Role of SARS-COV-2 and ACE2 in the pathophysiology of peripheral vascular diseases.

The occurrence of a novel coronavirus known as severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), created a serious challenge worldwide. SARS-CoV-2 has high infectivity, the ability to be transmitted even during the asymptomatic phase, and relatively low virulence, which has resulted in rapid transmission. SARS-CoV-2 can invade epithelial cells, hence, many patients infected with SARS-CoV-2 have suffered from vascular diseases (VDs) in addition to pulmonary manifestations. Accordingly, SARS-CoV-2 may can worsen the clinical condition of the patients with pre-existing VDs. Endothelial cells express angiotensin-converting enzyme 2 (ACE2). ACE2 is a biological enzyme that converts angiotensin (Ang)- 2 to Ang-(1-7). SARS-CoV-2 uses ACE2 as a cell receptor for viral entry. Thus, the SARS-CoV-2 virus promotes downregulation of ACE2, Ang-(1-7), and anti-inflammatory cytokines, as well as, an increase in Ang-2, resulting in pro-inflammatory cytokines. SARS-CoV-2 infection can cause hypertension, and endothelial damage, which can lead to intravascular thrombosis. In this review, we have concentrated on the effect of SARS-CoV-2 in peripheral vascular diseases (PVDs) and ACE2 as an enzyme in Renin-angiotensin aldosterone system (RAAS). A comprehensive search was performed on PubMed, Google Scholar, Scopus, using related keywords. Articles focusing on ("SARS-CoV-2", OR "COVID-19"), AND ("Vascular disease", OR "Peripheral vascular disease", OR interested disease name) with regard to MeSH terms, were selected. According to the studies, it is supposed that vascular diseases may increase susceptibility to severe SARS-CoV-2 infection due to increased thrombotic burden and endothelial dysfunction. Understanding SARS-CoV-2 infection mechanism and vascular system pathogenesis is crucial for effective management and treatment in pre-existing vascular diseases.

Current concepts of microRNA-mediated regulatory mechanisms in human pulp tissue-derived stem cells: a snapshot in the regenerative dentistry.

One of the most studied class of non-coding RNAs is microRNAs (miRNAs) which regulate more than 60% of human genes. A network of miRNA gene interactions participates in stem cell self-renewal, proliferation, migration, apoptosis, immunomodulation, and differentiation. Human pulp tissue-derived stem cells (PSCs) are an attractive source of dental mesenchymal stem cells (MSCs) which comprise human dental pulp stem cells (hDPSCs) obtained from the dental pulp of permanent teeth and stem cells isolated from exfoliated deciduous teeth (SHEDs) that would be a therapeutic opportunity in stomatognathic system reconstruction and repair of other damaged tissues. The regenerative capacity of hDPSCs and SHEDs is mediated by osteogenic, odontogenic, myogenic, neurogenic, angiogenic differentiation, and immunomodulatory function. Multi-lineage differentiation of PSCs can be induced or inhibited by the interaction of miRNAs with their target genes. Manipulating the expression of functional miRNAs in PSCs by mimicking miRNAs or inhibiting miRNAs emerged as a therapeutic tool in the clinical translation. However, the effectiveness and safety of miRNA-based therapeutics, besides higher stability, biocompatibility, less off-target effects, and immunologic reactions, have received particular attention. This review aimed to comprehensively overview the molecular mechanisms underlying miRNA-modified PSCs as a futuristic therapeutic option in regenerative dentistry.

Exosomes derived from cancer-associated fibroblasts mediate response to cancer therapy.

Cancer-associated fibroblasts (CAFs) are the prominent stromal cell population in the tumor microenvironment (TME), which play an indispensable role in cancer progression and response to therapy. CAFs provide communication between tumor cells and surrounding cells by secreting soluble biomolecules and extracellular vesicles (EVs). Exosomes are small membrane-bound EVs that contain various cargos, including growth factors, non-coding RNAs (ncRNAs), cytokines, and chemokines. These biomolecules can be transferred between cells within the TME and alter the behavior of recipient cells. Some studies have shown that exosomes secreted by CAFs contribute to resistance to chemotherapy and radiotherapy. This review focuses on CAF-derived exosomes in different types of tumors, with emphasis on resistance to chemotherapy and radiotherapy.

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.

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 Combination of Zerumbone with 5-Fluorouracil for Sensitizing Colorectal Cancer-Associated Fibroblasts to Treatment.

The present study aimed to evaluate the synergic effects of combination therapy on 5-fluorouracil (5-FU) resistance-cancer-associated fibroblasts (CAFs) to treatment. Chemotherapy resistance is an important challenge in colorectal cancer (CRC) eradication attention to the tumor microenvironment (TME) is very important. CAFs in the TME play an essential role in cancer chemoresistance and relapse. Additionally, many patients with advanced CRC show resistance to 5-FU therapy. Anti-tumorigenic activities of ZER, a chemopreventive compound derived from the rhizomes of the wild ginger, have been demonstrated. Synergistic and potentiating effects of combination therapy, using herbal and chemical drugs, can improve patients' response. At the first, CAFs were isolated from a CRC patient and sorted by fluorescent-activated cell sorting (FACS), then, confirmed by flow cytometry, and immunocytochemistry (ICC). The effect of 5-FU and ZER on the cell viability was investigated by MTT assay in a dose and time-dependent manner, after that, the expression of vimentin, ß-catenin, and survivin was quantified. Apoptosis, cell cycle, and invasion were analyzed by flow cytometry and scratch test, respectively. ZER could significantly sensitize CAFs cells to 5-FU. A combination of 5-FU + ZER revealed a marked decrease in the marker of interest in both mRNA and protein levels compared to control groups, including 5-FU, ZER treated, and untreated cells. Functional evaluation of cells in different groups presented significant suppression in migration of CAFs and an apparent increase in cell arrest and apoptosis by 5-FU + ZER treatment.