Characterization of Tomato Leaf Curl New Delhi Virus infecting cucurbits: Evidence for sap transmission in a host specific manner

Sponge gourd (Luffa cylindrica) is an economically important vegetable crop cultivated throughout India and this crop is severely affected by yellow mosaic disease caused by begomovirus. In this study, an attempt was made to transmit the begomovirus by sap. The causal agent was easily transmitted by sap to ridge gourd, sponge gourd and Nicotiana  benthamiana. Several factors affecting the efficient sap transmission of causal virus was identified. Use of two antioxidant (sodium sulphite and β-mercaptoethanol) and two abrasive (celite and corborundum) and application of inoculum on first true leaves and cotyledons by rubbing with cotton swab, dipped in inoculum resulted in significant higher rate of transmission. The sap inoculation protocol resulted in variable percentage of infected plants from different factors like buffer combinations, source of inoculum, age of inoculum, genotypes of test plants, and species of plants, temperature, seasons and organic materials. The most susceptible growth stage of ridge gourd plant to sap inoculation was seven days old seedlings that produced 100% infection. The sap transmission was confirmed by coat protein gene polymerase chain reaction (PCR) amplification, cloning and sequencing from infected plants. Sap transmission of begomovirus infecting luffa has not been reported previously in India.Keywords: Sap transmission, begomovirus, Tomato leaf curl New Delhi virus (ToLCNDV), cucurbitsAfrican Journal of Biotechnology Vol. 12(32), pp. 5000-500

Chronic inflammation's transformation to cancer : a nanotherapeutic paradigm

The body’s normal immune response against any invading pathogen that causes infection in the body results in inflammation. The sudden transformation in inflammation leads to the rise of inflammatory diseases such as chronic inflammatory bowel disease, autoimmune disorders, and colorectal cancer (different types of cancer develop at the site of chronic infection and inflammation). Inflammation results in two ways: short-term inflammation i.e., non-specific, involves the action of various immune cells; the other results in long-term reactions lasting for months or years. It is specific and causes angiogenesis, fibrosis, tissue destruction, and cancer progression at the site of inflammation. Cancer progression relies on the interaction between the host microenvironment and tumor cells along with the inflammatory responses, fibroblast, and vascular cells. The two pathways that have been identified connecting inflammation and cancer are the extrinsic and intrinsic pathways. Both have their own specific role in linking inflammation to cancer, involving various transcription factors such as Nuclear factor kappa B, Activator of transcription, Single transducer, and Hypoxia-inducible factor, which in turn regulates the inflammatory responses via Soluble mediators cytokines (such as Interleukin-6, Hematopoietin-1/Erythropoietin, and tumor necrosis factor), chemokines (such as Cyclooxygenase-2, C-X-C Motif chemokines ligand-8, and IL-8), inflammatory cells, cellular components (such as suppressor cells derived from myeloid, tumor-associated macrophage, and acidophils), and promotes tumorigenesis. The treatment of these chronic inflammatory diseases is challenging and needs early detection and diagnosis. Nanotechnology is a booming field nowadays for its rapid action and easy penetration inside the infected destined cells. Nanoparticles are widely classified into different categories based on their different factors and properties such as size, shape, cytotoxicity, and others. Nanoparticles emerged as excellent with highly progressive medical inventions to cure diseases such as cancer, inflammatory diseases, and others. Nanoparticles have shown higher binding capacity with the biomolecules in inflammation reduction and lowers the oxidative stress inside tissue/cells. In this review, we have overall discussed inflammatory pathways that link inflammation to cancer, major inflammatory diseases, and the potent action of nanoparticles in chronic inflammation-related diseases

Screening, Docking, and Molecular Dynamics Study of Natural Compounds as an Anti-HER2 for the Management of Breast Cancer

Breast cancer (BC) is one of the most frequent types of cancer that affect women. Human epidermal growth factor receptor-2 (HER2) is responsible for 20% of all BC cases. The use of anti-HER2 natural compounds in the cure of BC that is HER2-positive patients has resulted in significant increases in survival in both early and advanced stages. The findings of in-silico research support the use of ligands as possible HER2 inhibitors, and molecules with high free energy of binding may have considerable anti-BC action, making them candidates for future drug development. The inhibitory activity of selected ligands like ZINC43069427 and ZINC95918662 against HER2 was found to be −11.0 and −8.50 kcal/mol, respectively. The amino acid residues Leu726, Val734, Ala751, Lys753, Thr798, Gly804, Arg849, Leu852, Thr862, and Asp863 were found in common interaction as compared to the control compound Lapatinib. Molecular dynamics study calculations of these selected potent inhibitors were conducted and found to be stable over the 50 ns simulation time in terms of root mean square deviation (RMSD), root-mean square fluctuation (RMSF), radius of gyration (Rg), and solvent accessible surface area (SASA). In addition, there are several parameters such as absorption, distribution, metabolism, and excretion toxicity (ADMET), physicochemical, and drug-likeness that were checked and found in good range to be potential lead-like molecules. Several drug-likeness rules like Lipinski, Ghose, Veber, Egan, and Muegge were checked and found to be positive for these rules. Based on these calculations and different parameters, these top two selected natural compounds can be used as potential candidates for anti-HER2 for the management of BC

Recent Status of Nanomaterial Fabrication and Their Potential Applications in Neurological Disease Management

Abstract Nanomaterials (NMs) are receiving remarkable attention due to their unique properties and structure. They vary from atoms and molecules along with those of bulk materials. They can be engineered to act as drug delivery vehicles to cross blood-brain barriers (BBBs) and utilized with better efficacy and safety to deliver specific molecules into targeted cells as compared to conventional system for neurological disorders. Depending on their properties, various metal chelators, gold nanoparticles (NPs), micelles, quantum dots, polymeric NPs, liposomes, solid lipid NPs, microparticles, carbon nanotubes, and fullerenes have been utilized for various purposes including the improvement of drug delivery system, treatment response assessment, diagnosis at early stage, and management of neurological disorder by using neuro-engineering. BBB regulates micro- and macromolecule penetration/movement, thus protecting it from many kinds of illness. This phenomenon also prevents drug delivery for the neurological disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis, amyotrophic lateral sclerosis, and primary brain tumors. For some neurological disorders (AD and PD), the environmental pollution was considered as a major cause, as observed that metal and/or metal oxide from different sources are inhaled and get deposited in the lungs/brain. Old age, obesity, diabetes, and cardiovascular disease are other factors for rapid deterioration of human health and onset of AD. In addition, gene mutations have also been examined to cause the early onset familial forms of AD. AD leads to cognitive impairment and plaque deposits in the brain leading to neuronal cell death. Based on these facts and considerations, this review elucidates the importance of frequently used metal chelators, NMs and/or NPs. The present review also discusses the current status and future challenges in terms of their application in drug delivery for neurological disease management

Salicylic acid alleviates salinity-caused damage to foliar functions, plant growth and antioxidant system in Ethiopian mustard (Brassica carinata A. Br.)

Abstract Background Soil salinity is considered as one of the major environmental factors that has reduced plant productivity worldwide. This study investigates the impact of salinity on plant growth attributes, biochemical and physiological leaf characteristics in two cultivars (Adet and Merawi) of Brassica carinata and also explores the role of salicylic acid (SA) in mitigating the effect of salt stress. Methods Four-week-old cultivars were treated with NaCl (50, 100 and 150 mM) and SA (0.5 mM) and watered regularly with 100% field capacity. Thus, they were grown under eight different treatments (T1 = no NaCl, no SA; T2 = 0 mM NaCl with 0.5 mM SA; T3 = 50 mM NaCl without SA; T4 = 50 mM NaCl with 0.5 mM SA; T5 = 100 mM NaCl without SA; T6 = 100 mM NaCl with 0.5 mM SA; T7 = 150 mM NaCl without SA; and T8 = 150 mM NaCl with 0.5 mM SA). Nine-week-old cultivars were sampled for analyzing the growth attributes, plant water status, nitrate reductase activity, proline accumulation, photosynthetic traits, lipid peroxidation level and activity of antioxidant enzymes. Results Salinity treatments hampered the overall plant growth performance in a dose-dependent manner. Salinity also reduced photosynthetic efficiency by inhibiting chlorophyll synthesis, nitrate reductase activity, chlorophyll fluorescence, stomatal conductance, net photosynthetic and transpiration rates and plant water status. On the other hand, SA application alleviated the adverse effects of salinity and improved the performance of the studied parameters in both the cultivars. Higher dose of salinity increased proline production, but SA application mitigates this impact in both the cultivars studied. The activity of antioxidant enzymes increased under salt stress in a dose-dependent manner. SA treatment to normal or salinity-stressed plants increased the enzymes activity, showing that SA has a crucial role in modulating the cell redox balance and protecting the plants from oxidative damage. SA significantly reduced the salinity-caused effects on the overall performance of plants and their antioxidant systems in both the cultivars. Of the two cultivars, Adet was more tolerant to salinity than Merawi. Conclusions Foliar application of SA improved the performance of Ethiopian mustard cultivars and mitigated the damage caused by salt stress

IgY antibodies for the immunoprophylaxis and therapy of respiratory infections

Emergence of drug resistance among the causative organisms for respiratory tract infections represents a critical challenge to the global health care community. Further, although vaccination can prevent disease, vaccine development is impeded by several factors. Therefore, novel approaches to treat and manage respiratory infections are urgently needed. Passive immunization represents a possible alternative to meet this need. Immunoglobulin Y antibodies (IgYs) from the yolk of chicken eggs have previously been used against bacterial and viral infections in human and animals. Their advantages include lack of reaction with mammalian Fc receptors, low production cost, and ease of extraction. Compared to mammalian IgGs, they have higher target specificity and greater binding avidity. They also possess remarkable pathogen-neutralizing activity in the respiratory tract and lungs. In this review, we provide an overview of avian IgYs and describe their potential therapeutic applications for the prevention and treatment of respiratory infections

Delivery of siRNAs against MERS-CoV in Vero and HEK-293 cells: A comparative evaluation of transfection reagents

Background: A new coronavirus was identified in Jeddah, Saudi Arabia in 2012 and designated as Middle East Respiratory Syndrome Coronavirus (MERS-CoV). To date, this virus has been reported in 27 countries. The virus transmission to humans has already been reported from camels. Currently, there is no vaccine or antiviral therapy available against this virus. Methods: The siRNAs were in silico predicted, designed, and chemically synthesized by using the MERS-CoV-orf1ab region as a target. The antiviral activity was experimentally evaluated by delivering the siRNAs with Lipofectamine™ 2000 and JetPRIMER as transfection reagents in both Vero cell and HEK-293-T cell lines at two different concentrations (10.0 nM and 5.0 nM). The Ct value of quantitative Real-Time PCR (qRT-PCR) was used to calculate and determine the reduction of viral RNA level in both cell supernatant and cell lysate isolated from both cell lines. Results: The sequence alignment resulted in the selection of highly conserved regions. The orf1ab region was used to predict and design the siRNAs and a total of twenty-one siRNAs were finally selected from four hundred and twenty-six siRNAs generated by online software. Inhibition of viral replication and significant reduction of viral RNA was observed against selected siRNAs in both cell lines at both concentrations. Based on the Ct value, the siRNAs # 11, 12, 18, and 20 were observed to be the best performing in both cell lines at both concentrations. Conclusion: Based on the results and data analysis, it is concluded that the use of two different transfection reagents was significantly effective. But the Lipofectamine™ 2000 was found to be a better transfection reagent than the JetPRIMER for the delivery of siRNAs in both cell lines

Anti-S1 MERS-COV IgY Specific Antibodies Decreases Lung Inflammation and Viral Antigen Positive Cells in the Human Transgenic Mouse Model

The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 and causes severe and often fatal acute respiratory illness in humans. No approved prophylactic and therapeutic interventions are currently available. In this study, we have developed egg yolk antibodies (immunoglobulin Y (IgY)) specific for MERS-CoV spike protein (S1) in order to evaluate their neutralizing efficiency against MERS-CoV infection. S1-specific immunoglobulins were produced by injecting chickens with purified recombinant S1 protein of MERS-CoV at a high titer (5.7 mg/mL egg yolk) at week 7 post immunization. Western blotting and immune-dot blot assays demonstrated that the IgY antibody specifically bound to the MERS-CoV S1 protein. Anti-S1 antibodies were also able to recognize MERS-COV inside cells, as demonstrated by an immunofluorescence assay. Plaque reduction and microneutralization assays showed the neutralization of MERS-COV in Vero cells by anti-S1 IgY antibodies and non-significantly reduced virus titers in the lungs of MERS-CoV-infected mice during early infection, with a nonsignificant decrease in weight loss. However, a statistically significant (p = 0.0196) quantitative reduction in viral antigen expression and marked reduction in inflammation were observed in lung tissue. Collectively, our data suggest that the anti-MERS-CoV S1 IgY could serve as a potential candidate for the passive treatment of MERS-CoV infection

Bacterial Community and Genomic Analysis of Carbapenem-Resistant Acinetobacter baumannii Isolates from the Environment of a Health Care Facility in the Western Region of Saudi Arabia

The escalating transmission of hospital-acquired infections, especially those due to antimicrobial-resistant bacteria, is a major health challenge worldwide. In this study, a culturomic analysis of bacterial community in a tertiary care hospital in the western region of Saudi Arabia is performed using environmental samples. The genome sequencing of four Acinetobacter baumannii was performed on isolates recovered from an intensive care unit (ICU) environment and clinical samples. A total of 361 bacterial isolates from surface and air samples were identified by MALDI-TOF technique or 16S rRNA gene sequencing. The isolates were classified into 70 distinct species, including ESKAPE pathogens. Resistance in Gram-positive isolates was mainly found to be against benzylpenicillin, azithromycin, ampicillin, and trimethoprim/sulfamethoxazole. Carbapenem- and multidrug-resistant isolates of A. baumannii and Klebsiella pneumonia were found on the ICU surfaces. Genome sequencing revealed that the carbapenem-resistant A. baumannii isolate from ICU environment was linked with those of clinical origin. The isolate Ab133-HEnv was classified as a novel sequence type (ST2528) based on a new allele of Oxf_gdhB-286. Three beta-lactam-antibiotic-resistance genes, blaADC-25, blaOXA-23, and blaOXA-66, were found in most of the analyzed genomes. Collectively, the results of this study highlight the spread of antimicrobial-resistant nosocomial pathogens in a health care facility in Saudi Arabia