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This study involved cerebroprotective potential of aloe emodin (AE) by in silico molecular docking analysis against various cerebrotoxic proteins followed by in vivo activity on multiple occlusions and reperfusion of bilateral carotid arteries (MO/RCA) induced cerebral injury in experimental rats. Molecular docking studies were carried out to evaluate the binding affinity (or binding interaction) between AE and various proteins involved in apoptosis such as caspase-3 (CASP3) and Bcl-2-associated X protein (BAX), and proteins involved in inflammation such as interleukin-6 (IL-6), tumor necrosis factor α (TNF α), nitric oxide synthase (NOS), acid-sensing ion channel (ASIC) and glutamate receptor (GR) involved in cerebral stroke, and results were compared with that of standard drugs, minocycline, quercetin, and memantine. Cerebral ischemic reperfusion induced by MO/RCA was assessed for 10 mins reperfusion period as one cycle, and the experiment was conducted for up to 3 cycles in rats. After completion of 3 cycles, the rats were subjected to ethically acceptable animal euthanasia followed by isolation of the brains which were studied for the size of cerebral infarction, and biochemical parameters such as glutathione (GSH), malondialdehyde (MDA), catalase (CAT) were estimated from the brain homogenate. Further, histological studies were done to study neuronal contact. Results of molecular docking indicated that the AE exhibited interaction with active sites of cerebrotoxic proteins usually involved in protein functions or cerebrotoxicity. Biochemical results showed that in the untreated brain, MDA levels increased significantly, and decreased GSH and CAT levels were observed when compared to MO/RCA group, while treated rats showed a decrease in the levels of MDA and an increase in GSH and CAT levels as compared to MO/RCA rats. In comparison with sham rats and normal rats, histopathological analysis revealed neuronal damage in MO/RCA surgery rats which manifested as decreased intact neurons. However, treatment with AE 50 mg/kg b.wt. restored contact between neuronal cells. It can be concluded that AE showed cerebroprotective effect on RO/RCA with promising inhibition of cerebrotoxic proteins (apoptotic and neuroinflammatory) as evident from molecular docking studies. The cerebroprotective potential of AE could be due to its anti-inflammatory, antioxidant, and antiapoptotic principles.

Hyperglycemia is the fundamental cause of diabetes complications. The major consequence of hyperglycemia is the increased accumulation of advanced glycation end products (AGEs). AGE formation is initiated by nonenzymatic reactions between carbonyl groups of reducing sugars and free amino groups. These AGEs bring about an alteration in the structure of macromolecules, especially proteins by causing aggregation and crosslinking. The invention of novel antiglycation and antiaggregation compounds from different sources has received great attention. Several natural compounds and their active constituents have the property of reducing adverse effects of aggregation and glycation of proteins. Being an acceptable historical and culture-based treatment for various health issues, Nigella sativa is a phytomedicine that has been gaining worldwide recognition. Traditionally and recent research papers suggest its therapeutic significance for the treatment of various ailments like diabetes, cancer, liver diseases, etc. It is rich in many phytochemicals and medicinally important compound. The following book chapter deals with the role of N. sativa (black cumin) seeds and its active constituents in the prevention of glycation and glycation-induced aggregation and oxidation of macromolecules.

Chalcones are secondary metabolites belonging to the flavonoid (C6-C3-C6 system) family that are ubiquitous in edible and medicinal plants, and they are bioprecursors of plant flavonoids. Chalcones and their natural derivatives are important intermediates of the flavonoid biosynthetic pathway. Plants containing chalcones have been used in traditional medicines since antiquity. Chalcones are basically α,β-unsaturated ketones that exert great diversity in pharmacological activities such as antioxidant, anticancer, antimicrobial, antiviral, antitubercular, antiplasmodial, antileishmanial, immunosuppressive, anti-inflammatory, and so on. This review provides an insight into the chemistry, biosynthesis, and occurrence of chalcones from natural sources, particularly dietary and medicinal plants. Furthermore, the pharmacological, pharmacokinetics, and toxicological aspects of naturally occurring chalcone derivatives are also discussed herein. In view of having tremendous pharmacological potential, chalcone scaffolds/chalcone derivatives and bioflavonoids after subtle chemical modification could serve as a reliable platform for natural products-based drug discovery toward promising drug lead molecules/drug candidates.

Background Migraine, as the 7th most disabling neurological multi-symptomatic disease condition and 26.9% prevalence in Saudi females lacks studies on SNPs for their relation with migraine aura. Methods This study was conducted on 40 Arab ancestry young female subjects, among whom 50% cases with migraine and remaining controls were used to identify the migraine associated novels genes and risk variants. After quality controls, 3365343 missense, frameshift, missense splice region variants and insertion-deletion (indels) polymorphisms were tested for association to migraine. Results Seventeen significant (p value 9.091×10− 05) functional variants in 12 genes (RETNLB, SCAI, ADH4, ESPL1, CPT2, FLG, PPP4R1, SERPINB5, ZNF66, ETAA1, EXO1 and CPA6) were migraine risk associated including a stop gained frameshift (-13-14*SX) variant in the gene RETNLB (rs5851607; p value 3.446×10− 06). Gene analysis revealed that half of the significant novel migraine risk genes expressed in temporal lobe (p-value 0.0058) of the cerebral cortex. Conclusions This first study in female (22.10 ± 3.63 years) migrainers is the first one exploring migraine risk variants in Arab ancestry.

Over 30-35% of patients down with AML are caused by mutations of FLT3-ITD and FLT3-TKD which keeps the protein activated while it activates other signaling proteins downstream that are involved in cell proliferation, differentiation, and survival. As drug targets, many inhibitors are already in clinical practice. Unfortunately, the average overall survival rate for patients on medication suffering from AML is 5 years despite the huge efforts in this field. To perform docking simulation and ADMET studies on selected phytochemicals against FLT3 protein receptor for drug discovery against FLT3 induced AML, molecular docking simulation was performed using human FLT3 protein target (PDB ID: 6JQR) and 313 phytochemicals with standard anticancer drugs (Sorafenib and Gilteritinib in addition to other anticancer drugs). The crystal structure of the protein was downloaded from the protein data bank and prepared using Biovia Discovery Studio. The chemical structures of the phytochemicals were downloaded from the NCBI PubChem database and prepared using Open Babel and VConf softwares. Molecular docking was performed using PyRx on Autodock Vina. The ADMET properties of the best performing compounds were calculated using SwissADME and pkCMS web servers. The results obtained showed that glabridin, ellipticine and derivatives (elliptinium and 9-methoxyellipticine), mezerein, ursolic acid, formononetin, cycloartocarpesin, hypericin, silymarin, and indirubin are the best performing compounds better than sorafenib and gilteritinib based on their binding affinities. The top-performing compounds which had better binding and ADMET properties than sorafenib and gilteritinib could serve as scaffolds or leads for new drug discovery against FLT3 induced AML.Communicated by Ramaswamy H. Sarma.

The pandemic situation due to COVID-19 has crippled the lives of the whole world population and has affected almost every individual in one way or the other. Researchers have been intrigued due to the increasing number of strains and symptoms. Several approaches have been used to control the spread of this highly infectious disease: early detection of the infected individual, development of a suitable drug and containment of the spread of this virus. Although, several vaccines have been developed, they have shown to have their own limitations and side-effects. One of the measures which has been adopted by the global health agencies is to educate people (infected or uninfected) regarding the maintenance of strong immune system to prevent the infection and lessen the health complications. There are several important factors which determine the immunity of an individual. Eating balanced diet and maintaining the proper supplication of nutritional components are being suggested by health experts to keep the immunity strong. Minerals and vitamins must be maintained in the diet for proper health and immunity. Vitamins have various roles in human physiology. In this review, the relevance of vitamins in the maintenance of immunity has been discussed and reviewed in prevention of adverse health effects of COVID-19.

The significance of biomaterials is well appreciated in nanotechnology, and its use has resulted in major advances in biomedical sciences. Although, currently, very little data is available on the clinical trial studies for treatment of neurological conditions, numerous promising advancements have been reported in drug delivery and regenerative therapies which can be applied in clinical practice. Among the commonly reported biomaterials in literature, the self-assembling peptides and hydrogels have been recognized as the most potential candidate for treatment of common neurological conditions such as Alzheimer’s, Parkinson’s, spinal cord injury, stroke and tumors. The hydrogels, specifically, offer advantages like flexibility and porosity, and mimics the properties of the extracellular matrix of the central nervous system. These factors make them an ideal scaffold for drug delivery through the blood-brain barrier and tissue regeneration (using stem cells). Thus, the use of biomaterials as suitable matrix for therapeutic purposes has emerged as a promising area of neurosciences. In this review, we describe the application of biomaterials, and the current advances, in treatment of statistically common neurological disorders.

Flavonoids comprise a large group of structurally diverse polyphenolic compounds of plant origin and are abundantly found in human diet such as fruits, vegetables, grains, tea, dairy products, red wine, etc. Major classes of flavonoids include flavonols, flavones, flavanones, flavanols, anthocyanidins, isoflavones, and chalcones. Owing to their potential health benefits and medicinal significance, flavonoids are now considered as an indispensable component in a variety of medicinal, pharmaceutical, nutraceutical, and cosmetic preparations. Moreover, flavonoids play a significant role in preventing cardiovascular diseases (CVDs), which could be mainly due to their antioxidant, antiatherogenic, and antithrombotic effects. Epidemiological and in vitro/in vivo evidence of antioxidant effects supports the cardioprotective function of dietary flavonoids. Further, the inhibition of LDL oxidation and platelet aggregation following regular consumption of food containing flavonoids and moderate consumption of red wine might protect against atherosclerosis and thrombosis. One study suggests that daily intake of 100 mg of flavonoids through the diet may reduce the risk of developing morbidity and mortality due to coronary heart disease (CHD) by approximately 10%. This review summarizes dietary flavonoids with their sources and potential health implications in CVDs including various redox-active cardioprotective (molecular) mechanisms with antioxidant effects. Pharmacokinetic (oral bioavailability, drug metabolism), toxicological, and therapeutic aspects of dietary flavonoids are also addressed herein with future directions for the discovery and development of useful drug candidates/therapeutic molecules.

There are regular reports of extrapulmonary infections and manifestations related to the ongoing COVID-19 pandemic. Coronaviruses are potentially neurotropic, which renders neuronal tissue vulnerable to infection, especially in elderly individuals or in those with neuro-comorbid conditions. Complaints of ageusia, anosmia, myalgia, and headache; reports of diseases such as stroke, encephalopathy, seizure, and encephalitis; and loss of consciousness in patients with COVID-19 confirm the neuropathophysiological aspect of this disease. The brain is linked to pulmonary organs, physiologically through blood circulation, and functionally through the nervous system. The interdependence of these vital organs may further aggravate the pathophysiological aspects of COVID-19. The induction of a cytokine storm in systemic circulation can trigger a neuroinflammatory cascade, which can subsequently compromise the blood-brain barrier and activate microglia- and astrocyte-borne Toll-like receptors, thereby leading to neuronal tissue damage. Hence, a holistic approach should be adopted by healthcare professionals while treating COVID-19 patients with a history of neurodegenerative disorders, neuropsychological complications, or any other neuro-compromised conditions. Imperatively, vaccines are being developed at top priority to contain the spread of the severe acute respiratory syndrome coronavirus 2, and different vaccines are at different stages of development globally. This review discusses the concerns regarding the neuronal complications of COVID-19 and the possible mechanisms of amelioration.

The novel coronavirus disease (COVID-19) a global pandemic outbreak is an emerging new virus accountable for respiratory illness caused by SARS-CoV-2, originated in Wuhan city, Hubei province China, urgently calls to adopt prevention and intervention strategies. Several viral epidemics such as severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 to 2003 and H1N1 influenza in 2009 were reported since last two decades. Moreover, the Saudi Arabia was the epicenter for Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012. The CoVs are large family with single-stranded RNA viruses (+ssRNA). Genome sequence of 2019-nCoV, shows relatively different homology from other coronavirus subtypes, categorized in betacoronavirus and possibly found from strain of bats. The COVID-19 composed of exposed densely glycosylated spike protein (S) determines virus binding and infiltrate into host cells as well as initiate protective host immune response. Recently published reviews on the emerging SARS-CoV-2 have mainly focused on its structure, development of the outbreak, relevant precautions and management trials. Currently, there is an urgency of pharmacological intervention to combat this deadly infectious disease. Elucidation of molecular mechanism of COVID-19 becomes necessary. Based on the current literature and understanding , the aim of this review is to provide current genome structure, etiology, clinical prognosis as well as to explore the viral receptor binding together functional insight of SARS-CoV-2 infection (COVID-19) with treatment and preventive measures.

Background and Aim: In much scientific research, it has been found that antagonistic activity is one of the important properties of a probiotic bacterium to attach in the intestine to reduce attachment of pathogenic bacteria in the intestine. Lactobacillus sp., isolated from fermented dairy products, shows a positive impact on human health. This study was designed to study Lactobacillus sp. isolated from fermented dairy products for their antagonistic activity and probiotic potential. Methods: In this study, we used the Lactobacilli strain isolated from yogurt samples by a dilution plating method and were screened for their antagonistic activities and potential probiotics. The isolates were tested for their growth in the presence of 0.3% bile salt and pH 2.0 and 3.0. Results: Out of the 52 strains, 30 strains (60%) had survival rates above 90% after 2 h of incubation at pH values of 2.0 or 3.0. Further screening was performed for their growth at 0.3% bile salt. From 30 strains, only ten strains showed tolerance to 0.3% bile salt. Two 2 Lactobacilli strains exhibited antagonistic activity. Moreover, all eight strains were found suitable for the potential probiotic activity, included Lactobacillus casei MU01, MU02, Lactobacillus reuteri MU 113, Bifidobacterium lactis MU85, Lactobacillus salivarius MU18, MU31, Lactobacillus plantarum MU211 3032, and Lactobacillus buchneri MU37. Conclusions: This study suggests that eight strains showed good antagonistic activity and probiotic potential, which can be used as supplements for good human health.

Both in malignant and non-malignant disorders stem cell based therapies are increasingly being utilized with promising results. hematopoietic reconstitution comprises mainly of 3 types of cells bone marrow (BM), peripheral blood (PB), and umbilical cord blood (UCB). The readily available and abundant resource of stem cell is umbilical cord blood. However, the typical single UCB unit could fetch relatively low numbers of hematopoietic stem- and progenitor cells (HSPCs) and the associated delay in procuring them restrict its routine applicability. In the past decade, the clinical applications of UCBbased cell therapies have broadened with a growing number of diseases treated with hematopoietic stem cell (HSC) transplantation. The assessment of UCB unit hematopoietic stem cells (HSCs), such as CD34+ cells or CFUs (Colony forming units), may provide a more direct estimate of the hematopoietic potential of the unit than the TNC count. As interlaboratory standardization of these assays has been achieved, the selection of UCB units for banking based on quantitation of hematopoietic progenitors is currently not feasible. However, CFU assays provide the only reliable assessment of the viability of the CB unit, although great efforts have been made to develop flow cytometry methods for viability staining. Despite of extreme efforts to find strategies that would enable the ex vivo amplification of stem cells for transplantation globally, it has been proven difficult to culture the HSCs in the labs. Therefore, it is imperative to have clear understanding regarding integration of HSC self-renewal, proliferation, and differentiation, molecules participating in their regulation and clinical benefit after their modification. Attempts have been made to improve the quality of UCB units through e.g. standardization of bank procedures, of stem cell enumeration, and of the assessment of HPCs viability. Over 4000000 UCB units are currently available in international registries. However, a significant proportion of patients is still left without a suitable donor, necessitating further development of UCB banking process.

Objective: This study was undertaken to screen the epidemiology of hepatitis B virus (HBV) in ethnically distinct, tribal dominated and of lower socioeconomic status area. Methods: Briefly, 3 ml blood was collected from 50 random liver disease cases with jaundice, receiving care at Central Hospital, N.F. Railway, Guwahati, and Guwahati Medical College, with informed consent. The patients detected with hepatitis A virus (HAV)-immunoglobulin M positive status were included and were stratified as acute viral hepatitis and fulminant hepatitis failure based on the clinical profile. HAV genotyping was studied by polymerase chain reaction-direct sequencing-phylogenetic analysis approach. Statistical analysis was performed using SPSS 13.0 software. Result: A total of 50 cases were HBV infected. HBV infection was predominant in the young and adult age group. HBV-RNA was detected in 19 cases. Conclusion: This study shows that HBV genotype D is most commonly found hepatitis in all tribes of Assam and poor sanitation and alcohol consumption are a common reason for its widespread. Keywords: Genotype, Hepatitis B virus, Liver disease, Molecular epidemiology, Phylogenetic study.