MicroRNAs and exosomes: Small molecules with big actions in multiple myeloma pathogenesis.

Multiple myeloma (MM), an incurable hematologic malignancy of plasma cells increasing in the bone marrow (BM), has a complex microenvironment made to support proliferation, survival, and drug resistance of tumor cells. MicroRNAs (miRNAs), short non-coding RNAs regulating genes expression at posttranscriptional level, have been indicated to be functionally deregulated or abnormally expressed in MM cells. Moreover, by means of miRNAs, tumor microenvironment also modulates the function of MM cells. Consistently, it has been demonstrated that miRNA levels regulation impairs their interaction with the microenvironment of BM as well as create considerable antitumor feature even capable of overcoming the protective BM milieu. Communication between cancer stromal cells and cancer cells is a key factor in tumor progression. Finding out this interaction is important to develop effective approaches that reverse bone diseases. Exosomes, nano-vehicles having crucial roles in cell-to-cell communication, through targeting their cargos (i.e., miRNAs, mRNAs, DNAs, and proteins), are implicated in MM pathogenesis.

Exosomes and cancer: From oncogenic roles to therapeutic applications.

Exosomes belong to extracellular vehicles that were produced and secreted from most eukaryotic cells and are involved in cell-to-cell communications. They are an effective delivery system for biological compounds such as mRNAs, microRNAs (miRNAs), proteins, lipids, saccharides, and other physiological compounds to target cells. In this way, they could influence on cellular pathways and mediate their physiological behaviors including cell proliferation, tumorigenesis, differentiation, and so on. Many research studies focused on their role in cancers and also on potentially therapeutic and biomarker applications. In the current study, we reviewed the exosomes' effects on cancer progression based on their cargoes including miRNAs, long noncoding RNAs, circular RNAs, DNAs, mRNAs, proteins, and lipids. Moreover, their therapeutic roles in cancer were considered. In this regard, we have given a brief overview of challenges and obstacles in using exosomes as therapeutic agents.

The role of miR-146a in viral infection.

Cellular microRNAs (miRNAs) were identified as a key player in the posttranscriptional regulation of cellular-genes regulatory pathways. They also emerged as a significant regulator of the immune response. In particular, miR-146a acts as an importance modulator of function and differentiation cells of the innate and adaptive immunity. It has been associated with disorder including cancer and viral infections. Given its significance in the regulation of key cellular processes, it is not surprising which virus infection have found ways to dysregulation of miRNAs. miR-146a has been identified in exosomes (exosomal miR-146a). After the exosomes release from donor cells, they are taken up by the recipient cell and probably the exosomal miR-146a is able to modulate the antiviral response in the recipient cell and result in making them more susceptible to virus infection. In this review, we discuss recent reports regarding miR-146a expression levels, target genes, function, and contributing role in the pathogenesis of the viral infection and provide a clue to develop the new therapeutic and preventive strategies for viral disease in the future.

Leukemia-derived exosomes: Bringing oncogenic signals to blood cells.

Leukemia is a cancer, which is derived from leukocytes and precursors of leukocytes in the bone marrow. A large number of pivotal biological processes are linked to leukemia pathogenesis. More insights into these mechanisms can provide a better developing pharmacological platform for patients with leukemia. Among the different players in leukemia pathogenesis, exosomes have appeared as a new biological vehicle, which can transfer oncogenic signals to blood cells. Exosomes are nano-carriers, which enable transferring numerous cargos such as DNA fragments, RNAs, messenger RNAs, microRNAs, long noncoding RNA, and proteins. Targeting the contents of exosomes leads to the alteration of host cell behavior. Increasing evidence has indicated that leukemia-derived exosomes could be utilized as prognostic, diagnostic, and therapeutic biomarkers for individuals suffering from leukemia. In this regard, the importance of exosomes in terms of initiation and progression of leukemia was underlined in this study.

Therapeutic Applications of Curcumin and its Novel Formulations in the Treatment of Bladder Cancer: A Review of Current Evidence.

Bladder cancer, a life-threatening serious disease, is responsible for thousands of cancer-associated deaths worldwide. Similar to other malignancies, standard treatments of bladder cancer, such as Chemoradiotherapy, are not efficient enough in the affected patients. It means that, according to recent reports in the case of life quality as well as the survival time of bladder cancer patients, there is a critical requirement for exploring effective treatments. Recently, numerous investigations have been carried out to search for appropriate complementary treatments or adjuvants for bladder cancer therapy. Curcumin, a phenolic component with a wide spectrum of biological activities, has recently been introduced as a potential anti-cancer agent. It has been shown that this agent exerts its therapeutic effects via targeting a wide range of cellular and molecular pathways involved in bladder cancer. Herein, the current data on curcumin therapy for bladder cancer are summarized.

Resveratrol: A New Potential Therapeutic Agent for Melanoma?

Melanoma is the most life-threatening and aggressive class of skin malignancies. The incidence of melanoma has steadily increased. Metastatic melanoma is greatly resistant to standard antimelanoma treatments such as chemotherapy, and the 5-year survival rate of cases with melanoma who have a metastatic form of the disease is less than 10%. The contributing role of apoptosis, angiogenesis and autophagy in the pathophysiology of melanoma has been previously demonstrated. Thus, it is extremely urgent to search for complementary therapeutic approaches that could enhance the quality of life of subjects and reduce treatment resistance and adverse effects. Resveratrol, known as a polyphenol component present in grapes and some plants, has anti-cancer properties due to its function as an apoptosis inducer in tumor cells, and anti-angiogenic agent to prevent metastasis. However, more clinical trials should be conducted to prove resveratrol efficacy. Herein, for the first time, we summarize the current knowledge of anti-cancerous activities of resveratrol in melanoma.

Role of Resveratrol in Modulating microRNAs in Human Diseases: From Cancer to Inflammatory Disorder.

Cancer and inflammatory disorders are two important public health issues worldwide with significant socio.economic impacts. Despite several efforts, the current therapeutic platforms are associated with severe limitations. Therefore, developing new therapeutic strategies for the treatment of these diseases is a top priority. Besides current therapies, the utilization of natural compounds has emerged as a new horizon for the treatment of cancer and inflammatory disorders as well. Such natural compounds could be used either alone or in combination with the standard cancer therapeutic modalities such as chemotherapy, radiotherapy, and immunotherapy. Resveratrol is a polyphenolic compound that is found in grapes as well as other foods. It has been found that this medicinal agent displays a wide pharmacological spectrum, including anti-cancer, anti-inflammatory, anti-microbial, and antioxidant activities. Recently, clinical and pre-clinical studies have highlighted the anti-cancer and anti-inflammatory effects of resveratrol. Increasing evidence revealed that resveratrol exerts its therapeutic effects by targeting various cellular and molecular mechanisms. Among cellular and molecular targets that are modulated by resveratrol, microRNAs (miRNAs) have appeared as key targets. MiRNAs are short non-coding RNAs that act as epigenetic regulators. These molecules are involved in many processes that are involved in the initiation and progression of cancer and inflammatory disorders. Herein, we summarized various miRNAs that are directly/indirectly influenced by resveratrol in cancer and inflammatory disorders.

Quercetin and cancer: new insights into its therapeutic effects on ovarian cancer cells.

Ovarian cancer is known as a serious malignancy that affects women's reproductive tract and can considerably threat their health. A wide range of molecular mechanisms and genetic modifications have been involved in ovarian cancer pathogenesis making it difficult to develop effective therapeutic platforms. Hence, discovery and developing new therapeutic approaches are required. Medicinal plants, as a new source of drugs, could potentially be used alone or in combination with other medicines in the treatment of various cancers such as ovarian cancer. Among various natural compounds, quercetin has shown great anti-cancer and anti-inflammatory properties. In vitro and in vivo experiments have revealed that quercetin possesses a cytotoxic impact on ovarian cancer cells. Despite obtaining good results both in vitro and in vivo, few clinical studies have assessed the anti-cancer effects of quercetin particularly in the ovarian cancer. Therefore, it seems that further clinical studies may introduce quercetin as therapeutic agent alone or in combination with other chemotherapy drugs to the clinical setting. Here, we not only summarize the anti-cancer effects of quercetin but also highlight the therapeutic effects of quercetin in the ovarian cancer.

Cancer stem cells as therapeutic targets of pancreatic cancer.

The discovery of stem cells and their potential abilities in self-renewal and differentiation has opened a new horizon in medicine. Scientists have found a small population of stem cells in some types of cancers with the same functions as normal stem cells. There are two models for tumor progression: clonal (stochastic) and cancer stem cell (CSCs) models. According to the first model, all transformed cells in the tumor have carcinogenic potential and are able to proliferate and produce the same cells. The latter model, which has received more attention recently, considers the role of CSCs in drug resistance and tumor metastasis. Following the model, researchers have found that targeting CSCs may be a promising way in cancer therapy. This review describes CSC characteristics in general, while also focusing on CSC properties in the context of pancreatic cancer.

Therapeutic potentials of curcumin in the treatment of glioblstoma.

Glioblastoma multiforme (GBM), a greatly aggressive malignancy of the brain, is correlated with a poor prognosis and low rate of survival. Up to now, chemotherapy and radiation therapy after surgical approaches have been the treatments increasing the survival rates. The low efficacy of mentioned therapies as well as their side-effects has forced researchers to explore an appropriate alternative or complementary treatment for glioblastoma. In experimental models, it has been shown that curcumin has therapeutic potentials to fight against GBM. Given that curcumin has pharmacological effects against cancer stem cells, as major causes of resistance to therapy in glioblastoma cells. Moreover, it has been showed that curcumin exerts its therapeutic effects on GBM cells via affecting on apoptosis, oxidant system, and inflammatory pathways. Curcumin would possess a synergistic impact with chemotherapeutic agents. Herein, we summarized the current findings on curcumin as therapeutic agent in the treatment of GBM.