Green Synthesis and Characterization of Ginger-Derived Silver Nanoparticles and Evaluation of Their Antioxidant, Antibacterial, and Anticancer Activities.

The efficacy, targeting ability, and biocompatibility of plant-based nanoparticles can be exploited in fields such as agriculture and medicine. This study highlights the use of plant-based ginger nanoparticles as an effective and promising strategy against cancer and for the treatment and prevention of bacterial infections and related disorders. Ginger is a well-known spice with significant medicinal value due to its phytochemical constituents including gingerols, shogaols, zingerones, and paradols. The silver nanoparticles (AgNPs) derived from ginger extracts could be an important non-toxic and eco-friendly nanomaterial for widespread use in medicine. In this study, AgNPs were biosynthesized using an ethanolic extract of ginger rhizome and their phytochemical, antioxidant, antibacterial, and cytotoxic properties were evaluated. UV-visible spectral analysis confirmed the formation of spherical AgNPs. FTIR analysis revealed that the NPs were associated with various functional biomolecules that were associated with the NPs during stabilization. The particle size and SEM analyses revealed that the AgNPs were in the size range of 80-100 nm, with a polydispersity index (PDI) of 0.510, and a zeta potential of -17.1 mV. The purity and crystalline nature of the AgNPs were confirmed by X-ray diffraction analysis. The simple and repeatable phyto-fabrication method reported here may be used for scaling up for large-scale production of ginger-derived NPs. A phytochemical analysis of the ginger extract revealed the presence of alkaloids, glycosides, flavonoids, phenolics, tannins, saponins, and terpenoids, which can serve as active biocatalysts and natural stabilizers of metallic NPs. The ginger extracts at low concentrations demonstrated promising cytotoxicity against Vero cell lines with a 50% reduction in cell viability at 0.6-6 µg/mL. When evaluated for biological activity, the AgNPs exhibited significant antioxidant and antibacterial activity on several Gram-positive and Gram-negative bacterial species, including Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, and Staphylococcus aureus. This suggests that the AgNPs may be used against multi-drug-resistant bacteria. Ginger-derived AgNPs have a considerable potential for use in the development of broad-spectrum antimicrobial and anticancer medications, and an optimistic perspective for their use in medicine and pharmaceutical industry.

Bioequivalence, food effect and comparative pharmacokinetics of SUVN-1105, a novel granule formulation of abiraterone acetate, to Zytiga in healthy male subjects.

PURPOSE: SUVN-1105 is a novel formulation of abiraterone acetate which was developed to demonstrate improved bioavailability, compared to Zytiga and Yonsa, and to reduce the dose and eliminate the food effect. A Phase 1 study was conducted to assess the bioequivalence, food effect, and comparative pharmacokinetics of SUVN-1105 to Zytiga in healthy male subjects. METHODS: The study comprised of 2 segments. Segment 1 was a single-center, 4-period crossover, open-label, fixed treatment sequence, single-dose study to evaluate the safety and pharmacokinetics of SUVN-1105 (N = 12 subjects per period). Segment 2 was a single-center, open-label, single-dose, randomized, 4-period, 4-treatment, 4-sequence crossover study to evaluate bioequivalence and comparative pharmacokinetics of SUVN-1105 against Zytiga (N = 44) under overnight fasted, modified fasted, and fed conditions. RESULTS: Abiraterone exposures appeared to increase proportionately with SUVN-1105 dose (200 mg vs. 250 mg) in Segment 1. In Segment 2, abiraterone exposures of 250 mg SUVN-1105 in the fasted or fed conditions were higher than those of Zytiga 1000 mg in the overnight fasted conditions. Abiraterone exposures of 250 mg SUVN-1105 decreased in the fed conditions (64% and 29% decrease in Cmax and AUC, respectively) compared to overnight fasted conditions. CONCLUSIONS: The abiraterone exposures of 250 mg SUVN-1105 in the fasted or fed conditions fall within the abiraterone exposures of 1000 mg Zytiga in fasted and modified fasted conditions. Single doses of SUVN-1105 were safe and well-tolerated in healthy males both in the fasted and fed conditions.

The nematicidal potential of novel fungus, Trichoderma asperellum FbMi6 against Meloidogyne incognita.

One of the most damaging pests in vegetable crops is the root-knot nematode (Meloidogyne incognita) worldwide. The continuous use of nematicide is costly and has unintended consequences for human and environmental health. To minimize nematicides, eco-friendly integrated nematode management is required. Trichoderma, an antagonistic fungus has been explored to control root-knot nematode. The fungal bio-control strain FbMi6 was identified as Trichoderma asperellum (accession no. MT529846.1). T. asperellum FbMi6 showed substantial nematicidal activity in the laboratory, with egg hatch suppression (96.6%) and juvenile mortality (90.3%) of M. incognita. T. asperellum FbMi6 was examined under pot and field  conditions (after neem cake enrichment), both alone and in combination, and compared with controls. Application of T. asperellum FbMi6 enriched neem cake (1-ton ha-1) increased (28.3%) the okra yield and decreased (57.1%) nematode population as compared with control. T. asperellum FbMi6 enriched neem cake had higher polyphenol content (resistance enhancer) in okra compared with inoculated check.

Alleviating Drought Stress in Brassica juncea (L.) Czern & Coss. by Foliar Application of Biostimulants-Orthosilicic Acid and Seaweed Extract.

Agricultural productivity is negatively impacted by drought stress. Brassica is an important oilseed crop, and its productivity is often limited by drought. Biostimulants are known for their role in plant growth promotion, increased yields, and tolerance to environmental stresses. Silicon in its soluble form of orthosilicic acid (OSA) has been established to alleviate deteriorative effects of drought. Seaweed extract (SWE) also positively influence plant survival and provide dehydration tolerance under stressed environments. The present study was conducted to evaluate the efficacy of OSA and SWE on mitigating adverse effects of drought stress on Brassica genotype RH-725. Foliar application of OSA (2 ml/L and 4 ml/L) and SWE of Ascophyllum nodosum (3 ml/L and 4 ml/L) in vegetative stages in Brassica variety RH 725 under irrigated and rainfed condition revealed an increase in photosynthetic rate, stomatal conductance, transpirational rate, relative water content, water potential, osmotic potential, chlorophyll fluorescence, chlorophyll stability index, total soluble sugars, total protein content, and antioxidant enzyme activity; and a decrease in canopy temperature depression, proline, glycine-betaine, H2O2, and MDA content. Application of 2 ml/L OSA and 3 ml/L SWE at vegetative stage presented superior morpho-physiological and biochemical characteristics and higher yields. The findings of the present study will contribute to developing a sustainable cropping system by harnessing the benefits of OSA and seaweed extract as stress mitigators.

Amelioration Effect of Salicylic Acid Under Salt Stress in Sorghum bicolor L.

Salinity is a major abiotic stress, limiting plant growth and agriculture productivity worldwide. Salicylic acid is known to alleviate the negative effects of salinity. The present study demonstrated the impact of SA on sorghum, a moderately salt-tolerant crop, grown for food, fodder, fiber, and fuel. A screen house experiment was conducted using sorghum genotypes Haryana Jowar HJ 513 and HJ 541 under 4 salt levels (0, 5.0, 7.5, and 10.0 dS m-1 NaCl) and 3 SA (0, 25, and 50 mg dm-3) levels with 12 combinations. The leaves were assayed for electrolyte leakage percentage (ELP), i.e., 88.7 % in HJ 541 and 87.2 % in HJ 513, and osmolyte content. Proline content, total soluble carbohydrate content, and glycine betaine content increased considerably. Photosynthetic rate, transpiration rate, and stomatal conductance declined at higher salt levels. The specific enzymatic activities of SOD, CAT, and POX increased 41.1 %, 122.0 %, and 72.8 %, respectively, in HJ 513 under salt stress. Combinations of salt treatment and SA decreased ELP and enhanced osmolyte concentration, rates of gaseous exchange attributes, and also the antioxidant enzymatic activity in salt-stressed leaves. The study established that the specific activity of antioxidative enzymes is enhanced further by addition of SA which may protect the cells from oxidative damage under salt stress, thus mitigating salt stress and enhancing the yield of sorghum. SA can ameliorate the salt stress in plants by affecting the metabolic or physiological frameworks. SA application is an effective management strategy towards mitigating salt stress in order to meet agricultural production and sustainability.

Pinpointing Genomic Regions and Candidate Genes Associated with Seed Oil and Protein Content in Soybean through an Integrative Transcriptomic and QTL Meta-Analysis.

Soybean with enriched nutrients has emerged as a prominent source of edible oil and protein. In the present study, a meta-analysis was performed by integrating quantitative trait loci (QTLs) information, region-specific association and transcriptomic analysis. Analysis of about a thousand QTLs previously identified in soybean helped to pinpoint 14 meta-QTLs for oil and 16 meta-QTLs for protein content. Similarly, region-specific association analysis using whole genome re-sequenced data was performed for the most promising meta-QTL on chromosomes 6 and 20. Only 94 out of 468 genes related to fatty acid and protein metabolic pathways identified within the meta-QTL region were found to be expressed in seeds. Allele mining and haplotyping of these selected genes were performed using whole genome resequencing data. Interestingly, a significant haplotypic association of some genes with oil and protein content was observed, for instance, in the case of FAD2-1B gene, an average seed oil content of 20.22% for haplotype 1 compared to 15.52% for haplotype 5 was observed. In addition, the mutation S86F in the FAD2-1B gene produces a destabilizing effect of (ΔΔG Stability) -0.31 kcal/mol. Transcriptomic analysis revealed the tissue-specific expression of candidate genes. Based on their higher expression in seed developmental stages, genes such as sugar transporter, fatty acid desaturase (FAD), lipid transporter, major facilitator protein and amino acid transporter can be targeted for functional validation. The approach and information generated in the present study will be helpful in the map-based cloning of regulatory genes, as well as for marker-assisted breeding in soybean.

Retinal vein occlusion in COVID-19: A novel entity.

Coronavirus disease 2019 (COVID-19) is a form of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has been declared a pandemic by the World Health Organization (WHO). Ocular manifestations related to COVID-19 are uncommon with conjunctivitis being reported in a few cases. We report a unique case of vasculitic retinal vein occlusion (RVO) secondary to COVID-19 in a 52-year-old patient who presented with the diminution of vision in the left eye 10 days after he tested positive for SARS-CoV-2. All investigations for vasculitis were negative. This case supports the mechanism of thrombo-inflammatory state secondary to the "cytokine-storm" as the pathogenesis for systemic manifestations of COVID-19.

Orthosilicic acid (OSA) reduced grain arsenic accumulation and enhanced yield by modulating the level of trace element, antioxidants, and thiols in rice.

Arsenic (As), a toxic metalloid, is finding its route to human through intake of As-contaminated water and consumption of food grown on contaminated soil. Rice is the most As-affected crop. Present study is aimed to assess the impact of stabilized orthosilicic acid (a proprietary formulation for plant-available silicon (Si) and earlier used as fertilizer for rice to enhance growth and yield) in reducing the accumulation of As in rice grains. Application of arsenic in the form of arsenate (AsV) and arsenite (AsIII) significantly affected plant growth in a dose-dependent manner. Higher doses of AsV and AsIII (50 and 25 mg L-1 respectively) significantly decreased the yield attributes leading to lower yield. A significant accumulation of As in grain was observed in both AsV- and AsIII-exposed plants in a dose-dependent manner. Arsenic exposure also increased the level of Si in rice grains. Application of Si, either in soil or on leaves (foliar), greatly reduced grain As accumulation (up to 67% in AsV and 78% in AsIII) and enhanced the growth and yield of plants under As stress. The level of thiols and activities of antioxidant enzymes were also enhanced under Si application. Foliar Si application was more effective in increasing grain Si level and reducing grain As than soil Si. The level of other trace elements was also significantly enhanced by Si application irrespective of the presence or absence of As in comparison with control. Arsenic exposure constrained some of the trace elements, such as Zn and Co, which were restored by Si application. Results of the present study showed that the application of currently used Si formulation may effectively reduce grain As level even in highly As-contaminated soil and improve grain quality of rice.

Assessment of toxicity and tolerability of a combination vehicle; 5% Pharmasolve, 45% Propylene glycol and 50% Polyethylene glycol 400 in rats following repeated intravenous administration.

The selection of a suitable vehicle for administration of NCEs in non-clinical studies is always a challenge for poorly soluble compounds. Challenge is increased if the dose formulation is intended for intravenous (i.v.) administration where isotonic, biologically compatible pH and solution form is an absolute requirement. Vehicle toxicity and tolerability data are not readily available for a number of combination vehicles therefore, an i.v. tolerability studies was planned in rats with 5% v/v Pharmasolve (NMP), 45% v/v Propylene glycol (PG) and 50% v/v Polyethylene glycol (PEG) 400 combination, at dose volume of 0.5, 1, 2 and 5 mL/kg body weight for 28 days. The vehicle combination was administered via lateral tail vein and effects on clinical signs, body weights, feed consumption, clinical pathology and histopathology were evaluated. Clinical signs of toxicity like tremors, convulsions and death were noticed at 5 mL/kg during the course of the study. At 2 mL/kg, injection site injury without systemic toxicity was noticed. In conclusion, 1 mL/kg of a combination vehicle of 5% NMP, 45% PG and 55% PEG 400 can be administered intravenously once-a-day up to 28 days without any discomfort or injury to rats.

Mutagenicity and clastogenicity evaluation of tacrine by Ames and micronucleus assays.

Tacrine was evaluated for its mutagenic and clastogenic activities using the Ames bacterial reverse-mutation assay and the rodent bone marrow micronucleus assay. Tacrine was tested for mutagenic potential at six different concentrations, with 1,250 µg/plate as the highest concentration, followed by five lower concentrations with 2-fold spacing. In clastogenic evaluation, tacrine was administered orally to Wistar rats for 2 days at 5, 10, and 20 mg/kg body weights to assess micronucleus induction in bone marrow erythrocytes. In the Ames assay, tacrine showed nonmutagenicity in four tester strains of Salmonella typhimurium viz. TA98, TA100, TA102, and TA1535, but it was found to be mutagenic in the TA1537 tester strain, both in the presence and absence of a metabolic activation system. Tacrine was found to be nonclastogenic on bone marrow cells of rats at all doses tested and was found to be mutagenic in only the TA1537 strain of Salmonella.

Assessment of genetic diversity through RAPD, ISSR and AFLP markers in Podophyllum hexandrum: a medicinal herb from the Northwestern Himalayan region.

Total synthesis of podophyllotoxin is an expensive process and availability of the compound from the natural resources is an important issue for pharmaceutical companies that manufacture anticancer drugs. In order to facilitate reasoned scientific decisions on its management and conservation for selective breeding programme, genetic analysis of 28 populations was done with 19 random primers, 11 ISSR primers and 13 AFLP primer pairs. A total of 92.37 %, 83.82 % and 84.40 % genetic polymorphism among the populations of Podophyllum were detected using RAPD, ISSR and AFLP makers, respectively. Similarly the mean coefficient of gene differentiation (Gst) were 0.69, 0.63 and 0.51, indicating that 33.77 %, 29.44 % and 26 % of the genetic diversity resided within the population. Analysis of molecular variance (AMOVA) indicated that 53 %, 62 % and 64 % of the genetic diversity among the studied populations was attributed to geographical location while 47 %, 38 % and 36 % was attributed to differences in their habitats using RAPD, ISSR and AFLP markers. An overall value of mean estimated number of gene flow (Nm) were 0.110, 0.147 and 0.24 from RAPD, ISSR and AFLP markers indicating that there was limited gene flow among the sampled populations.