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.

Melatonin as an adjuvant treatment modality with doxorubicin.

Combination chemotherapy seems to be a beneficial choice for some cancer patients particularly when the drugs target different processes of oncogenesis; patients treated with combination therapies sometimes have a better prognosis than those treated with single drug chemotherapy. However, research has shown that this is not always the case, and this approach may only increase toxicity without having a significant effect in augmenting the antitumor actions of the drugs. Doxorubicin (Dox) is one of the most common chemotherapy drugs used to treat many types of cancer, but it also has serious side effects, such as cardiotoxicity, skin necrosis, testicular toxicity, and nephrotoxicity. Many studies have examined the efficiency of melatonin (MLT) as an anticancer agent. In fact, MLT is an anti-cancer agent that has various functions in inhibiting cancer cell proliferation, inducing apoptosis, and suppressing metastasis. Herein, we provide a comprehensive evaluation of the literature concerned with the role of MLT as an adjuvant in Dox-based chemotherapies and discuss how MLT may enhance the antitumor effects of Dox (e.g., by inducing apoptosis and suppressing metastasis) while rescuring other organs from its adverse effects, such as cardio- and nephrotoxicity.

Melatonin as an adjuvant treatment modality with doxorubicin.

Combination chemotherapy seems to be a beneficial choice for some cancer patients particularly when the drugs target different processes of oncogenesis; patients treated with combination therapies sometimes have a better prognosis than those treated with single drug chemotherapy. However, research has shown that this is not always the case, and this approach may only increase toxicity without having a significant effect in augmenting the antitumor actions of the drugs. Doxorubicin (Dox) is one of the most common chemotherapy drugs used to treat many types of cancer, but it also has serious side effects, such as cardiotoxicity, skin necrosis, testicular toxicity, and nephrotoxicity. Many studies have examined the efficacy of melatonin (MLT) as an anticancer agent. In fact, MLT is an anti-cancer agent that has various functions in inhibiting cancer cell proliferation, inducing apoptosis, and suppressing metastasis. Herein, we provide a comprehensive evaluation of the literature concerned with the role of MLT as an adjuvant in Dox-based chemotherapies and discuss how MLT may enhance the antitumor effects of Dox (e.g., by inducing apoptosis and suppressing metastasis) while rescuring other organs from its adverse effects, such as cardio- and nephrotoxicity.

Molecular basis of melatonin protective effects in metastasis: A novel target of melatonin.

Currently, cancer is ranked among the top ten causes of death worldwide. Despite the advances made in the field of cancer treatment, 5-year survival rates of various types of cancer are still low due to the recurrence of the disease and/or metastasis. Dissemination of cancer cells, infiltration into the blood vessels, migration to the targeted organs, extravasation, and colonization are the main steps of metastasis. Various factors and signaling pathways are involved in each of these steps. Melatonin (MLT) is a hormone derived from tryptophan and secreted by the pineal gland. This hormone has shown a variety of anti-tumor effects, including anti-oxidative activities, inhibiting the proliferation of tumor cells, inducing apoptosis, and suppressing metastasis. Due to these extensive effects, several studies have been conducted on the applications of MLT in treating different types of cancer. Herein, we review the mechanisms of MLT's effects on the metastasis inhibition of the most lethal types of cancer including the cancer of lung, breast, stomach, kidney, colon, liver, bladder, and pancreas. We discuss how MLT targets different molecules and signaling pathways in each step of the metastasis, such as angiogenesis, remodeling of the extracellular matrix, migration, and epithelial-to-mesenchymal transition.

DNA damage response and repair in the development and treatment of brain tumors.

DNA damage response (DDR) comprising DNA repair and cell-cycle checkpoint pathways, is considered as a protective process that maintains the integrity of the genome. However, this mechanism may not be favorable in the context of cancer. Indeed, studies have shown that DDR and repair mechanisms can be involved in the development of different cancers. Furthermore, they may lead to the failure of therapeutic approaches. Thus, studying these mechanisms can be beneficial in a better understanding of cancer development and developing more efficient treatments. Scopus, Google Scholar, and PubMed databases were used for searching articles published on "DNA damage response and DNA repair in the development and treatment of brain tumors". Herein, we review the literature on DNA damage response and DNA repair mechanisms in the development of brain tumors, such as glioma, glioblastoma, and medulloblastoma. Moreover, we summarize the studies that conducted on the role of targeting components of DNA damage response and DNA repair in treating different types of brain cancers, enhancing the currently available therapeutic approaches, and solving the problems in the field of brain cancer therapy.

Severe acute respiratory syndrome and thyroid: A molecular point of view.

SARS-CoV-2 and some other members of Coronaviridae family have recently forced a great deal of health, social, and economic issues globally. To that end, investigations have been oriented towards finding ways for reducing the burden of COVID-19. One of the occurrences which stands in the way of making the treatment of this disease less complicated is the way coronaviruses involve a variety of cells, tissues, organs, and even systems. This action is possible as a result of viral attachment to the angiotensin-converting enzyme 2 or ACE2. Thus, any kind of cell expressing ACE2 is prone to be affected by both SARS-COV and SARS-COV-2. Endocrine system is one of these at-risk systems. In this review, we have considered the relation between coronaviruses and one of the most essential organs of endocrine system: thyroid gland. This relation can be probed from two aspects: how underlying thyroid dysfunction can increase the risk of being infected by these viruses and how these viruses can alter the function of thyroid gland.

The role of polyphenols in overcoming cancer drug resistance: a comprehensive review.

Chemotherapeutic drugs are used to treat advanced stages of cancer or following surgery. However, cancers often develop resistance against drugs, leading to failure of treatment and recurrence of the disease. Polyphenols are a family of organic compounds with more than 10,000 members which have a three-membered flavan ring system in common. These natural compounds are known for their beneficial properties, such as free radical scavenging, decreasing oxidative stress, and modulating inflammation. Herein, we discuss the role of polyphenols (mainly curcumin, resveratrol, and epigallocatechin gallate [EGCG]) in different aspects of cancer drug resistance. Increasing drug uptake by tumor cells, decreasing drug metabolism by enzymes (e.g. cytochromes and glutathione-S-transferases), and reducing drug efflux are some of the mechanisms by which polyphenols increase the sensitivity of cancer cells to chemotherapeutic agents. Polyphenols also affect other targets for overcoming chemoresistance in cancer cells, including cell death (i.e. autophagy and apoptosis), EMT, ROS, DNA repair processes, cancer stem cells, and epigenetics (e.g. miRNAs).

Targeting microRNAs by curcumin: implication for cancer therapy.

In spite of all the investigations in the past 20 years that established a great body of knowledge in cancer therapy, utilizing some elderly methods such as plant compound administration might still be useful. Curcumin is a bioactive polyphenol, which has many anticancer properties but its capability in modulating miRNA expression has opened new doors in the field of cancer-targeted therapy. MiRNAs are a class of small noncoding RNAs that are able to regulate gene expression and signaling. In addition, some other effects of these RNAs such as modulating cell differentiation and regulation of cell cycle have made miRNAs great candidates for personalized cancer treatment. In this review, we try to find some answers to the questions on how curcumin exerts its impacts on cancer hallmarks through miRNAs and whether chemotherapy can be replaced by this beneficial plant compound.

The Effects of Sterol-Related Signaling Pathways on Glioma.

Gliomas are considered as one of the important brain tumors in adults due to their impact on life quality and cognitive functions. Current methods that are used for treating glioma are not satisfying enough. Understanding cellular and molecular events underlying its pathogenesis and progression may lead to the discovery of novel therapeutic approaches. Sterols are a subtype of steroids and are essential for the physiologic functions of eukaryotic cells. Sterols can be produced by protozoans and microheterotrophs. Moreover, they are found in some natural sources, such as plants, animals, fungi, microalgae, and yeasts. Besides the roles of sterols in physiologic processes, studies have shown that they are involved in pathologic processes, including tumorigenesis and tumor progression. As investigations have revealed, sterol-related signaling pathways are involved in glioma and targeting them may result in new therapeutic options for patients. Thus, we summarized some of the sterol-related signaling pathways in glioma and how they can be associated with other signaling pathways, including EGFR/PI3K/Akt/mTOR, P53, and retinoblastoma protein.

Targeting Wnt signaling pathway by polyphenols: implication for aging and age-related diseases.

Age is an important risk factor for different diseases. The same mechanisms that promote aging are involved in the development and progression of age-associated diseases. Polyphenols are organic compounds found in fruits and vegetables. Due to their beneficial properties (e.g. antioxidant and anti-inflammatory), polyphenols have been extensively used for treating chronic diseases. To exert their functions, polyphenols target various molecular mechanisms and signaling pathways, such as mTOR, NF-κB, and Wnt/ß-catenin. Wnt signaling is a critical pathway for developmental processes. Besides, dysregulation of this signaling pathway has been observed in various diseases. Several investigations have been conducted on Wnt inhibitors at pre-clinical stages, showing promising results. Herein, we review the studies dealing with the role of polyphenols in targeting the Wnt signaling pathways in aging processes and age-associated diseases, including cancer, diabetes, Alzheimer's disease, osteoporosis, and Parkinson's disease.

Anti-cancer properties of quercetin in osteosarcoma.

Osteosarcoma is a primary bone tumor. Although it is a rare disease in general, it is the most common primary bone tumor among children. Despite the significant advances made in the field of osteosarcoma treatment, the outcomes of this disease are still unfavorable. Besides, there is still no targeted therapy for osteosarcoma that can be used in clinical settings. Quercetin is a member of the phytochemical family which is used for different diseases including cardiovascular diseases, diabetes, and cancer. Its anti-cancer effects are examined in many types of cancer including breast, colon, lung, prostate, and pancreatic cancers and have shown promising results. Herein, the studies dealing with the antitumor roles of quercetin in osteosarcoma are reviewed in this article. We take a look into quercetin's ability to affect proliferation, apoptosis, invasion, and chemo-resistance of the osteosarcoma cells through regulating protein expression and signaling pathways.

DNA damage response and repair in osteosarcoma: Defects, regulation and therapeutic implications.

Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents which has the survival rate of 20% in its advanced stages. Osteosarcomas are mostly resistance to our common treatments. DNA damage response (DDR) is a specialized multistep process containing abundant proteins which are necessary for the survival of any cell and organism. DDR machinery detects a diversity of DNA lesions and inhibits the cell cycle progression if these lesions are not repairable. DDR is involved in aging, age-related diseases, and cancer. In recent years, DDR inhibitors have gained the attention of researches due to their potentials in offering novel therapeutic targets and improving the response of many cancers to either chemo- or radio-therapy. In this regard, we tried to gather a great body of evidence about the role of DDR ingredients in osteosarcoma's initiation/progression, prognosis, and treatment.

Coagulopathy: Another side effect of coronavirus infection.

Recently, coronavirus disease 2019 (COVID-19) has been considered as a major health problem around the globe. This severe acute respiratory syndrome has a bunch of features, such as high transmission rate, which are adding to its importance. Overcoming this disease relies on a complete understanding of the viral structure, receptors, at-risk cells or tissues, and pathogenesis. Currently, researches have shown that besides the lack of a proper anti-viral therapeutic method, complications provided by this virus are also standing in the way of decreasing its mortality rate. One of these complications is believed to be a hematologic manifestation. Commonly, three kinds of coagulopathies are detected in COVID-19 patients: disseminated intravascular coagulation (DIC), pulmonary embolism (PE), and deep vein thrombosis (DVT). In this paper, we have reviewed the relation between these conditions and coronavirus-related diseases pathogenesis, severity, and mortality rate.

Molecular and biological functions of gingerol as a natural effective therapeutic drug for cervical cancer.

Cervical cancer is one of the most common and important gynecological cancers, which has a global concern with an increasing number of patients and mortality rates. Today, most women in the world who suffer from cervical cancer are developing advanced stages of the disease. Smoking and even exposure to secondhand smoke, infections caused by the human papillomavirus, immune system dysfunction and high-risk individual-social behaviors are among the most important predisposing factors for this type of cancer. In addition, papilloma virus infection plays a more prominent role in cervical cancer. Surgery, chemotherapy or radical hysterectomy, and radiotherapy are effective treatments for this condition, the side effects of these methods endanger a person's quality of life and cause other problems in other parts of the body. Studies show that herbal medicines, including taxol, camptothecin and combretastatins, have been shown to be effective in treating cervical cancer. Ginger (Zingiber officinale, Zingiberaceae) is one of the plants with valuable compounds such as gingerols, paradols and shogoals, which is a rich source of antioxidants, anti-cancer and anti-inflammatory agents. Numerous studies have reported the therapeutic effects of this plant through various pathways in cervical cancer. In this article, we look at the signaling mechanisms and pathways in which ginger is used to treat cervical cancer.

Curcumin anti-tumor effects on endometrial cancer with focus on its molecular targets.

Curcumin is extracted from turmeric and shows a variety of properties that make it a useful agent for treating diseases and targeting different biological mechanisms, including apoptosis, angiogenesis, inflammation, and oxidative stress. This phenolic compound is safe even at high doses. However, it has poor bioavailability. The incidence rates of endometrial cancer (EC) that is one of the most prevalent gynecological malignancies is increasing. Meanwhile, the onset age of EC has been decreased in past few years. Besides, EC does not show a convenient prognosis, particularly at advanced stages. Based on this information, discovering new approaches or enhancing the available ones is required to provide better care for EC patients. In this review, we cover studies concerned with the anti-tumor effects of curcumin on EC. We focus on molecular mechanisms that are targeted by curcumin treatment in different processes of cancer development and progression, such as apoptosis, inflammation, and migration. Furthermore, we present the role of curcumin in targeting some microRNAs (miRNAs) that may play a role in EC.

Chitosan applications in studying and managing osteosarcoma.

Osteosarcoma has a high prevalence among children and adolescents. Common treatments of this disease are not promising enough. Molecular processes involved in the pathogenesis of osteosarcoma are not fully understood. Besides, the remnants of tumor cells after surgery can cause bone destruction and recurrence of the disease. Thus, there is a need to develop novel drugs or enhancing the currently-used drugs as well as identifying bone-repairing methods. Chitosan is a natural compound produced by the deacetylation of chitin. Research has shown that chitosan can be used in various fields due to its beneficial effects, such as biodegradability and biocompatibility. Regarding cancer, chitosan exerts several anti-tumor activities. Moreover, it can be used in diagnostic techniques, drug delivery systems, and cell culture methods. Herein, we aim to discuss the potential roles of chitosan in studying and treating osteosarcoma. We review the literature on chitosan's applications as a drug delivery system and how it can be combined with other substances to improve its ability of local drug delivery. We take a look into the studies concerning the possible benefits of chitosan in the field of bone tissue engineering and 3D culturing. Furthermore, anti-cancer activities of different compounds of chitosan are reviewed.

Melatonin as a potential inhibitor of kidney cancer: A survey of the molecular processes.

Studies have shown that despite the decreasing mortality rates of kidney cancer patients, its incidence is increasing. Therefore, a comprehensive re-evaluation of treatment options is necessary to provide appropriate treatments for the increasing number of patients. Moreover, the side effects caused by surgery, which is the main treatment of this disease, may lead to higher morbidity rates. Consequently, new safer approaches must be examined and considered. Major advancements have been made in the field of targeted agents as well as treatments based on immunotherapy since renal cell carcinoma (RCC) does not respond well to chemotherapy. While the therapeutic options for this cancer are increasing, the resulting complexity of selecting the best strategy for treating the patients is daunting. Moreover, each therapeutic option must be evaluated concerning toxicity, cost, and clinical advantages. Several characteristics, which are beneficial for cancer therapies have been attributed to melatonin. For decades, investigations have explored the application of melatonin in the treatment of cancer; insufficient attention has been paid to this molecule at the clinical level. Melatonin plays a role in cancer therapy due to its anti-tumor effects as well as by enhancing the efficacy of other drugs as an adjuvant. In this review, we discuss different roles of melatonin in the treatment of kidney cancer. The studies concerned with the applications of melatonin as an adjuvant in the immunotherapy of patients with kidney cancer are summarized. Also, we highlight the apoptotic and anti-angiogenic effects of melatonin on renal cancer cells which are mediated by different molecules (e.g., HIF-1 and VEGF, ADAMTS1, and MMP-9) and signaling pathways (e.g., P56, P52, and JNK). Furthermore, we take a look into available data on melatonin's ability to reduce the toxicities caused by kidney carcinogens, including ochratoxin A, potassium bromate, and Fe-NTA.

An Insight into the Sex Differences in COVID-19 Patients: What are the Possible Causes?

Studies have reported a sex bias in case fatalities of COVID-19 patients. Moreover, it is observed that men have a higher risk of developing a severe form of the disease compared to women, highlighting the importance of disaggregated data of male and female COVID-19 patients. On the other hand, other factors (eg, hormonal levels and immune functions) also need to be addressed due to the effects of sex differences on the outcomes of COVID-19 patients. An insight into the underlying causes of sex differences in COVID-19 patients may provide an opportunity for better care of the patients or prevention of the disease. The current study reviews the reports concerning with the sex differences in COVID-19 patients. It is explained how sex can affect angiotensin converting enzyme-2 (ACE2), that is a key component for the pathogenesis of COVID-19, and summarized the gender differences in immune responses and how sex hormones are involved in immune processes. Furthermore, the available data about the impact of sex hormones on the immune functions of COVID-19 cases are looked into.

Anti-tumor activities of probiotics in cervical cancer.

Cervical cancer is considered as an important malignancy among women worldwide. Currently-used treatments of cervical cancer are reported to be cytotoxic for patients. Moreover, these therapies have shown some side effects which can negatively affect the lives of women suffering from this cancer. Therefore, there is need for anti-tumor agents that are less toxic than common therapeutic drugs. Besides, applying agents for preventing or reducing the side effects of cervical cancer therapies can be effective in improving the life quality of cervical cancer patients. Studies have shown that probiotics have several effects on biological processes. One of the most prominent aspects in which probiotics play a role is in the field of cancer. There are multiple studies which have focused on the functions of probiotics in diagnosis, prevention, or treatment of cancer. Besides their direct anti-tumor activities, probiotics can be used as an additional agent for enhancing or modulating other diagnostic and therapeutic methods. Herein, the effects of probiotics on cervical cancer cells are discussed, which may be useful in the prevention and treatment of this cancer. We review the studies concerned with the roles of probiotics in modulating and reducing the gastrointestinal adverse effects caused by cervical cancer therapies. Furthermore, we cover the investigations focusing on the combination of probiotics with other drugs for diagnosis or treatment of cervical cancer.

COVID-19 and pregnancy: a review of current knowledge.

BACKGROUND: Since December 2019, coronavirus disease 2019 (COVID-19) has become a major health problem that is spreading all over the world. Several viral infections such as SARS, MERS, and influenza have been associated with adverse pregnancy outcomes. The question arises whether pregnant women are at greater risk of complications related to COVID-19 compared to other people What complications should we expect in the fetuses whose mothers were infected? AIMS: This review aims to provide a summary of studies on symptoms of COVID-19 and the possible risks of COVID-19 among pregnant women, as well as complications in fetuses and neonates whose mothers were infected with COVID-19. METHODS: The included data were provided from Web of Science, Cochrane, PubMed, and Scopus which are extracted from the published studies in English until April 2nd, 2020 that contained data on the risk of COVID-19 in pregnancy. RESULTS: The early symptoms of patients with COVID-19 were fever, cough, dyspnea, myalgia, and fatigue; while production of sputum, headache, hemoptysis, and diarrhea were other symptoms which were less common. There is no evidence of vertical maternal-fetal transmission in pregnant women with COVID-19. CONCLUSIONS: The clinical findings in pregnant women with COVID-19 are not significantly different compared to other patients, and pregnant women with COVID-19 are not at a higher risk of developing critical pneumonia compared to non-pregnant women. Although, there has been no sign of vertical infection in infants, but maternal infection can cause serious problems such as preterm labour and fetal distress.