Exploring the Potent Combination of Quercetin-Boronic Acid, Epalrestat, and Urea Containing Nanoethosomal Keratolytic Gel for the Treatment of Diabetic Neuropathic Pain: In Vitro and In Vivo Studies.

Transdermal penetration of therapeutic moieties from topical dosage forms always remains a challenge due to the presence of permeation impeding keratin which should be addressed. The purpose of the study was to formulate quercetin and 4-formyl phenyl boronic acid (QB complex) used for the preparation of nanoethosomal keratolytic gel (EF3-G). The QB complex was confirmed by Fourier transform infrared spectroscopy while skin permeation, viscosity, and epalrestat entrapment efficiency were used for the optimization of nanoethosomal gel. The keratolytic effect of the proposed nanoethosomal gel with urea (QB + EPL + U) was calculated in rat and snake skin. The spherical shape of nanoethosomes was confirmed by scanning electron microscopy. According to the findings of stability studies, viscosity decreases as temperature increases, proving their thermal stability. The negative charge of optimized EF3 with 0.7 PDI proved narrow particle size distribution with homogeneity. Optimized EF3 showed two folds increase of epalrestat permeation in highly keratinized snake skin as compared to rats' skin after 24 h. Antioxidant behaviors of EF3 (QB) > QB complex > quercetin > ascorbic acid proved reduction of oxidative stress in DPPH reduction analysis. Interestingly, the hot plate and cold allodynia test in the diabetic neuropathic rat model reduced 3-fold pain as compared to the diabetic control group which was further confirmed by in vivo biochemical studies even after the eight week. Conclusively, ureal keratolysis, primary dermal irritation index reduction, and improved loading of epalrestat render the nanoethosomal gel (EF3-G) ideal for the treatment of diabetic neuropathic pain.

Comparative transcriptome analysis of Gossypium hirsutum L. in response to sap sucking insects: aphid and whitefly.

BACKGROUND: Cotton (Gossypium hirsutum L.) is a major fiber crop that is grown worldwide; it faces extensive damage from sap-sucking insects, including aphids and whiteflies. Genome-wide transcriptome analysis was performed to understand the molecular details of interaction between Gossypium hirsutum L. and sap-sucking pests, namely Aphis gossypii (Aphid) and Bemisia tabacci (Whiteflies). Roche's GS-Titanium was used to sequence transcriptomes of cotton infested with aphids and whiteflies for 2 h and 24 h. RESULTS: A total of 100935 contigs were produced with an average length of 529 bp after an assembly in all five selected conditions. The Blastn of the non-redundant (nr) cotton EST database resulted in the identification of 580 novel contigs in the cotton plant. It should be noted that in spite of minimal physical damage caused by the sap-sucking insects, they can change the gene expression of plants in 2 h of infestation; further change in gene expression due to whiteflies is quicker than due to aphids. The impact of the whitefly 24 h after infestation was more or less similar to that of the aphid 2 h after infestation. Aphids and whiteflies affect many genes that are regulated by various phytohormones and in response to microbial infection, indicating the involvement of complex crosstalk between these pathways. The KOBAS analysis of differentially regulated transcripts in response to aphids and whiteflies indicated that both the insects induce the metabolism of amino acids biosynthesis specially in case of whiteflies infestation at later phase. Further we also observed that expression of transcript related to photosynthesis specially carbon fixation were significantly influenced by infestation of Aphids and Whiteflies. CONCLUSIONS: A comparison of different transcriptomes leads to the identification of differentially and temporally regulated transcripts in response to infestation by aphids and whiteflies. Most of these differentially expressed contigs were related to genes involved in biotic, abiotic stresses and enzymatic activities related to hydrolases, transferases, and kinases. The expression of some marker genes such as the overexpressors of cationic peroxidase 3, lipoxygenase I, TGA2, and non-specific lipase, which are involved in phytohormonal-mediated plant resistance development, was suppressed after infestation by aphids and whiteflies, indicating that insects suppressed plant resistance in order to facilitate their infestation. We also concluded that cotton shares several pathways such as phagosomes, RNA transport, and amino acid metabolism with Arabidopsis in response to the infestation by aphids and whiteflies.

Salt stress tolerance of methylotrophic bacteria Methylophilus sp. and Methylobacterium sp. isolated from coal mine spoils.

Two methylotrophic strains of Bina coalmine spoil BNV7b and BRV25 were identified based on physiological traits and 16S rDNA sequence as Methylophilus and Methylobacterium species.' The strains exhibited similar carbon utilization but differed in N utilization and their response to the metabolic inhibitors. Methylophilus sp. was less tolerant to salt stress and it viability declined to one tenth within 4 h of incubation in 2M NaCI due to membrane damage and leakage of the intracellular electrolytes as evident from malondiaaldehyde (MDA) assay. In 200 mM NaCI, they exhibited increased superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) activity while in 500 mM NaCI, enzyme activities declined in Methylophilus sp. and increased in Methylobacterium sp. Among exogenously applied osmoprotectants proline was most efficient; however, polyols (mannitol, sorbitol and glycerol) also supported growth under lethal NaCI concentration.

Phytoremediation potential of Solanum viarum Dunal and functional aspects of their capitate glandular trichomes in lead, cadmium, and zinc detoxification.

In the present scenario, remediation of heavy metals (HMs) contaminated soil has become an important work to be done for the well-being of human and their environment. Phytoremediation can be regarded as an excellent method in environmental technologies. The present contemporary research explores the Solanum viarum Dunal function as a potential accumulator of hazardous HMs viz. lead (Pb), cadmium (Cd), zinc (Zn), and their combination (CHM). On toxic concentrations of Pb, Cd, Zn, and their synergistic exposure, seeds had better germination percentage and their 90d old aerial tissues accumulated Pb, Cd, and Zn concentrations ranging from 44.53, 84.06, and 147.29 mg kg-1 DW, respectively. Pattern of accumulation in roots was as Zn 70.08 > Pb 48.55 > Cd 42.21 mg kg-1DW. Under HMs treatment, positive modulation in physiological performances, antioxidant activities suggested an enhanced tolerance along with higher membrane stability due to increased levels of lignin, proline, and sugar. Phenotypic variations were recorded in prickles and roots of 120 d old HM stressed plants, which are directly correlated with better acclimation. Interestingly, trichomes of the plant also showed HM accumulation. Later, SEM-EDX microanalysis suggested involvement of S. viarum capitate glandular trichomes as excretory organs for Cd and Zn. Thus, the present study provides an understanding of the mechanism that makes S. viarum to function as potent accumulator and provides information to generate plants to be used for phytoremediation.

Bioprospects of Endophytic Bacteria in Plant Growth Promotion and Ag-Nanoparticle Biosynthesis.

In this study, five endophytic bacterial strains, namely Rhizobium pusense (MS-1), Bacillus cereus MS-2, Bacillus flexus (MS-3), Methylophilus flavus (MS-4), and Pseudomonas aeruginosa (MS-5), were used to investigate their potential role in the enhancement of growth yields of two types of tomato varieties, viz. hybrid and local, and in the biosynthesis of silver nanoparticles (AgNPs). The inoculation of bacterial strains enhanced the root and shoot length, biomass, and leaf chlorophyll contents. The fruit weight of the tomato (kg/plant) was also higher in the bacteria inoculated plants of both hybrid and local varieties than in the control (untreated). A significant increase was recorded in the fruit yield (g/plant) in all the treatments, whereas Methylophilus flavus (MS-4) inoculated plants yielded nearly 2.5 times more fruit weight compared to the control in the hybrid variety and two times higher in the local variety. The response to M. flavus as a microbial inoculant was greater than to the other strains. Biosynthesis of Ag nanoparticles was also carried out using all five endophytic bacterial strains. The weakest producers of AgNPs were Rhizobium pusense (MS-1) and Methylophilus flavus (MS-4), while Bacillus cereus MS-2, Bacillus flexus (MS-3), and Pseudomonas aeruginosa (MS-5) were strong producers of AgNPs. Nanoparticles were further characterized using high-resolution scanning electron microscopy (HR-SEM), transmission electron microscopy (TEM), Fourier transform infrared (FTIR), UV-Vis spectrophotometry, and X-ray diffraction (XRD) analysis, and revealed cuboidal shaped AgNPs in the Bacillus cereus MS-2 strain. In addition, the biosynthesized AgNPs showed antibacterial activity against various pathogenic and endophytic bacterial strains.

Isolation and Characterization of Endophytes Bacterial Strains of Momordica charantia L. and Their Possible Approach in Stress Management.

In the present study, eight endophytic bacterial strains, namely Bacillus licheniformis R1, Bacillus sp. R2, Agrobacterium tumefaciens R6, uncultured bacterium R11, Bacillus subtilis RS3, Bacillus subtilis RS6, uncultured bacterium RS8 and Lysinibacillus fusiformis RS9, were isolated from the root of Momordica charantia L. All the strains, except R6 exhibited positive for IAA production, siderophore production, and phosphate solubilization during plant growth-promoting traits analysis. Strains invariably utilized glucose and sucrose as a carbon source during substrate utilization, while yeast extract, ammonium sulphate, ammonium chloride, glycine, glutamine, and isoleucine as nitrogen sources. In addition, Spectinomycin was found as the most effective during antibiotic sensitivity TEST, followed by Chloramphenicol, Erythromycin, Rifampicin and Kanamycin, while Polymixin B was found least effective, while strains R1, R6, and RS8 were sensitive to all the antibiotics. Strains R1 and RS6 were able to withstand tolerance up to 10% of NaCl. The strains showing resistance against broad-spectrum antibiotics, especially chloramphenicol, can be used in hospital waste management. In addition, strains with a tolerance of 10 % of NaCl can improve plant growth in the saline affected area.

Biotechnological aspects of plants metabolites in the treatment of ulcer: A new prospective.

Ulcer is one of the most common diseases affecting throughout the world population. The allopathic treatment of ulcer adversely affects the health by causing harmful side effects. Currently, many herbal plants and secondary metabolites have been used for the ulcer treatment. In the present review, many herbal plants and their parts (root, rhizome, bark, leaves and fruits) have been listed in the table are currently being used for ulcer treatment. These metabolites are responsible for ulcer-neutralization or anti-inflammatory properties. In silico study, plant metabolites showed interaction between protodioscin (secondary metabolites of Asparagus racemosus) and interferon-γ (virulent factor of gastric ulcer) during molecular docking. All the residues of interferon-γ exhibited hydrophobic interactions with plant metabolites. These interactions helps in understanding the plant secondary metabolites vis a vis will open a new door in the research field of new drug discovery and designing for the ulcer treatment.

Endophytic bacteria: a new source of bioactive compounds.

In recent years, bioactive compounds are in high demand in the pharmaceuticals and naturopathy, due to their health benefits to human and plants. Microorganisms synthesize these compounds and some enzymes either alone or in association with plants. Microbes residing inside the plant tissues, known as endophytes, also produce an array of these compounds. Endophytic actinomycetes act as a promising resource of biotechnologically valuable bioactive compounds and secondary metabolites. Endophytic Streptomyces sp. produced some novel antibiotics which are effective against multi-drug-resistant bacteria Antimicrobial agents produced by endophytes are eco-friendly, toxic to pathogens and do not harm the human. Endophytic inoculation of the plants modulates the synthesis of bioactive compounds with high pharmaceutical properties besides promoting growth of the plants. Hydrolases, the extracellular enzymes, produced by endophytic bacteria, help the plants to establish systemic resistance against pathogens invasion. Phytohormones produced by endophytes play an essential role in plant development and drought resistance management. The high diversity of endophytes and their adaptation to various environmental stresses seem to be an untapped source of new secondary metabolites. The present review summarizes the role of endophytic bacteria in synthesis and modulation of bioactive compounds.

Isolation and characterization of bacterial endophytes of Curcuma longa L.

Fourteen endophytic bacterial isolates were isolated from the rhizome of Curcuma longa L. were characterized on the basis of morphology, biochemical characteristics and 16S rRNA gene sequence analysis. The isolates were identified to six strains namely Bacillus cereus (ECL1), Bacillus thuringiensis (ECL2), Bacillus sp. (ECL3), Bacillus pumilis (ECL4), Pseudomonas putida (ECL5), and Clavibacter michiganensis (ECL6). All the strains produced IAA and solubilized phosphate and only two strains produced siderophore (ECL3 and ECL5) during plant growth promoting trait analysis. All the endophytic strains utilized glucose, sucrose and yeast extract as a carbon source where as glycine, alanine, cystine and glutamine as nitrogen source. The strains were mostly sensitive to antibiotic chloramphenicol followed by erythromycin while resistant to polymixin B. The endophytic strains effectively inhibit the growth of Escherichia coli, Klebsiella pneumoniae and some of the fungal strain like Fusarium solani and Alterneria alternata. The strain ECL2 and ECL4 tolerated maximum 8 % of NaCl concentration where as strains ECL5 and ECL6 6 % in salinity tolerance.

The curation of genetic variants: difficulties and possible solutions.

The curation of genetic variants from biomedical articles is required for various clinical and research purposes. Nowadays, establishment of variant databases that include overall information about variants is becoming quite popular. These databases have immense utility, serving as a user-friendly information storehouse of variants for information seekers. While manual curation is the gold standard method for curation of variants, it can turn out to be time-consuming on a large scale thus necessitating the need for automation. Curation of variants described in biomedical literature may not be straightforward mainly due to various nomenclature and expression issues. Though current trends in paper writing on variants is inclined to the standard nomenclature such that variants can easily be retrieved, we have a massive store of variants in the literature that are present as non-standard names and the online search engines that are predominantly used may not be capable of finding them. For effective curation of variants, knowledge about the overall process of curation, nature and types of difficulties in curation, and ways to tackle the difficulties during the task are crucial. Only by effective curation, can variants be correctly interpreted. This paper presents the process and difficulties of curation of genetic variants with possible solutions and suggestions from our work experience in the field including literature support. The paper also highlights aspects of interpretation of genetic variants and the importance of writing papers on variants following standard and retrievable methods.