Exploring the medicinally important secondary metabolites landscape through the lens of transcriptome data in fenugreek (Trigonella foenum graecum L.).

Fenugreek (Trigonella foenum-graecum L.) is a self-pollinated leguminous crop belonging to the Fabaceae family. It is a multipurpose crop used as herb, spice, vegetable and forage. It is a traditional medicinal plant in India attributed with several nutritional and medicinal properties including antidiabetic and anticancer. We have performed a combined transcriptome assembly from RNA sequencing data derived from leaf, stem and root tissues. Around 209,831 transcripts were deciphered from the assembly of 92% completeness and an N50 of 1382 bases. Whilst secondary metabolites of medicinal value, such as trigonelline, diosgenin, 4-hydroxyisoleucine and quercetin, are distributed in several tissues, we report transcripts that bear sequence signatures of enzymes involved in the biosynthesis of such metabolites and are highly expressed in leaves, stem and roots. One of the antidiabetic alkaloid, trigonelline and its biosynthesising enzyme, is highly abundant in leaves. These findings are of value to nutritional and the pharmaceutical industry.

Incidence and severity of COVID-19 infection post-vaccination: a survey among Indian doctors.

PURPOSE: The rollout of COVID-19 vaccines began in India in January 2021, with healthcare professionals being the first to receive vaccination. The purpose of this research was to study the incidence and severity of COVID-19 infections among Indian doctors, following vaccination with ChAdOx1 nCoV-19 or BBV152. METHODS: We conducted an online voluntary survey among Indian doctors who received one or two doses of ChAdOx1 nCoV-19 or BBV152. Questions pertaining to the incidence and severity of COVID-19 infection following vaccination were asked. Data thus obtained were analysed. RESULTS: 9146 doctors were included in this study. 8301 of these received ChAdOx1 nCoV-19, while 845 received BBV152. 2842 (31.07%) respondents reported having a COVID-19 infection following vaccination. Presence of pre-existing medical comorbidities was associated with a higher incidence, while prior COVID-19 infection and two doses of either vaccine were associated with a lower incidence of COVID-19 infection post-vaccination. Exposure to COVID-19 patients on a daily basis did not increase the incidence of COVID-19 infection among doctors who were vaccinated. Increasing age, male gender, presence of pre-existing medical comorbidities, and daily exposure to COVID-19 patients were associated with increased severity of COVID-19 infection after vaccination. Two doses of either vaccine resulted in less severity of disease compared to one dose. CONCLUSION: ChAdOx1 nCoV-19 and BBV152 confer immunity against severe forms of COVID-19 infections. COVID-19 infections prior to vaccination result in a lower incidence of breakthrough infection. Presence of pre-existing medical comorbidities is associated with increased incidence and severity of breakthrough infections.

Development and Evaluation of Clove and Cinnamon Supercritical Fluid Extracts-Loaded Emulgel for Antifungal Activity in Denture Stomatitis.

Denture stomatitis (DS), usually caused by Candida infection, is one of the common denture-related complications in patients wearing dentures. Clove and cinnamon oils have been acknowledged for their anti-inflammatory, antimicrobial activity, and antifungal effects in the oral cavity. The aim of this study, therefore, was to prepare clove/cinnamon oils-loaded emulgel and to assess its efficacy in treating Candida albicans-associated denture stomatitis. Central composite design was adopted to formulate and optimize clove/cinnamon extracts-loaded emulgel. The formulated preparations were assessed for their physical appearance, particle size, viscosity, spreadability, and in-vitro drug release. In addition, in-vivo therapeutic experiments were conducted on 42 patients with denture stomatitis. The prepared emulgel formulations showed good physical characteristics with efficient drug release within 3 h. In addition, in-vivo antifungal studies revealed that the optimized formula significantly (p < 0.001) reduced Candida colony counts from the denture surface, compared to commercially available gel (240.38 ± 27.20 vs. 398.19 ± 66.73 CFU/mL, respectively). Furthermore, the optimized formula and succeeded in alleviating denture stomatitis-related inflammation with a better clinical cure rate compared to commercially available gel Collectively, herbal extracts-loaded emulgel might be considered an evolution of polyherbal formulations and might represent a promising alternative to the existing allopathic drugs for the treatment of denture stomatitis, with better taste acceptability and no side effects.

Immune profile and responses of a novel dengue DNA vaccine encoding an EDIII-NS1 consensus design based on Indo-African sequences.

The ongoing COVID-19 pandemic highlights the need to tackle viral variants, expand the number of antigens, and assess diverse delivery systems for vaccines against emerging viruses. In the present study, a DNA vaccine candidate was generated by combining in tandem envelope protein domain III (EDIII) of dengue virus serotypes 1-4 and a dengue virus (DENV)-2 non-structural protein 1 (NS1) protein-coding region. Each domain was designed as a serotype-specific consensus coding sequence derived from different genotypes based on the whole genome sequencing of clinical isolates in India and complemented with data from Africa. This sequence was further optimized for protein expression. In silico structural analysis of the EDIII consensus sequence revealed that epitopes are structurally conserved and immunogenic. The vaccination of mice with this construct induced pan-serotype neutralizing antibodies and antigen-specific T cell responses. Assaying intracellular interferon (IFN)-γ staining, immunoglobulin IgG2(a/c)/IgG1 ratios, and immune gene profiling suggests a strong Th1-dominant immune response. Finally, the passive transfer of immune sera protected AG129 mice challenged with a virulent, non-mouse-adapted DENV-2 strain. Our findings collectively suggest an alternative strategy for dengue vaccine design by offering a novel vaccine candidate with a possible broad-spectrum protection and a successful clinical translation either as a stand alone or in a mix and match strategy.

GenDiS database update with improved approach and features to recognize homologous sequences of protein domain superfamilies.

Since proteins evolve by divergent evolution, proteins with distant homology to each other may or may not bear similar functions. Improved computational approaches are required to recognize distant homologues that are functionally similar. One of the methods of assigning function to sequences is to use profiles derived from sequences of known structure. We describe an update of the Genomic Distribution of protein structural domain Superfamilies (GenDiS) database, namely GenDiS+, which provides a projection of SCOP superfamily members on the sequence space (NR database, NCBI). The sequences are validated using structure-based sequence alignment profiles and domain and full-length sequence alignments. GenDiS+ is a `tour de force' for detecting homologues within around 160 000 taxonomic identifiers, starting from nearly 11 000 domains of known structure. Features, like full-sequence alignment and phylogeny, domain sequence alignment and phylogeny, list of associated structural and sequence domains with strength of interactions, links to databases like Pfam, UniProt and ModBase and list of sequences with a PDB structure, are provided.

Genome-wide survey of remote homologues for protein domain superfamilies of known structure reveals unequal distribution across structural classes.

Domains are the basic building blocks of proteins which can combine to give rise to different domain architectures. Annotation of domains in a sequence is the first step towards understanding the biological function. Since there are a limited number of folds and evolutionarily related proteins have a similar structure, function can be inferred through remote homology. Computational sequence searches were performed for remote homologues on genomes of around ∼160 000 different organisms, starting from nearly 11 000 superfamily queries of known structure. Case studies revealed that most of the associated domains are involved in the same biological process. Using all the proteins predicted to have at least one structural domain, a coverage of 61% of Pfam families was achieved which is higher than the existing methods (43.36% by SIFTS). Taxonomic analysis of the proteins revealed 493 superfamilies in all the major kingdoms of life and a few lateral gene transfers between viruses and cellular organisms. The distribution of remote homologues across different classes, folds and superfamilies was studied and reveals that sequences are unequally distributed across structural classes. Finally, domain architectures were computed for the homologues and these data were compiled for each superfamily and organism.

Antifungal response of oral-associated candidal reference strains (American Type Culture Collection) by supercritical fluid extract of nutmeg seeds for geriatric denture wearers: An in vitro screening study.

OBJECTIVES: Since time immemorial, plants have continued to play a predominant role in the maintenance of human health as sources of medicinal compounds. Several effective antifungal agents are available for oral Candida infections; the failure is not uncommon because isolates of Candida albicans may exhibit resistance to the drug during therapy. The present study aimed to identify an alternative, inexpensive, simple, and effective method of preventing and controlling the candidal infection. METHODOLOGY: All the procured and authenticated nutmeg seeds were dried in shade and cleaned by hand sorting. The crushed seeds were passed through mesh no. 40 individually. About 50 g of powdered nutmeg seeds was loaded in the supercritical fluid extractor unit using supercritical CO2 as extracting solvent in accordance with the methods of Nguyen et al. Supercritical fluid (SFE) extraction was done using CO2 gas without any cosolvents. RESULTS: The nutmeg extract displayed antifungal activity with the effective zone of inhibition ranging from 18.0 to 12.0 mm when compared with nystatin as positive control. CONCLUSION: This paper described the in vitro antibacterial activity, and phytochemical analysis of SFE extract of nutmeg (Myristica fragrans) evaluated against C. albicans (American Type Culture Collection 10231) through agar well diffusion method. SFE of nutmeg seeds can be used as an adjunct to conventional therapy for oral candidiasis.

Mucosal vaccines: a paradigm shift in the development of mucosal adjuvants and delivery vehicles.

Mucosal immune responses are the first-line defensive mechanisms against a variety of infections. Therefore, immunizations of mucosal surfaces from which majority of infectious agents make their entry, helps to protect the body against infections. Hence, vaccinization of mucosal surfaces by using mucosal vaccines provides the basis for generating protective immunity both in the mucosal and systemic immune compartments. Mucosal vaccines offer several advantages over parenteral immunization. For example, (i) ease of administration; (ii) non-invasiveness; (iii) high-patient compliance; and (iv) suitability for mass vaccination. Despite these benefits, to date, only very few mucosal vaccines have been developed using whole microorganisms and approved for use in humans. This is due to various challenges associated with the development of an effective mucosal vaccine that can work against a variety of infections, and various problems concerned with the safe delivery of developed vaccine. For instance, protein antigen alone is not just sufficient enough for the optimal delivery of antigen(s) mucosally. Hence, efforts have been made to develop better prophylactic and therapeutic vaccines for improved mucosal Th1 and Th2 immune responses using an efficient and safe immunostimulatory molecule and novel delivery carriers. Therefore, in this review, we have made an attempt to cover the recent advancements in the development of adjuvants and delivery carriers for safe and effective mucosal vaccine production.

Management of medical records: facts and figures for surgeons.

Medical records are the document that explains all detail about the patient's history, clinical findings, diagnostic test results, pre and postoperative care, patient's progress and medication. If written correctly, notes will support the doctor about the correctness of treatment. Inspite of knowing the importance of proper record keeping in India, it is still in the initial stages. Medical records are the one of the most important aspect on which practically almost every medico-legal battle is won or lost. This article discusses the various aspect of record maintenance.

Priming stimulation enhances the depressant effect of low-frequency repetitive transcranial magnetic stimulation.

Low-frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) can depress the excitability of the cortex locally and has been proposed for the treatment of disorders such as schizophrenia and epilepsy. Some have speculated that the depressant effect is related to long-term depression (LTD) of cortical synapses. Because in vitro LTD can be enhanced by pretreatment of synapses with higher-frequency stimulation, we hypothesized that if rTMS depression had mechanisms in common with LTD, higher-frequency priming would increase it also. In 25 healthy volunteers in two experiments, we measured motor-evoked potentials (MEPs) from TMS of the motor cortex to define the baseline response. Subthreshold rTMS (6 Hz, fixed rate or frequency modulated) was used to prime the motor cortex, followed by suprathreshold 1 Hz stimulation for 10 min at just above the MEP threshold. Over the next 60 min, we recorded MEPs every 10 sec and found significant increases in the amount of cortical depression with both types of 6 Hz priming rTMS relative to sham. The MEP depression from 6 Hz-primed 1 Hz rTMS showed no evidence of decay after 60 min. Pretreatment with 6 Hz primes both 1 Hz rTMS depression and LTD. Although not conclusive evidence, this strengthens the case for overlapping mechanisms and suggests a potent new technique for enhancing low-frequency rTMS depression that may have experimental and clinical applications.