PlantAFP: a curated database of plant-origin antifungal peptides.

Emerging infectious diseases (EIDs) are a severe problem caused by fungi in human and plant species across the world. They pose a worldwide threat to food security as well as human health. Fungal infections are increasing now day by day worldwide, and the current antimycotic drugs are not effective due to the emergence of resistant strains. Therefore, it is an urgent need for the finding of new plant-origin antifungal peptides (PhytoAFPs). Huge numbers of peptides were extracted from different plant species which play a protective role against fungal infection. Hundreds of plant-origin peptides with antifungal activity have already been reported. So there is a requirement of a dedicated platform which systematically catalogs plant-origin peptides along with their antifungal properties. PlantAFP database is a resource of experimentally verified plant-origin antifungal peptides, collected from research articles, patents, and public databases. The current release of PlantAFP database contains 2585 peptide entries among which 510 are unique peptides. Each entry provides comprehensive information of a peptide that includes its peptide sequence, peptide name, peptide class, length of the peptide, molecular mass, antifungal activity, and origin of peptides. Besides this primary information, PlantAFP stores peptide sequences in SMILES format. In order to facilitate the user, many tools have been integrated into this database that includes BLAST search, peptide search, SMILES search, and peptide-mapping is also included in the database. PlantAFP database is accessible at http://bioinformatics.cimap.res.in/sharma/PlantAFP/.

A novel synthesis of 2-arylbenzimidazoles in molecular sieves-MeOH system and their antitubercular activity.

Arylbenzimidazoles have been synthesized as antimycobacterial agents. An efficient synthesis has been developed for 2-arylbenzimidazoles from o-phenylenediamines and aromatic aldehydes in molecular sieves-methanol system. The methodology is straightforward to get 2-arylbenzimidazoles (3a-3z) in excellent yields with high chemoselectivity over 2-aryl-1-benzylbenzimidazoles (4a-4z). All these benzimidazole analogues were evaluated against M. tuberculosis in BACTEC radiometric assay. The compounds 4y and 4z exhibited potential antitubercular activity against M. tuberculosis H37RV, MIC at 16 µM and 24 µM respectively. The best compound of the series i.e. compound 4y was well tolerated by Swiss-albino mice in acute oral toxicity. Compound 4y possessing a diarylbenzimidazole core, can further be optimized for better activity.

The Difficult Neck in Facelifting.

As the popularity and acceptance of facial and cervical rejuvenation procedures grows, surgeons are increasingly encountering patients with less favorable anatomical characteristics for rhytidectomy. These patients will typically display an obtuse cervicomental angle, underprojected chin, excess cervical adiposity, and platysmal banding, in addition to ptotic submandibular glands, tenacious jowls, and prejowl volume deficits. Recognition of these problems and the correct application of available techniques to address the difficult neck in facelifting are critical in maximizing success.

Virtual screening, ADMET profiling, molecular docking and dynamics approaches to search for potent selective natural molecules based inhibitors against metallothionein-III to study Alzheimer's disease.

MOTIVATION: Metallothionein-III (MT-III) displays neuro-inhibitory activity and is involved in the repair of neuronal damage. An altered expression level of MT-III suggests that it could be a mitigating factor in Alzheimer's disease (AD) neuronal dysfunction. Currently there are limited marketed drugs available against MT-III. The inhibitors are mostly pseudo-peptide based with limited ADMET. In our present study, available database InterBioScreen (natural compounds) was screened out for MT-III. Pharmacodynamics and pharmacokinetic studies were performed. Molecular docking and simulations of top hit molecules were performed to study complex stability. RESULTS: Study reveals potent selective molecules that interact and form hydrogen bonds with amino acids Ser-6 and Lys-22 are common to established melatonin inhibitors for MT-III. These include DMHMIO, MCA B and s27533 derivatives. The ADMET profiling was better with comparable interaction energy values. It includes properties like blood brain barrier, hepatotoxicity, druggability, mutagenicity and carcinogenicity. Molecular dynamics studies were performed to validate our findings.

Gallic acid-based indanone derivative interacts synergistically with tetracycline by inhibiting efflux pump in multidrug resistant E. coli.

The purpose of the present study was to study the synergy potential of gallic acid-based derivatives in combination with conventional antibiotics using multidrug resistant cultures of Escherichia coli. Gallic acid-based derivatives significantly reduced the MIC of tetracycline against multidrug resistant clinical isolate of E. coli. The best representative, 3-(3',4,'5'-trimethoxyphenyl)-4,5,6-trimethoxyindanone-1, an indanone derivative of gallic acid, was observed to inhibit ethidium bromide efflux and ATPase which was also supported by in silico docking. This derivative extended the post-antibiotic effect and decreased the mutation prevention concentration of tetracycline. This derivative in combination with TET was able to reduce the concentration of TNFα up to 18-fold in Swiss albino mice. This derivative was nontoxic and well tolerated up to 300 mg/kg dose in subacute oral toxicity study in mice. This is the first report of gallic acid-based indanone derivative as drug resistance reversal agent acting through ATP-dependent efflux pump inhibition.

In silico investigation of cholesterol-lowering drugs to find potential inhibitors of dehydrosqualene synthase in Staphylococcus aureus.

Staphylococcus aureus is a lethal pathogen that can cause various bacterial infections. This study targets the CrtM enzyme of S. aureus, which is crucial for synthesizing golden carotenoid pigment: staphyloxanthin, which provides anti-oxidant activity to this bacterium for combating antimicrobial resistance inside the host cell. The present investigation quests for human SQS inhibitors against the CrtM enzyme by employing structure-based drug design approaches including induced fit docking (IFD), molecular dynamic (MD) simulations, and binding free energy calculations. Depending upon the docking scores, two compounds, lapaquistat acetate and squalestatin analog 20, were identified as the lead molecules exhibit higher affinity toward the CrtM enzyme. These docked complexes were further subjected to 100 ns MD simulation and several thermodynamics parameters were analyzed. Further, the binding free energies (ΔG) were calculated for each simulated protein-ligand complex to study the stability of molecular contacts using the MM-GBSA approach. Pre-ADMET analysis was conducted for systematic evaluation of physicochemical and medicinal chemistry properties of these compounds. The above study suggested that lapaquistat acetate and squalestatin analog 20 can be selected as potential lead candidates with promising binding affinity for the S. aureus CrtM enzyme. This study might provide insights into the discovery of potential drug candidates for S. aureus with a high therapeutic index. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03862-y.

Cationic starch: A functionalized polysaccharide based polymer for advancement of drug delivery and health care system - A review.

Research and development in health care industry is in persistence progression. To make it more patient-friendly or to get maximum benefits from it, special attention to different advanced drug delivery system (ADDS) is employed that delivers the drug at the target site and will be able to sustain/control release of drugs. ADDS should be non-toxic, biodegradable, biocompatible along with desirable showing physicochemical and functional properties. These drug delivery systems can be totally based on polymers, either with natural or synthetic polymers. The molecular weight of polymer can be tuned and different groups of polymers can be modified or substituted with other functional groups. Degree of substitution is also tailored. Cationic starch in recent years is exploited in drug delivery, tissue engineering and biomedicine. Due to their abundant availability, low cost, easy chemical modification, low toxicity, biodegradability and biocompatibility, extensive research is now being carried out. Our present discussion will shed light on the usage of cationic starch in health care system.

CLICK-chemoproteomics and molecular dynamics simulation reveals pregnenolone targets and their binding conformations in Th2 cells.

Pregnenolone (P5) is synthesized as the first bioactive steroid in the mitochondria from cholesterol. Clusters of differentiation 4 (CD4+) and Clusters of differentiation 8 (CD8+) immune cells synthesize P5 de novo; P5, in turn, play important role in immune homeostasis and regulation. However, P5's biochemical mode of action in immune cells is still emerging. We envisage that revealing the complete spectrum of P5 target proteins in immune cells would have multifold applications, not only in basic understanding of steroids biochemistry in immune cells but also in developing new therapeutic applications. We employed a CLICK-enabled probe to capture P5-binding proteins in live T helper cell type 2 (Th2) cells. Subsequently, using high-throughput quantitative proteomics, we identified the P5 interactome in CD4+ Th2 cells. Our study revealed P5's mode of action in CD4+ immune cells. We identified novel proteins from mitochondrial and endoplasmic reticulum membranes to be the primary mediators of P5's biochemistry in CD4+ and to concur with our earlier finding in CD8+ immune cells. Applying advanced computational algorithms and molecular simulations, we were able to generate near-native maps of P5-protein key molecular interactions. We showed bonds and interactions between key amino acids and P5, which revealed the importance of ionic bond, hydrophobic interactions, and water channels. We point out that our results can lead to designing of novel molecular therapeutics strategies.

In silico screening and molecular dynamics of phytochemicals from Indian cuisine against SARS-CoV-2 MPro.

SARS-CoV-2 cause fatal infection in 213 countries accounting for the death of millions of people globally. In the present study, phytochemicals from spices were assessed for their ability to interact with SARS-CoV-2 MPro. Structure based virtual screening was performed with 146 phytochemicals from spices using Autodock Vina. Phytochemicals with binding energy ≥ -8.0 kcal/mol were selected to understand their interaction with MPro. Virtual screening was further validated by performing molecular docking to generate favorable docked poses and the participation of important amino acid residues. Molecular dynamics simulation for the docked poses was performed to study thermodynamic properties of the protein, ligand and protein-ligand complexes. The finding shows that cinnamtannin B2 and cyanin showed favorable binding affinity values with SARS-CoV-2 MPro. The results are comparable in terms of docked poses, important amino acid participation and thermodynamic properties with the standard control drugs remdesivir, benazepril and hydroxychloroquine diphosphate. Prime MM-GBSA was employed for end-point binding energy calculation. Binding to domain I and II of MPro were mediated through the OH, SH, NH2 and non-polar side chain of amino acids. Cinnamtannin B2 and cyanin binds to MPro with many sub sites within the active site with RMSD and RMSF within 4 Å. The results computed using Prime MM-GBSA show that cinnamtannin B2 (-68.54940214 kcal/mol) and cyanin (-62.1902835 kcal/mol) have better binding affinity in comparison to hydroxychloroquine diphosphate (-54.00912412 kcal/mol) and benazepril (-53.70242369 kcal/mol). The results provide a basis for exploiting cinnamtannin B2 and cyanin as a starting point potential candidate for the development of drug against SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

PhytoAFP: In Silico Approaches for Designing Plant-Derived Antifungal Peptides.

Emerging infectious diseases (EID) are serious problems caused by fungi in humans and plant species. They are a severe threat to food security worldwide. In our current work, we have developed a support vector machine (SVM)-based model that attempts to design and predict therapeutic plant-derived antifungal peptides (PhytoAFP). The residue composition analysis shows the preference of C, G, K, R, and S amino acids. Position preference analysis shows that residues G, K, R, and A dominate the N-terminal. Similarly, residues N, S, C, and G prefer the C-terminal. Motif analysis reveals the presence of motifs like NYVF, NYVFP, YVFP, NYVFPA, and VFPA. We have developed two models using various input functions such as mono-, di-, and tripeptide composition, as well as binary, hybrid, and physiochemical properties, based on methods that are applied to the main data set. The TPC-based monopeptide composition model achieved more accuracy, 94.4%, with a Matthews correlation coefficient (MCC) of 0.89. Correspondingly, the second-best model based on dipeptides achieved an accuracy of 94.28% under the MCC 0.89 of the training dataset.

Development and Characterization of Natural Product Derived Macromolecules Based Interpenetrating Polymer Network for Therapeutic Drug Targeting.

Interpenetrating polymer network (IPN)-based bead formulations were exploited by cross-linking different hydrophilic polymers in different combinations and at different ratios. Polyvinyl alcohol, xanthan gum, guar gum, gellan gum, and sodium alginate (Na-alginate) were used in this work as hydrophilic polymers to enhance the solubility of diclofenac sodium and also to target the delivery at preferred locations. IPN beads based on polysaccharides were prepared by the ionic gelation method. Differential scanning calorimetry, powder X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy data showed that the IPN microbeads solubilized and encapsulated the drug within the network. We found over 83% encapsulation efficiency of the drug delivery system for the drug, and this efficiency increased with the concentration of the polymer. Ex vivo experiments using the goat intestine revealed that the IPN microbeads were able to adhere to the intestinal epithelium, a mucoadhesive behavior that could be beneficial to the drug pharmacokinetics, while in vitro experiments in phosphate buffer showed that the IPN enabled significant drug release. We believe that these IPN microbeads are an excellent drug delivery system to solubilize drug molecules and ensure adhesion to the intestinal wall, thereby localizing the drug release to enhance bioavailability of poorly soluble drugs.

Physicochemical Characterization, Molecular Docking, and In Vitro Dissolution of Glimepiride-Captisol Inclusion Complexes.

This present study investigated the effect of Captisol, a chemically modified cyclodextrin, on the in vitro dissolution of glimepiride. We prepared glimepiride-Captisol complexes of different mass ratios (1:1, 1:2, and 1:3 w/w) by a physical mixing or freeze-drying technique, and found that complexation with Captisol enhanced the water solubility of glimepiride. Molecular docking and dynamic simulation predicted complex formation; at the same time, Fourier transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffractometry, and scanning electron microscope indicated molecular interactions that support complexation. We also found that an inclusion complex was better than a physical mixture in enhancing the complexation of glimepiride with Captisol and enhancing water solubility. Phase solubility study of the glimepiride-Captisol complex showed an AL-type profile, implying the formation of a 1:1 inclusion complex. The study also revealed that pH influenced the stability of the complex because the stability constant of the glimepiride-Captisol complex was higher in distilled water of pH ∼6.0 than in phosphate buffer of pH 7.2.

Comparison of W-Plasty and Straight-Line Trichophytic Closure on Aesthetic Outcomes of Occipital Hairline Scars in Rhytidectomy.

IMPORTANCE: Incision placement and design in rhytidectomy is critical for patient satisfaction. OBJECTIVE: To evaluate the aesthetic outcome of W-plasty vs traditional straight-line (SL) trichophytic closure techniques on posterior occipital hairline scars in rhytidectomy. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted at the Buckingham Center for Facial Plastic Surgery. Clinical history and operative reports were reviewed for 46 patients who underwent rhytidectomy (23 using W-plasty and 23 using SL technique) between June 1, 2014 and August 31, 2015. Blinded photographic analysis of 1-year postoperative photographs was performed. INTERVENTIONS: The posterior occipital hairline incision was primarily closed with either a W-plasty or SL trichophytic technique. MAIN OUTCOMES AND MEASURES: Standard photographs of the posterior occipital incision site obtained after the 1-year postoperative mark were reviewed and scored in a blinded fashion by 3 nonphysician medical staff members using a modified Manchester Scar Scale (MSS: from 0 [best possible outcome] to 24 [worst possible outcome]). Interrater reliability was assessed via Cronbach α testing. RESULTS: There were 23 patients in each group. The W-plasty and SL groups were similar in terms of age (mean [SD] age, 59.6 [6.3] years and 64.1 [7.3] years, respectively), sex (21 [91%] and 21 [91%] women, respectively), race-ethnicity, and absence of risk factors (smoking and diabetes) predisposing to poor wound healing (0 and 0 smoking/diabetes, respectively). Mean (SD) follow-up times for the W-plasty and SL groups were 388 (38.8) and 475 (100.1) days, respectively. No statistical difference was demonstrated in the mean aggregate MSS scores from all evaluators between the W-plasty group and the SL group (reviewer 1: 5.69 vs 5.86, P = .60; reviewer 2: 10.09 vs 9.56, P = .65; and reviewer 3: 5.30 vs 6.17, P = .08). Overall interrater reliability for the MSS scores was 0.56. CONCLUSION AND RELEVANCE: Primary W-plasty and SL trichophytic closures in the posterior occipital hairline appear to yield highly acceptable and similar cosmetic outcomes under objective blinded evaluation. These techniques can be used with success to help minimize conspicuous scarring after rhytidectomy. LEVEL OF EVIDENCE: 3.

Novel Use of a Volumizing Hyaluronic Acid Filler for Treatment of Infraorbital Hollows.

IMPORTANCE: Hyaluronic acid filler can be safely used as a soft-tissue filler for correction of infraorbital hollowing. It has a high overall patient satisfaction profile among patients. OBJECTIVE: To report safety and patient satisfaction outcomes of Juvéderm Voluma XC for correction of infraorbital hollows. DESIGN, SETTING, AND PATIENTS: This was a retrospective observational study performed at a private ambulatory facial plastic and reconstructive surgery practice. Participants were all patients 21 to 85 years old who presented to our practice and underwent Juvéderm Voluma XC treatment for correction of infraorbital hollows as a singular intervention from February 2016 to March 2017. INTERVENTIONS: Injection of Juvéderm Voluma XC to the tear trough, nasojugal fold, and/or palpebromalar groove. MAIN OUTCOMES AND MEASURES: Primary outcome measures include the number of recorded short- and long-term adverse events, need for additional treatment, and patient questionnaire FACE-Q scores. RESULTS: A total of 202 eyes were treated in 101 patients with a mean follow-up of 12 months. Patients were principally female (90 [89%]) with an average age of 54 years (range, 21-85 years). Most patients (99) had Fitzpatrick grade 1 to 4 skin type (98%) and had an infraorbital hollows score of 2 to 4 (89 [88%]). The average initial treatment volume was 1 mL with 18 patients (18%) requiring additional treatment within 3 months. The average time until additional treatment was 35.7 days. Adverse effects include bruising (in 10 [10%], contour irregularities (2 [2%]), swelling (3 [3%]), and Tyndall effect (1 [1%]). Hyaluronidase was required in 3 patients (3%). Forty-one patients completed the FACE-Q Satisfaction With Eyes survey, and 42 patients completed the FACE-Q Satisfaction With Decision survey (41% and 42%). Overall mean (SD) patient satisfaction (based on FACE-Q scores) was 71.1% (27.3) and 65.6% (31.3), respectively. CONCLUSIONS AND RELEVANCE: Juvéderm Voluma XC has a high patient satisfaction profile and an acceptable safety profile for the correction of infraorbital hollowing. LEVEL OF EVIDENCE: 4.

Electrospinning over Solvent Casting: Tuning of Mechanical Properties of Membranes.

We put forth our opinion regarding the enhanced plasticity and modulation of mechanical properties of polymeric films obtained through electrospinning process in this article. In majority of the pharmaceutical, biomedical, and packaging applications, it is desirable that polymer based matrices should be soft, flexible, and have a moderate toughness. In order to convert inflexible and brittle polymers, adjuvants in the form of plasticizers are added to improve the flexibility and smoothness of solvent casted polymer films. However, many of these plasticizers are under scrutiny for their toxic effects and environmental hazards. In addition, plasticizers also increase the cost of end products. This has motivated the scientific community to investigate alternate approaches. The changes imparted in membrane casted by electrospinning were tried to be proved by SEM, Mechanical property study, DSC and XRD studies. We have showed dramatic improvement in flexibility of poly(ε-caprolactone) based nanofiber matrix prepared by electrospinning method whereas solvent casting method without any plasticizer produced very brittle, inflexible film of PCL. Modulation capacity of mechanical properties is also recorded. We tried to support our opinion by citing several similar findings available in the open literature. The electrospinning method helps in plasticization and in tuning mechanical properties.

The effect of Benzothiazolone-2 on the expression of Metallothionein-3 in modulating Alzheimer's disease.

INTRODUCTION: Metallothioneins (MTs) are a class of ubiquitously occurring low-molecular-weight cysteine- and metal-rich proteins containing sulfur-based metal clusters. MT-3 exhibits neuro-inhibitory activity. The possibility to enhance the expression of MT-3 or protect it from degradation is an attractive therapeutic target, because low levels of MT-3 were found in brains of Alzheimer's disease (AD) patients. OBJECTIVES: The primary objective of this study was to test an enhancement of MT-3 cellular concentration after MT-3 binding treatment, which could prevent MT-3 degradation. METHODS: MTT assay, flow-cytometry, fluorescence microscopy, quantitative real-time polymerase chain reaction, and immunodetection of MT3 were used for analysis of effect of STOCK1N-26544, STOCK1N-26929, and STOCK1N-72593 on immortalized human microglia-SV40 cell line. RESULTS: All three tested compounds enhanced concentration of MT-3 protein in cells and surprisingly also mRNA concentration. IC50 values of tested molecules exceeded about ten times the concentration that was needed for induction of MT-3 expression. The tested compound Benzothiazolone-2 enhanced apoptosis and necrosis, but it was not of severe effect. About 80% of cells were still viable. There was no serious ROS-generation and no severe decrease in mitochondria numbers or stress induced endoplasmic reticulum changes after test treatments. The selected compound showed stable hydrophobic and electrostatic interaction during MT-3 ligand interaction. CONCLUSION: Benzothiazolone-2 compounds significantly enhanced MT-3 protein and mRNA levels. The compounds can be looked upon as one of the probable lead compounds for future drug designing experiments in the treatment of Alzheimer's disease.

Biochemical Effects of Exercise on a Fasciocutaneous Flap in a Rat Model.

IMPORTANCE: An overwhelming amount of data suggest that cardiovascular exercise has a positive effect on the mind and body, although the precise mechanism is not always clear. OBJECTIVE: To assess the clinical and biochemical effects of voluntary cardiovascular exercise on pedicled flaps in a rodent model. DESIGN, SETTING, AND PARTICIPANTS: Eighteen adult Sprague-Dawley male rats were randomized into a resting animal group (RAG) (n=9) and an exercise animal group (EAG) (n=9) for 14 days (July 23, 2013, through July 30, 2013). A pedicled transposition flap was performed on the ventral surface of the rat, and biopsy specimens were taken from the proximal, middle, and distal portions on postoperative days 0, 2, 5, and 9. Flap survival was analyzed planimetrically, and biopsy specimens were analyzed by hematoxylin-eosin-stained microscopy and immunoblotting. The housing, exercise, surgery, and analysis of the rats were conducted at a single basic science research laboratory at the tertiary care center campus of Thomas Jefferson University in Philadelphia, Pennsylvania. EXPOSURES: The rats were caged for 14 days or housed in a cage connected to an exercise wheel and pedometer. MAIN OUTCOMES AND MEASURES: Study measures were gross and micrographic necrosis and expression of proteins within cell survival and apoptosis pathways. RESULTS: A total of 18 rats were studied, 9 in the RAG and 9 in the EAG. the mean (SEM) amount of necrosis in flaps was 41.3% (3%) in the RAG rats and 10.5% (3.5%) in the EAG rats (P < .001). Immunoblotting revealed increased Caspase-9 activity resulting in poly-(adenosine diphosphate-ribose) polymerase 1 cleavage in the RAG vs the EAG, as well as lower phosphorylated protein kinase B (also known as Akt), signal transducer and activator of transcription 3, and total B-cell leukemia/lymphoma 2 protein levels. Throughout the postoperative period, the cumulative vascular endothelial growth factor A levels of the EAG flaps were significantly higher than those of the RAG flaps (2.30 vs 1.25 fold induction [FI], P = .002), with differences of 2.76 vs 1.54 FI in the proximal segment, 2.40 vs 1.20 FI in the middle segment, and 1.90 vs 0.79 FI in the distal segment. A similar response was noted when comparing phosphorylated Akt, with cumulative mean (SEM) p-Akt expression levels of 0.62 (0.04) for RAG and 1.98 (0.09) for EAG (P = .002 between the 2 groups). CONCLUSIONS AND RELEVANCE: Voluntary preoperative exercise improves survival in pedicled fasciocutaneous flaps; the EAG rats had less necrosis, decreased apoptotic markers, and increased amounts of vascular endothelial growth factor A and prosurvival proteins. These results have implications to increase flap survival in other mammal populations, such as humans. LEVEL OF EVIDENCE: 3.

Molecular docking based virtual screening of natural compounds as potential BACE1 inhibitors: 3D QSAR pharmacophore mapping and molecular dynamics analysis.

Beta-site APP cleaving enzyme1 (BACE1) catalyzes the rate determining step in the generation of Aß peptide and is widely considered as a potential therapeutic drug target for Alzheimer's disease (AD). Active site of BACE1 contains catalytic aspartic (Asp) dyad and flap. Asp dyad cleaves the substrate amyloid precursor protein with the help of flap. Currently, there are no marketed drugs available against BACE1 and existing inhibitors are mostly pseudopeptide or synthetic derivatives. There is a need to search for a potent inhibitor with natural scaffold interacting with flap and Asp dyad. This study screens the natural database InterBioScreen, followed by three-dimensional (3D) QSAR pharmacophore modeling, mapping, in silico ADME/T predictions to find the potential BACE1 inhibitors. Further, molecular dynamics of selected inhibitors were performed to observe the dynamic structure of protein after ligand binding. All conformations and the residues of binding region were stable but the flap adopted a closed conformation after binding with the ligand. Bond oligosaccharide interacted with the flap as well as catalytic dyad via hydrogen bond throughout the simulation. This led to stabilize the flap in closed conformation and restricted the entry of substrate. Carbohydrates have been earlier used in the treatment of AD because of their low toxicity, high efficiency, good biocompatibility, and easy permeability through the blood-brain barrier. Our finding will be helpful in identify the potential leads to design novel BACE1 inhibitors for AD therapy.

Antioxidant, Antimicrobial Activity and Medicinal Properties of Grewia asiatica L.

Since ancient time, India is a well known subcontinent for medicinal plants where diversity of plants is known for the treatment of many human disorders. Grewia asiatica is a dicot shrub belonging to the Grewioideae family and well known for its medicinally important fruit commonly called Falsa. G. asiatica, a seasonal summer plant is distributed in the forest of central India, south India, also available in northern plains and western Himalaya up to the height of 3000 ft. Fruits of G. asiatica are traditionally used as a cooling agent, refreshing drink, anti-inflammatory agent and for the treatment of some urological disorders. Recent advancement of Falsa researches concluded its antimicrobial and anti-diabetic activity. Since ancient time medicinal plants are traditionally used for the treatment of different diseases G. asiatica fruit is the edible and tasty part of the plant, now considered as a valuable source of unique natural product for the development of medicines which are used in different disease conditions like anti-diabetic, anti-inflammatory, anti-cancerous and antimicrobial. Now a days, G. asiatica is being used in different Ayurvedic formulation for the cure of different types of diseases. Different pharmacological investigations reveal the presence of phenols, saponnins, flavonoids and tannins compound in the fruits. Present review highlights the phytopharmacological and different traditional use of G. asiatica which is mentioned in ancient Ayurvedic texts. This review stimulates the researchers and scientists for further research on G. asiatica.

Envisaging the Regulation of Alkaloid Biosynthesis and Associated Growth Kinetics in Hairy Roots of Vinca minor Through the Function of Artificial Neural Network.

Artificial neural network based modeling is a generic approach to understand and correlate different complex parameters of biological systems for improving the desired output. In addition, some new inferences can also be predicted in a shorter time with less cost and labor. As terpenoid indole alkaloid pathway in Vinca minor is very less investigated or elucidated, a strategy of elicitation with hydroxylase and acetyltransferase along with incorporation of various precursors from primary shikimate and secoiridoid pools via simultaneous employment of cyclooxygenase inhibitor was performed in the hairy roots of V. minor. This led to the increment in biomass accumulation, total alkaloid concentration, and vincamine production in selected treatments. The resultant experimental values were correlated with algorithm approaches of artificial neural network that assisted in finding the yield of vincamine, alkaloids, and growth kinetics using number of elicits. The inputs were the hydroxylase/acetyltransferase elicitors and cyclooxygenase inhibitor along with various precursors from shikimate and secoiridoid pools and the outputs were growth index (GI), alkaloids, and vincamine. The approach incorporates two MATLAB codes; GRNN and FFBPNN. Growth kinetic studies revealed that shikimate and tryptophan supplementation triggers biomass accumulation (GI = 440.2 to 540.5); while maximum alkaloid (3.7 % dry wt.) and vincamine production (0.017 ± 0.001 % dry wt.) was obtained on supplementation of secologanin along with tryptophan, naproxen, hydrogen peroxide, and acetic anhydride. The study shows that experimental and predicted values strongly correlate each other. The correlation coefficient for growth index (GI), alkaloids, and vincamine was found to be 0.9997, 0.9980, 0.9511 in GRNN and 0.9725, 0.9444, 0.9422 in FFBPNN, respectively. GRNN provided greater similarity between the target and predicted dataset in comparison to FFBPNN. The findings can provide future insights to calculate growth index, alkaloids, and vincamine in combination to different elicits.