Department of Pediatrics, Division of Hematology, Oncology and Bone Marrow Transplantation, University of Miami School of Medicine, Miami, FL 33136, USA
Dr. Sunil Joshi
Department of Pediatrics, Division of Hematology, Oncology and Bone Marrow Transplantation, University of Miami School of Medicine, Miami, FL 33136, USA
Autophagy (self-eating) is a conserved cellular degradation process that plays important roles in maintaining homeostasis and preventing nutritional, metabolic, and infection-mediated stresses. Autophagy dysfunction can have various pathological consequences, including tumor progression, pathogen hyper-virulence, and neurodegeneration. This review describes the mechanisms of autophagy and its associations with other cell death mechanisms, including apoptosis, necrosis, necroptosis, and autosis. Autophagy has both positive and negative roles in infection, cancer, neural development, metabolism, cardiovascular health, immunity, and iron homeostasis. Genetic defects in autophagy can have pathological consequences, such as static childhood encephalopathy with neurodegeneration in adulthood, Crohn’s disease, hereditary spastic paraparesis, Danon disease, X-linked myopathy with excessive autophagy, and sporadic inclusion body myositis. Further studies on the process of autophagy in different microbial infections could help to design and develop novel therapeutic strategies against important pathogenic microbes. This review on the progress and prospects of autophagy research describes various activators and suppressors, which could be used to design novel intervention strategies against numerous diseases and develop therapeutic drugs to protect human and animal health.
Infectious laryngotracheitis (ILT) is a highly contagious upper respiratory tract disease of chicken caused by a Gallid herpesvirus 1 (GaHV-1) belonging to the genus Iltovirus, and subfamily Alphaherpesvirinae within Herpesviridae family. The disease is characterized by conjunctivitis, sinusitis, oculo-nasal discharge, respiratory distress, bloody mucus, swollen orbital sinuses, high morbidity, considerable mortality and decreased egg production. It is well established in highly dense poultry producing areas of the world due to characteristic latency and carrier status of the virus. Co-infections with other respiratory pathogens and environmental factors adversely affect the respiratory system and prolong the course of the disease. Latently infected chickens are the primary source of ILT virus (ILTV) outbreaks irrespective of vaccination. Apart from conventional diagnostic methods including isolation and identification of ILTV, serological detection, advanced biotechnological tools such as PCR, quantitative real-time PCR, next generation sequencing, and others are being used in accurate diagnosis and epidemiological studies of ILTV. Vaccination is followed with the use of conventional vaccines including modified live attenuated ILTV vaccines, and advanced recombinant vector vaccines expressing different ILTV glycoproteins, but still these candidates frequently fail to reduce challenge virus shedding. Some herbal components have proved to be beneficial in reducing the severity of the clinical disease. The present review discusses ILT with respect to its current status, virus characteristics, epidemiology, transmission, pathobiology, and advances in diagnosis, vaccination and control strategies to counter this important disease of poultry.
A novel coronavirus designated as SARS-CoV-2 in February 2020 by World Health organization (WHO) was identified as main cause of SARS like pneumonia cases in Wuhan city in Hubei Province of China at the end of 2019. This been recently declared as Global Pandemic by WHO. There is a global emergency to identify potential drugs to treat the SARS-CoV-2. Currently, there is no specific treatment against the new virus. There is a urgency to identifying potential antiviral agents to combat the disease is urgently needed. An effective and quick approach is to test existing antiviral drugs against. Whole genome analysis and alignment carried out using BLASTn, SMART BLAST and WebDSV 2.0 had shown more than 238 ORF’s coding for proteins mostly origin from Bat SARS coronavirus and root genomic origin from Archaea. Molecular docking results against protein targets Furin, papain like proteases, RdRp and Spike glycoprotein had shown paritaprevir, ritonavir, entecavir and chloroquine derivatives are the best drugs to inhibit multi targets of coronavirus infection including natural compounds corosolic acid, baicalin and glycyrrhizic acid with minimal inhibitory concentrations. Thus we propose use of paritaprevir, entecavir, ritonavir and chloroquine derivatives as best drug combination along with niacinamide, folic acid and zinc supplements to treat novel coronavirus infection. We also propose use of plant protease inhibitors (PI’s) and Anti-IL8, IL-6, IL-2 as future drug models against coronavirus.
The success of tissue transplantation from a healthy donor to a diseased individual (allo-transplantation) is regulated by the immune systems of both donor and recipient. Developing a state of specific non‐reactivity between donor and recipient, while maintaining the salutary effects of immune function in the recipient, is called “immune (transplantation) tolerance”. In the classic early post‐transplant period, minimizing bidirectional donor ←→ recipient reactivity requires the administration of immunosuppressive drugs, which have deleterious side effects (severe immunodeficiency, opportunistic infections, and neoplasia, in addition to drug-specific reactions and organ toxicities). Inducing immune tolerance directly through donor and recipient immune cells, particularly via subsets of immune regulatory cells, has helped to significantly reduce side effects associated with multiple immunosuppressive drugs after allo‐transplantation. The innate and adaptive arms of the immune system are both implicated in inducing immune tolerance. In the present article, we will review innate immune subset manipulations and their potential applications in hematopoietic stem cell transplantation (HSCT) to cure malignant and non-malignant hematological disorders by inducing long-lasting donor ←→ recipient (bidirectional) immune tolerance and reduced graft-versus-host disease (GVHD). These innate immunotherapeutic strategies to promote long‐term immune allo-transplant tolerance include myeloidderived suppressor cells (MDSCs), regulatory macrophages, tolerogenic dendritic cells (tDCs), Natural Killer (NK) cells, invariant Natural Killer T (iNKT) cells, gamma delta T (γδ‐T) cells and mesenchymal stromal cells (MSCs).
SARS-CoV-2, a global pandemic originated from Wuhan city of China in the month of December 2019. There is an urgency to identify potential antibodies to neutralize the virus and also as a diagnostic tool candidate. At present palliative treatments using existing antiviral drugs are under trails to treat SARS-CoV-2.Whole Genome sequence of Wuhan market sample of SARS-CoV-2 was obtained from NCBI Gene ID MN908947.3.Spike protein sequence PDB ID 6VSB obtained from RCSB database. Spike protein sequence had shown top V gene match with IGLV1-44*01, IGLV1-47*02 and has VL type chain. Whole Genome sequence had shown top V gene match with IGHV1-38-4*01 and has VH type chain. VD chain had shown link to allele HLA-A0206 80%, HLA-A0217 80%, HLA-A2301 75%, HLA-A0203 75%, HLA-A0202 70% and HLA-A0201 55% of binding levels. Some conserved regions of spike protein had shown strong binding affinity with HLA-A-0*201, HLA-A24, HLA-B-5701 and HLA-B-5703 alpha chains. Synthetic Fab construct BCR type antibody IgG (CR5840) had shown Polyspecific binding activity with spike glycoprotein when compared with available Anti-SARS antibody CR3022.Thus we propose CR5840 Fab constructed antibody as potential neutralizing antibody for SARS-CoV-2. Based on germline analysis we also propose cytotoxic T lymphocyte epitope peptide selective system as effective tool for the development of SARS-CoV-2 vaccine.
6 November 2021 in International Journal of Scientific and Research Publications