Light-Based Therapy: Novel Approach to Treat COVID-19.

The pandemic outbreak of Coronavirus disease 2019 (COVID-19) which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), is a new viral infection in all countries around the world. An increase in inflammatory cytokines, fever, dry cough, and pneumonia are the main symptoms of COVID-19. A shared of growing clinical evidence confirmed that cytokine storm correlates with COVID-19 severity which is also a crucial cause of death from COVID-19. The success of anti-inflammatory therapies in the recovery process of COVID-19 patients has been well established. Over the years, phototherapy (PhT) has been identified as a promising non-invasive treatment approach for inflammatory conditions. New evidence suggests that PhT as an anti-inflammatory therapy may be effective in treating acute respiratory distress syndrome (ARDS) and COVID-19. This review aims to a comprehensive overview of the direct and indirect effects of anti-inflammatory mechanisms of PhT in ARDS and COVID-19 patients.

miR-1290 contributes to oncogenesis and angiogenesis via targeting of THBS1, DKK3 and, SCAI.

Introduction: Colorectal cancer (CRC) is the third most common cancer in the world with high mortality, hence, understanding the molecular mechanisms involved in the tumor progression are important for CRC diagnosis and treatment. MicroRNAs (miRNAs) are key gene expression regulators that can function as tumor suppressors or oncogenes in tumor cells, and modulate angiogenesis as a critical process in tumor metastasis. MiR-1290 has been demonstrated as an onco-miRNA in various types of cancer, however, the role of miR-1290 in CRC is not fully understood. This study aimed to investigate the oncogenic and angiogenic potential of miR-1290 in CRC. Methods: Lenti-miR-1290 was transduced into HCT116, SW480, and human umbilical vein endothelial cells (HUVECs). By bioinformatics analysis, we identified thrombospondin 1 (THBS1) as a novel predicted target for miR-1290. Quantitative real-time PCR, western blotting, and luciferase reporter assay were used to demonstrate suppression of miR-1290 target genes including THBS1, Dickkopf Wnt signaling pathway inhibitor 3 (DKK3), and suppressor of cancer cell invasion (SCAI) in HCT116 and HUVECs. Cell cycle analysis, proliferation, migration and, tube formation were determined by flow cytometry, MTT, wound healing, and tube formation assays, respectively. Results: MiR-1290 significantly decreased the expression of THBS1, DKK3, and SCAI. We demonstrated that miR-1290 enhanced proliferation, migration, and angiogenesis partially through suppression of THBS1, DKK3, and SCAI in CRC. Conclusion: These results suggest a novel function of miR-1290 which may contribute to tumorigenesis and angiogenesis in CRC.

Cellular Therapy: The Hope for Covid-19.

Coronaviruses (CoVs) are a group of very diverse viruses that cause a broad spectrum of diseases from mild to severe enteric, respiratory, systemic diseases, and common cold or pneumonia among humans and animals. This virus is associated with Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS), and lung disease that lead to Acute Respiratory Distress Syndrome (ARDS). In December 2019, researchers identified a novel coronavirus type, called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), which was associated with symptoms of high fever, dry cough, headache, diarrhea, and reduction of White Blood Cells (WBC). Coronavirus-associated acute respiratory disease was named Coronavirus Disease 19 (COVID-19). No proven treatment has been discovered for COVID-19 so far, but researchers are trying to find the best effective way to treat this disease. Therefore, therapeutic strategies that facilitate the recovery of COVID-19 patients and reduce life-threatening complications are urgently needed now. Today, Mesenchymal Stem Cells (MSCs) and their secretion are utilized as one of the most applied tools to treat various diseases such as inflammation and cancer. MSC-derived vesicles are rich in various growth factors, cytokines, and interleukins that are produced and secreted under different physiological or pathological conditions. These vesicles were considered a suitable and effective tool in regeneration medicine because of their high power in repairing damaged tissues and modulating immune responses. Recently, evidence has shown MSC-derived vesicles through reduced expression of pro-inflammatory cytokines could improve damaged tissues in COVID-19 patients. In addition to MSCs and MSC-derived exosomes, Natural Killer (NK) cells, T cells, and platelet lysates were used against viral infection. In this review, we tried to provide an overview of MSC secretion and immune cells for COVID-19 therapy.

Angioregulatory microRNAs in breast cancer: Molecular mechanistic basis and implications for therapeutic strategies.

Background: Cancer-associated angiogenesis is a fundamental process in tumor growth and metastasis. A variety of signaling regulators and pathways contribute to establish neovascularization, among them as small endogenous non-coding RNAs, microRNAs (miRNAs) play prominent dual regulatory function in breast cancer (BC) angiogenesis. Aim of Review: This review aims at describing the current state-of-the-art in BC angiogenesis-mediated by angioregulatory miRNAs, and an overview of miRNAs dysregulation association with the anti-angiogenic response in addition to potential clinical application of miRNAs-based therapeutics. Key Scientific Concepts of Review: Angioregulatory miRNA-target gene interaction is not only involved in sprouting vessels of breast tumors but also, trans-differentiation of BC cells to endothelial cells (ECs) in a process termed vasculogenic mimicry. Using canonical and non-canonical angiogenesis pathways, the tumor cell employs the oncogenic characteristics such as miRNAs dysregulation to increase survival, proliferation, oxygen and nutrient supply, and treatment resistance. Angioregulatory miRNAs in BC cells and their microenvironment have therapeutic potential in cancer treatment. Although, miRNAs dysregulation can serve as tumor biomarker nevertheless, due to the association of miRNAs dysregulation with anti-angiogenic resistant phenotype, clinical benefits of anti-angiogenic therapy might be challenging in BC. Hence, unveiling the molecular mechanism underlying angioregulatory miRNAs sparked a booming interest in finding new treatment strategies such as miRNA-based therapies in BC.

The state of the art of biomedical applications of optogenetics.

BACKGROUND AND OBJECTIVE: Optogenetics has opened new insights into biomedical research with the ability to manipulate and control cellular activity using light in combination with genetically engineered photosensitive proteins. By stimulating with light, this method provides high spatiotemporal and high specificity resolution, which is in contrast to conventional pharmacological or electrical stimulation. Optogenetics was initially introduced to control neural activities but was gradually extended to other biomedical fields. STUDY DESIGN: In this paper, firstly, we summarize the current optogenetic tools stimulated by different light sources, including lasers, light-emitting diodes, and laser diodes. Second, we outline the variety of biomedical applications of optogenetics not only for neuronal circuits but also for various kinds of cells and tissues from cardiomyocytes to ganglion cells. Furthermore, we highlight the potential of this technique for treating neurological disorders, cardiac arrhythmia, visual impairment, hearing loss, and urinary bladder diseases as well as clarify the mechanisms underlying cancer progression and control of stem cell differentiation. CONCLUSION: We sought to summarize the various types of promising applications of optogenetics to treat a broad spectrum of disorders. It is conceivable to expect that optogenetics profits a growing number of patients suffering from a range of different diseases in the near future.

Ultrasound and Sonogenetics: A New Perspective for Controlling Cells with Sound.

An important challenge in neurobiology is to stimulate a single neuron, especially in deep areas of the brain. The optogenetics methods need a surgical operation to convey light sources to targeted cells. Nowadays, non-invasive tools such as sonogenetics with the ability to modulate and visualizing cellular and molecular processes have attracted much attention. The study of the biological functions of living organisms always requires tools for monitoring and imaging dynamically. Current sonogenetic approaches use ultrasound as a non-invasive tool to precisely control cellular function. In general, sonogenetics includes the development of mechano-sensitive proteins, approaches for introducing their genes to specific cells, targeted stimulation, and finally, reading the outcome. Hence, to prepare a short review of emerging technology sonogenetics, we summarized the introduction of sound waves, the mechano-sensitive proteins commonly used in sonogenetics, and potential therapeutic applications of sonogenetics for biological research and medicine. This short review would beneficiate in the translation of sonogenetics from present in-vitro and in-vivo investigations to clinical therapies.

Optogenetic Stimulation of Primary Cardiomyocytes Expressing ChR2.

Introduction: Non-clinical cardiovascular drug safety assessment is the main step in the progress of new pharmaceutical products. Cardiac drug safety testing focuses on a delayed rectifier potassium channel block and QT interval prolongation, whereas optogenetics is a powerful technology for modulating the electrophysiological properties of excitable cells. Methods: For this purpose, the blue light-gated ion channel, channelrhodopsin-2 (ChR2), has been introduced into isolated primary neonatal cardiomyocytes via a lentiviral vector. After being subjected to optical stimulation, transmembrane potential and intracellular calcium were assessed. Results: Here, we generated cardiomyocytes expressing ChR2 (light-sensitive protein), that upon optical stimulation, the cardiomyocytes depolarized result from alterations of membrane voltage and intracellular calcium. Conclusion: This cell model was easily adapted to a cell culture system in a laboratory, making this method very attractive for therapeutic research on cardiac optogenetics.

Network Analysis of Common Genes and Transcriptional Factors between Celiac Disease and Inflammatory Bowel Diseases.

BACKGROUND Understanding the associations among different disorders remarkably improves their diagnosis and treatments. Celiac disease is the most complicated and prevalent form of immune-mediated diseases. On the other hand, inflammatory bowel diseases lead to inflammation of the intestine with an unknown cause. Although inflammatory bowel diseases have been often thought of as an autoimmune disorder, they can be triggered by whatever that can lead to the inflammation in the whole bowel. Henceforth, both aforementioned diseases are related to autoimmune attacks and cause a sort of inflammatory event, which exploring trade-off among them supposedly will lead to discovering important genes and, in turn, to the possible common therapeutic protocols. In the current study, we aimed to determine the correlation between the common genes in celiac disease and inflammatory bowel diseases. METHODS 314 and 851 genes correlated with celiac disease and inflammatory bowel diseases respectively extracted from DisGeNET were subjected to an in-silico data analysis framework to mine prognosticates genes and the associated pathways. RESULTS 149 shared genes between these diseases regulated by highlighted transcription factors NFKB1, IRF1, STAT1, HSF1, GATA3 were characterized as discriminating molecules, which by further screening were enriched in pathways mostly involved in apoptosis, T cell activation, and cytokine, chemokine, and interleukin signaling. CONCLUSION We observed that the identified common genes were associated with a wide range of pathogenic mechanisms underlying these diseases.

Modulation of cardiac optogenetics by vitamin A.

Cardiac optogenetics is an emergent research area and refers to the delivery of light-activated proteins to excitable heart tissue and the subsequent use of light for controlling the electrical function with high spatial and temporal resolution. Channelrhodopsin-2 (ChR2) is a light-sensitive ion channel with the chromophore, all trans retinal, derived from vitamin A (all-trans-retinol; retinol). In this study, we explored whether exogenous vitamin A can be a limiting factor in the light responsiveness of cardiomyocytes-expressing ChR2. We showed that in cardiomyocytes virally transduced with ChR2 (H134R)-enhanced yellow fluorescent protein, vitamin A supplements lower than 10 µM significantly increased ChR2 expression. Adding 1 µM vitamin A changed light-induced transmembrane potential difference significantly, whereas 5 µM dramatically induced membrane depolarization and triggered intracellular calcium elevation. We concluded that vitamin A supplementation can modulate the efficiency of ChR2 and provide a complementary strategy for improving the performance of optogenetic tools.

Gossypol enhances radiation induced autophagy in glioblastoma multiforme.

Malignant gliomas (glioblastoma multiforme) are the most aggressive of the primary brain tumors. Radiotherapy is an important tool for treatment of cancer but malignant gliomas are usually resistant to radiotherapy and other adjuvant therapies. Thus new drugs are needed to increase the efficiency of radiotherapy in order to improve the therapeutic outcome of tumor patients. Recent investigations showed that gossypol, natural polyphenolic compound produced by cotton plants, is a promising agent against solid tumors. The current study was defined to evaluate whether the combinatorial effect of radiation and gossypol would induce higher level of cell death on U-87 MG than single agent treatment and its possible mechanism of action. Clonogenic survival assay showed that ionizing radiation plus gossypol significantly inhibited clonogenic growth of irradiated cells as compared with either treatment alone. Acridine orange/etidium bromide staining confirmed that there was no significant increase in necrotic and apoptotic cells, but irradiated cells in combination with gossypol showed a significant increase in accumulation of acidic vesicular organelle. The results obtained herein indicated that gossypol is a promising drug that induced autophagic cell death in radioresistant malignant glioma.

Therapeutic potential of gossypol: an overview.

CONTEXT: Polyphenols are naturally occurring compounds found in fruits, vegetables, cereals, and beverages. Polyphenols occupy a unique place in biological science for their pharmacological properties. Gossypol is a polyphenolic compound that has attracted attention because of its biological effects. OBJECTIVE: Gossypol is reported to exhibit antifertility, antioxidant, anticancer, antivirus, antiparasitic, and antimicrobial properties and lower plasma cholesterol. These are summarized with attention to the mechanisms of activity. METHODS: This review summarizes the results of studies obtained in a comprehensive search of ScienceDirect, PubMed, Scirus, and Web of Science. RESULTS AND CONCLUSION: The results of these studies provide a comprehensive understanding of the biological action of gossypol and its potential for the prevention of and therapy for resistant tumors and chronic human diseases such as HIV, malaria, and psoriasis.