Current Molecular Medicine - Volume 22, Issue 7, 2022

Objective: This mini-review of literature aimed to discuss the obstacles and benefits of vaccination in the era of the current pandemic, either the COVID-19 vaccines, which are on their way to be released, or the influenza vaccines, regarding which much debate is ongoing concerning their effectiveness for ameliorating the severity of the COVID-19 pandemic. Methodology: A literature search was done till November 2020 in the PubMed database. Results: Pathophysiology behind the COVID-19 vaccination, the related obstacles and future perspectives are discussed in detail. Discussion on influenza vaccination during the pandemic, along with the most recent guidelines, is also presented. Conclusion: During the COVID-19 pandemic, influenza vaccination is mandatory for all individuals, provided that there are no contraindications. Three SARS-CoV-2 vaccines are being released till the time being, while FDA approval for monoclonal antibodies for the treatment of at-risk outpatients to lower hospitalization rates is ongoing.

On December 31, 2019, the World Health Organization received a report of several pneumonia cases in Wuhan, China. The causative agent was later confirmed as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Since then, the SARS-CoV-2 virus has spread throughout the world, giving rise in 2020 to the 2019 coronavirus (COVID-19) pandemic, which, according to the world map of the World Health Organization, has, until May 18, 2021, infected 163,312,429 people and caused 3,386,825 deaths throughout the world. Most critical patients progress rapidly to acute respiratory distress syndrome (ARDS) and, in underlying form, septic shock, irreversible metabolic acidosis, blood coagulation dysfunction, or hemostatic and thrombotic anomalies have been reported as the leading causes of death due to COVID-19. The main findings in severe and fatal COVID-19 patients make it clear that platelets play a crucial role in developing severe disease cases. Platelets are the enucleated cells responsible for hemostasis and thrombi formation; thus, platelet hyperreactivity induced by pro-inflammatory microenvironments contributes to the "cytokine storm" that characterizes the more aggressive course of COVID- 19.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2) has a high mortality rate due to widespread infection and strong immune system reaction. Interleukins (ILs) are among the main immune factors contributing to the deterioration of the immune response and the formation of cytokine storms in coronavirus 2019 (COVID-19) infections. Introduction: This review article aimed at investigating the relationship between virus structure, risk factors, and patient plasma interleukin levels in infections caused by the coronavirus family. Methods: The keywords "interleukin," "coronavirus structure," "plasma," and "risk factors" were searched to find a relationship among different interleukins, coronavirus structures, and risk factors in ISI, PUBMED, SCOPUS, and Google Scholar databases. Results: Patients with high-risk conditions with independent panels of immune system markers are more susceptible to death caused by SARS-CoV-2. IL-4, IL-10, and IL-15 are probably secreted at different levels in patients with coronavirus infections despite the similarity of inflammatory markers. SARS-CoV-2 and SARS-CoV increase the secretion of IL-4, while it remains unchanged in MERS-CoV infection. MERS-CoV infection demonstrates increased IL-10 levels. Although IL-10 levels usually increase in SARS-CoV infection, different levels are recorded in SARS-CoV-2, i.e., it increases in some patients while it decreases in others. This difference may be due to factors such as the patient's condition and the pathogenicity of SARS-CoV-2. MERS-CoV increases IL-15 secretion while its levels remain unchanged in SARS-CoV-2. The levels of IL-15 in patients with SARS-CoV have not been studied. Conclusion: In conclusion, the different structures of SARS-CoV-2, such as length of spike or nonstructural proteins (NSPs) and susceptibility of patients due to differences in their risk factors, may lead to differences in immune marker secretion and pathogenicity. Therefore, identifying and controlling interleukin levels can play a significant role in managing the symptoms and developing individual-specific treatments.

Cluster of differentiation (CD155), formerly identified as poliovirus receptor (PVR) and later as immunoglobulin molecule, is involved in cell adhesion, proliferation, invasion and migration. It is a surface protein expressed mostly on normal and transformed malignant cells. The expression of the receptor varies based on the origin of tissue. The expression of the protein is determined by factors involved in the sonic hedgehog pathway, Ras-MEK-ERK pathway and during stressful conditions like DNA damage response. The protein uses an alternate splicing mechanism, producing four isoforms, two being soluble (CD155β and CD155γ) and two being transmembrane protein (CD155α and CD155δ). Apart from being a viral receptor, researchers have identified CD155 to play important roles in cancer research and the cell signaling field. The receptor is recognized as a biomarker for identifying cancerous tissue. The receptor interacts with molecules involved in the cells’ defense mechanism. The immunesurveillance role of CD155 is being deciphered to understand the mechanistic approach it utilizes as an onco-immunologic molecule. CD155 is a non-MHC-I ligand which helps in identifying non-self to NK cells via an inhibitory TIGIT ligand. The TIGIT–CD155 pathway is a novel MHC-I-independent education mechanism for cell tolerance and activation of NK cells. The receptor also has a role in metastasis of cancer and transendothelial mechanism. In this review, the authors discuss the virus-host interaction that occurs via a single transmembrane receptor, the poliovirus infection pathway, which is being exploited as a therapeutic pathway. The oncolytic virotherapy is now a promising modality for curing cancer.

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-COV-2 has afflicted millions of lives globally and disrupted almost all the activities of mankind. Under such pressing circumstances when no effective therapeutics are available, a fast and accurate diagnosis of the coronavirus is the only way out to limit the transmission. Since the inception of COVID-19, the demand for diagnostic tests has increased day by day and RT-PCR is the commonly used screening test that is not only time-consuming but requires sophisticated resources. To address the increasing rate of spread of COVID-19, there is an urgent need for more diagnostic tools as the research on vaccines is still at a rudimentary level. This review summarizes an inventory of the diverse and currently available diagnostic methods based on nucleic acid and serology along with some of those working on novel principles viz. CRISPR, biosensors, and NGS. Additionally, accessible diagnostic kits that are already approved by the US and European authorities for the diagnosis of COVID-19 are also suggested that will help in selecting the most effective tests under the given scenario. Taken together, this review will pave way for further strengthening the research on the rapid and safer diagnostics of SARS-COV-2.

The coronavirus disease emerged in December 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome-related coronavirus 2 (SARS-CoV-2). Its rapid global spread has brought an international health emergency and urgent responses for seeking efficient prevention and therapeutic treatment. This has led to imperative needs for illustration of the molecular pathogenesis of SARS-CoV-2, identification of molecular targets or receptors, and development of antiviral drugs, antibodies, and vaccines. In this study, we investigated the current research progress in combating SARS-CoV-2 infection. Based on the published research findings, we first elucidated, at the molecular level, SARS-CoV-2 viral structures, potential viral host-cell-invasion, pathogenic mechanisms, main virus-induced immune responses, and emerging SARS-CoV-2 variants. We then focused on the main virus- and host-based potential targets and summarized and categorized effective inhibitory molecules based on drug development strategies for COVID-19 that can guide efforts for the identification of new drugs and treatment for this problematic disease. Current research and development of antibodies and vaccines were also introduced and discussed. We concluded that the main virus entry route- SARS-CoV-2 spike protein interaction with ACE2 receptors played a key role in guiding the development of therapeutic treatments against COVID-19. Four main strategies may be considered in developing molecular therapeutics, and drug repurposing is likely to be an easy, fast and low-cost approach in such a short period of time with urgent need of antiviral drugs. Additionally, the quick development of antibody and vaccine candidates has yielded promising results, but the wide-scale deployment of safe and effective COVID-19 vaccines remains paramount in solving the pandemic crisis. As new variants of the virus emerge, the efficacy of these vaccines and treatments must be closely evaluated. Finally, we discussed the possible challenges of developing molecular therapeutics for COVID-19 and suggested some potential future efforts. Despite the limited availability of literature, our attempt in this work to provide a relatively comprehensive overview of current SARS-CoV-2 studies can be helpful for quickly acquiring the key information of COVID-19 and further promoting this important research to control and diminish the pandemic.

Ketogenic diet and ketone bodies gained significant attention in recent years due to their ability to influence the specific energy metabolism and restoration of mitochondrial homeostasis that can help in hindering the progression of many metabolic diseases, including diabetes and neurodegenerative diseases. A ketogenic diet consists of high fat and low carbohydrate contents, which makes the body glucose deprived and rely on alternative sources (ketone bodies) for energy. It has been initially designed and supplemented for the treatment of epilepsy, and, later, its influence on many energyderiving biochemical pathways made it a highly sorted food supplement for many metabolic diseases and even for bodybuilding and calorie restriction in healthy individuals. Among the reported therapeutic action over a range of diseases, neurodegenerative disorders, especially Alzheimer’s disease, gained the attention of many researchers and clinicians because of the higher benefits of the ketogenic diet on this disease. Complex pathology and multiple influencing factors of Alzheimer’s disease make exploration of its therapeutic strategies a demanding task. It was a common phenomenon that energy deprivation in neurological disorders, including Alzheimer’s disease, progress rapidly. The ability of ketone bodies to stabilize the mitochondrial energy metabolism makes it a suitable intervening agent. In this review, we will discuss various research progress made with regards to ketone bodies/ketogenic diet for the management of Alzheimer’s disease and elaborate in detail about the mechanisms that are influenced during their therapeutic action.

Objective: Breast cancer is the most frequent cancer among women and the most important cause of death. Surgery and chemotherapy are the common treatment of breast cancer, but increasing drug resistance has created many challenges in its treatment. The present study aimed to investigate the anti-cancer function of free and nano-encapsulated hydroxytyrosol on the MCF-7 breast cancer cell line. Methods: The poly lactide-co-glycolide-co-polyacrylic acid (PLGA-co-PAA) nanoencapsulated Hydroxytyrosol was synthesized, and the MTT assay was performed to evaluate the anti-proliferative and anti-tumor effects of both free and nano-encapsulated Hydroxytyrosol. After the extraction of RNA from the treated and control cancer cells, cDNA synthesis was performed and the expression of P21, P27, and Cyclin D1 genes was evaluated by Real-Time PCR. Results: The results of the study showed that free (12 ppm and 72 hours) and nanoencapsulate (10 ppm and 24 hours) hydroxytyrosol resulted in 50% death (IC50) of the cancer cells and increased by increasing the concentration and time. Also, free and nano-encapsulated hydroxytyrosol increased the expression of P21 and P27 genes and reduced the expression of Cyclin D1 in breast cancer cells. In general, the nanoencapsulated hydroxytyrosol showed more anticancer function than the free hydroxytyrosol. Conclusion: The present study illustrated that hydroxytyrosol could lead to cell death in MCF-7 breast cancer by regulating the cell cycle. Also, the nano-encapsulation of Hydroxytyrosol enhanced the Hydroxytyrosol anticancer function by PLGA-co-PAA. However, for more accurate results, further studies on animal models are necessary.

Objective: The treatment of liver failure by stem cell transplantation has attracted growing interest. Herein, we aim to explore the role of sodium butyrate (NaB) in the hepatic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) under liver-specific factors induction in vitro and vivo. Materials & Methods: We isolated BM-MSCs from the mononuclear cell fraction of rabbit bone marrow samples and identified the cells by Immunophenotypic analysis. We investigated the effects of different concentrations and induction conditions. The histone deacetylase inhibitor NaB induced hepatic differentiation of BM-MSCs under liverspecific factors induction in vitro. Morphological features, liver-specific gene and protein expression, and functional analyses in vitro and vivo were performed to evaluate the hepatic differentiation of BM-MSCs. Results: Our results showed that pre-treated NaB inhibited the expression of the liverspecific protein in a dose-dependent manner. The induction efficiency of NaB with 24h pre-treatment was higher than that of NaB continuous intervention. 0.5 mM 24h NaB pre-treated cells can improve liver tissue damage in vivo. The liver ALB, AAT, and the serum TP were significantly increased, while the serum ALT was significantly reduced. Conclusion: Continuous NaB treatment can inhibit BM-MSCs proliferation in a dosedependent manner at a certain concentration range. 0.5 mM 24h pre-treatment of NaB enhanced differentiation of BM-MSCs into hepatocytes and improved liver injury in vitro and vivo.