Role of the dynamin-related protein 2 family and SH3P2 in clathrin-mediated endocytosis in Arabidopsis thaliana.

Clathrin-mediated endocytosis (CME) is vital for the regulation of plant growth and development through controlling plasma membrane protein composition and cargo uptake. CME relies on the precise recruitment of regulators for vesicle maturation and release. Homologues of components of mammalian vesicle scission are strong candidates to be part of the scission machinery in plants, but the precise roles of these proteins in this process are not fully understood. Here, we characterised the roles of the plant dynamin-related protein 2 (DRP2) family (hereafter DRP2s) and SH3-domain containing protein 2 (SH3P2), the plant homologue to recruiters of dynamins, such as endophilin and amphiphysin, in CME by combining high-resolution imaging of endocytic events in vivo and characterisation of the purified proteins in vitro. Although DRP2s and SH3P2 arrive similarly late during CME and physically interact, genetic analysis of the sh3p123 triple mutant and complementation assays with non-SH3P2-interacting DRP2 variants suggest that SH3P2 does not directly recruit DRP2s to the site of endocytosis. These observations imply that, despite the presence of many well-conserved endocytic components, plants have acquired a distinct mechanism for CME.

Mutational screening of GDAP1 in dysphonia associated with Charcot-Marie-Tooth disease: clinical insights and phenotypic effects.

INTRODUCTION: Mutations in GDAP1 (Ganglioside-induced differentiation-associated protein 1) gene are linked to Charcot-Marie-Tooth disease (CMT), a Heterogenous group of disorders with multiple phenotypes, characterized by peripheral nerve dysfunction that can lead to vocal cord paralysis and diaphragmatic dysfunction. MAIN BODY: All three affected children of this chosen family have manifested the same clinical symptoms with progressive weakness, mild sensory impairment, and absent tendon reflexes in their early years. Electrodiagnostic analysis displayed an axonal type of neuropathy in affected patients. Sequencing of the GDAP1 gene was requested for all members of the family. Diagnostic assessments included pulmonary and vocal cord function tests, as well as phrenic and peripheral nerve conduction studies. Pathogenicity of GDAP1 variant p.Pro419Leu with axonal CMT2 and autosomal recessive inheritance was confirmed via in silico analysis. Patients with GDAP1 mutations showed dysphonia, speech difficulties, and the characteristic symptoms of CMT. The severity of symptoms correlated with the presence of a type of GDAP1 mutation. Patients with normal vocal cords and pulmonary function exhibited milder symptoms compared to those with GDAP1 mutations. Our study provides clinical insights into the phenotypic effects of GDAP1 mutations in CMT patients. The findings highlight the adverse clinical course and severe disability associated with GDAP1 mutations, including weak limb and laryngeal muscles. CONCLUSION: Patients with GDAP1 mutations and autosomal recessive neuropathy present with dysphonia and require interventions such as surgery, braces, physical therapy, and exercise. Early diagnosis and comprehensive clinical evaluations are crucial for managing CMT patients with GDAP1 mutations.

Formulation Development and Investigations on Therapeutic Potential of Nanogel from Beta vulgaris L. Extract in Testosterone-Induced Alopecia.

The objective of the present study was to develop a novel nanogel containing Beta vulgaris L. hydroalcoholic extract and assess its efficacy for treating testosterone-induced alopecia. Beta vulgaris L. leaf hydroalcoholic extract nanogel (BVEN) was prepared by ionic gelation method, incorporated in carbopol 934 gel. Optimization of particle size and entrapment efficiency as the responses was carried out by central composite design response surface methodology. Prepared nanoparticles were evaluated for entrapment efficiency, particle size, zeta potential, polydispersity index, Fourier transform infrared spectroscopy, transmission electron microscopy, and differential scanning calorimetry. Nanogel was evaluated for pH, colour, appearance and homogeneity, viscosity, spreadability, in vitro release study, and stability studies. Further, 2.5% and 5% BVEN were also evaluated for antialopecic activity in Swiss albino mice by using parameters as hair growth initiation, testosterone content, total protein, prostate weight measurement, hair follicular density, anagen/telogen ratio, and histopathological studies. The resulting nanoparticles had better entrapment efficiency with particle size of 274 nm, polydispersity index of 0.259, and zeta potential of +28.8. BVEN pH 6.5, drug content, i.e., quercetin 99.84 ± 1.30% and stigmasterol 99.89 ± 1.52%, spreadability 20.3 ± 0.5925 g cm/sec, and viscosity 110 × 105 cps were observed. Stability studies showed that nanogel was stable at 4°C ± 2°C/60% ± 5% RH. It was found that 5% BVEN showed better antialopecic activity as compared to 2.5% BVEN.

New Insight into the Pharmacological Importance of Atropine as the Potential Inhibitor of AKR1B1 via Detailed Computational Investigations: DFTs, ADMET, Molecular Docking, and Molecular Dynamics Studies.

The aim of this research is to investigate the quantum geometric properties and chemical reactivity of atropine, a pharmaceutically active tropane alkaloid. Using density functional theory (DFT) computations with the B3LYP/SVP functional theory basis set, the most stable geometry of atropine was determined. Additionally, a variety of energetic molecular parameters were calculated, such as the optimized energy, atomic charges, dipole moment, frontier molecular orbital energies, HOMO-LUMO energy gap, molecular electrostatic potential, chemical reactivity descriptors, and molecular polarizability. To determine atropine's inhibitory potential, molecular docking was used to analyze ligand interactions within the active pockets of aldo-keto reductase (AKR1B1 and AKR1B10). The results of these studies showed that atropine has greater inhibitory action against AKR1B1 than AKR1B10, which was further validated through molecular dynamic simulations by analyzing root mean square deviation (RMSD) and root mean square fluctuations (RMSF). The results of the molecular docking simulation were supplemented with simulation data, and the ADMET characteristics were also determined to predict the drug likeness of a potential compound. In conclusion, the research suggests that atropine has potential as an inhibitor of AKR1B1 and could be used as a parent compound for the synthesis of more potent leads for the treatment of colon cancer associated with the sudden expression of AKR1B1.

Chemical aspects of polyphenol-protein interactions and their antibacterial activity.

The hunt for novel antibiotics has become a global public health imperative due to the rise in multidrug-resistant microorganisms, untreatable infection cases, overuse, and inefficacy of modern antibiotics. Polyphenols are getting much attention in research due to their multiple biological effects; their use as antimicrobial agents is attributed to their activity and that microbes have a hard time developing resistance to these natural compounds. Polyphenols are secondary metabolites produced in higher plants. They are known to possess various functional properties in the human body. Polyphenols also exhibit antibacterial activities against foodborne pathogens. Their antibacterial mechanism is based on inhibiting bacterial biofilm formation or inactivating enzymes. This review focused on polyphenol-protein interactions and the creation of this complex as a possible antibacterial agent. Also, different phenolic interactions on bacterial proteins, efflux pump, cell membrane, bacterial adhesion, toxins, and other bacterial proteins will be explored; these interactions can work in a synergic combination with antibiotics or act alone to assure bacterial inhibition. Additionally, our review will focus on polyphenol-protein interaction as a possible strategy to eradicate bacteria because polyphenols have shown a robust enzyme-inhibitory characteristic and a high tendency to complex with proteins, a response that neutralizes any bactericidal potential.

Antimalarial phytochemicals as potential inhibitors of SARS-CoV-2 guanine N7-methyltransferase (nsp 14): an integrated computational approach.

The inhibition of capping enzymes such as guanine-N7-methyltransferase (GMT) is an attractive target for regulating viral replication, transcription, virulence, and pathogenesis. Thus, compounds that target the Severe Acute Respiratory Syndrome Corona Virus 2 GMT (S2GMT) will enhance drug development against COVID-19. In this study, an in-house library of 249 phytochemicals from African medicinal plants was screened using computational approaches including homology modeling, molecular docking, molecular dynamic simulations, binding free energy calculations based on molecular mechanics/Poisson-Boltzmann surface area (MMPBSA) and Absorption-Distribution-Metabolism-Excretion-Toxicity (ADMET) analysis for inhibitors of S2GMT. The top-ten ranked phytochemicals (TTRP) obtained from the docking analysis to S2GMT were further docked to SARS-COV N7-MTase. Among the TTRP, the top-four ranked phytocompounds (TFRP) viz: 3 alkaloids (Isocryptolepine, 10'-Hydroxyusambarensine and Isostrychnopentamine) and a flavonoid (Mulberrofuran F) interacted strongly with critical catalytic residues whose interference either reduce or completely abolish N7-MTase activity, indicating their potential as capping machinery disruptors. The interactions of TFRP with the catalytic residues of S2GMT were preserved in a 100 ns simulated dynamic environment, thereby, demonstrating high degree of structural stability. The MMPBSA binding free energy calculations corroborated the docking scores with biscryptolepine having the highest binding free energy to S2GMT. The TFRP showed favourable drug-likeness and ADMET properties over a wide range of molecular descriptors. Therefore, the TFRP can be further explored as potential S2GMT inhibitors in in vitro and in vivo experiments.Communicated by Ramaswamy H. Sarma.

Ackee (Blighia sapida K.D. Koenig) Leaves and Arils Methanolic Extracts Ameliorate CdCl2-Induced Oxidative Stress Biomarkers in Drosophila melanogaster.

Different ethnomedical benefits have been documented on different parts of Ackee (Blighia sapida); however, their roles in ameliorating oxidative damages are not well established. CdCl2 inhibitory effects on some oxidative-stress biomarkers and ameliorative potentials of Ackee leaves (AL) and arils (AS) methanolic extracts were studied using Drosophila melanogaster as a model. One to 3-day-old D. melanogaster flies were orally exposed to different concentrations of CdCl2 in their diet for 7 days. The fly's survival profile and negative geotaxis assays were subsequently analysed. Methanolic extracts of AL and AS treatments showed negative geotaxis behaviour, and extracts were able to ameliorate the effect of Cd2+ on catalase and GST activities and increase total thiol and GSH levels, while it reduced the H2O2 generation (p ≤ 0.05) when compared to the control. Furthermore, Cd2+ exhibited noncompetitive and uncompetitive enzyme inhibition on catalase and GST activities, respectively, which may have resulted in the formation of Enzyme-substrate-Cd2+ transition complexes, thus inhibiting the conversion of substrate to product. This study, thus, suggests that the Cd2+ mechanism of toxicity was associated with oxidative damage, as evidenced by the alteration in the oxidative stress-antioxidant imbalance, and that the AL and AS extracts possess essential phytochemicals that could alleviate possibly deleterious oxidative damage effects of environmental pollutants such as CdCl2. Thus, Ackee plant parts possess essential phytonutrients which could serve as valuable resources in heavy metal toxicity management.

Hypoxia-Inducible Factor 1 and Preeclampsia: A New Perspective.

PURPOSE OF REVIEW: Preeclampsia (PE) is a serious and distinct type of pregnancy-induced hypertension, with an incidence of 2-8% worldwide. PE is defined as pregnancy-related hypertension with proteinuria and peripheral edema after 20 weeks of gestation. Hypoxic placenta triggers the release of inflammatory and humoral substances into maternal circulation, leading to induction of oxidative stress, lipid peroxidation, endothelial dysfunction, and peripheral vasoconstriction. The objective of the present narrative review was to find the association between PE and hypoxia-inducible factor 1 (HIF-1) in pregnant women from a new perspective. RECENT FINDINGS: HIF-1 is the key transcription factor that regulates cellular responses to hypoxia and low oxygen tension. HIF-1α is involved in the differentiation and growth of the placenta mainly in the first and second trimesters. During normal gestation, HIF-1α responds to the alterations in oxygen tension, cytokine, and angiogenic factors release. HIF-1α is considered a key biomarker of placental function and vascularization during pregnancy. HIF-1α plays a crucial role in the pathogenesis of PE through activation of anti-angiogenic and inhibition of proangiogenic factors. As well, HIF-1α increases the expression of the p38MAPK and NLRP3 inflammasomes, which promote placental inflammation and dysfunction. HIF-1α acts as a potential link between inflammatory signaling pathways and the development of PE.

Identification and environment-friendly biocontrol potential of five different bacteria against Aphis punicae and Aphis illinoisensis (Hemiptera: Aphididae).

The current work is aimed at isolating and identifying new Entomopathogenic bacterium (EPB) strains associated with Steinernema feltiae and assessing the EPB's biocontrol potential on Aphis punicae and Aphis illinoisensis adults in the laboratory. From S. feltiae, five bacterial isolates were isolated and molecularly characterized. Lysinibacillus xylanilyticus strain TU-2, Lysinibacillus xylanilyticus strain BN-13, Serratia liquefaciens strain TU-6, Stenotrophomonas tumulicola strain T5916-2-1b, and Pseudochrobactrum saccharolyticum strain CCUG are the strains. Pathogenicity tests demonstrated that bacterial cells were more toxic against the two aphid species than bacterial cell-free supernatants. S. tumulicola strain T5916-2-1b cells and filtrate were reported to have the strongest potential to kill A. punicae and A. illinoisensis individuals within 6 h after treatment, with 100% mortality of both insects 24 and 48 h after treatment. Based on the results of the study, it looked like endogenous Steinernema-associated EPB could be used directly as a biocontrol agent for A. punicae and A. illinoisensis.

Circulating microRNA203 and its target genes' role in psoriasis pathogenesis.

Numerous microRNAs (miRNAs) have been found to have an aberrant expression in the peripheral blood or psoriasis patients' lesions. Psoriasis was shown to have the abnormal expression of microRNA-203 (miR-203). It is a skin-specific signal that governs cellular proliferation in a protein kinase C-dependent manner and is mostly generated by keratinocytes. This work evaluated the expression levels of the circulating miR-203 target genes SOCS3, SOCS6, TP63, TNF-, IL8, and IL24 in psoriasis patients. Using a relative quantitation PCR technique, we determined the expression levels of miR-203 and its target genes (SOCS3, SOCS6, TP63, TNF-, IL8, and IL24) in the plasma of 120 psoriatic patients and matched healthy controls. The disease characteristics of the patients were then correlated with the expression results. We also conducted numerous enrichment analyses for the diseases, functions, and pathways connected to the under-researched biomarkers. Compared to healthy controls, psoriatic patients had significantly increased levels of miR-203 expression; 7.1 (4.4-9.9). In contrast, psoriatic patients had significantly lower expression of all the examined genes compared to healthy controls. Regarding all the study biomarkers, the receiver operating characteristic (ROC) curve analysis demonstrated significant sensitivity and specificity for differentiating between psoriatic patients and healthy controls. According to the results of the disease matching score generated by miR-203 and its target genes, psoriasis was ranked first with a score of 4.45. The third-place finisher with a value of 3.98, it also demonstrated that miR-203 and its target genes are connected to various skin disorders. Our results show that miR-203 contributes to psoriasis pathogenesis not only locally in skin lesions but also in circulation, indicating that it may contribute to the systemic symptoms of the illness. MiR-203 overexpression in psoriasis suggests that miR-203 may be involved in an anti-inflammatory response because it targets both SOCS gene family members and pro-inflammatory cytokines.

Evaluation of the Anti-Cancer Potential of Rosa damascena Mill. Callus Extracts against the Human Colorectal Adenocarcinoma Cell Line.

Chemotherapy is an aggressive form of chemical drug therapy aiming to destroy cancer cells. Adjuvant therapy may reduce hazards of chemotherapy and help in destroying these cells when obtained from natural products, such as medical plants. In this study, the potential therapeutic effect of Rosa damascena callus crude extract produced in vitamin-enhanced media is investigated on colorectal cancer cell line Caco-2. Two elicitors, i.e., L-ascorbic acid and citric acid at a concentration of 0.5 g/L were added to the callus induction medium. Callus extraction and the GC-MS analysis of methanolic crude extracts were also determined. Cytotoxicity, clonogenicity, proliferation and migration of Caco-2 colorectal cancer cells were investigated using MTT cytotoxicity, colony-forming, Ki-67 flow cytometry proliferation and Migration Scratch assays, respectively. Our results indicated that L-ascorbic acid treatment enhanced callus growth parameters and improved secondary metabolite contents. It showed the least IC50 value of 137 ug/mL compared to 237 ug/mL and 180 ug/mL in the citric acid-treated and control group. We can conclude that R. damascena callus elicited by L-ascorbic acid improved growth and secondary metabolite contents as well as having an efficient antiproliferative, anti-clonogenic and anti-migratory effect on Caco-2 cancer cells, thus, can be used as an adjuvant anti-cancer therapy.

Genetic evaluation of Jatropha backcross hybrid clones (BC4F1) for yield and oil quality.

Jatropha curcas is a tropical species that has been recognized as a promising biodiesel plant. During 2018-2021, researchers at Forest College and Research Institute, Mettupalayam, elicited information on Jatropha's biochemical characteristics, growth performance, variability, and association studies for biometric variables using five backcross (BC4F1) hybrid clones of Jatropha with a control variety TNMC 7. In terms of seed yield, two hybrid clones, CJH 13 (1,218.60 g) and CJH 12 (1,034.40 g), outperformed the other hybrid clones. The seed oil content was higher in CJH 5 (34.19%). The seed oil content had moderate PCV (16.49%) and GCV (16.39%) values, as well as high heritability (99%) and genetic advance (33.56%) as a percentage of the mean. The number of fruits per bunch (0.845 and 0.850) and the number of bunches per branch (0.771 and 0.788) had significant positive phenotypic and genotypic correlations with seed yield, respectively. The iodine numbers, cetane numbers, and saponification values of all hybrid clones were acceptable and satisfactory and were in good compliance with Indian and international biodiesel standards.

Soil Nitrogen Transformation Process Influenced by Litterfall Manipulation in Two Subtropical Forest Types.

Nitrogen (N) is often recognized as the primary limiting nutrient element for the growth and production of forests worldwide. Litterfall represents a significant pathway for returning nutrients from aboveground parts of trees to the soils and plays an essential role in N availability in different forest ecosystems. This study explores the N transformation processes under litterfall manipulation treatments in a Masson pine pure forest (MPPF), and Masson pine and Camphor tree mixed forest (MCMF) stands in subtropical southern China. The litterfall manipulation included litterfall addition (LA), litterfall removal (LR), and litterfall control (LC) treatments. The project aimed to examine how litterfall inputs affect the soil N process in different forest types in the study region. Results showed that soil ammonium N (NH4 +-N) and nitrate N (NO3 --N) content increased under LA treatment and decreased under LR treatment compared to LC treatment. LA treatment significantly increased soil total inorganic N (TIN) content by 41.86 and 22.19% in MPPF and MCMF, respectively. In contrast, LR treatment decreased the TIN content by 10 and 24% in MPPF and MCMF compared to LC treatment. Overall, the soil net ammonification, nitrification, and N mineralization rates were higher in MCMF than in MPPF; however, values in both forests were not significantly different. LA treatment significantly increased annual net ammonification, nitrification, and mineralization in both forest types (p < 0.05) compared to LC treatment. LR treatment significantly decreased the values (p < 0.05), except for ammonification, where LR treatment did not differ substantially compared to LC treatment. Our results suggested that changes in litterfall inputs would significantly alter soil N dynamics in studied forests of sub-tropical region. Moreover, mixed forest stands have higher nutrient returns due to mixed litter and higher decomposition compared to pure forest stands.

Molecular markers-based DNA fingerprinting coupled with morphological diversity analysis for prediction of heterotic grouping in sunflower (Helianthus annuus L.).

Cultivated sunflower holds a very narrow genetic base and the efficient utilization of available genetic diversity is very important for a successful breeding program. In the present study, 109 sunflower genotypes were assessed for diversity paneling through a combined approach of morphological and molecular markers analysis. Morphological parameters including days to flower initiation, days to flower completion, plant height, stem curvature, number of leaves per plant, leaf area, head diameter, hundred seed weight, and seed yield per plant were studied. Simple sequence repeats (40 DNA markers) were deployed for diversity profiling. Data were analyzed by both univariate and multivariate statistics. SD and coefficient of variation confirm the presence of significant amounts of genetic variation for all the morphological parameters. Cluster Analysis and Principal Component Analysis further confirm the presence of distinct grouping patterns in the studied material. Cluster analysis of both morphological and molecular analysis revealed that restorer lines tend to group separately from A, B, and open-pollinated lines. Further grouping, at the sub-cluster level, revealed six distinct sub-clusters in each of the two major clusters. In total, 12 genotypes, 6 CMS lines (CMS-HAP-12, CMS-HAP-54, CMS-HAP-56, CMS-HAP-99, CMS-HAP-111, and CMS-HAP-112) and 6 restorer lines (RHP-38, RHP-41, RHP-53, RHP-68, RHP-69, and RHP-71) could be used as potential parents for hybrid development. As genotypes of similar genetic backgrounds tend to group closer, it is deduced that one genotype with the highest seed yield per plant could be used for further hybrid breeding programs in sunflowers.

Large-scale transcriptomic analysis of coding and non-coding pathological biomarkers, associated with the tumor immune microenvironment of thyroid cancer and potential target therapy exploration.

Papillary thyroid carcinoma (PTC) is the most prevalent endocrine malignancy with a steadily increasing global incidence in recent decades. The pathogenesis of PTC is poorly understood, and the present diagnostic protocols are deficient. Thus, identifying novel prognostic biomarkers to improve our understanding of the mechanisms of pathogenesis, diagnosis, and designing therapeutic strategies for PTC is crucial. In this study, we integrated 27 PTC transcriptomic datasets and identified overlapping differentially expressed genes (DEGs) and differentially expressed microRNAs, collectively known as thyroid tumor-enriched proteins (TTEPs), and TTEmiRs, respectively. Our integrated bioinformatics analysis revealed that TTEPs were associated with tumor stages, poor surgical outcomes, distant metastasis, and worse prognoses in PTC cohorts. In addition, TTEPs were found to be associated with tumor immune infiltrating cells and immunosuppressive phenotypes of PTC. Enrichment analysis suggested the association of TTEPs with epithelial-to-mesenchymal transition (EMT), cell-matrix remodeling, and transcriptional dysregulation, while the TTEmiRs (miR-146b-5p and miR-21-5p) were associated with the modulation of the immune response, EMT, migration, cellular proliferation, and stemness. Molecular docking simulations were performed to evaluate binding affinities between TTEPs and antrocinnamomin, antcin, and antrocin, the bioactive compounds from one of the most reputable Taiwan indigenous medicinal plants (Antrodia camphorata). Our results revealed that antcin exhibited higher binding efficacies toward FN1, ETV5, and NRCAM, whereas antrocin demonstrated the least. Among the targets, fibronectin (FN1) demonstrated high ligandability potential for the compounds whereas NRCAM demonstrated the least. Collectively, our results hinted at the potential of antcin for targeting TTEPs. In conclusion, this comprehensive bioinformatics analysis strongly suggested that TTEPs and TTEmiRs could be used as potential diagnostic biomarker signatures and be exploited as potential targets for therapeutics development.

Quercetin-3-O-ß-D-Glucopyranoside-Rich Fraction from Spondias mombin Leaves Halted Responses from Oxidative Stress, Neuroinflammation, Apoptosis, and Lipid Peroxidation in the Brain of Dichlorvos-Treated Wistar Rats.

Dichlorvos (2,3-dichlorovinyl dimethyl phosphate or DDVP), is a popular organophosphate (OP) with several domestic, industrial, and agricultural uses and applications in developing countries [...].

Biochemical and tissue physiopathological evaluation of the preclinical efficacy of Solanum torvum Swartz leaves for treating oxidative impairment in rats administered a ß-cell-toxicant (STZ).

The current study evaluated the protective role of Solanum torvum Swartz against diabetes-induced oxidative stress and tissue impairment in streptozotocin (STZ)-intoxicated rats. Rats with STZ (40 mg/kg intraperitoneally (i.p.))-induced diabetes were divided into five groups (n = 5) and treated with (i) normal saline, (ii) 150 mg/kg body weight (BW) of the ethanol extract of S. torvum leaf (EESTL), (ii) 300 mg/kg BW EESTL, (iv) 100 mg/kg BW metformin, and (v) 50 m/kg BW metformin + 100 mg/kg BW EESTL orally for 21 days. Our results revealed that the EESTL displayed dose-dependent ferric-reducing antioxidant power (FRAP) activity, scavenged DPPH radicals (IC50) = 13.52 ± 0.45 µg/mL), and inhibited lipid peroxidation in an in vitro models. In addition, the EESTL demonstrated dose-dependent inhibitory activity against α-amylase (IC50 =138.46 ± 3.97 µg/mL) and promoted glucose uptake across plasma membranes of yeast cells in a manner comparable to that of metformin. Interestingly, the extract demonstrated in vivo blood glucose normalization effects with concomitant increased activities of antioxidant parameters (superoxide dismutase (SOD), catalase, and reduced glutathione (GSH)) while decreasing malondialdehyde (MDA) levels when compared to untreated rats. Similarly, serum biochemical alterations, and tissues (liver, kidney, and pancreases) histopathological aberrations in untreated rats with STZ-induced diabetes were attenuated by treatment with the EESTL. Biometabolite characterization of the extract identified gallic acid (45.81 ppm), catechin (1.18 ppm), p-coumaric acid (1.43e-1 ppm), DL-proline 5-oxo-methyl ester (9.16 %, retention time (RT): 8.57 min), salicylic acid (3.26% and 7.61 min), and butylated hydroxytoluene (4.75%, RT: 10.18 min) as the major polyphenolic compounds in the plant extract. In conclusion, our study provides preclinical evidence of the antioxidant properties and oxidative stress-preventing role of S. torvum in STZ-dosed diabetic rats. Taken together, the EESTL represents a reserve of bioactive metabolites for managing diabetes and associated complications.

Mutivariate optimization strategy for the sonication-based extraction of Nardostachys jatamansi roots and analysis for chemical composition, anti-oxidant and acetylcholinesterase inhibitory potential.

Extracts from medicinal plants are generally obtained by conventional methods like percolation and maceration. Owing to limitations of traditional methods and to meet the rising demand of extracts, the development of new green approaches is need of hour. In the present research, we have developed an ultrasound-assisted extraction (UAE) method for the Nardostachys jatamansi (NJ) D. Don, DC roots and optimized the extraction parameters for possible improved extract yield. A multivariate optimization strategy using the Centre Composite Design coupled with response surface methodology was applied. A numerical optimization approach accurately predicted the extraction conditions (sonication time âˆ¼ 20 min, ethanol âˆ¼ 70 % and a liquid/solid ratio of about 21:1). Scanning electron microscopy of the plant samples after UAE also indicated the cavitation effect due to sound waves. GC-MS analysis of the optimized ultrasound extract (OUNJ) confirmed improvement in the concentration of various secondary metabolites like jatamansone (91.8 % increase), spirojatamol (42.3 % increase), globulol (130.4 % increase), sitosterol (84.6 % increase) as compared to the soxhlet extract (SXNJ). Different anti-oxidant parameters (DPPH, Glutathione, Catalase SOD and NO) were also significantly altered (p < 0.05) in the optimized extracts. The IC50 to inhibit acetylcholinesterase activity (AChE) in vitro and its concentration in brain homogenates were significantly (p < 0.05) improved by OUNJ extract as compared to the SXNJ ones. To conclude, we can say that established optimized conditions for UAE of N. jatamansi roots not only reduce the extraction time but also improved the pharmacological potential of the extracts.

QbD-based rivastigmine tartrate-loaded solid lipid nanoparticles for enhanced intranasal delivery to the brain for Alzheimer's therapeutics.

Alzheimer's disease (AD) is a neurodegenerative disease that affects a wide range of populations and is the primary cause of death in various countries. The treatment of AD is still restricted to oral conventional medicines that act only superficially. Fabrication of intranasal solid lipid nanoparticulate system for the uptake of therapeutic agents will act as a convincing approach with limited off-site toxicity and increased pharmacological activity. The objective of this study was to formulate, optimize, and evaluate the efficiency of rivastigmine tartrate (RT)-loaded intranasal solid lipid nanoparticles (SLNs) employing the solvent-evaporation diffusion method. To optimize the formulation parameters, the central composite design (CCD) was used. Lipid concentration (X1) and surfactant concentration (X2) were considered to be independent variables, while particle size (Y1), percentage entrapment efficiency (Y2), and percentage drug release (Y3) were considered as responses. The solid lipid was glyceryl monostearate, while the surfactant was polysorbate 80. The optimized formulation has a particle size of 110.2 nm, % entrapment efficiency of 82.56%, and % drug release of 94.86%. The incompatibility of drug excipients was established by differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). Nasal histopathology tests on sheep mucosa revealed that the developed SLNs were safe to utilize for intranasal delivery with no toxicity. Ex vivo permeation investigations revealed that the flux and diffusion coefficients for RT solid lipid nanoparticles and RT solution were 3.378 g/cm2 /h and 0.310-3 cm2 /h, respectively. Stability studies demonstrated that the developed SLNs were stable when stored under various storage conditions. The viability and vitality of adopting a lipid particle delivery system for improved bioavailability via the intranasal route were also established in the in vivo pharmacokinetic investigations. According to the histopathological and pharmacokinetic investigations, the developed formulations were safe, non-lethal, efficient, and robust. These results suggest the potentiality provided by rivastigmine tartrate-loaded solid lipid nanoparticles for nasal delivery.

Morpho-Cultural and Pathogenic Variability of Sclerotinia sclerotiorum Causing White Mold of Common Beans in Temperate Climate.

The present systematic research on cultural, morphological, and pathogenic variability was carried out on eighty isolates of Sclerotinia sclerotiorum collected from major common bean production belts of North Kashmir. The isolates were found to vary in both cultural and morphological characteristics such as colony color and type, colony diameter, number of days for sclerotia initiation, sclerotia number per plate, sclerotial weight, and size. The colony color ranged between white and off-white with the majority. The colony was of three types, in majority smooth, some fluffy, and a few fluffy-at-center-only. Colony diameter ranged between 15.33 mm and 29 mm after 24 h of incubation. The isolates took 4 to 7 days for initiation of sclerotia and varied in size, weight, and number per plate ranging between 14 and 51.3. The sclerotial arrangement pattern on plates was peripheral, sub peripheral, peripheral, and subperipheral, arranged at the rim and scattered. A total of 22 Mycelial compatibility groups (MCGs) were formed with seven groups constituted by a single isolate. The isolates within MCGs were mostly at par with each other. The six isolates representing six MCGs showed variability in pathogenicity with isolate G04 as the most and B01 as the least virulent. The colony diameter and disease scores were positively correlated. Sclerotia were observed to germinate both myceliogenically and carpogenically under natural temperate conditions of Kashmir. Germplasm screening revealed a single resistant line and eleven partially resistant lines against most virulent isolates.