Current Molecular Medicine - Volume 21, Issue 6, 2021

Severe acute respiratory syndrome-associated coronavirus 2 (SARS-CoV-2) is an extremely pathogenic virus belonging to the family of Coronaviridae. First identified in Wuhan, China in December 2019 after an epidemiological investigation of an emerging cluster of pneumonia of unknown etiology, SARS-CoV-2 was declared the cause of a pandemic on March 11 by the World Health Organization (WHO), pointing to the over 118000 cases of Coronavirus disease 2019 (COVID-19) in over 110 countries. Despite the promising results of drug repositioning studies in the treatment of COVID-19, the evidence of their safety and efficacy remains inconclusive. Cell based therapy has been proven safe and possibly effective in treating multiple lung injuries and diseases, but its potential use in the treatment of COVID-19 has not been yet elucidated. Our aim in this review is to provide an overview of the immunomodulatory effect and the regenerative capacity of stem cells and their secretome in the treatment of many diseases including lung injuries. Those findings may contribute to a better understanding of the potential of stem cell therapy in SARS-CoV-2 infection and its potential use in order to find a solution for this healthcare crisis.

The pandemic of coronavirus disease 2019 (COVID-19) has become a threat to human life and society. Scientists and clinicians are struggling with the intrusive SARS-CoV-2 virus to enhance their knowledge about its pathogenesis and find an effective medicine and vaccine to combat its complications. Till now, they have learned that this SARS-CoV-2 has not infected all people exposed to this virus, and also severe respiratory illnesses have not been observed in all infected patients. Patients over 65 or with underlying diseases are more vulnerable to develop severe disease. Based on this premise, a highly challenging question is why some people are more susceptible to this virus and others are not. The present study was aimed to review the current information, which explains the broad spectrum of COVID-19 presentation. Here, we discussed how genetic background, immune system, underlying disease, smoking status, as well as age, race, and gender affect COVID-19 susceptibility.

Genome editing is an addition, deletion, or replacement of a gene to remove or initiating explicit and preferred characters in the genome. Utilizing gene-editing tools like CRISPR-Cas9 technology could be accomplished either by gene-based methodology or protein-based technology that has been under scrutiny for the protracted time wherein physical techniques, viral and non-viral strategies have been utilized together. Transplanting ex vivo CRISPR edited cells empowers screening of single guide RNAs with high-throughput and CRISPR based screening in organoids transplantation to validate cancer cells including colorectal carcinoma in various phases of its development and treatment.CRISPR knockout screens have recognized genes that drive interest in colon cancer to develop hallmarks, especially in some cancer cell lines with single guide RNA, to disclose drug resistance mechanisms. One advantage of this method is to deal with CRISPR knockout genomic screening, which disrupts gene expression, rather than the partial knockdown that is mostly done with RNA interference and CRISPR/Cas technology. This technique is used to treat different forms of cancer because of its proficient editing of the target gene, along with the CRISPR/Cas system. Latest research has shown that the CRISPR/Cas gene-editing technique has theoretically reformed the expression in colorectal carcinoma of long non-coding RNA. For the next decade CRISPR/Cas9 technology will positively fuel the development of more in vivo gene editing clinical trials in colon cancer and will have an enormous impact on molecular medicine.

Tumor-derived exosomes contain biological contents such as proteins, lipids, RNA (miRNAs, mRNAs, lncRNA), and DNA for intracellular communication. Meanwhile, studies have shown the role of exosomes in cancer progression, metastasis, and therapeutic resistance. Furthermore, tumor exosomes have received growing attention due to their potential as novel therapeutic protocols for the treatment of cancers. Adenosine nucleoside, which is a derivative of ATP, is highly elevated in the tumor microenvironment by CD39 and CD73 enzymatic activity. Recently, it is distinguished that cancer cell-derived exosomes carry CD39 and CD73 on their surface and may contribute to rising adenosine levels in the tumor microenvironment. In this review, we summarize the evidence of CD39/CD73-bearing exosomes and their role in cancer development, progression, invasion, angiogenesis, metastasis and their application in the selection of the appropriate strategy to treat different types of cancer.

Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) are a growing public health problem. There is a paucity of sensitive biomarkers to detect AKI, early CKD, and ameliorate extra-renal complications. Klotho protein, detected mainly in the kidneys, regulates renal health and functions as a co-receptor for fibroblast growth factor 23 (FGF-23) signaling. It is now coming to be known for its extreme pleiotropic actions. These include cytoprotection via anti-oxidation, anti-senescence, anti-apoptosis, renoprotective effects, promotion of angiogenesis and vascularisation, inhibition of fibrogenesis, and stem cell preservation. Emerging clinical studies suggest kidney damage to be a perpetual state of renal Klotho deficiency. In AKI, Klotho levels in plasma and/or urine possibly will serve as an initial biomarker for kidney parenchymal injury. In CKD, Klotho levels may also be an indicator of early disease as well as predict the rate of progression. Earlier studies using ELISA as a technique reveal a correlation between plasma Klotho, eGFR, serum creatine, and Blood Urea Nitrogen (BUN) levels. Thereby preventing the decline of Klotho levels by various mechanisms can retard CKD advancement and improve renal function. Substantial data indicate Klotho can be therapeutically included as an individualized regimen for managing CKD patients. Considerable research is required in investigating the role of soluble Klotho as a biomarker in patients with different types and severity of kidney diseases, which will be highlighted in our review.

Non-alcoholic fatty liver disease is a chronic metabolic disorder representing the most common cause of chronic liver disease in western civilization and one of the main causes of cirrhosis with a significant impact on all-cause mortality in the most advanced phases. It is characterized by hepatic fat accumulation in the absence of significant ethanol consumption, virus infection or other specific causes of liver disease. Accumulation of fat in liver tissue occurs as a consequence of the imbalance between overconsumption of high-fat diet and increased de novo lipogenesis and decreased lipid disposal. Novel dietary and pharmacological therapies for the prevention of fatty liver disease and the progression to cirrhosis are an actual field of study but still poorly understood. In this perspective, the current review aims to summarise and clarify the transcription factor NFΚB effects, which may exert among non-alcoholic fatty liver diseases and their progression. Through extensive previous research, it has become clear that several signaling pathways are involved: metabolic dysregulation (such as free fatty acids increase, adipokine alteration, insulin resistance), oxidative stress and inflammation contribute together in a “vicious circle” to the pathogenesis of non-alcoholic fatty liver diseases. Within this, NFΚB signaling is a primary factor in inflammatory reactions and diseases, with important molecular connections between metabolic, oxidative, immune and inflammation systems.

Background: Cellular senescence is a state of stable growth arrest triggered by mitogenic and metabolic stressors. Ageing and a high-fat diet (HFD) are proven inducers of senescence in various organs, presenting a challenge for ageing populations worldwide. Our previous study demonstrated that ROS scavenger N-acetylcysteine (NAC) can improve insulin resistance (IR) and chronic inflammation in diet-induced obesity mice, an effect better achieved through early intervention. We, herein, investigate whether NAC can improve cellular senescence in a diet-induced obesity mouse model, and whether a legacy effect is presented with early intervention. Materials and Methods: For a twelve-month treatment course, all C57B/L6 mice were fed a chow diet (CD), high-fat high-sucrose diet (HFD), CD+NAC^1-12 (NAC intervention 1st-12th month), HFD+NAC^1-12, and HFD+NAC^1-6 (NAC intervention 1st-6th month). Staticalanalysis was used to analyze the different markers of cellular senescence and inflammation. Results: Throughout the study, the HFD group exhibited significantly increased body weight (BW) and body fat, markers of senescence, decreased motor activity (MA) and impaired glucose tolerance. Compared to the HFD group, the HFD+NAC^1-12 group exhibited increased MA, decreased BW and body fat, improved glucose tolerance, and decreased senescence markers.The HFD+NAC^1-6 group showed similar effects to the HFD+NAC^1-12 group, despite discontinuing NAC for 6 months. Our study showed that NAC significantly increased MA in both HFD+NAC^1-12 and HFD+NAC^1-6 groups, and improved HFD-induced mitochondrial and intracellular ROS expression, DNA and protein oxidative damage, and adipose tissue inflammation. Conclusion: Legacy effect was indeed presented in HFD-induced cellular senescence with NAC intervention, with possible mechanisms being persistently increased motor activity and anti-oxidative stress effects.