Effect of melatonin as a therapeutic strategy against intrauterine growth restriction: a mini-review of current state.

Intrauterine growth restriction (IUGR) or intrauterine growth retardation is a condition that the fetus does not grow as expected. And the biometric profile does not match with the age of fetus. This condition is associated with increased mortality and morbidity of the neonates along with increased risk of cardiovascular, lung, and central nervous system damage. Despite close monitoring of high-risk mothers and the development of new therapeutic approaches, the optimal outcome has not been achieved yet that it indicates the importance of investigations on new therapeutic approaches. Melatonin (MLT) is a neurohormone mainly produced by the pineal gland and has a wide range of effects on different organs due to the broad dispersion of its receptors. Moreover, melatonin is produced by the placenta and also its receptors have been found on the surface of this organ. Not only studies showed the importance of this neurohormone on growth and development of fetus but also they proved its highly anti-oxidant properties. As in IUGR the oxidative stress and inflammation increased melatonin could counteract these changes and improved organ's function. In this study, we found that use of MLT could be a good clinical approach for the treatment of IUGR as its high anti-oxidant activity and vasodilation could dampen the mechanisms lead to the IUGR development.

The beneficial influences of vitamin D intake on inflammation and oxidative stress in infertile women with polycystic ovary syndrome.

Objective: Oxidative stress and inflammation play a vital function in the pathophysiology of polycystic ovary syndrome (PCOS) and infertility. The aim of this work was to control the impacts of vitamin D intake on metabolic profiles in infertile subjects with PCOS. Trial design and methods: This randomized, double-blinded, placebo-controlled clinical trial was carried out among 40 infertile women with PCOS. Subjects were randomly divided into two intervention groups to take either 50 000 IU vitamin D (n=20) or placebo (n=20) weekly for 8 weeks. Metabolic profiles and few inflammatory cytokines expression evaluated on peripheral blood mononuclear cells (PBMCs) of participants, using real-time polymerase chain reaction (RT-PCR) method. Results: Vitamin D intake decreased high-sensitivity C-reactive protein (hs-CRP) (-0.9±1.1 vs. 0.3±0.9 mg/l, P=0.002) and elevated total antioxidant capacity (TAC) levels (49.2±60.2 vs. -50.6±161.8 mmol/l, P=0.02) compared with placebo; but no significant effects on other metabolic parameters were observed. Moreover, a significant downregulation of tumor necrosis factor alpha (TNF-α) expression (P=0.03) was observed after taking vitamin D compared with the placebo. Conclusions: Overall, vitamin D intake for eight weeks had beneficial impacts on hs-CRP, TAC, and TNF-α among infertile women with PCOS.

The effect of coenzyme Q10 intake on metabolic profiles in women candidates for in-vitro fertilization: a randomised trial.

Objective: Infertility and the pathogenesis of polycystic ovarian syndrome (PCOS) are both influenced by insulin resistance and dyslipidemia. Presumably, adding coenzyme Q10 (CoQ10) to these patients' diets will be beneficial. Therefore, this study aimed to examine the effects of CoQ10 supplementation on metabolic profiles in women candidates for in-vitro fertilization (IVF). Trial design and methods: For this randomized, double-blinded, parallel, placebo-controlled clinical experiment, 40 PCOS-positive infertile women who were IVF candidates were included. They ranged in age from 18 to 40. The 20 participants in the two intervention groups received either CoQ10 or a placebo for 8 weeks. The expression of glucose transporter 1 (GLUT-1), peroxisome proliferator-activated receptor gamma (PPAR-γ), low-density lipoprotein receptor (LDLR), as well as metabolic profiles such as insulin metabolism and lipid profiles were evaluated. Quantitative RT-PCR determined the expression of GLUT-1, PPAR-γ, and LDLR on peripheral blood mononuclear cells. Lipid profiles and fasting glucose were assessed using enzymatic kits, and insulin was determined using Elisa kit. Results: In comparison to the placebo, CoQ10 supplementation significantly reduced blood insulin levels (-0.3±1.0 vs. 0.5±0.7, P=0.01) and insulin resistance (-0.1±0.2 vs. 0.1±0.2, P=0.01), and increased PPAR-γ expression (P=0.01). In infertile PCOS patients' candidates for IVF, CoQ10 supplementation showed no appreciable impact on other metabolic profiles. Also, CoQ10 supplementation revealed no significant impact on GLUT-1 (P=0.30), or LDLR (P=0.27) expression. Within-group changes in insulin levels (P=0.01) and insulin resistance (P=0.01) showed a significant elevation in the placebo group. When we adjusted the analysis for baseline BMI, baseline values of variables, and age, our findings were not affected. Conclusions: Eight weeks of CoQ10 supplementation demonstrated positive benefits on PPAR-γ expression, insulin resistance, and serum insulin in infertile PCOS women candidates for IVF.

Melatonin affects the expression of microRNA-21: A mini-review of current evidence.

Melatonin (MLT) is an endogenous hormone produced by pineal gland which possess promising anti-tumor effects. Anti-inflammatory and anti-oxidant properties of MLT, along with its immunomodulatory, proapoptotic, and anti-angiogenic properties, are often referred to the main mechanisms of its anti-tumor effects. Recent evidence has suggested that epigenetic alterations are also involved in the anti-tumor properties of MLT. Among these MLT-induced epigenetic alterations is modulation of the expression of several oncogenic and tumor suppressor microRNAs(miRNAs). MiRNAs are among the most promising and potential therapeutic and diagnostic tools in different diseases and enhanced the development of better therapeutic drugs. Suppression of oncomicroRNAs such as microRNA-21, - 20a, and - 27a as well as, up-regulation of microRNA-34 a/c are among the most important effects of MLT on microRNAs homeostasis. Recently, miR-21 has attracted the attention of scientists due to the its wide range of effects on different cancers and diseases. Regulation of this RNA may be a key to the development of better therapeutic targets. The present review will summarize the findings of in vitro and experimental studies of MLT-induced impacts on the expression of microRNAs which are involved in different models and numerous stages of tumor initiation, growth, metastasis, and chemo-resistance.

Melatonin as a Promising Agent for Cancer Treatment: Insights into its Effects on the Wnt/beta-catenin Signaling Pathway.

In recent years, substantial advances have been made in cancer treatment modalities. Yet, within the last three decades, neither cancer incidence nor the cancer-induced mortality rate has changed. Available anti-cancer chemotherapeutics possess remarkably restricted effectiveness and often have severe adverse effects. Hence, the identification of novel pharmaceutical agents that do not exhibit these major disadvantages is imperative. Melatonin, an important endogenous molecule synthesized and secreted by the pineal gland, is a promising chemical agent that has been comprehensively assessed over the last decades for its anti-inflammatory and anti-cancer properties. Melatonin is reportedly a significant inhibitor of cancer initiation, progression, and metastasis. The anti-- cancer potential of melatonin is principally mediated by reversing the up-regulated amounts of different transcription factors, growth factors, inflammatory cytokines, protein kinases, and other oncogenic agents. Also, melatonin often has signifcant inhibitory effects on cancer cell proliferation through either promoting apoptosis or inducing cell cycle arrest. The current review provides an insight into melatonin-induced effects against various human cancers with a particular focus on the regulation of Wnt/ß-catenin signaling pathway.

MiRNAs: Emerging Agents for Therapeutic Effects of Polyphenols on Ovarian Cancer.

In terms of female reproductive tract cancers, ovarian cancer remains the principal reason for mortality globally and is notably difficult to identify in its early stages. This fact highlights the critical need to establish prevention strategies for patients with ovarian cancer, look for new robust diagnostic and prognostic markers, and identify potential targets of response to treatment. MicroRNAs (miRNAs) are one of the novel treatment targets in cancer treatment. Thus, understanding the part of miRNAs in the pathogenesis and metastasis of ovarian cancer is at the center of researchers' attention. MiRNAs are suggested to play a role in modulating many essential cancer processes, like cell proliferation, apoptosis, differentiation, adhesion, epithelial-mesenchymal transition (EMT), and invasion. In two recent decades, natural polyphenols' anti-cancer features have been a focal point of research. Meanwhile, polyphenols are good research subjects for developing new cancer treatments. Polyphenols can modify miRNA expression and impact the function of transcription factors when used as dietary supplements. Multiple works have indicated the impact of polyphenols, including quercetin, genistein, curcumin, and resveratrol, on miRNA expression in vitro and in vivo. Here, we provide an in-depth description of four polyphenols used as dietary supplements: quercetin, genistein, curcumin, and resveratrol, and we summarize what is currently known about their regulatory abilities on influencing the miRNA functions in ovarian tumors to achieve therapeutic approaches.

Modulation of Long Non-coding RNAs and MicroRNAs by Quercetin as a Potential Therapeutical Approach in Cancer: A Comprehensive Review.

Cancer can take years to develop, both at its beginning and during its development. All typical epithelial cancers have a long latency period, sometimes 20 years or more, and if they are clinically detected, distinct genes may include infinite mutations. Long non-coding RNAs (LncRNAs) are a subset of RNAs that regulate many biological processes, including RNA processing, epigenetic control, and signal transduction. Current studies show that lncRNAs, which are dysregulated in cancer, play a significant function in the growth and spread of the illness. LncRNAs have been connected to the overexpression of specific proteins that function in tumors' spread and growth. Moreover, through translational inhibition, microRNAs (miRNAs) regulates gene expression sequence specifically. Apart from that, non-coding RNAs known as miRNAs, with a length of around 22 nucleotides, controls gene expressions in a sequence-specific way either by preventing translation or degrading messenger RNA (mRNA). Quercetin appears to have a significant role in altering miRNA and lncRNA expression, which is linked to variations in the production of oncogenes, tumor suppressors, and proteins produced from cancer. Quercetin may change the earliest epigenetic modifications related to cancer prevention in addition to its usual antioxidant or anti-inflammatory effects. It would be beneficial to have more in-depth information on how Quercetin modulates miRNAs and lncRNAs to use it as a cancer therapeutic strategy. Here, we go through what is known about Quercetin's potential to modulate miRNAs and lncRNAs in various malignancies.

CircRNAs as a novel class of potential diagnostic biomarkers in bipolar disorders.

Bipolar disorder (BD) is a severe mood disorder with uncertain causes and debilitating signs and symptoms. Gene expression is crucial to the pathophysiology of BD and could be influenced by genetic or epigenetic factors, by either direct modification of mRNA templates or by regulation of post-transcriptional translation. Recent evidence has shown that several critical processes in psychiatric diseases, such as neuronal activity or plasticity, synaptic transmission, and neuronal depolarization, have all been linked to circular RNAs (circRNAs). The circRNA profile of neuronal cells, which may be easily ascertained by a liquid biopsy, may shed light on the molecular pathophysiology of psychiatric disorders, including BD. This approach could aid in future development in diagnosis and treatment. In this review, we provide an in-depth understanding of the roles of circRNAs in the pathophysiology of BD and offer new insight into their potential as emerging diagnostic tools and therapeutic targets.

Circular RNAs: pivotal role in the leukemogenesis and novel indicators for the diagnosis and prognosis of acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy and affected patients have poor overall survival (OS) rates. Circular RNAs (circRNAs) are a novel class of non-coding RNAs (ncRNAs) with a unique loop structure. In recent years, with the development of high-throughput RNA sequencing, many circRNAs have been identified exhibiting either up-regulation or down-regulation in AML patients compared with healthy controls. Recent studies have reported that circRNAs regulate leukemia cell proliferation, stemness, and apoptosis, both positively and negatively. Additionally, circRNAs could be promising biomarkers and therapeutic targets in AML. In this study, we present a comprehensive review of the regulatory roles and potentials of a number of dysregulated circRNAs in AML.

Modulation of long non-coding RNAs by resveratrol as a potential therapeutic approach in cancer: A comprehensive review.

LncRNAs, or long non-coding RNAs, are a subset of RNAs that play a regulatory role in a wide range of biological functions, including RNA processing, epigenetic regulation, and signal transduction. Recent research indicates that lncRNAs play a key role in the development and spread of cancer by being dysregulated in the disease. In addition, lncRNAs have been linked to the overexpression of certain proteins that are involved in tumor development and progression. Resveratrol has anti-inflammatory and anti-cancer properties that it exerts through regulating different lncRNAs. By the regulation of tumor-supportive and tumor-suppressive lncRNAs, resveratrol acts as an anti-cancer agent. By downregulating the tumor-supportive lncRNAs DANCR, MALAT1, CCAT1, CRNDE, HOTAIR, PCAT1, PVT1, SNHG16, AK001796, DIO3OS, GAS5 and H19, and upregulating MEG3, PTTG3P, BISPR, PCAT29, GAS5, LOC146880, HOTAIR, PCA3, NBR2, this herbal remedy causes apoptosis and cytotoxicity. For the purpose of using polyphenols in cancer therapy, it would be helpful to have more in-depth knowledge about lncRNA modulation via resveratrol. Here, we discuss the current knowledge and future promise of resveratrol as modulators of lncRNAs in different cancers.

Quercetin modulates signal transductions and targets non-coding RNAs against cancer development.

In recent decades, various investigations have indicated that natural compounds have great potential in the prevention and treatment of different chronic disorders including different types of cancer. As a bioactive flavonoid, Quercetin (Qu) is a dietary ingredient enjoying high pharmacological values and health-promoting effects due to its antioxidant and anti-inflammatory characterization. Conclusive in vitro and in vivo evidence has revealed that Qu has great potential in cancer prevention and development. Qu exerts its anticancer influences by altering various cellular processes such as apoptosis, autophagy, angiogenesis, metastasis, cell cycle, and proliferation. In this way, Qu by targeting numerous signaling pathways as well as non-coding RNAs regulates several cellular mechanisms to suppress cancer occurrence and promotion. This review aimed to summarize the impact of Qu on the molecular pathways and non-coding RNAs in modulating various cancer-associated cellular mechanisms.

Therapeutic effects of melatonin on endometriosis, targeting molecular pathways: Current knowledge and future perspective.

Endometriosis, the very serious disease in women creates a huge financial burden worldwide, which is comparable to diabetes mellitus. In addition to the typical pelvic pain, endometriosis is related to low life quality and decreased work efficiency; clinical consequences include mood complaints, metabolic impairments, inflammation, immunologic problems, and elevated malignancy risks. Several risk factors are correlated with endometriosis including elevated oxidative and nitrosative stress, long-lasting inflammation, raised immune tolerance, as well as autoimmunity. Melatonin is a natural molecule present throughout both the plant and animal kingdoms. It has numerous functions as an antioxidant and anti-inflammatory agent. Due to the anti-proliferative, antioxidant, anti-inflammatory, and anti-invasive features of melatonin, it performances as a beneficial agent to limit endometriosis; this involves several pathways including antiestrogenic, antioxidant, anti-inflammatory, and anti-apoptosis effects, as well as reducing the growth of E2-induced endometriotic tissue. Moreover, melatonin can favor sleep quality and decrease the unwanted signs in the patients. However, most of the data on melatonin accured from experimental works and additional clinical trials are needed. This review summarizes what is currently known regarding the influence of melatonin on endometriosis. AVAILABILITY OF DATA AND MATERIAL: Not applicable.

The role of dietary polyphenols in alternating DNA methylation in cancer.

Natural products such as curcumin, quercetin, and resveratrol have been shown to have antitumor effectsand several studies have examined their role in treating cancer, either alone or in combination with other chemotherapeutic drugs. These compounds are capable of affecting different cancer-related mechanisms, such as proliferation, inflammation, invasion, and metastasis. Along with all of the benefits of these agents, affecting epigenetic processes is one of the most important aspects of their impact. Epigenetic modifications can be categorized into three main processes that include DNA methylation, histone modification, and regulation of small non-coding RNAs. Therefore, targeting DNA methylation can be used as a cancer treatment strategy by identifying or developing methylation modulators. Herein, we take a look into the studies investigating the role of natural products (e.g. curcumin, resveratrol, epigallocatechin gallate (EGCG), and quercetin) in alternating the DNA methylation status of various cancer cells. We discuss how these compounds reduce the expression of enzymes mediating the methylation of tumor suppressor genes and thereby, increasing the expression of tumor suppressors while reactivating antitumor signaling pathways.

Energy-aware virtual machines allocation by krill herd algorithm in cloud data centers.

The growing demand for computational power has led to the emergence of large-scale data centers that consume massive amounts of energy, thus resulting in high operating costs and CO2 emission. Furthermore, cloud computing environments are required to provide a high Quality of Service (QoS) to their clients and, therefore, need to handle power shortages. An optimized virtual machine allocation to physical hosts lowers energy consumption and allows for high-quality services. In this study, a novel solution was proposed for the allocation of virtual machines to physical hosts in cloud data centers using the Krill Herd algorithm, which is the fastest collective intelligence algorithm recently introduced. The performance of the proposed method was evaluated using the CloudSim simulator, and the results are suggestive of a 35% reduction in energy consumption.

Spontaneous ileocecal perforation induced by deep endometriosis.

Bowel endometriosis is a rare condition that may cause catastrophic complications necessitating immediate medical attention. This report describes the case of a patient diagnosed with endometriosis-induced bowel perforation. Albeit rare, bowel perforations caused by endometriosis should be considered in the differential diagnosis of women of reproductive age with abdominal pain.