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Abstract: Statins are HMG-CoA reductase inhibitors and decrease plasma low-density lipoprotein cholesterol (LDL-C) levels. They are well tolerated, and because of their LDL-C-lowering effect, they are utilized to decrease the risk of atherosclerosis and cardiovascular disease. However, statins have pleiotropic effects, including immunomodulatory, anti-inflammatory, antioxidant, and anticancer. Currently, oral administration is the only Food and Drug Administration (FDA)-approved route of administration for statins. However, other administration routes have demonstrated promising results in different pre-clinical and clinical studies. For instance, statins also seem beneficial in dermatitis, psoriasis, vitiligo, hirsutism, uremic pruritus, and graft-versus-host disease. Topically applied statins have been studied to treat seborrhea, acne, rhinophyma, and rosacea. They also have beneficial effects in contact dermatitis and wound healing in animal studies, (HIV) infection, osseointegration, porokeratosis, and some ophthalmologic diseases. Topical and transdermal application of statins is a non-invasive drug administration method that has shown significant results in bypassing the first-pass metabolism in the liver, thereby reducing possible adverse effects. This study reviews the multifaceted molecular and cellular impacts of statins, their topical and transdermal application, novel delivery systems, such as nanosystems for topical and transdermal administration and the challenges concerning this approach.

Lung cancer is a malignant disease with a frequency of various morbidity, mortality, and poor prognosis in patients that the conventional therapeutic approaches are not efficient sufficiently. Recently, with the discovery of exosomes, researchers have examined new approaches in the development, diagnosis, treatment, and drug delivery of various cancer, such as lung cancer, and display various its potential. Investigation of exosome-derived lung cancer cells contents and preparation of their exhaustive profile by advanced technics such as labeling exosome with nanoparticle and types of mass spectroscopy methods will assist researchers for take advantage of the specific properties of exosomes. Moreover, scientists will present encouraging ways for the treatment of lung cancer with loaded of drugs, proteins, microRNA, and siRNA in specific antigen targeted exosomes. This manuscript will include brief details on the role of exosomes as a novel prognostic biomarker (by the content of lipid, surface and internal protein, miRNAs, and LnRNAs) and therapeutic agent (as vaccine and targeted drug delivery) in lung cancer.

The human amniotic membrane (HAM) is widely used as a natural scaffold in tissue engineering due to its excellent biological characteristics, including anti-microbial, anti-inflammatory, low immunogenicity, and pro-angiogenic properties. This study aimed to develop simple and cost-effective protocols for the decellularization of HAM (d-HAM) using detergent-free methods, i.e., mechanical force (brushing) and physical treatment (heating 45-55 °C). The effectiveness of the methods of interest was compared with a chemical-based approach (EDTA + NaOH + NH

Skin defects are among the most prevalent and serious problems worldwide; it is necessary to provide appropriate coverage in order to reduce possible mortality risk and accelerate wound healing. In this study, we have designed a series of extracellular matrix (ECM)-mimicking nanofibrous scaffolds composed of both natural (gelatin (GEL) and chitosan (CS)) and synthetic (poly(ε-caprolactone) (PCL) and poly (vinyl alcohol) (PVA)) polymers. The 3D constructs (PCL/GEL-PVA/CS) were reinforced with 5% (w/w) of platelet lysate (PL) for promoting cells viability and mobility. The physicochemical characterizations of nanofibers confirmed suitable hydrophilicity, controlled degradability, and water uptake of 250.31 ± 62.74%, and 222.425 ± 86.37% for the PCL/GEL-PVA/CS and PCL/GEL-PVA/CS + PL nanofibers, respectively. The scanning electron microscopy (SEM) images exhibited the mean diameter of the fabricated fibers (PCL/GEL-PVA/CS) in the range of 454 ± 257 nm. The blended samples (PCL/GEL-PVA/CS) were also confirmed to have higher ultimate tensile stress (UTS) (3.71 ± 0.32 MPa). From a biological point of view, the fabricated scaffolds showed appropriate blood compatibility and great potential to avoid bacterial invasion. Altogether, the tailored fabrication of PCL/GEL-PVA/CS nanofibers may be considered a suitable construct for epidermal wound healing.

Pulmonary fibrosis (PF) is the devastating consequence of various inflammatory diseases of the lung. PF leads to a reduction of lung function, respiratory failure, and death. Several molecular pathways are involved in PF, such as inflammatory cytokines including tumor necrosis factor α (TNFα), tumor necrosis factor β1 (TNFβ1), interleukin 6 (IL-6), and interleukin 4 (IL-4), reactive oxygen species, matrix metalloproteases, and transforming growth factor-beta (TGF-β). Targeting these processes involved in the progression of PF is essential for the treatment of this disease. Natural products, including plant extracts and active compound that directly target the processes involved in PF, could be suitable therapeutic options with less adverse effects. In the present study, we reviewed the protective effects and the therapeutic role of various bioactive compounds from plants in PF management.

INTRODUCTION In recent years, studies have boosted our knowledge about the biology and disorders of articular cartilage. In this regard, the design of hydrogel-based scaffolds has advanced to improve cartilage repair. However, the efficacy of knee cartilage repair using hydrogels remains unclear. The aim of systematic review and meta-analysis was to scrutinize the efficiency of hydrogel-based therapy in correcting cartilage defects of knee (femoral condyle, patella, tibia plateau and trochlea). METHODS The search was conducted in PubMed to gather articles published from 2004/1/1 to 2019/10/01, addressing the effects of implant of hydrogel on knee joint cartilage regeneration. The Cochrane Collaboration's tool for estimating the risk of bias was applied to check the quality of articles. The clinical data for meta-analysis was recorded using the visual analog scale (VAS), Lysholm score, WOMAC, and IKDC. The guidelines of Cochrane Handbook for Systematic Reviews of Interventions were utilized to conduct the review and meta-analysis in the RevMan 5.3 software. RESULTS The search resulted in 50 clinical trials that included 2846 patients, 986 of whom received cell-based hydrogel implants while 1860 patients used hydrogel without cell. There were significant differences comparing the pain scores based on the VAS (MD: -2.97; 95% CI: -3.15 to -2.79, P

Coronavirus disease 2019 (COVID‐19) outbreak is an ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) with considerable mortality worldwide. The main clinical manifestation of COVID‐19 is the presence of respiratory symptoms, but some patients develop severe cardiovascular and renal complications. There is an urgency to understand the mechanism by which this virus causes complications so as to develop treatment options. Curcumin, a natural polyphenolic compound, could be a potential treatment option for patients with coronavirus disease. In this study, we review some of the potential effects of curcumin such as inhibiting the entry of virus to the cell, inhibiting encapsulation of the virus and viral protease as well as modulating various cellular signaling pathways. This review provides a basis for further research and development of clinical applications of curcumin for the treatment of newly emerged SARS‐CoV‐2. This article is protected by copyright. All rights reserved.

Since September 2020, the world has had more than 28 million cases of coronavirus disease 2019 (COVID-19). Many countries are facing a second wave of the COVID-19 outbreak. A pressing need is evident for the development of a potent vaccine to control the SARS-CoV-2. Institutions and companies in many countries have announced their vaccine research programs and progress against the COVID-19. While most vaccines go through the designation and preparation stages, some of them are under evaluation for efficacy among animal models and clinical trials, and three approved vaccine candidates have been introduced for limited exploitation in Russia and China. An effective vaccine must induce a protective response of both cell-mediated and humoral immunity and should meet the safety and efficacy criteria. Although the emergence of new technologies has accelerated the development of vaccines, there are several challenges on the way, such as limited knowledge about the pathophysiology of the virus, inducing humoral or cellular immunity, immune enhancement with animal coronavirus vaccines, and lack of an appropriate animal model. In this review, we firstly discuss the immune responses against SARS-CoV-2 disease, subsequently, give an overview of several vaccine platforms for SARS-CoV-2 under clinical trials and challenges in vaccine development against this virus.

Fibromodulin (FMOD) is known as one of very important extracellular matrix small leucine-rich proteoglycans. This small leucine-rich proteoglycan has critical roles in the extracellular matrix organization and necessary for repairing of tissue in many organs. Given that the major task of FMOD is the modulation of collagen fibrillogenesis. However, recently observed that FMOD plays very important roles in the modulation of a variety of pivotal biological processes including angiogenesis, regulation of TGF-β activity, and differentiation of human fibroblasts into pluripotent cells, inflammatory mechanisms, apoptosis and metastatic related phenotypes. Besides these roles, FMOD has been considered as a new tumor-related antigen in some malignancies such as lymphoma, leukemia, and leiomyoma. Taken together, these findings proposed that FMOD could be introduced as diagnostic and therapeutic biomarkers in treatment of various cancers. Herein, for first time, we highlighted the various roles of FMOD in the cancerous conditions. Moreover, we summarized the diagnostic and therapeutic applications of FMOD in cancer therapy.

SARS-CoV-2 as a new global threat has affected global population for one year. Despite the great effort to eradicate this infection, there are still some challenges including different viral presentation, temporal immunity in infected individuals and variable data of viral shedding. We studied 255 COVID-19 suspected individuals to assess the viral shedding duration and also the antibody development against SARS-CoV-2 among the cases. Real Time RT-PCR assay was applied to determine the virus presence and SARS-CoV-2 antibodies were evaluated using SARS-CoV-2 IgM and IgG kits. 113 patients were confirmed for COVID-19 infection. The patients were followed until negative PCR achieved. The median viral shedding among studied population was obtained 34.16 (±17.65) days which was not significantly associated with age, sex and underlying diseases. Shiver and body pain were found in prolonged form of the infection and also patients who had gastrointestinal problems experienced longer viral shedding. Moreover, IgG was present in 84% of patients after 150 days. According to this data, the median viral shedding prolongation was 34.16 days which indicates that 14 days isolation might not be enough for population. In addition, IgG profiling indicated that it is persistent in a majority of patients for nearly 6 months which has brought some hopes in vaccine efficacy and application.

One of the most lethal cancers among women is breast cancer. MicroRNAs (miRNAs) can be of great importance in the early detection of breast cancer. This study aimed to investigate some miRNAs in the serum of patients with breast cancer compared with the control group. Total RNA was extracted from the serum of patients with breast cancer and healthy volunteers. The expression levels of miRNAs and the genes were assessed using real-time reverse transcriptase-polymerase chain reaction with specific primers. Our data showed that miR-25 and miR-133 were downregulated, and miR-17 was upregulated in patients with breast cancer. Upregulation of miR-17 is related to the poor survival time and increased cell proliferation. The reduced expression of miR-133 and miR-25 is significantly associated with clinical stage, metastasis, and survival time of patients with breast cancer. Expressions of miRNAs miR-17, miR-25, and miR-133 are altered in patients with clinical stage, metastasis, poor survival time.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, which is associated with impairments of memory, thinking, language, and reasoning. Despite extensive research aiming at the treatment of AD, durable and complete remissions are rare. Hence, new therapeutic approaches are required. Among various therapeutic approaches, stem cells (ie, neural stem cells, mesenchymal stem cells, and embryonic stem cells) and delivery of protective genes such as encoding nerve growth factor, APOE, and glial cell-derived neurotrophic factor have generated promise in AD therapy. Here, we summarized a variety of effective therapeutic approaches (ie, stem cells, and genes) in AD therapy.

Metastasis is known to be one of the important factors associated with cancer-related deaths worldwide. Several cellular and molecular targets are involved in the metastasis process. Among these targets, matrix metalloproteinases (MMPs) play central roles in promoting cancer metastasis. MMPs could contribute toward tumor growth, angiogenesis, migration, and invasion via degradation of the extracellular matrix and activation of pre-pro-growth factors. Therefore, identification of various cellular and molecular pathways that affect MMPs could contribute toward a better understanding of the metastatic pathways involved in various tumors. Micro-RNAs are important targets that could affect MMPs. Multiple lines of evidence have indicated that deregulation of various micro-RNAs, including miR-9, Let-7, miR-10b, and miR-15b, affects metastasis of tumor cells via targeting MMPs.

Inflammatory processes and proinflammatory cytokines have a key role in the cellular processes of neurodegenerative diseases and are linked to the pathogenesis of functional and mental health disorders. Tumor necrosis factor alpha has been reported to play a major role in the central nervous system in Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis and many other neurodegenerative diseases. Therefore, a potent proinflammatory/proapoptotic tumor necrosis factor alpha could be a strong candidate for targeted therapy. Plant derivatives have now become promising candidates as therapeutic agents because of their antioxidant and chemical characteristics, and anti-inflammatory features. Recently, phytochemicals including flavonoids, terpenoids, alkaloids, and lignans have generated interest as tumor necrosis factor alpha inhibitor candidates for a number of diseases involving inflammation within the nervous system. In this review, we discuss how phytochemicals as tumor necrosis factor alpha inhibitors are a therapeutic strategy targeting neurodegeneration.