Advances in chitosan-based drug delivery systems in melanoma: A narrative review.

Melanoma accounts for the minority of skin cancer cases. However, it has the highest mortality rate among the subtypes of skin cancer. At the early stages of the disease, patients show a good prognosis after the surgery, but developing metastases leads to a remarkable drop in patients' 5-year survival rate. Despite the advances made in the therapeutic approaches to this disease, melanoma treatment is still facing several obstacles. Systemic toxicity, water insolubility, instability, lack of proper biodistribution, inadequate cellular penetration, and rapid clearance are some of the challenges that should be addressed in the field of melanoma treatment. While various delivery systems have been developed to circumvent these challenges, chitosan-based delivery platforms have indicated significant success. Chitosan that is produced by the deacetylation of chitin can be formulated into different materials (e.g., nanoparticle, film, and hydrogel) due to its characteristics. Both in vitro and in vivo studies have reported that chitosan-based materials can be used in drug delivery systems while offering a solution for the common problems in this area, such as enhancing biodistribution and skin penetration as well as the sustained release of the drugs. Herein, we reviewed the studies concerning the role of chitosan as a drug delivery system in melanoma and discussed how these drug systems are used for delivering chemotherapeutic drugs (e.g., doxorubicin and paclitaxel), genes (e.g., TRAIL), and RNAs (e.g., miRNA199a and STAT3 siRNA) successfully. Furthermore, we take a look into the role of chitosan-based nanoparticles in neutron capture therapy.

Potential Mechanisms of Melatonin in Osteosarcoma and Bone-Related Neoplasms: Updated Review.

Melatonin (N-acetyl-5-methoxytryptamine) is a secretory product of the pineal gland. A great number of studies have been investigating the functions of this indoleamine in various diseases. Excessive proliferation, reduction in apoptosis, increased angiogenesis, invasion, and metastasis are all processes associated with cancerous tissues. In several cancer types, melatonin is reported to significantly impact these processes. Although bone cancer is relatively rare, it is a serious disease that often becomes metastatic, leading to an unsatisfactory prognosis. In recent decades, significant advances have been made in the therapeutic strategies for bone cancer. Nevertheless, few changes have occurred to patients' outcomes or therapeutic methods. Currently used therapeutic strategies including chemotherapy and radiotherapy often show serious side effects. Moreover, therapeutic options are not sufficient in certain cases, such as metastatic forms of the disease. Therefore, there is a need for a more precise definition of the molecular pathways and cellular functions associated with bone cancer to find novel therapeutic approaches. With such advances, the development of new effective therapies for patients with advanced stage or metastatic forms of the disease will be achieved, resulting in an improved prognosis. This review summarizes what is known about the functions of melatonin in osteosarcoma and Ewing's sarcoma. We explain the underlying mechanisms of action by which melatonin serves as an antitumor agent in bone cancer as well as provide an insight into its synergistic effects with other chemotherapeutic drugs.

Resveratrol Effects on Molecular Pathways and MicroRNAs in Gastrointestinal Cancers.

Gastrointestinal (GI) cancers are one of the most prevalent types of neoplasms worldwide. The incidence of GI cancers is increasing rapidly. Despite all advances in the management of GI cancers, treatment options for these disorders are still limited and there are no effective therapeutic approaches. Hence, finding new treatment strategies seems to be necessary to decrease mortality in patients with such cancers. The application of natural products has found a prominent role in the management of some neoplastic disorders. Resveratrol is a phytochemical found in various fruits and plants such as red grapes and tea. Recently, the effects of resveratrol on the microRNAs in the management of some neoplastic disorders have been investigated. This review is aimed to illustrate the molecular pathways related to resveratrol and evaluate the impacts of resveratrol on the different microRNAs in the milieu of the prevention and treatment of GI cancers.

Effects of empagliflozin on the expression of kisspeptin gene and reproductive system function in streptozotocin-induced diabetic male rats.

One of the main health concerns of diabetes is testicular dysfunction and impairment of reproductive function and sperm quality which can cause male infertility. kisspeptin is a hypothalamic neuropeptide hormone that is involved in the regulation of energy metabolism, gonadotrophin-releasing hormone (GnRH), and reproductive function. In the present study, the therapeutic effects of empagliflozin (sodium-glucose co-transporter 2 inhibitors) on kisspeptin expression along with reproductive function were investigated in diabetic male Wistar rats. Diabetes was induced by a single dose injection of 60 mg/kg streptozotocin. Empagliflozin in doses of 10 and 25 mg/kg body weight was used for 8 weeks. Serum samples, testis, epididymis, and pancreas tissues were collected at the end of the experiments. Lipid profiles, oxidative stress markers, blood hormones, expression of kisspeptin along with pathological alterations of the testis were assayed using real-time PCR, biochemical, and histological technics. Data have shown that empagliflozin improved hyperglycemia, reproductive impairment, oxidative stress condition, and histopathological alterations of pancreatic and testis tissues in diabetic animals. It improved the serum levels of sex hormones, insulin, leptin, and the expression of kisspeptin in the testes tissues. Spermatogenesis is also improved in treated animals. Data indicated that the administration of empagliflozin can ameliorate symptoms of diabetes. It probably has promising antidiabetic potential and may improve the male infertility of diabetic subjects. To our knowledge, this is the first experimental evidence for the potential impact of empagliflozin on kisspeptin expression in diabetic male rats.

Virus, Exosome, and MicroRNA: New Insights into Autophagy.

Autophagy is known as a conserved self-eating mechanism that contributes to cells to degrade different intracellular components (i.e., macromolecular complexes, aggregated proteins, soluble proteins, organelles, and foreign bodies). Autophagy needs formation of a double-membrane structure, which is composed of the sequestered cytoplasmic contents, called autophagosome. There are a variety of internal and external factors involved in initiation and progression of autophagy process. Viruses as external factors are one of the particles that could be associated with different stages of this process. Viruses exert their functions via activation and/or inhibition of a wide range of cellular and molecular targets, which are involved in autophagy process. Besides viruses, a variety of cellular and molecular pathways that are activated and inhibited by several factors (e.g., genetics, epigenetics, and environment factors) are related to beginning and developing of autophagy mechanism. Exosomes and microRNAs have been emerged as novel and effective players anticipated in various stages of autophagy. More knowledge in these pathways and identification of accurate roles of them could help to provide better therapeutic approaches in several diseases such as cancer. We highlighted the roles of viruses, exosomes, and microRNAs in the autophagy processes.

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.

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.

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.

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.

Molecular and cellular mechanisms of melatonin in breast cancer.

Breast cancer is considered as one of the most important health problems due to its poor prognosis and high rate of mortality and new diagnosed cases. Annually, a great number of deaths are reported in men and women; this means that despite all the improvements in cancer diagnosis and treatment, still, an intense need for more effective approaches exists. Melatonin is a multivalent compound which has a hand in several cellular and molecular processes and therefore, is an appropriate candidate for treatment of many diseases like cancer. Currently, considerable properties of this agent have oriented the research towards investigating its effects specifically in breast cancer. In this review, we gathered a bunch of evidence in order to give a new sight for breast cancer treatment utilizing melatonin. We expect that in coming years, melatonin will become one of the most common therapeutic drugs with lesser side-effects than other chemotherapeutic drugs.

Effects of Berberine on Leukemia with a Focus on Its Molecular Targets.

Leukemia is common among both women and men worldwide. Besides the fact that finding new treatment methods may enhance the life quality of patients, there are several problems that we face today in treating leukemia patients, such as drugs' side effects and acquired resistance to chemotherapeutic drugs. Berberine is a bioactive alkaloid found in herbal plants (e.g., Rhizoma coptidis and Cortex phellodendri) and exerts several beneficial functions, including anti-tumor activities. Furthermore, berberine exerts antiproliferative and anti-inflammatory effects. Up to now, some studies have investigated the roles of berberine in different types of leukemia, including acute myeloid leukemia and chronic lymphocytic leukemia. In this review, a detailed description of the roles of berberine in leukemia is provided. We discuss how berberine involves different molecular targets (e.g., interleukins and cyclins) and signaling pathways (e.g., mTOR and PI3K) to exert its anti-tumor functions and how berberine is effective in leukemia treatment when combined with other therapeutic drugs.

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.

Molecular Signaling Pathways as Potential Therapeutic Targets in Osteosarcoma.

Among primary bone malignancies, osteosarcoma (OS) is the most common form causing morbidity and mortality in both adults and children. The interesting point about this malignancy is that nearly 10-20% of its newly diagnosed cases have developed metastasis. This adds up to the fact that the survival rate of both metastatic and non-metastatic patients of osteosarcoma has not changed in the past 30 years; therefore, it has been suggested that we need to revise our therapeutic options for OS. In recent years, diverse signaling pathways have drawn the attention of the scientific community since they can be great candidates for treating complicated diseases, such as cancer. In this review, we have tried to explain the pathophysiology of osteosarcoma with the help of different signaling pathways taking part in its initiation/progression and explore how this pathway can be targeted for providing more efficient methods.

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.

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.