Insight into the cardioprotective effects of melatonin: shining a spotlight on intercellular Sirt signaling communication.

Cardiovascular diseases (CVDs) are the leading causes of death and illness worldwide. While there have been advancements in the treatment of CVDs using medication and medical procedures, these conventional methods have limited effectiveness in halting the progression of heart diseases to complete heart failure. However, in recent years, the hormone melatonin has shown promise as a protective agent for the heart. Melatonin, which is secreted by the pineal gland and regulates our sleep-wake cycle, plays a role in various biological processes including oxidative stress, mitochondrial function, and cell death. The Sirtuin (Sirt) family of proteins has gained attention for their involvement in many cellular functions related to heart health. It has been well established that melatonin activates the Sirt signaling pathways, leading to several beneficial effects on the heart. These include preserving mitochondrial function, reducing oxidative stress, decreasing inflammation, preventing cell death, and regulating autophagy in cardiac cells. Therefore, melatonin could play crucial roles in ameliorating various cardiovascular pathologies, such as sepsis, drug toxicity-induced myocardial injury, myocardial ischemia-reperfusion injury, hypertension, heart failure, and diabetic cardiomyopathy. These effects may be partly attributed to the modulation of different Sirt family members by melatonin. This review summarizes the existing body of literature highlighting the cardioprotective effects of melatonin, specifically the ones including modulation of Sirt signaling pathways. Also, we discuss the potential use of melatonin-Sirt interactions as a forthcoming therapeutic target for managing and preventing CVDs.

Circular RNAs and cervical cancer: friends or foes? A landscape on circRNA-mediated regulation of key signaling pathways involved in the onset and progression of HPV-related cervical neoplasms.

Cervical cancer (CC) is a common gynecologic malignancy, accounting for a significant proportion of women death worldwide. Human papillomavirus (HPV) infection is one of the major etiological causes leading to CC onset; however, genetic, and epigenetic factors are also responsible for disease expansion. Circular RNAs (circRNAs), which are known as a particular subset of non-coding RNA (ncRNA) superfamily, with covalently closed loop structures, have been reported to be involved in the progression of diverse diseases, especially neoplasms. In this framework, abnormally expressed circRNAs are in strong correlation with CC pathogenesis through regulating substantial signaling pathways. Also, these RNA molecules can be considered as promising biomarkers and therapeutic targets for CC diagnosis/prognosis and treatment, respectively. Herein, we first review key molecular mechanisms, including Wnt/ß-catenin, MAPK, and PI3K/Akt/mTOR signaling pathways, as well as angiogenesis and metastasis, by which circRNAs interfere with CC development. Then, diagnostic, prognostic, and therapeutic potentials of these ncRNA molecules will be highlighted in depth.

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.

A spotlight on the interplay between Wnt/ß-catenin signaling and circular RNAs in hepatocellular carcinoma progression.

Hepatocellular carcinoma (HCC) is one of the deadliest cancers due to multifocal development and distant metastasis resulting from late diagnosis. Consequently, new approaches to HCC diagnosis and treatment are required to reduce mortality rates. A large body of evidence suggests that non-coding RNAs (ncRNAs) are important in cancer initiation and progression. Cancer cells release many of these ncRNAs into the blood or urine, enabling their use as a diagnostic tool. Circular RNAs (CircRNAs) are as a members of the ncRNAs that regulate cancer cell expansion, migration, metastasis, and chemoresistance through different mechanisms such as the Wnt/ß-catenin Signaling pathway. The Wnt/ß-catenin pathway plays prominent roles in several biological processes including organogenesis, stem cell regeneration, and cell survival. Aberrant signaling of both pathways mentioned above could affect the progression and metastasis of many cancers, including HCC. Based on several studies investigated in the current review, circRNAs have an effect on HCC formation and progression by sponging miRNAs and RNA-binding proteins (RBPs) and regulating the Wnt/ß-catenin signaling pathway. Therefore, circRNAs/miRNAs or RBPs/Wnt/ß-catenin signaling pathway could be considered promising prognostic and therapeutic targets in HCC.

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.

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.

Melatonin targeting non-coding RNAs in cancer: Focus on mechanisms and potential therapeutic targets.

Despite, melatonin is mainly known as a regulatory factor for circadian rhythm, its notable role in other fundamental biological processes, such as redox homeostasis and programmed cell death, has been found. In this line, a growing body of evidence indicated that melatonin could apply an inhibitory effect on the tumorigenic processes. Hence, melatonin might be considered an efficient adjuvant agent for cancer treatment. Besides, the physiological and pathological functions of non-coding RNAs (ncRNAs) in various disease, particularly cancers, have been expanded over the past two decades. It is well-established that ncRNAs can modulate the gene expression at various levels. Thereby, ncRNAs can regulate the numerous biological processes, including cell proliferation, cell metabolism, apoptosis, and cell cycle. Recently, targeting the ncRNAs expression provides a novel insight in the therapeutic approaches for cancer treatment. Moreover, accumulating investigations have revealed that melatonin could impact the expression of different ncRNAs in a multiple disorders, including cancer. Therefore, in the precent study, we discuss the potential roles of melatonin in modulating the expression of ncRNAs and the related molecular pathways in different types of cancer. Also, we highlighted its importance in therapeutic application and translational medicine in cancer treatment.

Melatonin and 5-fluorouracil combination chemotherapy: opportunities and efficacy in cancer therapy.

Combined chemotherapy is a treatment method based on the simultaneous use of two or more therapeutic agents; it is frequently necessary to produce a more effective treatment for cancer patients. Such combined treatments often improve the outcomes over that of the monotherapy approach, as the drugs synergistically target critical cell signaling pathways or work independently at different oncostatic sites. A better prognosis has been reported in patients treated with combination therapy than in patients treated with single drug chemotherapy. In recent decades, 5-fluorouracil (5-FU) has become one of the most widely used chemotherapy agents in cancer treatment. This medication, which is soluble in water, is used as the first line of anti-neoplastic agent in the treatment of several cancer types including breast, head and neck, stomach and colon cancer. Within the last three decades, many studies have investigated melatonin as an anti-cancer agent; this molecule exhibits various functions in controlling the behavior of cancer cells, such as inhibiting cell growth, inducing apoptosis, and inhibiting invasion. The aim of this review is to comprehensively evaluate the role of melatonin as a complementary agent with 5-FU-based chemotherapy for cancers. Additionally, we identify the potential common signaling pathways by which melatonin and 5-FU interact to enhance the efficacy of the combined therapy. Video abstract.

Molecular typing of the actin gene of Trichomonas vaginalis isolates in Tehran, Iran.

Trichomonas vaginalis is a protozoan parasite that causes trichomoniasis with worldwide distribution. This study evaluated actin genotypes of T. vaginalis isolates using PCR-RFLP and sequence analysis in Tehran, Iran. Overall, 850 vaginal samples were collected from women admitted to hospitals affiliated with the Iran University of Medical Sciences in Tehran from 2020-to 2021. The samples were examined by wet mount and cultured. The parasites were harvested, and PCR-RFLP was performed using three endonuclease enzymes of HindII, MseI, and RsaI on all T. vaginalis isolates. Digestion patterns were then compared, and the genotype of these isolates was defined. The PCR products were sequenced. Overall, 12 (1.4%) isolates of T. vaginalis were identified from 850 vaginal samples collected. The most common genotypes were genotype E, seven (58.3%) and genotype G, three (25%), followed by genotype I, two (%16.7), using PCR-RFLP patterns and sequencing. No pattern indicative of mixed infection was found. PCR-RFLP is a proper technique to detect different T. vaginalis isolates, and noticeable polymorphism was found between isolates. Genotype E was the most common genotype in the studied group. The phylogenetic analysis indicated the T. vaginalis genotype E isolates in a distinct group compared to the genotypes G and I that evolved from a common ancestor.

P wave duration and dispersion and QT interval in multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is one of the most frequent disorders of central nervous system, resulting in autonomic disturbances. Some electrocardiographic changes have been reported in these patients that can lead to arrhythmia. In this study we compared P wave duration and dispersion and QT interval of MS patients to healthy control subjects. MATERIAL AND METHODS: Eighty four multiple sclerosis patients and 84 healthy, age and sex-matched volunteers were included. A 12-lead electrocardiogram was undertaken in order to measure minimal and maximal P wave duration, P wave dispersion (PWD) and QT interval. RESULTS: In patient group, mean P wave duration, maximum P wave duration and PWD were significantly longer than control group. QT interval was longer in patient group but the difference was not significant. CONCLUSION: In this study, P wave duration and P wave dispersion was found to be higher in MS patients than healthy control subjects.