Efficacy and Nuances of Precision Molecular Engineering for Hodgkin's Disease to a Gene Therapeutic Approach.

Gene therapy is a particularly useful treatment for nervous system genetic diseases, including those induced especially by infectious organisms and antigens, and is being utilized to treat Hodgkin's disease (HD). Due to the possible clonal relationship between both disorders, immunotherapy directed against CD20 positive cells may be a more effective treatment in patients with persistent HD and NHL. HL growth can be inhibited both in vitro and in vivo by AdsIL-13Ralpha2. High-dose treatment combined with stem cell transplantation has been effective in treating HIV-negative lymphoma that has progressed to high-risk or relapsed disease. For therapy, LMP2-specific CTL will be used. Furthermore, it is possible to view the cytotoxicity of genetically modified adenoviruses that express proteins such as p27Kip1, p21Waf1, and p16INK4A as a foundational element for (2,5)-derived ALCL genetic treatment for Hodgkin's disease.

Arboviruses: Transmission and Host Resistance.

In this review, there is a complete description of the classes of arboviruses, their evolutionary process, virus characterization, disease transmission methods; it also describes about the vectors involved in transmission and their mood of transmission, both biologically as well as non-biologically and, about host, the resistance mechanism in host, and artificial methods of preventing those viral transmissions. Arboviruses transmitted to hosts by some vectors such as mosquitoes, ticks, etc. The virus replicates in the host can be prevented by some host resistance mechanisms like RNA interference (RNAi), which degrade virus RNA by its antiviral activity, insect repellents, IGRs, and PI technology.

Advances in the Management of Neuroblastoma.

Neuroblastoma is a malignant tumor of neuroblasts, immature nerve cells found in several areas of the body. It usually affects children under age of 5. As usual, the tumor has ability to grow rapidly and to expand vastly which ultimately leads to death. Mostly, management decisions can be drawn by the prediction of the stage of the disease as well as age at the time of its diagnosis. There are four main stages of neuroblastoma, and treatment is according to the low and high risk of the disease. Several cytotoxic agents along with other therapies (antibody therapy, gene therapy, and even immunological therapies, antiangiogenic therapy, etc.) are used. Immunotherapy also has an important treatment option used nowadays for neuroblastoma. The discovery of major neuroblastoma-predisposition gene anaplastic lymphoma kinase cause somatic transformation or gene strengthening in diagnosed neuroblastoma. Promising new antiangiogenic strategies have also been introduced for the treatment of neuroblastoma with multiple mylomas. To manage numerous myelomas and cancers, including neuroblastoma, bone marrow transplantation and peripheral blood stem cell transplantation may be used.

Human Oropharyngeal Candidiasis: From Etiology to Current Treatment.

Oral candidiasis is a common but most harmful oral cavity infection caused by yeast-like fungus, this condition is called Oropharyngeal candidiasis. There are various species of candida that are responsible for oral cavity fungal infection including mostly Candida albicans. Different candida infections may be acute and chronic. Cell-mediated immunity, humoral immunity, and granulocytes are the immune factors for the cause of this infection. Different antifungal drugs like nystatin, fluconazole, and amphotericin are used to treat oral cavity fungal infections.

AIDS Dementia Complex: Neurotoxicity in AIDS Patients.

AIDS dementia complex (ADC) is a nervous system disorder that harms the neurons in different parts of the brain. Various features are involved in altering the normal activities of neurons. Neurotoxicity is induced due to HIV viral proteins such as gp120, SDF, Tat, etc. These proteins target macrophages, glial cells, astrocytes, and release neurotoxins. These neurotoxins proved harmful for the neurons, caused apoptotic cell death by raising calcium, glutamate level and by producing various free radicals such as nitric oxide (NO·). Lipid peroxidation and lipids rafts also play a vital role in producing toxicity and apoptotic cell death. Membrane associated oxidative stress, cognitive impairment, and high level of HNE (4-hydroxynonenal); all are involved in ADC pathogenesis.

In-silico studies of inhibitory compounds against protease enzymes of SARS-CoV-2.

In December 2019, a COVID-19 outbreak caused by SARS-CoV-2 raised worldwide health concerns. In this case, molecular docking and drug repurposing computational approaches were engaged to check the efficiency of plant-based inhibitory compounds against SARS-CoV-2 main protease enzyme and papain-like protease enzyme. Twenty phytochemical inhibitory compounds were collected. Then these compounds were screened based on Lipinski's rule. As a result of this screening eleven compounds were further selected. Quantitative structure-activity relationships analysis was done before molecular docking to check especially the antiviral activity of inhibitory compounds. Docking validation of these compounds was checked by using online server Database of Useful Decoys: Enhanced. Binding affinity value, and pharmacokinetic properties of Aloin compound indicated that it can be used against main protease enzyme of SARS-CoV-2. So, it makes it a promising compound to follow further in cell and biochemical-based assays to explore its potential use against COVID-19.

Herbal Formulation Comprised of Methanol Extracts of Tribulus terristris L. and Zingiber officinale Roscoe Has Antihypertensive Effects.

People prefer to use medicinal plants rather than chemical compounds because they are low cost and have fewer adverse events. Zingiber officinale Roscoe is a natural dietary rhizome with anti-oxidative, anti-inflammatory and anti-carcinogenic properties. Tribulus terrestris L. has been used for the treatment of impotence, to enhance sexual drive and performance and for its diuretic and uricosuric effects. The aim of this study was to evaluate the combined effect of 2 extracts, Tribulus terristris and Zingiber officinale (TZ) for antioxidant, enzyme modulation, liver function, kidney function, blood profile and anti-hypertensive effects, which may pave the way for possible therapeutic applications. Antioxidant potential was measured with the 2,2-diphenyl-1-picryl-hydrazyl-hydrate free radical method antioxidant assay (DPPH) and kojic acid was used as the standard drug for tyrosine inhibition assay. The effect of TZ on biochemical parameters of the liver (alanine transferase [ALT], alkaline phosphatase [ALP], aspartate aminotransferase [AST], total serum protein, total serum albumin, serum bilirubin), kidney (blood urea and creatinine) and hematology (hemoglobin, red blood cells [RBC], platelets, thin-layer chromatography, neutrophils, eosinophils, lymphocytes, monocytes, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration) of Wister rats were studied by administering 100, 250 and 500 mg/kg-1 body weight TZ dose orally for 28 days. Antihypertensive effects were measured by the invasive method. The results showed that the scavenging percentage of TZ was 78.5 to 80.4, with an IC50 value of 1166.7 µg/ ml and tyrosinase inhibition was 72% compared with 93% for kojic acid. Different doses (100, 250 and 500 mg/kg) did not show an increase in serum biomarkers of liver and renal parameters. A significant increase in hemoglobin, erythrocytes, hematocrit, white blood cells (WBC) and lymphocytes with no significant increase/decrease in platelet count was observed but blood pressure was significantly decreased. Therefore, we concluded that TZ is safe and can be used in the treatment of hypertension.

ß-lapachone: A Promising Anticancer Agent with a Unique NQO1 Specific Apoptosis in Pancreatic Cancer.

Cancer, one of the major health problems all over the world, requires more competent drugs for clinical use. One recent possible chemotherapeutic drug under research is ß-lapachone. ß- lapachone (1,2-naphthoquinone) has promising activity against those tumors showing raised levels of Nicotinamide di-phosphate Quinone Oxidoreductases-1 (NQO1). NQO1 is found to be up-regulated in pancreatic tumor cells, and thus ß-lapachone could generate cytotoxicity in various cancers like pancreatic tumors. ß-lapachone harborage independent growth and clonogenic cell survival in agar. The cell-killing effects of ß-lapachone can be stopped by using dicumarol, an inhibitor of NAD(P)H Quinone Oxidoreductases-1. In previously established pancreatic cancer xenografts in mice, ß- lapachone inhibited the tumor growth when given orally rather than when combined with cyclodextrin to improve its bioavailability.

Analgesic and Anti-Inflammatory Properties of Two Hydrogel Formulations Comprising Polyherbal Extract.

Background: Nature represents a basic source of medicinal scaffolds that can develop into potent drugs used in the treatment of many diseases. Aim: The present study was planned to evaluate the combined effects of polyherbal methanolic extract of the herbs (fruit of capsicum, bark of cinnamon, rhizome of turmeric and rhizome of ginger) that were individually well known for their analgesic and anti-inflammatory activities. Furthermore, we aimed to develop hydrogel formulation of this polyherbal extract and to characterize and evaluate its analgesic and anti-inflammatory potential. Materials and Methods: Zingiber officinale (R.), Capsicum annuum (L.), Curcuma longa (L.), and Cinnamomum verum (J.) polyherbal extract (GCTC) was prepared by maceration and evaluated for analgesic and anti-inflammatory potential. Then, two different types of hydrogel formulation were prepared. One is pH-based hydrogel in which carbopol-940 was used and the other is temperature-based gel in which methocel-K100 was used as gelling agent. Different concentrations of polyherbal extract (GCTC), at 1%, 3% and 5%, were used in hydrogel formulation. These prepared hydrogel formulations were characterized and evaluated for analgesic and anti-inflammatory potential. Results: Results show that polyherbal extract and all the developed formulations of polyherbal extract (GCTC), at concentrations of 1%, 3% and 5%, have significant analgesic and anti-inflammatory effects with good appearance, homogeneity, spreadability, extrudability and stability. Conclusion: It was concluded from this project that polyherbal extract (GCTC) and its hydrogel have significant analgesic and anti-inflammatory potential.

Biologically synthesized iron nanoparticles (FeNPs) from Phoenix dactylifera have anti-bacterial activities.

Nanotechnology is a vast field of science with the most vibrant and conspicuous applications. The green synthesis approach is cost-effective, eco-friendly, and produces the most stable metal-based nanoparticles without the use of toxic chemicals. This study presents the green synthesis of iron nanoparticles (FeNPs). For biosynthesis of FeNPs, Phoenix dactylifera extract was used as a reducing agent and iron sulfate heptahydrate (FeSO4·7H2O) was used as a substrate. FeNPs were characterized by different techniques including UV-Visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), and nano zeta-sizer analysis. The antimicrobial activity of FeNPs synthesized by using an aqueous extract of Phoenix dactylifera was evaluated against Escherichia coli, Bacillus subtilis, Micrococcus leutus, and Klebsiella pneumoniae. A notable color change from yellow to black confirmed the synthesis of FeNPs. The sharp peak at 450 nm UV-Visible spectroscopy confirmed the synthesis of FeNPs. FTIR showed the presence of O-H and C=C stretching due to the presence of phenol and alkene functional groups. The average size of FeNPs was 6092 d.nm. The results of antimicrobial activity showed that FeNPs exhibit different potential against different bacterial strains with a maximum 25 ± 0.360 zone of inhibition against Escherichia coli. Thus, green synthesized FeNPs could be used as potential antimicrobial agents.

Design, synthesis and biological evaluations of 2-aminothiazole scaffold containing amino acid moieties as anti-cancer agents.

Due to the emerging mortality rate of colorectal cancer there is a high need for the management and control of this disease. Although several treatment approaches are being developed day by day yet the high incidence rate of colorectal cancer is still not controlled. To ease in the development of treatment therapies for colorectal cancer two derivatives of ethyl 2-aminothiazole 4-carboxylate were designed and synthesized. The compounds Ethyl 2-(2-(1,3-dioxoisoindolin-2-yl)acetamido)thiazole-4-carboxylate (5a) and ethyl 2-(2-(1,3-dioxoisoindolin-2-yl)-3-phenylpropanamido)thiazole-4-carboxylate (5b) were characterized and studied for their anti-cancer activities. The in silico molecular modeling studies were performed against the target protein beta-catenin which is an important player in the progression of colorectal cancer. The in silico ADMET studies were performed to assess the basic physicochemical properties of these compounds. The in vitro antiproliferative assay and the enzyme inhibitory assay was performed to validate the role of these compounds in the colorectal cancer. The preliminary cytotoxic assay and the MTT assay of the compounds 5a and 5b against the colorectal cancer cell line HCT 116 showed 60% inhibition of cell proliferation with IC50 of 0.72µM and 1.55µM, respectively. The standard methotrexate showed IC50 of 0.7µM showing potent inhibitory action of these compounds. The in vitro validation of the anti-cancer effect of both compounds revealed significant inhibition of beta-catenin concentration at higher doses as compared to control. Both the in vitro and in vivo assays of compounds showed effective anti-cancer activities and depicts the future potential of these compounds in colorectal cancer.

REVIEW: Nanobiotechnology: Cradle for revolution in drug carrier systems.

The role of nanobiotechnology in the treatment of diseases is limitless. In this review we tried to focus main aspects of nanotechnology in drug carrier systems for treatment and diagnosis of various diseases such as cancer, pulmonary diseases, infectious diseases, vaccine development, diabetes mellitus and the role of nanotechnology on our economy and its positive social impacts on our community. We discussed here about the different "Biotechnano Strategies" to develop new avenues and ultimately improve the treatment of multiple diseases.

Physicochemical, antidiarrheal and antidiabetic potential of super food (Moringa oleifera Lam.).

There is a long history of natural products for the treatment of infections and diseases. The objective of present study was to investigate the organoleptic, microscopic, physico-chemical, phytochemical, antidiarrheal and antidiabetic potential of leaf, flowering bud and stem bark of Moringa oleifera L. Macroscopic, microscopic, physico-chemical parameters and phytochemical screening were carried out. Diarrhea was induced with castor oil (10ml/kg), verapamil (3, 10 and 30mg/kg) were used as standard antidiarrheal drug and extract of Moringa oleifera at (100, 300 and 1000mg/kg) was used for treatment. Alpha glucosidase inhibitory assay was carried out by using acarbose (0.5mM) and extracts (5.0 mg/Ml). Diabetes was induced by alloxan (150mg/kg), while glibenclamide (10mg/kg) was used as standard drug, and extracts (at the doses of 500mg/kg) were used to determine the antidiabetic activity. Results showed the presence of primary and secondary metabolites, treatment at the dose of 1.0g/kg of leaf, flowering bud and stem bark showed 94 ±2.527, 85.42±5.460 and 84.58±6.138% protection respectively whereas verapamil (10mg/kg) showed 94.84±3.27% protection. Alpha glucosidase inhibition of stem bark (0.5mg/ml) was 95.43±1.47 and flowering bud 94.78±1.25 whereas acarbose (5mM) inhibition was 92.23±0.14%. Stem bark and flowering bud extract (500mg/kg) decreases the blood glucose level from 388.5±35.83 to 226.3±47.10 and 322.5±48.35 to 173.8±29.5 respectively whereas glibenclamide (10 mg/kg) decreases the blood glucose level from 320.7±22.9 to 146.3±17.7 and increases the body weight of the experimental animal. It was concluded from the results that stem bark has strong antidiabetic potential while leaves of the plant have promising antidiarrheal effect.

Biogenic selenium nanoparticles (SeNPs) from citrus fruit have anti-bacterial activities.

Nanotechnology deals with the synthesis of materials and particles at nanoscale with dimensions of 1-100 nm. Biological synthesis of nanoparticles, using microbes and plants, is the most proficient method in terms of ease of handling and reliability. Core objectives of this study were to synthesize metallic nanoparticles using selenium metal salt from citrus fruit extracts, their characterization and evaluation for antimicrobial activities against pathogenic microbes. In methodology, simple green method was implicated using sodium selenite salt solution and citrus fruit extracts of Grapefruit and Lemon as precursors for synthesizing nanoparticles. Brick red color of the solution indicated towards the synthesis of selenium nanoparticles (SeNPs). Nanoparticle's initial characterization was done by UV-Vis Spectrophotometry and later FTIR analysis and DLS graphs via Zetasizer were obtained for the confirmation of different physical and chemical parameters of the nanoparticles. Different concentrations of SeNPs were used for antimicrobial testing against E. coli, M. luteus, B. subtilis and K. pneumoniae comparative with the standard antibiotic Ciprofloxacin. SeNPs possessed significant antimicrobial activities against all the bacterial pathogens used. Conclusively, SeNPs made from citrus fruits can act as potent antibacterial candidates.

qPCR Analysis Reveals Association of Differential Expression of SRR, NFKB1, and PDE4B Genes With Type 2 Diabetes Mellitus.

Background: Type 2 diabetes mellitus (T2DM) is a heterogeneous, metabolic, and chronic condition affecting vast numbers of the world's population. The related variables and T2DM associations have not been fully understood due to their diverse nature. However, functional genomics can facilitate understanding of the disease. This information will be useful in drug design, advanced diagnostic, and prognostic markers. Aim: To understand the genetic causes of T2DM, this study was designed to identify the differentially expressed genes (DEGs) of the disease. Methods: We investigated 20 publicly available disease-specific cDNA datasets from Gene Expression Omnibus (GEO) containing several attributes including gene symbols and clone identifiers, GenBank accession numbers, and phenotypic feature coordinates. We analyzed an integrated system-level framework involving Gene Ontology (GO), protein motifs and co-expression analysis, pathway enrichment, and transcriptional factors to reveal the biological information of genes. A co-expression network was studied to highlight the genes that showed a coordinated expression pattern across a group of samples. The DEGs were validated by quantitative PCR (qPCR) to analyze the expression levels of case and control samples (50 each) using glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as the reference gene. Results: From the list of 50 DEGs, we ranked three T2DM-related genes (p < 0.05): SRR, NFKB1, and PDE4B. The enriched terms revealed a significant functional role in amino acid metabolism, signal transduction, transmembrane and intracellular transport, and other vital biological functions. DMBX1, TAL1, ZFP161, NFIC (66.7%), and NR1H4 (33.3%) are transcriptional factors associated with the regulatory mechanism. We found substantial enrichment of insulin signaling and other T2DM-related pathways, such as valine, leucine and isoleucine biosynthesis, serine and threonine metabolism, adipocytokine signaling pathway, P13K/Akt pathway, and Hedgehog signaling pathway. The expression profiles of these DEGs verified by qPCR showed a substantial level of twofold change (FC) expression (2-ΔΔCT) in the genes SRR (FC ≤ 0.12), NFKB1 (FC ≤ 1.09), and PDE4B (FC ≤ 0.9) compared to controls (FC ≥ 1.6). The downregulated expression of these genes is associated with pathophysiological development and metabolic disorders. Conclusion: This study would help to modulate the therapeutic strategies for T2DM and could speed up drug discovery outcomes.

Mini-Review: molecular elucidations of hutchinson-gilford progeria syndrome: A hope for managing horrors of premature aging in children.

Hutchinson-Gilford Progeria syndrome (or Progeria) is an exceptionally rare genetic disorder in children. It is caused by a rare point mutation in the lamin gene. It encodes lamin A protein, resulting in the de-shaping of nuclear membrane. This altered structure of the nuclear membrane renders the nucleus unstable. The shortened lifespan of the nucleus makes the cell liable for rapid ageing. Children are healthy by appearance when they are born but the signs appear after 12-24 months of age. Cardiovascular system is greatly affected which became a reason for the death of most of the patients of progeria. Stiffened joints disturb the bone movements; and alopecia affects the appearance of the patient. Rate of occurrence of the disease is one per four hundred thousand of people, though both sexes are equally affected.

Malignant Melanoma: Skin Cancer-Diagnosis, Prevention, and Treatment.

Melanoma is a skin cancer caused by a malignancy of melanocytes. Incidence of melanoma is rapidly increasing worldwide, which results in public health problems. Primary extracutaneous melanomas can be ocular, gastrointestinal, mucosal, leptomeningeal, genitourinary, and lymphatic. The relationship between exposure to ultraviolet (UV) light and development of melanoma is intensively acute and complex, and intermittent sun exposure greatly increases the risk of melanoma. It is the fifth most common type of cancer in men number and the sixth most common in women. The diagnosis of melanoma is made through clinical assessment of the pigmented by health care professionals. Architectural features of malignant melanoma including asymmetry, confluence of growth, marked cellularity, and poor circumscription. The cytological feature of malignant melanoma include an irregular and thick nuclear membrane and prominent nucleoli. The preventive measures include reducing exposure to UV light and the sun. The early detection of skin cancer greatly reduces both short- and long-term morbidity and mortality. The treatment and follow-up with the doctor for melanoma patients may differ because of the stage of the tumor and the primary lesion. The typical therapy for malignant melanoma is surgical excision, immunotherapy such as interleukin 2 (IL-2), gene therapy, and biochemotherapy.

Systems-level differential gene expression analysis reveals new genetic variants of oral cancer.

Oral cancer (OC) ranked as eleventh malignancy worldwide, with the increasing incidence among young patients. Limited understanding of complications in cancer progression, its development system, and their interactions are major restrictions towards the progress of optimal and effective treatment strategies. The system-level approach has been designed to explore genetic complexity of the disease and to identify novel oral cancer related genes to detect genomic alterations at molecular level, through cDNA differential analysis. We analyzed 21 oral cancer-related cDNA datasets and listed 30 differentially expressed genes (DEGs). Among 30, we found 6 significant DEGs including CYP1A1, CYP1B1, ADCY2, C7, SERPINB5, and ANAPC13 and studied their functional role in OC. Our genomic and interactive analysis showed significant enrichment of xenobiotics metabolism, p53 signaling pathway and microRNA pathways, towards OC progression and development. We used human proteomic data for post-translational modifications to interpret disease mutations and inter-individual genetic variations. The mutational analysis revealed the sequence predicted disordered region of 14%, 12.5%, 10.5% for ADCY2, CYP1B1, and C7 respectively. The MiRNA target prediction showed functional molecular annotation including specific miRNA-targets hsa-miR-4282, hsa-miR-2052, hsa-miR-216a-3p, for CYP1B1, C7, and ADCY2 respectively associated with oral cancer. We constructed the system level network and found important gene signatures. The drug-gene interaction of OC source genes with seven FDA approved OC drugs help to design or identify new drug target or establishing novel biomedical linkages regarding disease pathophysiology. This investigation demonstrates the importance of system genetics for identifying 6 OC genes (CYP1A1, CYP1B1, ADCY2, C7, SERPINB5, and ANAPC13) as potential drugs targets. Our integrative network-based system-level approach would help to find the genetic variants of OC that can accelerate drug discovery outcomes to develop a better understanding regarding treatment strategies for many cancer types.

Pharmacological and Genomic Approaches in Management of Cystic Fibrosis.

Cystic fibrosis (CF) is an inherited recessive autosomal disorder that affects the lungs, the digestive system, and secretory glands. It is a lethal condition caused by a mutation in the gene cystic-fibrosis-transmembrane-conductance- regulator (CFTR), which leads to defects in ion channels and results in obstruction of mucus in airway channels. Unbalanced ion exchange causes impaired water transport and accumulation of viscous mucus in the air way leads to bacterial colonization, for example, with Staphylococcus aureus. The most common mutation is the deletion of nucleotides in epithelial membrane; hence, it is a multiple-organ-defective disease that mostly effects the lungs. Researchers are working on gene therapy that aims to introduce a normal CFTR gene copy into the epithelial cells of lungs. Several approaches have been designed to improve transepithelial ion transport in CF patients. Normal CFTR gene delivery has been performed using viral and nonviral vectors, but these approaches are not more efficient against the cell barriers. Enzymes may be used that inhibit the sphingolipid to provide proper microenvironment for the CFTR gene product. Thymosin alpha-1 has also been reported as a potential corrector in treatment of CF.

CRISPR/Cas: A Successful Tool for Genome Editing in Animal Models.

CRISPR/Cas9 is an innovative molecular tool that is utilized in advanced biological applications. This review focuses on modifying the genomes of a wide range of animals by CRISPR/Cas9 for greater usability and higher efficiency, providing an overview of the function and mechanism of this system and the utilization of this system for medicinal research. The type II CRISPR-Cas system is found in the Enterobacteriaceae bacteria family, which uses this system as a defense against invading phages and plasmids. This system can be engineered to direct its action toward a targeted site for the modification of a specific genome.