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1.
Indian Pediatr ; 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38584409

RESUMEN

OBJECTIVE: To determine the most appropriate cut-off values of Waist Circumference (WC) and Waist-to-Height Ratio (WHtR) for diagnosing moderate acute malnutrition (MAM) and severe acute malnutrition (SAM) in under-five children. METHODS: This cross-sectional diagnostic accuracy study was conducted between January 2021 and August 2022 in the Department of Pediatrics of a tertiary hospital in Delhi. Children aged 6 months to 5 years attending the outpatient or emergency services were included in the study. Detailed clinical evaluation and anthropometry including measurement of WC were done at enrollment. Body mass index (BMI) and WHtR were calculated. Malnutrition was classified as per the WHO criteria. Receiver operating characteristic curves (sensitivity, specificity) for WC and WHtR (absolute values) were drawn against the standard test of WHO definitions for MAM and SAM to determine the most appropriate cut-offs for diagnosing MAM and SAM. RESULTS: 1500 children with a median (IQR) age of 29 (14, 43) months were enrolled; 21% children had MAM and 11% had SAM as per the WHO criteria. WC < 44.5 cm (sensitivity 74.1%, specificity 71.1%) and WHtR < 0.565 (sensitivity 75.6%, specificity 33.7%) was the best cut-off to identify MAM, whereas WC < 42.3 cm (sensitivity 67.5%, specificity 81.3%) and WHtR < 0.563 (sensitivity 81.3%, specificity 33.4%) was the best cut-off to diagnose SAM. CONCLUSIONS: Waist circumference (< 44.5 cm for MAM; < 42.3 cm for SAM) had a reasonably good sensitivity and specificity for diagnosing MAM and SAM, but the same was not true for WHtR.

2.
J Family Med Prim Care ; 13(2): 471-476, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38605800

RESUMEN

Background: Intense marketing of fast-food items impacts the eating habits among children and adolescents. Various studies suggest that increased screen time leads to increased fast-food consumption and decreased sleep duration, both of which are linked to obesity in growing age. Objectives: To assess screen time and dietary habits among the study group and to estimate their effect on sleep deprivation and obesity. Methods: This cross-sectional study was conducted from January 2019 to December 2019 in three schools in Amritsar selected by lottery method of simple random sampling. Out of 4,226 students, 355 overweight and obese students were interviewed regarding their dietary habits. An informed written assent was taken from the mothers. The information was collected on a semi-structured, pre-designed questionnaire by interviewing the mothers of students between 6 and 11 years of age and the students of 12-16 years. Results: 94.4% of students preferred fast foods to regular meals and 58.3% were in the habit of skipping breakfast. 59.4% had a history of daily intake of fast foods while 76.1% had a habit of consuming fast foods while watching television. Only 31.7% had an adequate sleeping pattern of 9-11 hours and 79.7% of the students had a screen time of over 3 hours. Conclusions: More the screen time, the more the chances of missing meals. Being awake for a long odd time leads to increased consumption of foods/snacks furthermore. Regarding the harmful effects of fast foods, the source of information was from schools, but only 41.4% were aware about these effects.

3.
Epilepsy Behav ; 151: 109608, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38183927

RESUMEN

BACKGROUND: Patients with epilepsy suffer from depression and anxiety that reduces quality of life. Cognitive behavioral therapy (CBT) among various non pharmacological treatment recommended for depression and anxiety. Since there are several articles reporting CBT treatment for depression in patients with epilepsy, we conduct a meta-analysis to evaluate the effectiveness of CBT for adult patients with epilepsy. METHODS: Four electronic databases PubMed, Scopus, Embase, and the Cochrane library searched for relevant studies. A detailed "RISK of bias" assessment has been done for included studies. Funnel plot was used for assessing publication Bias. R Software- RStudio 2022 was used to calculate standard mean difference (SMD). The study has been registered in PROSPERO (CRD42023447655). RESULTS: Eventually, a Total 13 studies involving 1222 patients met the eligibility criteria. There was decline in the Patient Health Questionnaire (PHQ) [SMD = -0.42, 95 % CI = -0.63 to -0.22], Neurologic Disorder Depression Inventory-Epilepsy (NDDI-E) [SMD = -0.53, 95 % CI = -0.75 to -0.31], Beck depression Inventory (BDI) [SMD = -0.69, 95 % CI = -1.08 to -0.30], Hospital Anxiety and Depression Scale-Depression (HADS-D) [SMD = -0.73 , 95 % CI = -0.94 to -0.52] and Hospital Anxiety and Depression Scale Anxiety subscale (HADS-A) [SMD = -0.66, 95 % CI = -0.87 to -0.45] score of the CBT group than that of the control group at post-intervention. The results showed that the improvement in QOLIE-31 score of the CBT group than that of the control group [SMD = 0.67, 95 % CI = 1.33] at post-intervention. CONCLUSION: The result of our study showed that Cognitive behavioral therapy is a superior therapy for treating anxiety and depression in epilepsy patients. CBT was effective in improving Quality of life in patients with epilepsy. However, the sample size varied across the trials, additional high-quality studies are needed in the future.


Asunto(s)
Terapia Cognitivo-Conductual , Epilepsia , Adulto , Humanos , Depresión/etiología , Depresión/terapia , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Terapia Cognitivo-Conductual/métodos , Ansiedad/etiología , Ansiedad/terapia , Epilepsia/complicaciones , Epilepsia/terapia
4.
Biometals ; 37(1): 185-209, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37792256

RESUMEN

Cr (VI) hampers plant growth and yield by reducing essential nutrient uptake as it competes for phosphate and sulfate transporters. Nitric oxide (NO) and mycorrhization play important roles in mitigating Cr (VI) toxicity. Present study aimed to compare the potential of AMF (Arbuscular mycorrhizal fungi)-Rhizoglomus intraradices and NO (0.25 mM) in alleviating Cr (VI) stress (0, 10 and 20 mg/kg) in two differentially tolerant pigeonpea genotypes (Pusa 2001 and AL 201). Cr (VI) toxicity reduced growth, mycorrhizal colonization, nutrient uptake, and overall productivity by inducing reactive oxygen species (ROS) generation, with AL 201 more sensitive than Pusa 2001. NO and AM enhanced activities of soil enzymes, thereby increasing nutrients availability as well as their uptake, with AM more effective than NO. Both amendments reduced oxidative stress and restricted Cr (VI) uptake by increasing the activities of antioxidant and S- assimilatory enzymes, with Pusa 2001 more responsive than AL 201. NO was relatively more efficient in regulating cysteine-H2S system by increasing the activities of biosynthetic enzymes (ATP-sulfurylase (ATPS), O-acetylserine thiol lyase (OASTL), D-cysteine desulfhydrase (DCD) and L-cysteine desulfhydrase (LCD), while AM significantly increased glutathione reductase (GR), γ-glutamylcysteine synthetase (γ-ECS) enzymes activities and resultant glutathione (GSH), phytochelatins (PCs), and non-protein thiols (NP-SH) synthesis. Moreover, co-application of NO and AM proved to be highly beneficial in negating the toxic effects of Cr (VI) due to functional complementarity between them. Study suggested the combined use of NO and AM as a useful strategy in re-establishing pigeonpea plants growing in Cr (VI)-stressed environments.


Asunto(s)
Cromo , Micorrizas , Cromo/toxicidad , Cisteína , Óxido Nítrico/farmacología , Compuestos de Sulfhidrilo , Suelo , Cistationina gamma-Liasa , Glutatión/metabolismo , Genotipo
5.
Chemosphere ; 346: 140631, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37939922

RESUMEN

Growing mechanization has released higher concentrations of toxic metals in water and sediment, which is a critical concern for the environment and human health. Recent studies show that naturally occurring and synthetic iron sulfide particles are efficient at removing these hazardous pollutants. This review seeks to provide a concise summary of the evolution in the production of iron sulfide particles, specifically nanoparticles, through the years. This review presents an outline of the synthesis process for the most dominant forms of iron sulfide: mackinawite (FeS), pyrite (FeS2), pyrrhotite (Fe1-x S), and greigite (Fe3S4). The review confirms that both natural forms of iron sulfide and modified forms of iron sulfide are highly effective at removing different heavy metals and metalloids from water. Concurrently, this review reveals the interaction mechanism between toxic metals and iron sulfide, along with the impact of conditions for remedy and rectification. None the less, modifications and future investigations into the synthesis of novel iron sulfides, their use to adsorb diverse environmental pollutants, and their fate after injection into polluted aquifers, remain crucial to maximizing pollution control.


Asunto(s)
Compuestos Ferrosos , Metales Pesados , Humanos , Sulfuros , Agua
6.
Nanoscale ; 15(47): 19369-19380, 2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-38014549

RESUMEN

The low surface-charge density, poor stability and irreparable surface of triboelectric materials under harsh environments are still some obstacles for developing high-performance triboelectric nanogenerators (TENGs). In particular, a two-dimensional MXene material's surface is likely to be corroded by water molecules under high humidity conditions owing to its hydrophilic nature, limiting the output performance and stability of TENGs. Herein, an approach for fabricating a humidity- and contamination-resistant MXene-based TENG is established using the electrospinning technique. First, nanofibrous layers of MXene/MoS2 composites blended in a cellulosic polymer matrix were prepared, benefitting the high surface roughness and controlled air-trapping pores. Furthermore, the prepared nanofibrous layers were chemically modified with stearic acid (SA), which enhances the hydrophobicity and electronegativity of MXene/MoS2 composites. In a typical synthesis, four different compositions of MXene/MoS2/cellulose acetate nanofibers were prepared, which illustrates that an increasing concentration of MoS2 could effectively tune the surface oxidation, hydrophilic nature, and surface roughness of MXene as well as induce a piezoelectricity-enhanced triboelectric potential. On the other side, the SA modification ultimately generated a superhydrophobic surface with low surface energy and a high water contact angle of ∼154°. The integrated TENG displayed an enhanced output voltage of ∼140 V and an instantaneous power density of ∼2975 mW cm-2 with long-term stability under high humidity conditions. Additionally, the self-cleaning properties were demonstrated, ensuring the sustainability and reusability of the TENG in a contaminated environment. Moreover, the fabricated MXene-based superhydrophobic layer can harvest the energy on dripping water droplets based on the liquid-solid contact-electrification TENG mode. Overall, this work paves the way for the design and development of humidity- and contamination-resistant triboelectric materials and guides the study of harvesting of distributed environmental energy efficiently.

7.
Int J Biometeorol ; 67(10): 1619-1628, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37495744

RESUMEN

The study was carried out to compare the in vitro and in vivo heat shock responses of cattle and buffaloes. The expression of heat responsive genes (HSP70 and HSF family) were studied in vitro in peripheral blood mononuclear cells (PBMCs) of cattle and buffalo. In vivo observations on animals were carried out to investigate the physiological responses of cattle and buffalo at different THI over a period of 14 months. The study indicated that onset and severity of heat stress at different THI varied significantly between cattle and buffalo. Rectal temperature (RT) showed a significant (p < 0.05) increase at THI 67 in buffaloes and at THI 68 in cattle. Significant (p < 0.01) differences in RT between the species were observed at THI 71, 72, and 73. Respiration rate (RR) significantly (p < 0.05) increased at THI 70 in both the species and significant (p < 0.05) differences in RR were observed between the species at THI 65, 68, 69, and 74. THI had significant (p < 0.05) effect on blood glucose and blood electrolytes of the species with increased levels at higher THI. Serum AST and ALT levels showed less pronounced changes over increasing THI. Heat stress-associated expressions of HSP 70 genes followed temporal changes with incremental THI. The expression of HSPA8 was consistent at lower THI whereas upregulation of HSPA1A and HSPA1L was evident at higher THI. The study concludes that changes in physiological parameters such as RT and RR occur in a phasic pattern in both species and onset of heat stress was early in buffalo as compared to cattle.


Asunto(s)
Búfalos , Leucocitos Mononucleares , Animales , Bovinos , Respuesta al Choque Térmico/genética , Proteínas HSP70 de Choque Térmico/genética , Frecuencia Respiratoria , Calor , Humedad
8.
Langmuir ; 39(8): 2995-3005, 2023 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-36786558

RESUMEN

Developing cost-effective and earth-abundant noble-metal-free electrocatalysts is imperative for the imminent electrochemical society. Two-dimensional Ti3C2TX (MXene) exhibits tunable properties with high electrical conductivity and a large specific surface area, which improve its electrochemical performance. Herein, the low-temperature annealing method is used to enrich MXene with a maximum number of Ti-O terminals without formation of titanium dioxide (TiO2) under neutral pH conditions. MXene annealed at 200 °C is found to have a large number of Ti-O termination groups, resulting in a large electrochemically active surface area and increased active sites (-O termination groups) and hence excellent electrocatalytic performance compared to other samples as well as previous reported work. The optimized sample is found to show the lowest overpotential value of 0.07 V at 10 mA cm-2 and a Tafel slope of 0.15 V dec-1 toward the hydrogen evolution reaction (HER), whereas for the methanol oxidation reaction (MOR), the current density is 18.08 mA cm-2, and the onset potential is -0.51 V. In addition, it also shows long-term stability and durability toward HER as well as MOR.

9.
Stem Cell Rev Rep ; 19(2): 475-490, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-35986129

RESUMEN

RNA-binding proteins (RBPs) are pivotal for regulating gene expression as they are involved in each step of RNA metabolism. Several RBPs are essential for viable growth and development in mammals. RNA-binding motif 47 (RBM47) is an RRM-containing RBP whose role in mammalian embryonic development is poorly understood yet deemed to be essential since its loss in mouse embryos leads to perinatal lethality. In this study, we attempted to elucidate the significance of RBM47 in cell-fate decisions of mouse embryonic stem cells (mESCs). Downregulation of Rbm47 did not affect mESC maintenance and the cell cycle but perturbed the expression of primitive endoderm (PrE) markers and increased GATA4 + PrE-like cells. However, the PrE misregulation could be reversed by either overexpressing Rbm47 or treating the knockdown mESCs with the inhibitors of FGFR or MEK, suggesting an implication of RBM47 in regulating FGF-ERK signaling. Rbm47 knockdown affected the multi-lineage differentiation potential of mESCs as it regressed teratoma in NSG mice and led to a skewed expression of differentiation markers in serum-induced monolayer differentiation. Further, lineage-specific differentiation revealed that Rbm47 is essential for proper differentiation of mESCs towards neuroectodermal and endodermal fate. Taken together, we assign a hitherto unknown role(s) to RBM47 in a subtle regulation of mESC differentiation.


Asunto(s)
Endodermo , Células Madre Embrionarias de Ratones , Proteínas de Unión al ARN , Animales , Ratones , Diferenciación Celular/genética , Desarrollo Embrionario , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo
10.
Folia Microbiol (Praha) ; 67(5): 757-775, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35523991

RESUMEN

Wilt (Fusarium oxysporum f. sp. lentis; Fol) is one of the major diseases of lentil worldwide. Two hundred and thirty-five isolates of the pathogen collected from 8 states of India showed substantial variations in morphological characters such as colony texture and pattern, pigmentation and growth rate. The isolates were grouped as slow (47 isolates), medium (118 isolates) and fast (70 isolates) growing. The macroconidia and microconidia (3.0-77.5 × 1.3-8.8 µm for macroconidia and 1.8-22.5 × 0.8-8.0 µm for microconidia for length × width) were variable in size and considering the morphological features, the populations were grouped into 12 categories. Seventy representative isolates based on their morphological variability and place of origin were selected for further study. A set of 10 differential genotypes was identified for virulence analysis and based on virulence patterns on these 10 genotypes, 70 Fol isolates were grouped into 7 races. Random amplified polymorphic DNA (RAPD), universal rice primers (URPs), inter simple sequence repeats (ISSR) and sequence-related amplified polymorphism (SRAP) were used for genetic diversity analysis. URPs, ISSR and SRAP markers gave 100% polymorphism while RAPD gave 98.9% polymorphism. The isolates were grouped into seven clusters at genetic similarities ranging from 21 to 80% using unweighted paired group method with arithmetic average analysis. The major clusters include the populations from northern and central regions of India in distinct groups. All these three markers proved suitable for diversity analysis, but their combined use was better to resolve the area specific grouping of the isolates. The sequences of rDNA ITS and TEF-1α genes of the representative isolates were analysed. Phylogenetic analysis of ITS region grouped the isolates into two major clades representing various races. In TEF-1α analysis, the isolates were grouped into two major clades with 28 isolates into one clade and 4 remaining isolates in another clade. The molecular groups partially correspond to the lentil growing regions of the isolates and races of the pathogen.


Asunto(s)
Cicer , Fusarium , Lens (Planta) , Variación Biológica Poblacional , Cartilla de ADN , ADN Ribosómico , Fusarium/genética , Variación Genética , Lens (Planta)/genética , Filogenia , Enfermedades de las Plantas , Técnica del ADN Polimorfo Amplificado Aleatorio
11.
ACS Appl Mater Interfaces ; 14(22): 25135-25146, 2022 Jun 08.
Artículo en Inglés | MEDLINE | ID: mdl-35613701

RESUMEN

N95 respirator face masks serve as effective physical barriers against airborne virus transmission, especially in a hospital setting. However, conventional filtration materials, such as nonwoven polypropylene fibers, have no inherent virucidal activity, and thus, the risk of surface contamination increases with wear time. The ability of face masks to protect against infection can be likely improved by incorporating components that deactivate viruses on contact. We present a facile method for covalently attaching antiviral quaternary ammonium polymers to the fiber surfaces of nonwoven polypropylene fabrics that are commonly used as filtration materials in N95 respirators via ultraviolet (UV)-initiated grafting of biocidal agents. Here, C12-quaternized benzophenone is simultaneously polymerized and grafted onto melt-blown or spunbond polypropylene fabric using 254 nm UV light. This grafting method generated ultrathin polymer coatings which imparted a permanent cationic charge without grossly changing fiber morphology or air resistance across the filter. For melt-blown polypropylene, which comprises the active filtration layer of N95 respirator masks, filtration efficiency was negatively impacted from 72.5 to 51.3% for uncoated and coated single-ply samples, respectively. Similarly, directly applying the antiviral polymer to full N95 masks decreased the filtration efficiency from 90.4 to 79.8%. This effect was due to the exposure of melt-blown polypropylene to organic solvents used in the coating process. However, N95-level filtration efficiency could be achieved by wearing coated spunbond polypropylene over an N95 mask or by fabricating N95 masks with coated spunbond as the exterior layer. Coated materials demonstrated broad-spectrum antimicrobial activity against several lipid-enveloped viruses, as well as Staphylococcus aureus and Escherichia coli bacteria. For example, a 4.3-log reduction in infectious MHV-A59 virus and a 3.3-log reduction in infectious SuHV-1 virus after contact with coated filters were observed, although the level of viral deactivation varied significantly depending on the virus strain and protocol for assaying infectivity.


Asunto(s)
Compuestos de Amonio , Virus , Antivirales/farmacología , Máscaras , Respiradores N95 , Polímeros/farmacología , Polipropilenos
12.
Bioprocess Biosyst Eng ; 45(6): 1019-1031, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35355104

RESUMEN

Xylitol is a well-known sugar alcohol with exponentially rising market demand due to its diverse industrial applications. Organic agro-industrial residues (OAIR) are economic alternative for the cost-effective production of commodity products along with addressing environmental pollution. The present study aimed to design a process for xylitol production from OAIR via microbial fermentation with Pseudomonas gessardii VXlt-16. Parametric analysis with Taguchi orthogonal array approach resulted in a conversion factor of 0.64 g xylitol/g xylose available in untreated sugarcane bagasse hydrolysate (SBH). At bench scale, the product yield increased to 71.98/100 g (0.66 g/L h). 48.49 g of xylitol crystals of high purity (94.56%) were recovered after detoxification with 2% activated carbon. Cost analysis identified downstream operations as one of the cost-intensive parts that can be countered by adsorbent recycling. Spent carbon, regenerated with acetic acid washing can be reused for six cycles effectively and reduced downstream cost by about ≈32%. The strategy would become useful in the cost-effective production of several biomass-dependent products like proteins, enzymes, organic acids, as well.


Asunto(s)
Saccharum , Xilitol , Celulosa/química , Costos y Análisis de Costo , Fermentación , Hidrólisis , Pseudomonas , Saccharum/metabolismo , Xilosa/metabolismo
13.
Indian J Psychiatry ; 63(5): 433-438, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34789930

RESUMEN

AIMS: Special drive campaigns on substance use disorders (SUDs) in India are usually organized in educational institutes, non-governmental organizations, or few selected localities. Hard to reach communities of construction, prison, and industrial sites quite often remain uncovered. MATERIALS AND METHODS: During a month-long special drive in 2019, under a cross-sectional study, we reached these communities of Solan town through awareness camps and incorporated standardized screening tools for evaluating morbidity patterns of SUDs. RESULTS: Statistically significant relationship existed between 360 participants (90.8% males, 9.2% females; mean age of 33 years) and their educational levels with χ2 (1, n = 360) =130.59, P = 0.000. Fagerstrom's scale inferred very high nicotine dependence in 10.6%, 7.9%, and 2.4% of prisoners, industrial workers, and laborers, respectively. Whereas, Fagerstrom scale for smokeless tobacco revealed 31% of significant dependence potential amongst laborers. Alcohol use disorder identification test revealed 28 persons with harmful alcohol dependence. Drug abuse screening test revealed 13.6% of prisoners having moderate level drug abuse potential. The Kruskal-Wallis test showed a statistically significant difference, in levels and potential of substance use in construction, prison, and industrial sites. CONCLUSION: The study proved the utility of special drives in evaluating SUDs morbidity patterns in hard-to-reach communities.

14.
Mol Cell Biochem ; 476(12): 4493-4505, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34499322

RESUMEN

RNA-binding proteins (RBPs) are critical players in the post-transcriptional regulation of gene expression and are associated with each event in RNA metabolism. The term 'RNA-binding motif' (RBM) is assigned to novel RBPs with one or more RNA recognition motif (RRM) domains that are mainly involved in the nuclear processing of RNAs. RBM47 is a novel RBP conserved in vertebrates with three RRM domains whose contributions to various aspects of cellular functions are as yet emerging. Loss of RBM47 function affects head morphogenesis in zebrafish embryos and leads to perinatal lethality in mouse embryos, thereby assigning it to be an essential gene in early development of vertebrates. Its function as an essential cofactor for APOBEC1 in C to U RNA editing of several targets through substitution for A1CF in the A1CF-APOBEC1 editosome, established a new paradigm in the field. Recent advances in the understanding of its involvement in cancer progression assigned RBM47 to be a tumor suppressor that acts by inhibiting EMT and Wnt/[Formula: see text]-catenin signaling through post-transcriptional regulation. RBM47 is also required to maintain immune homeostasis, which adds another facet to its regulatory role in cellular functions. Here, we review the emerging roles of RBM47 in various biological contexts and discuss the current gaps in our knowledge alongside future perspectives for the field.


Asunto(s)
Desaminasas APOBEC-1/metabolismo , Neoplasias/patología , Edición de ARN , Proteínas de Unión al ARN/metabolismo , Vertebrados/crecimiento & desarrollo , Desaminasas APOBEC-1/genética , Animales , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Proteínas de Unión al ARN/genética
15.
Comput Methods Programs Biomed ; 209: 106347, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34399152

RESUMEN

BACKGROUND AND OBJECTIVES: Overexpression of prosurvival Bcl-2 family members make tumor cells resistant to conventional cancer therapeutic agents. It is commonly observed feature in many different types of human tumors. Hence, small-molecules as Bcl-2 inhibitors may have a promising therapeutic potential for the treatment of human cancer. The given study focusses on development of novel and small Bcl-2 inhibitors using ligand-based drug design approach. METHODS: Ligand based pharmacophore was generated using the PHASE tool of Schrödinger and screened ZINC database through ZINCPharmer webserver to identify compounds with similar features. Compounds having good fitness score were selected for molecular docking and binding interactions were compared with drugs in market as well as trials. QSAR model was generated using advanced AutoQSAR tool and validated for prediction of unknown compounds. QSAR prediction of in silico active identified three potential compounds and were subjected to investigate stability by molecular dynamics simulations and MM-PBSA binding energy calculations. RESULTS: Study identified three in silico potential molecules with good stability and binding affinity. Further substructure search and pIC50 value prediction has identified six more molecules. Total nine molecules have demonstrated good drug likeness features. CONCLUSION: Final oral rat LD50 calculation of nine molecules has identified three hit molecules i.e., ZINC76760927, ZINC76768675 and ZINC52767796 for further in vitro and in vivo testing as safe and potential Bcl-2 inhibitors.


Asunto(s)
Neoplasias , Relación Estructura-Actividad Cuantitativa , Animales , Ligandos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Neoplasias/tratamiento farmacológico , Ratas
16.
Int J Pept Res Ther ; 27(3): 1799-1813, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33850482

RESUMEN

It is well established fact that peptides from various foods offer human health benefits displaying diverse functionalities. Millets considered as super foods is a major alternative in recent days for traditional diet being rich in proteins and fibre along with trace minerals and vitamins. In this connection, proteins from Buckwheat and Quinoa were digested by in vitro simulation digestion for the generation of peptides, analyzed by nLC-MS/MS and the functional annotations of the identified proteins/peptides were carried out. The study led to the identification of 34 small peptides and their parent proteins clustered into 4 gene functional groups and their localization prediction indicated their involvement in energy metabolism, transport and storage. Interestingly, the identified peptides maximally displayed DPP-IV and ACE inhibitions. The present study was extended to unravel ACE-2 inhibition targeting COVID-19 by selecting ACE-2-Spike binding domain for molecular docking studies. The NWRTVKYG interacted with the ACE-2-Spike interface displaying the feasible binding energy (- 213.63) and docking score (- 12.43) and the MD simulation revealed the ability of the peptide in stabilizing the protein-peptide composite. The present investigation thus establishes newer vista for food derived peptides having ACE-2 inhibitory potential as tentative strategy for SARS-CoV-2 therapeutics.

17.
J Tradit Complement Med ; 10(2): 158-165, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32257879

RESUMEN

Plant-based synthesis of nanoparticles has generated worldwide interest because of cost-effectiveness, eco-friendly nature and plethora of applications. In the present investigation, antimicrobial potential of silver nanoparticles (AgNPs) of methanolic extract of Aegle marmelos fruit has been investigated. Agar well diffusion method was used for determining antimicrobial activity of solvent extracts (viz., petroleum ether, chloroform, acetone, methanol and aqueous), and AgNPs. Among these, methanolic extract of A. marmelos showed highest inhibitory activity against B. cereus (16.17 ±â€¯0.50 mm) followed by P. aeruginosa (13.33 ±â€¯0.62 mm) and E. coli. Phytochemical analysis of methanolic extract of A. marmelos revealed the presence of tannins, saponins, steroids, alkaloids, flavonoids, and glycosides. AgNPs synthesized using A. marmelos methanolic extract, characterized by UV-Visible spectroscopy, atomic force microscopy, dynamic light scattering, and X-ray diffraction showed a peak at 436 nm and size ranged between 159 and 181 nm. Evaluation of the antimicrobial potential of green synthesized AgNPs recorded the highest inhibitory activity against B. cereus (19.25 ±â€¯0.19 mm) followed by P. aeruginosa (16.50 ±â€¯0.30 mm) and S. dysentriae. The minimum inhibitory concentration (MIC) of synthesized AgNPs was found to be in the range of 0.009875-0.0395 mg/100 µl which was quite lower than the MIC of crude extract i.e. 0.0781-0.3125 mg/100 µl. The results obtained indicated that the different crude extracts of A. marmelos plant as well as AgNPs have a strong and effective antimicrobial potential that provide a marvelous source for the development of new drug molecules of herbal origin which may be used for the welfare of humanity.

18.
Pharmacol Rep ; 72(2): 456-464, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32048262

RESUMEN

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease of the elderly. Current therapies are only symptomatic, and have no disease-modifying effect. Therefore, disease progresses continuously over time, presenting with both motor and non-motor features. The precise molecular basis for PD is still elusive, but the aggregation of the protein alpha-synuclein (α-syn) is a key pathological hallmark of the disease and is, therefore, a major focus of current research. Considering the intrinsic properties of cell-penetrating peptides (CPPs) for mediating drug delivery of neurotherapeutics across the blood brain barrier (BBB), these might open novel opportunities for the development of new solutions for the treatment of brain-related aspects of PD and other neurodegenerative disorders. METHODS: Here, we synthesized solid-phase CPPs using an amphipathic model peptide (MAP) conjugated with the drug Rasagiline (RAS), which we named RAS-MAP, and evaluated its effect on α-syn inclusion formation in a human cell-based model of synucleinopathy. RESULTS: We found that treatment with RAS-MAP at low concentrations (1-3 µM) reduced α-syn aggregation in cells. CONCLUSIONS: For the first time, we report that conjugation of a current drug used in the therapy of PD with CPP reduces α-syn aggregation, which might prove beneficial in PD and other synucleinopathies.


Asunto(s)
Péptidos de Penetración Celular/química , Portadores de Fármacos/química , Indanos/farmacología , Fármacos Neuroprotectores/farmacología , Agregación Patológica de Proteínas/prevención & control , alfa-Sinucleína/metabolismo , Barrera Hematoencefálica/metabolismo , Técnicas de Cultivo de Célula , Línea Celular Tumoral , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Humanos , Indanos/administración & dosificación , Fármacos Neuroprotectores/administración & dosificación , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Técnicas de Síntesis en Fase Sólida
19.
Anesth Essays Res ; 14(3): 412-419, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-34092851

RESUMEN

BACKGROUND: During the administration of general anesthesia, direct laryngoscopy and endotracheal intubation cause an increase in heart rate, arterial pressure, and dysrhythmias in upto 90% of patients. These changes can be particularly hazardous for patients with cerebral or coronary diseases. Both clonidine and gabapentin have been used for anesthetic effects, but a better drug for controlling hemodynamic parameters is being investigated. AIMS: The study was done to evaluate and compare the efficacy of oral clonidine 0.3 mg and oral gabapentin 900 mg as a premedication for attenuation of pressor response to laryngoscopy and endotracheal intubation. MATERIALS AND METHODS: After obtaining approval from the ethics committee, 75 patients, American Society of Anesthesiologists physical status classes I and II between the ages of 18 and 60 years scheduled to undergo elective noncardiac surgical procedure were enrolled in the study. Patients were randomized into three groups of 25 each who received 0.3 mg clonidine, 900 mg gabapentin, and placebo. The hemodynamic parameters were recorded at various time intervals along with any adverse effects. STATISTICAL ANALYSIS: Quantitative variables were compared using unpaired t-test between the two groups and ANOVA for three groups. Qualitative variables were compared using the Chi-square test/Fisher's exact test. P < 0.05 was considered statistically significant. RESULTS: In our study, we found that both clonidine and gabapentin are effective premedicants by oral route 2 h before induction of anesthesia to blunt the hemodynamic response to laryngoscopy and intubation as compared to placebo. Between clonidine and gabapentin, clonidine was found to be more effective with respect to blunting of systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP), although found to be statistically significant only at 15 min with respect to SBP and DBP. CONCLUSION: Using clonidine or gabapentin, one can effectively provide stable hemodynamic conditions during laryngoscopy and endotracheal intubation, but more so with clonidine.

20.
J Biomol Struct Dyn ; 38(8): 2207-2214, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31179877

RESUMEN

In this work, we have studied the effect of size and aqueous medium on the low-frequency dynamics, physical properties like melting temperature and glass transition temperature and chemical properties like catalytic activation energy of spherical virus using Lindemann's criteria and Arrhenius relation under their dynamic limit. The melting temperature and catalytic activation energy decrease with decreasing size of spherical virus. The glass transition temperature which increases with decreasing size of the virus is analyzed through the size dependent melting temperature. The melting temperature and catalytic activation energy of spherical virus of particular size increases when it is embedded in glycerol or water due to mismatch of the physical properties at the interface of virus and surrounding medium. In addition, the glass transition temperature of free and glycerol/water embedded virus using low-frequency vibrational modes has been calculated under the framework of elastic continuum approximation model. The glass transition temperature of spherical virus decreases with size when embedded in glycerol or water. A correlation between [Formula: see text] and [Formula: see text] is also drawn for spherical viruses. The study can be useful for spherical virus borne therapy i.e. in detecting and killing of the spherical viruses using a principle based on acoustic phonons (sound waves) resonance.Communicated by Ramaswamy H. Sarma.


Asunto(s)
Virus , Agua , Vidrio , Glicerol , Temperatura
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