Mesenchymal Stem Cells Versus Covid-19. Can They Win the Battle?

Mesenchymal stem cells (MSCs) are multipotent stem cells with numerous features potentially useful in various pathologies. It has been shown that MSCs have regenerative potential due to modulation of immune system response, inflammation diminishing, trans differentiation into various types of cells, proangiogenetic and anti fibrotic influence. Besides all of these traits, MSCs posses anti viral capacity and have been further employed in clinical trails since last year. Here, we revised immunomodulatory, biological and antiviral traits of MSCs, but also pathogenesis of Covid-19 and it’s impact on immune system. Conspicuously, there is a growing number of studies examining effect of MSCs in patients suffering from Covid-19 pneumonia and ARDS. Since MSCs are in theory capable of healing lung injury and inflammation, here we discuss hypothesis, pros and cons of MSCs treatment in Covid-19 patients. Finally, we debate if MSCs based therapy can be promising tool for Covid-19 lung pathologies.

Effects of Puerarin on the Prevention and Treatment of Cardiovascular Diseases

Puerarin, an isoflavone glycoside derived from Pueraria lobata (Willd.) Ohwi, has been identified as a pharmacologically active component with diverse benefits. A large number of experimental and clinical studies have demonstrated that puerarin is widely used in the treatment of a variety of diseases. Among them, cardiovascular diseases (CVDs) are the leading cause of death in the world, and therefore remain one of the most prominent global public health concerns. In this review, we systematically analyze the preclinical investigations of puerarin in CVDs, such as atherosclerosis, cardiac hypertrophy, heart failure, diabetic cardiovascular complications, myocardial infarction, stroke and hypertension. In addition, the potential molecular targets of puerarin are also discussed. Furthermore, we summarize the clinical trails of puerarin in the treatment of CVDs. Finally, the therapeutic effects of puerarin derivatives and its drug delivery systems are overviewed.

P.022 The effect of vagus nerve stimulation on the quality of sleep in medically refractory epileptic patients

Background: The quality of sleep is frequently impacted in patients with epilepsy. Vagus Nerve Stimulation is a relatively common treatment used in patients with medically resistant epilepsy. Some studies show an improvement in quality of life, however, there is limited data on the impact on sleep quality. Methods: A database analysis was conducted on Medline, Embase, and Cochrane to find studies that examined the VNS’s effect on quality of sleep in medically resistant epilepsy. These studies included randomized clinical trails, case studies or reports, cohort studies, and systematic reviews. Results: 75 papers were reviewed and 16 studies from eight countries were included in the analysis. A total of 93 patients with ages ranged from 10 – 49 were included. Analyzing the change in the quality of sleep after VNS was evaluated using Multiple Sleep Latency Test. The literature showed that at low stimulus intensities, VNS treatment improves daytime sleepiness in patients. However, VNS setting titration has a dose-dependent effect on obstructive sleep apnea where higher VNS frequencies are related to higher apnea events. Conclusions: Limited data is available on the impact of VNS on the quality of sleep. Further studies are required to evaluate the improvement of sleep in patients with VNS.

An updated Review on Therapeutic Potential of Entrectinib as a Promising TrK, ROS 1, and ALK Inhibitor in Solid Tumors and Lung Cancer

Entrectinib is a selective inhibitor of tyrosine kinases , tropomyosin receptor kinases that targets oncogenic rearrangements in Neurotropic Tyrosine Receptor kinase, c-ros oncogene 1 and Anaplastic lymphoma kinase used for the treatment of various solid tumors. Entrectinib gained its first worldwide approval in Japan in June 2019 for the treatment of NTRK fusion-positive, advanced or recurring solid tumours in adults and children. In august 15, 2019 drug got FDA approval for the treatment of solid tumors in adult and children aged 12 and above. This article summarizes current status of Entrectinib from ongoing clinical trails and ideal place for drug in therapy.

Retrospective feasibility study of Mycobacterium tuberculosis modified lipoprotein as a potential biomarker for TB detection in children

Background: Current TB diagnostic methods available have been developed for adults and development efforts have neglected the differences in disease and sampling that occur between adults and children. Diagnostic challenges are even greater in HIV co-infected children and infants. Methods and results: We established a sandwich ELISA assay to detect Mycobacterium tuberculosismodified lipoprotein (TLP) ex vivo in plasma. The study population contains plasma samples from 21 patients with active TB and 24 control samples with no TB, collected in the International Maternal Pediatric Adolescent AIDS Clinical Trails (IMPAACT) P1041 study. Retrospective analysis was performed and the result demonstrate that TLP level is associated with TB disease. Conclusions: Plasma levels of TLP associate with active TB disease in HIV positive subjects and can be used as an indicator for TB detection in children.

Recombinant Fc-fusion vaccine of RBD induced protection against SARS-CoV-2 in non-human primate and mice

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to infect people globally. The increased COVID-19 cases and no licensed vaccines highlight the need to develop safe and effective vaccines against SARS-CoV-2 infection. Multiple vaccines candidates are under pre-clinical or clinical trails with different strengths and weaknesses. Here we developed a pilot scale production of a recombinant subunit vaccine (RBD-Fc Vacc) with the Receptor Binding Domain of SARS-CoV-2 S protein fused with the Fc domain of human IgG1. RBD-Fc Vacc induced SARS-CoV-2 specific neutralizing antibodies in non-human primates and mice, and the antibodies induced in macaca fascicularis neutralized three divergent SARS-CoV2 strains, supporting broader neutralizing ability. Three times immunizations protected Macaca fascicularis (20ug or 40ug per dose) and mice (10ug or 20ug per dose) from SARS-CoV-2 infection respectively, including the protection against SARS-CoV-2 adapted virus MASCp6 which contains N501Y mutation, a key residue increasing binding affinity to human and murine ACE2. These data support clinical development of SARS-CoV-2 vaccines and provide a promising strategy to prevent different stains of SARS-CoV-2 infection. RBD-Fc Vacc is currently being assessed in randomized controlled phase 1/II human clinical trails

Preliminary clinical experience applying donor-derived cell-free DNA to discern rejection in pediatric liver transplant recipients

Donor-derived cell-free DNA (dd-cfDNA) has been of major interest recently as a non-invasive marker of graft injury, but has not yet been extensively tested in children. From May to September in 2019, a total of 76 pediatric patients receiving a liver graft were enrolled and there were 27 patients excluded. Ultimately plasma samples and matched liver specimens from 49 patients were successfully collected whenever rejection was suspected clinically. Dd-cfDNA were analyzed and then compared to biopsy. Of these, 11 (22.4%) patients were found to have rejection by biopsy. Dd-cfDNA levels were higher among patients with rejection compared to those with no rejection. In subgroup analysis, dd-cfDNA% among patients with rejection differed from those with EBV/CMV infection and DILI patients. Similarly, observations were available concerning dd-cfDNA (cp/mL). The AUC for dd-cfDNA% and dd-cfDNA (cp/mL) were 0.878, 0.841, respectively, both of which were higher than conventional LFTs. For rejection, dd-cfDNA% ≥ 28.7% yielded a sensitivity of 72.7%, specificity 94.7% and dd-cfDNA (cp/mL) ≥ 2076 cp/mL, yielded a sensitivity of 81.8%, specificity 81.9%. Of note, the dd-cfDNA distribution was significantly different between whole liver and LLS transplantation. In the setting of pediatric LTx, dd-cfDNA appears to be a sensitive biomarker indicating the presence of rejection.International Clinical Trails Registry Platform: ChiCTR1900022406.

Recombinant Fc-fusion vaccine of RBD induced protection against SARS-CoV-2 in non-human primate and mice

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to infect people globally. The increased COVID-19 cases and no licensed vaccines highlight the need to develop safe and effective vaccines against SARS-CoV-2 infection. Multiple vaccines candidates are under pre-clinical or clinical trails with different strengths and weaknesses. Here we developed a pilot scale production of a recombinant subunit vaccine (RBD-Fc Vacc) with the Receptor Binding Domain of SARS-CoV-2 S protein fused with the Fc domain of human IgG1. RBD-Fc Vacc induced SARS-CoV-2 specific neutralizing antibodies in non-human primates and human ACE2 transgenic mice. The antibodies induced in macaca fascicularis neutralized three divergent SARS-CoV2 strains, suggesting a broader neutralizing ability. Three times immunizations protected Macaca fascicularis (20ug or 40ug per dose) and mice (10ug or 20ug per dose) from SARS-CoV-2 infection respectively. These data support clinical development of SARS-CoV-2 vaccines for humans. RBD-Fc Vacc is currently being assessed in randomized controlled phase 1/II human clinical trails.SummaryThis study confirms protective efficacy of a SARS-CoV-2 RBD-Fc subunit vaccine.