13 )., Conclusions/interpretation: These results confirm the associations of CREBRF variants with higher BMI and lower risk of diabetes and, importantly, they suggest that these variants contribute to the risk of obesity and diabetes in Oceanic populations.