Nourishing the Cognition with Millets: A Comprehensive Review of Their Nutritional Impact and Potential as Cognitive Enhancers.

Cognition is the mental processes and abilities involved in acquiring, storing, retrieving and using it for decision making. Cognitive decline due to aging, lifestyle factor, chronic health conditions, genetic, and environmental factors are rising global concern and propose a potential threat to the cognitive health. The nutritional imbalance has led to increase in cognitive disorders around the world. Millets can be a nutritional intervention for promoting cognitive health and preventing cognitive decline. Millets has abundant phenolic compounds, flavonoids, and antioxidants to protect against oxidative stress-induced cognitive impairment. Millets exert neuroprotective effects by modulating pathways involved in neuronal-survival, synaptic-plasticity, and release of brain-derived neurotrophic factor. Millets demonstrates anti-inflammatory properties by regulating inflammatory-pathways and suppressing cytokines associated with cognitive impairment. Millets maintain healthy gut microbiota by producing metabolites such as short-chain fatty acids, which influence brain function and cognition. However, further research is needed to elucidate the underlying mechanisms and on optimizing the proportion do exploit its potential. Implementing millet-based dietary strategies through public health initiatives and educational programs can be a practical approach to support cognitive health across populations. Harnessing the potential of millets as a nutritional intervention offers a promising avenue for promoting cognitive health and improving the quality of life.

Exploring the mitochondrial genome of Caridina pseudogracilirostris: a comparative analysis within the Atyidae Family.

BACKGROUND: Caridina pseudogracilirostris is a highly adaptive estuarine species found in brackish waters and marshes along the southwestern and southern coastal regions of India. METHODS AND RESULTS: The whole mitochondrial genome of C. pseudogracilirostris is 15,451 bp in length with 59.3% AT content and encodes 37 genes, including 22 tRNAs, 13 protein-coding genes, and two rRNAs, which are arranged in a distinctive pattern similar to most crustaceans. ML and BI methods were used for phylogenetic analysis of C. pseudogracilirostris clustered with other Caridina species, supporting the monophyly of the Caridina genus within the Atyidae family. The fully annotated mitochondrial genome of C. pseudogracilirostris was submitted to GenBank under accession number OQ534868.1. CONCLUSIONS: We are the first to report on the C. pseudogracilirostris whole mitochondrial genome, which provides a valuable resource for future research on genetics, evolution, phylogenetics, etc., among Caridina species and other species. The phylogenetic investigation supports the monophyly of the Caridina genus within the Atyidae family and emphasizes the value of mitochondrial genome data in determining the evolutionary relationships among crustaceans.

In silico exploration of antioxidants as oxidation protectant for PITRM1 peptidase activity, an Alzheimer disease target.

To find efficient antioxidants to protect oxidation prone cysteine residues of the peptidase PITRM1 using molecular docking and simulation techniques. A total of 50 antioxidants were docked with PITRM1 at the oxidation prone region Cys89 and Cys96 using Autodock Vina software. The lowest socred compounds were predicted for its Blood brain barrier permeability using LightBBB. Molecular dynamic simulations of the PITRM1 and Ascorbic acid/Silymarin complex were performed using the GROMACS 2020.1 package and the free energy calculations were performed using gmx_MMPBSA. The RMSD, RMSF, Rg, Minimum distance and Hydrogen bonds were also evaluated. Silymarin, Ascorbic acid, Naringenin, Gallic acid, Chlorogenic acid, Rosmarinic acid, (-)-Epicatechin, Genistein showed a docking score of above -5.3 kcal/mol. Silymarin and Ascorbic acid were predicted to cross the Blood Brain Barrier. Molecular dynamic simulation and mmPBSA analysis revealed that Silymarin showed a positive free energy implying no affinity to PITRM1 and ascorbic acid has low ΔG with -13.13 kJ/mol. The stability of the ascorbic acid complex was high (RMSD: 0.160 ± 0.018 nm, Minimum Distance: 0.163 ± 0.001 nm and four hydrogen bonds) and fluctuation induced due to ascorbic acid was low. Ascorbic acid was found to effectively interact with the cysteine oxidation prone region and can have a potential role in reducing the oxidised cysteine in PITRM1 to modulate its peptidase activity.

Functionalized Sulfur-Containing Heterocyclic Analogs Induce Sub-G1 Arrest and Apoptotic Cell Death of Laryngeal Carcinoma In Vitro.

In this study, we speculate that the hydroxyl-containing benzo[b]thiophene analogs, 1-(3-hydroxybenzo[b]thiophen-2-yl) ethanone (BP) and 1-(3-hydroxybenzo[b]thiophen-2-yl) propan-1-one hydrate (EP), might possess antiproliferative activity against cancer cells. Hydroxyl-containing BP and EP show selectivity towards laryngeal cancer cells (HEp2), with IC50 values of 27.02 ± 1.23 and 35.26 ± 2.15 µM, respectively. The hydroxyl group present in the third position is responsible for the anticancer activity and is completely abrogated when the hydroxyl group is masked. BP and EP enhance the antioxidant enzyme activity and reduce the ROS production, which are correlated with the antiproliferative effect in HEp-2 cells. An increase in the BAX/BCL-2 ratio occurs during the BP and EP treatment and activates the caspase cascade, resulting in apoptosis stimulation. It also arrests the cells in the Sub-G1 phase, indicating the induction of apoptosis. The molecular docking and simulation studies predicted a strong interaction between BP and the CYP1A2 protein, which could aid in combinational therapy by enhancing the bioavailability of the drugs. BP and EP possess an antioxidant property with low antiproliferative effects (~5.18 µg/mL and ~7.8 µg/mL) as a standalone drug, therefore, they can be combined with other drugs for effective chemotherapy that might trigger the effect of pro-oxidant drug on healthy cells.

PITRM1 interaction studies with amyloidogenic nonapeptide mutants of familial Alzheimer's disease.

Amyloid ß-protein (ABP) is found to be the major cause for the development of neurodegeneration which leads to Alzheimer's. The Aß nonapeptide segment, QKLVFFAED (amino acids 15-23) is the highly amyloidogenic central region of Aß. Familial mutation in Aß increases the aggregation property of the peptide compared to the Native (Wild) amyloid-beta (Aß) and these mutations fall on the Aß nonapeptide segment. The catalytic activity of pitrilysin metallopeptidase 1(PITRM1) with familial mutant Aß (Flemish, Arctic, Dutch, Italian and Iowa) during interaction is examined using molecular dynamic simulation. The molecular dynamics simulation of PITRM1 and the Aß nonapeptide segment showed similar RMSD with respect to stability. The active site amino acid (AA) H108, hydrophobic pocket AA residues L111, F123, F124, and L127 and the basic pocket AA residues R888 and H896 showed similar interactions with both wild and familial Aß. The molecular level interaction between amyloid beta and PITRM1 were similar in the wild and familial mutants except for the Arctic mutant. The hydrophobic interaction was commonly observed between the S1 hydrophobic pocket and the LVFF region, the Arctic mutant showed less hydrogen bond formation consistently when compared to other complexes. This molecular information on catalytic activity suggests that modulating inactive PITRM1 or an increase in expression of PITRM1 can help in eliminating different kinds of familial mutant Aß in neurodegenerative cells.Communicated by Ramaswamy H. Sarma.

Diversity of Conopeptides and Conoenzymes from the Venom Duct of the Marine Cone Snail Conus bayani as Determined from Transcriptomic and Proteomic Analyses.

Marine cone snails are predatory gastropods characterized by a well-developed venom apparatus and highly evolved hunting strategies that utilize toxins to paralyze prey and defend against predators. The venom of each species of cone snail has a large number of pharmacologically active peptides known as conopeptides or conotoxins that are usually unique in each species. Nevertheless, venoms of only very few species have been characterized so far by transcriptomic approaches. In this study, we used transcriptome sequencing technologies and mass spectrometric methods to describe the diversity of venom components expressed by a worm-hunting species, Conus bayani. A total of 82 conotoxin sequences were retrieved from transcriptomic data that contain 54 validated conotoxin sequences clustered into 21 gene superfamilies including divergent gene family, 17 sequences clustered to 6 different conotoxin classes, and 11 conotoxins classified as unassigned gene family. Seven new conotoxin sequences showed unusual cysteine patterns. We were also able to identify 19 peptide sequences using mass spectrometry that completely overlapped with the conotoxin sequences obtained from transcriptome analysis. Importantly, herein we document the presence of 16 proteins that include five post-translational modifying enzymes obtained from transcriptomic data. Our results revealed diverse and novel conopeptides of an unexplored species that could be used extensively in biomedical research due to their therapeutic potentials.

Mass spectrometric identification and denovo sequencing of novel conotoxins from vermivorous cone snail (Conus inscriptus), and preliminary screening of its venom for biological activities in vitro and in vivo.

Venom of Conus inscriptus, a vermivorous cone snail found abundantly in the southern coastal waters was studied to yield conotoxins through proteomic analysis. A total of 37 conotoxins (4 with single disulfide bonds, 20 with two disulfide bonds and 11 three disulfide-bonded peptides) were identified using mass spectrometric analysis. Among them, amino acid sequences of 11 novel conopeptides with one, two and three disulfides belonging to different classes were derived through manual de novo sequencing. Based on the established primary sequence, they were pharmacologically classified into α conotoxins, µ conotoxins and contryphans. Except In1696 all other conopeptides have undergone C-terminal amidation. The natural venom exhibited 50% lethality at 304.82 µg/mL against zebrafish embryo and 130.31 µg/mL against brine shrimp nauplii. The anticonvulsant study of natural venom effectively reduced the locomotor activity against pentylenetetrazole (PTZ) treated zebrafish. This concludes that the venom peptides from Conus inscriptus exhibit potential anticonvulsant function, which leads to the discovery of lead molecules against seizures.

In silico approach on sequential and structural variability in oryzacystatin and its interaction with cysteine protease enzymes of insect.

Phytoprotease inhibitors (PI) are important defence compounds produced by plants against microbes and insect herbivory. Oryzacystatins (OCs) are a group of protease inhibitors from Oryza sativa L. that are specific against cysteine protease enzymes. This study revealed the evolutionary relationship of eleven different oryzacystatins from rice and their interaction with cysteine protease enzymes from brown planthopper (BPH) and striped stem borer (SSB). Three-dimensional structure of eleven different oryzacystatins and six cysteine protease enzymes were homologically modelled, and their interaction was analysed to explore the sequence heterogeneity, structural variability and functional significance. OC XI and OC V showed higher docking score and hydrogen bond interaction with all the six tested cysteine protease enzymes. N terminal glycine residue, central conserved QVVXG, C terminal AVVXXXPW regions are involved in interacting with the active site residue of protease enzymes. Substitution of N terminal glycine by any other residue in OC VI significantly reduced the interaction efficiency with cysteine proteases. In OC XI, glutamine in the fourth position of QVVXG showed higher interaction efficiency with all cysteine proteases than serine at the fourth amino acid position. N terminal glycine plays a vital role in OC XI for interacting with active sites of cysteine protease enzymes whereas, in the OC V central conserved region QVVSG and C terminal PW region plays a major part in the interaction. However, either N terminal or C terminal region along with the central conserved region of oryzacystatin is involved in mediating an efficient interaction with the active site residues of cysteine proteases. Molecular dynamic (MD) simulation study revealed the stability of the OC X1 - cathepsin O2 like and OC V - cathepsin F like complexes during a simulation for 20 ns. Insilico results of the present study predict the potential of oryzacystatins interaction with cysteine protease enzymes of insects.

Molecular Dynamics Validation of Crizotinib Resistance to ALK Mutations (L1196M and G1269A) and Identification of Specific Inhibitors.

Anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patients are mostly treated with ALK tyrosine kinase inhibitors (TKIs). Crizotinib is the first generation ALK inhibitor practiced as a primary chemo to combat cancer cells followed by second generation inhibitor ceritinib which are effective against crizotinib resistant ALK mutations. However, patients treated with these drugs invariably relapsed because of the development of new drug resistance mutations. In this study we explored the crizotinib resistance in the presence of ALK mutations L1196M and G1269A through molecular dynamics simulation studies. Further mutation specific inhibitors CID 71748211 and CID 71728095 were identified to potentially inhibit ALK with mutations L1196M and G1269A, respectively. This computational investigation in-sighted the molecular factors involved in crizotinib resistance which enhanced in the identification of new ALK drugs that brings individualized medicine to treat ALK positive NSCLC patients with specific mutations. J. Cell. Biochem. 118: 3462-3471, 2017. © 2017 Wiley Periodicals, Inc.