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.

Gold-based hybrid nanostructures: more than just a pretty face for combinational cancer therapy.

The early diagnosis together with an efficient therapy of cancer is essential to treat cancer patients and to enhance their quality of life. The use of nanostructures, as a newer technology, has demonstrated proven benefits as efficient cancer theranostic agents in numerous recent studies. Having a tunable surface plasmon resonance, gold nanostructures have been the subject of many recent studies as excellent imaging and photothermal therapy agents. However, the potential cytotoxicity and weak stability of gold nanostructures necessitate further modifications using biocompatible materials for biological applications. Based on the composition of the final structure, these gold-based hybrid nanostructures (GHNs) could be divided into five major groups; each of which has specific pros and cons. Understanding the strengths and weaknesses of each group helps scientists to optimize GHN designs with multiple functions by synergizing the benefits of different groups. This review aims to summarize the advancements in GHN design and provide a perspective view of future requirements for successful GHN-based targeted combinational cancer theranostic platforms.

Doxorubicin/Cisplatin-Loaded Superparamagnetic Nanoparticles As A Stimuli-Responsive Co-Delivery System For Chemo-Photothermal Therapy.

INTRODUCTION: To date, numerous iron-based nanostructures have been designed for cancer therapy applications. Although some of them were promising for clinical applications, few efforts have been made to maximize the therapeutic index of these carriers. Herein, PEGylated silica-coated iron oxide nanoparticles (PS-IONs) were introduced as multipurpose stimuli-responsive co-delivery nanocarriers for a combination of dual-drug chemotherapy and photothermal therapy. METHODS: Superparamagnetic iron oxide nanoparticles were synthesized via the sonochemical method and coated by a thin layer of silica. The nanostructures were then further modified with a layer of di-carboxylate polyethylene glycol (6 kDa) and carboxylate-methoxy polyethylene glycol (6 kDa) to improve their stability, biocompatibility, and drug loading capability. Doxorubicin (DOX) and cisplatin (CDDP) were loaded on the PS-IONs through the interactions between the drug molecules and polyethylene glycol. RESULTS: The PS-IONs demonstrated excellent cellular uptake, cytocompatibility, and hemocompatibility at the practical dosage. Furthermore, in addition to being an appropriate MRI agent, PS-IONs demonstrated superb photothermal property in 0.5 W/cm2 of 808 nm laser irradiation. The release of both drugs was effectively triggered by pH and NIR irradiation. As a result of the intracellular combination chemotherapy and 10 min of safe power laser irradiation, the highest cytotoxicity for iron-based nanocarriers (97.3±0.8%) was achieved. CONCLUSION: The results of this study indicate the great potential of PS-IONs as a multifunctional targeted co-delivery system for cancer theranostic application and the advantage of employing proper combination therapy for cancer eradication.

Inorganic nanomaterials for chemo/photothermal therapy: a promising horizon on effective cancer treatment.

During the last few decades, nanotechnology has established many essential applications in the biomedical field and in particular for cancer therapy. Not only can nanodelivery systems address the shortcomings of conventional chemotherapy such as limited stability, non-specific biodistribution and targeting, poor water solubility, low therapeutic indices, and severe toxic side effects, but some of them can also provide simultaneous combination of therapies and diagnostics. Among the various therapies, the combination of chemo- and photothermal therapy (CT-PTT) has demonstrated synergistic therapeutic efficacies with minimal side effects in several preclinical studies. In this regard, inorganic nanostructures have been of special interest for CT-PTT, owing to their high thermal conversion efficiency, application in bio-imaging, versatility, and ease of synthesis and surface modification. In addition to being used as the first type of CT-PTT agents, they also include the most novel CT-PTT systems as the potentials of new inorganic nanomaterials are being more and more discovered. Considering the variety of inorganic nanostructures introduced for CT-PTT applications, enormous effort is needed to perform translational research on the most promising nanomaterials and to comprehensively evaluate the potentials of newly introduced ones in preclinical studies. This review provides an overview of most novel strategies used to employ inorganic nanostructures for cancer CT-PTT as well as cancer imaging and discusses current challenges and future perspectives in this area.

Role or Synergistic Interaction of Adenosine and Vitamin D3 Alongside High-Intensity Interval Training and Isocaloric Moderate Intensity Training on Metabolic Parameters: Protocol for an Experimental Study.

BACKGROUND: Obesity is known as one of the major causes of epidemiologic diseases worldwide; therefore, the introduction of treatment strategies by medical professionals, such as the use of various medicines and exercise programs to reduce fat or prevent obesity, is on the rise. Recently, researchers have shown special interest in assessing the effect of lipolytic adenosine and vitamin D deficiency, as well as the effect of exercise, on decreasing body fat percentage. OBJECTIVE: This study has been designed to examine the effect of adenosine and vitamin D3 injections, in conjunction with high-intensity interval training and isocaloric moderate-intensity training, on the metabolic parameters of obesity induced by a high-fat diet. METHODS: This is an experimental study using 92 Wistar rats. At 6 weeks of age, the rats' weights will be recorded, after which they will have 1 week to adapt to their new environment before being divided into 12 groups. The rats will participate in a 2-stage experimental intervention, including a 13-week fattening diet phase followed by a 12-week exercise training phase consisting of an exercise program and the injection of adenosine and vitamin D3. Groups 1 and 2 will have a normal diet, and the other groups will have a diet of 40% fat, with free access to food and water up to the second half of the second stage of the study (end of the sixth week of training). After termination of the interventions, tissue collection and molecular assessments (blood for biochemical, tissues for gene expression analyses, and anthropometrical indexes) will be performed. RESULTS: The project was initiated in April 2017 and completed in December 2017. Data analysis is under way, and the first results are expected to be submitted for publication in November 2018. CONCLUSIONS: We hypothesize that weight loss-induced molecular changes and upregulation will be observed in line with an increase in lipolysis and beta oxidation in muscle and fat tissue as a result of performing isocaloric training in drug-receiving rats and groups on a high-fat diet. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/10753.