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1.
J Hypertens ; 42(9): 1573-1580, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39088765

RESUMEN

BACKGROUND: The relationship between self-rated health (SRH) and cardiovascular events in individuals with hypertension, but without diabetes mellitus, is understudied. METHODS: We performed a post hoc analysis of data from SPRINT (Systolic Blood Pressure Intervention Trial). SRH was categorized into excellent, very good, good and fair/poor. Using multivariable Cox regression, we estimated hazard ratios and 95% confidence intervals (CIs) for the association of SRH with both all-cause mortality and a composite of cardiovascular events (the primary outcome), which was defined to include myocardial infarction (MI), other acute coronary syndromes, stroke, acute decompensated heart failure, and cardiovascular death. RESULTS: We included 9319 SPRINT participants (aged 67.9 ±â€Š9 years, 35.6% women) with a median follow-up of 3.8 years. Compared with SRH of excellent, the risk [hazard ratio (95% CI)] of the primary outcome associated with very good, good, and fair/poor SRH was 1.11(0.78-1.56), 1.45 (1.03-2.05), and 1.87(1.28-2.75), respectively. Similarly, compared with SRH of excellent, the risk of all-cause mortality [hazard ratio (95% CI)] associated with very good, good, and fair/poor SRH was 1.13 (0.73-1.76), 1.72 (1.12-2.64), and 2.11 (1.32-3.38), respectively. Less favorable SRH (LF-SRH) was also associated with a higher risk of each component of the primary outcome and serious adverse events (SAE). CONCLUSION: Among individuals with hypertension, SRH is independently associated with the risk of incident cardiovascular events, all-cause mortality, and SAE. Our study suggest that guidelines should consider the potential significance of including SRH in the clinical history of patients with hypertension.


Asunto(s)
Enfermedades Cardiovasculares , Hipertensión , Humanos , Hipertensión/complicaciones , Hipertensión/epidemiología , Femenino , Masculino , Anciano , Persona de Mediana Edad , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/epidemiología , Autoinforme , Incidencia , Factores de Riesgo , Estado de Salud
2.
Pathogens ; 13(7)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-39057771

RESUMEN

Plants face many environmental challenges and have evolved different strategies to defend against stress. One strategy is the establishment of mutualistic associations with endophytic microorganisms which contribute to plant defense and promote plant growth. The fungal entomopathogen Metarhizium robertsii is also an endophyte that can provide plant-protective and growth-promoting benefits to the host plant. We conducted a greenhouse experiment in which we imposed stress from deficit and excess soil moisture and feeding by larval black cutworm (BCW), Agrotis ipsilon, to maize plants that were either inoculated or not inoculated with M. robertsii (Mr). We evaluated plant growth and defense indicators to determine the effects of the interaction between Mr, maize, BCW feeding, and water stress. There was a significant effect of water treatment, but no effect of Mr treatment, on plant chlorophyl, height, and dry biomass. There was no effect of water or Mr treatment on damage caused by BCW feeding. There was a significant effect of water treatment, but not Mr treatment, on the expression of bx7 and rip2 genes and on foliar content of abscisic acid (ABA), 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one (DIMBOA), and gibberellin 19 (GA19), whereas GA53 was modulated by Mr treatment. Foliar content of GA19 and cis-Zeatin (cZ) was modulated by BCW feeding. In a redundancy analysis, plant phenology, plant nutrient content, and foliar DIMBOA and ABA content were most closely associated with water treatments. This study contributes toward understanding the sophisticated stress response signaling and endophytic mutualisms in crops.

3.
Alzheimers Dement ; 20(7): 4602-4612, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-38842100

RESUMEN

INTRODUCTION: We investigated the effect vigorous physical activity (VPA) on the risk of incident mild cognitive impairment (MCI) and probable dementia among individuals with high-risk hypertension. METHODS: Baseline self-reported frequency of VPA was categorized into low VPA (<1 session/week), and high VPA (≥1 session/week). We used multivariate Cox regression analysis to examine the association of VPA categories with incident MCI and probable dementia events. RESULTS: Participants in the high VPA category, compared with low VPA, experienced lower events rates (per 1000 person-years) of MCI (13.9 vs 19.7), probable dementia (6.3 vs 9.0), and MCI/probable dementia (18.5 vs 25.8). In the multivariate Cox regression model, high VPA, compared with low VPA, was associated with lower risk of MCI, probable dementia, and MCI/probable dementia (HR [95% CI]: 0.81 [0.68-0.97], 0.80 [0.63-1.03], and 0.82 [0.70-0.96]), respectively. DISCUSSION: This study provides evidence that VPA may preserve cognitive function in high-risk patients with hypertension. HIGHLIGHTS: Hypertension is associated with an increased risk of cognitive impairment Physical activity (PA) is associated with a lower risk of decline in cognition The effect of ≥1 sessions of vigorous-intensity PA (VPA) per week was assessed This analysis included SPRINT MIND trial participants with high-risk hypertension ≥1 VPA sessions/week was associated with lower risk of future cognitive impairment.


Asunto(s)
Disfunción Cognitiva , Ejercicio Físico , Hipertensión , Humanos , Disfunción Cognitiva/epidemiología , Masculino , Femenino , Hipertensión/epidemiología , Anciano , Demencia/epidemiología , Incidencia , Factores de Riesgo , Persona de Mediana Edad
4.
Front Biosci (Landmark Ed) ; 29(4): 165, 2024 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-38682212

RESUMEN

The Editors-in-Chief have retracted the article titled "[Neuroprotection against Aluminum Chloride-Induced Hippocampus Damage in Albino Wistar Rats by Leucophyllum frutescens (Berl.) I.M. Johnst. Leaf Extracts: A Detailed Insight into Phytochemical Analysis and Antioxidant and Enzyme Inhibition Assays]" ([1]) due to significant concerns regarding the reliability and integrity of the data presented. After the publication of the article, several issues were brought to our attention regarding the originality and authenticity of the visual data within the manuscript. Specifically, Figure 4 of the article contains images that are identical to those in the previously published papers [2, 3]. This duplication of images raises serious questions about the validity of the results and the adherence to ethical standards of research. Despite multiple attempts to contact the authors for an explanation and an opportunity to address these concerns, no satisfactory response was provided. Given the lack of accountability and the serious nature of the academic misconduct implied, the Editor-in-Chief, after careful consideration and in accordance with the publication's ethical guidelines, has decided to retract the article.

5.
Nanomedicine (Lond) ; 19(11): 965-978, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38593058

RESUMEN

Aims: Desvenlafaxine (DES) in conventional dosage forms shows initial burst release after oral administration, leading to exaggeration of its side effects. These side effects can be overcome by a sustained-release dosage form using the chemically inert, low-melting-point lipid Compritol® 888 ATO, as it reduces initial burst release. Materials & methods: The potential of DES-loaded solid lipid nanoparticles (DES-SLNs) synthesized by ultrasonication-assisted hot-melt encapsulation to modify the release of DES was investigated. Results: The entrapment efficiency of DES-SLNs was 65.90% with the in vitro release profile showing a sustained-release behavior achieving 81% cumulative release within 16 h without initial burst release. Conclusion: DES-SLNs are a potential carrier for sustained release of water-soluble antidepressant drugs such as DES.


[Box: see text].


Asunto(s)
Preparaciones de Acción Retardada , Succinato de Desvenlafaxina , Liberación de Fármacos , Nanopartículas , Succinato de Desvenlafaxina/química , Nanopartículas/química , Preparaciones de Acción Retardada/química , Ácidos Grasos/química , Portadores de Fármacos/química , Antidepresivos/química , Tamaño de la Partícula , Lípidos/química , Humanos , Composición de Medicamentos/métodos
6.
Front Chem ; 12: 1379463, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38680459

RESUMEN

Background: V. canescens Wall, a plant renowned for its ethno-medical properties, was investigated in this study for its antioxidant potential based on its wide therapeutic applications in traditional healthcare systems. The study aimed to assess the antioxidant potential of the plant extract/fractions and to predict the active phytochemicals using computational techniques. Methods: Five fractions were obtained from the crude methanolic extract of Viola canescens, and six concentrations (25, 50, 75, 100, 125, and 150 µg/mL) were prepared for each fraction. The antioxidant activity of these fractions was evaluated using the Tetraoxomolybdate (VI) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. In-silico docking studies and molecular dynamic simulations were conducted to further elucidate the molecular interactions underlying the antioxidant activity. Results: The aqueous extract of V. canescens exhibited significant antioxidant and free radical scavenging activity against DPPH. Additionally, the crude flavonoid extract demonstrated moderate activity with IC50 value of 57.863 µg/mL, indicating potent inhibition of cell growth. In-silico docking studies revealed a strong interaction between emetine and the aromatase protein, suggesting its potential as an antioxidant. Conclusion: The study findings highlight the antioxidant potential of V. canescens extract, indicating its suitability as a source of natural antioxidants. These results suggest its potential application in pharmaceutical preparations aimed at harnessing antioxidant properties for therapeutic purposes.

7.
Sci Rep ; 14(1): 449, 2024 01 03.
Artículo en Inglés | MEDLINE | ID: mdl-38172191

RESUMEN

The coronavirus (COVID-19) pandemic has not only had a severe impact on global health but also poses a threat to the environment. This research aims to explore an innovative approach to address the issue of increased waste generated by the pandemic. Specifically, the study investigates the utilization of discarded face masks in combination with recycled concrete aggregate (RCA) and Silica Fume (SFM) in civil construction projects. The disposable face masks were processed by removing the ear loops and nose strips, and then cutting them into small fibers measuring 20 mm in length, 5 mm in width, and 0.46 mm in thickness, resulting in an aspect ratio of 24. Various proportions of SFM and RCA were incorporated into the concrete mix, with a focus on evaluating the compressive strength, split tensile strength, and durability of the resulting material. The findings indicate that the addition of SFM led to improvements in both compressive and split tensile strength, while no significant impact on durability was observed.


Asunto(s)
Administración de Residuos , Administración de Residuos/métodos , Dióxido de Silicio , Máscaras , Materiales de Construcción , Residuos Industriales/análisis
8.
Saudi Pharm J ; 32(2): 101939, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38261891

RESUMEN

Many Ruellia species have been utilized in traditional medicine and despite the prevalent use of Ruellia tweediana in folk medicine, its antioxidant potential and polyphenol content have not been investigated. Therefore, the present study aimed to explore the medicinal value of R. tweediana by evaluating its total phenolic (TPC) and flavonoid contents (TFC), GC-MS analysis, antioxidant, antibacterial, and enzyme inhibition activities. The TPC and TFC of the extract/fractions were assessed using the Folin-Ciocalteu and aluminum trichloride methods, respectively. To determine the antioxidant capacity, five different assays were used: DPPH, ABTS, CUPRAC, FRAP, and metal chelating assays. The inhibition activity against α-glucosidase, α-amylase, cholinesterases, and lipoxygenase enzymes was also analyzed. Furthermore, GC-MS was performed for chemical screening of non-polar fraction. The methanol extract showed the maximum TPC (167.34 ± 2.23 mg GAE/g) and TFC (120.43 ± 1.71 mg RE/g) values among all the tested samples. GC-MS screening of the n-hexane fraction showed the presence of 40 different phytoconstituents. The results demonstrated the highest scavenging potential of the methanol extract against DPPH (167.79 ± 2.75 mg TE/g) and ABTS (255.32 ± 2.91 mg TE/g) radicals, as well as the metal-reducing capacity measured by CUPRAC (321.34 ± 3.09 mg TE/g), FRAP (311.32 ± 2.91 mg TE/g), and metal chelating assay (246.78 ± 10.34 mg EDTAE/g). Notably, the n-hexane fraction revealed the highest α-glucosidase and α-amylase inhibition activity (186.8 ± 2.84 and 179.7 ± 4.32 mg ACAE/g, respectively) while methanol extract showed highest acetylcholinesterase and butyrylcholinesterase inhibition activity (198.6 ± 3.31 and 184.3 ± 2.92 mg GALE/g, respectively). The GC-MS identified Lupeol showed best binding affinity with all docked enzymes as compared to standard compounds. The presence of bioactive phytoconstituents showed by GC-MS underscores the medicinal importance of R. tweediana, making it a promising candidate for natural medicine.

9.
Reprod Domest Anim ; 59(1): e14502, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38059393

RESUMEN

Testicular development and spermatogenesis are complex phenomena controlled by various genetic factors, including miRNA-based post-transcriptional gene expression regulation. Exploring the miRNA expression patterns during testicular development in Dezhou donkeys would enhance our understanding of equine fertility and spermatogenesis. In this investigation, we examined the testicular miRNA profiles at various stages of development. The experimental animals were divided into three groups based on their developmental stages: 2 months old (juvenile: n = 3), 12 months old (adolescent; n = 3) and 24 months old (adult; n = 3) donkeys. Total RNA was extracted from dissected testicles for miRNA sequencing and analysis. In total, 586 miRNAs, including 451 known miRNAs and 135 novel miRNAs, were identified. Among identified miRNAs, 315 displayed age-dependent expression differences. The levels of miRNA expression in the juvenile group were significantly higher than in the adolescent or adult groups. The MiR-483 exhibited the maximum fold change between juvenile and adolescent groups. Several screened genes, including SLC45A4 and TFCP2L1, have been linked to male reproductive pathways in donkeys. In addition, miR-744 was predicted to regulate SPIN2B, a gene implicated in spermatocyte cell cycle progression and genomic integrity of spermatozoa. These results contribute to our comprehension of microRNA regulation during testicular development and spermatogenesis in Dezhou donkeys. The identified microRNAs and their target genes have the potential to serve as biomarkers for evaluating the reproductive capacity of stud donkeys.


Asunto(s)
MicroARNs , Testículo , Masculino , Animales , Caballos/genética , Testículo/metabolismo , Equidae/genética , Espermatogénesis/genética , MicroARNs/genética , MicroARNs/metabolismo , Espermatocitos
10.
Plant Sci ; 340: 111968, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38157889

RESUMEN

Grain Width and Weight 2 (GW2) is an E3-ubiquitin ligase-encoding gene that negatively regulates the size and weight of the grain in cereal species. Therefore, disabling GW2 gene activity was suggested for enhancing crop productivity. We show here that CRISPR/Cas-mediated mutagenesis of the barley GW2.1 homologue results in the development of elongated grains and increased protein content. At the same time, GW2.1 loss of function induces a significant grain yield deficit caused by reduced spike numbers and low grain setting. We also show that the converse effect caused by GW2.1 absence on crop yield and protein content is largely independent of cultivation conditions. These findings indicate that the barley GW2.1 gene is necessary for the optimization between yield and grain traits. Altogether, our data show that the loss of GW2.1 gene activity in barley is associated with pleiotropic effects negatively affecting the development of generative organs and consequently the grain production. Our findings contribute to the better understanding of grain development and the utilisation of GW2.1 control in quantitative and qualitative genetic improvement of barley.


Asunto(s)
Grano Comestible , Hordeum , Grano Comestible/genética , Hordeum/genética , Fenotipo , Mutación
11.
PLoS One ; 18(12): e0294348, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38064451

RESUMEN

The study presents a meshless computational approach for simulating the three-dimensional multi-term time-fractional mobile-immobile diffusion equation in the Caputo sense. The methodology combines a stable Crank-Nicolson time-integration scheme with the definition of the Caputo derivative to discretize the problem in the temporal direction. The spatial function derivative is approximated using the inverse multiquadric radial basis function. The solution is approximated on a set of scattered or uniform nodes, resulting in a sparse and well-conditioned coefficient matrix. The study highlights the advantages of meshless method, particularly their simplicity of implementation in higher dimensions. To validate the accuracy and efficacy of the proposed method, we performed numerical simulations and compared them with analytical solutions for various test problems. These simulations were carried out on computational domains of both rectangular and non-rectangular shapes. The research highlights the potential of meshless techniques in solving complex diffusion problems and its successful applications in groundwater contamination and other relevant fields.


Asunto(s)
Agua Subterránea , Modelos Teóricos , Movimientos del Agua , Soluciones , Difusión
12.
Mol Syndromol ; 14(6): 469-476, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38058757

RESUMEN

Introduction: Split hand and foot malformation (SHFM) or ectrodactyly is a rare limb deformity characterized by median cleft of the hand and foot with impaired or missing central rays. It can occur as an isolated anomaly or in association with abnormalities of other body parts. Methods: After delineating the clinical features of two families (A-B), with non-syndromic SHFM, exome and Sanger sequencing were employed to search for the disease-causing variants. Results: Analysis of exome and Sanger sequencing data revealed two causative variants in the WNT10B gene in affected members of the two families. This included a novel missense change [c.338G>C; p.(Gly113Ala)] in family A and a previously reported frameshift variant [c.884-896delTCCAGCCCCGTCT; p.(Phe295Cysfs*87)] in family B. Conclusion: Our findings add a novel variant in WNT10B gene as the underlying cause of SHFM. The finding adds to the growing body of knowledge about the genetic basis of developmental disorders and provides valuable insights into the molecular mechanisms that regulate limb development.

13.
PLoS One ; 18(11): e0289143, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38011108

RESUMEN

To defend against damage from environmental stress, plants have evolved strategies to respond to stress efficiently. One such strategy includes forming mutualist relationships with endophytes which confer stress-alleviating plant defensive and growth promoting effects. Metarhizium robertsii is an entomopathogen and plant-protective and growth-promoting endophyte. To determine the context dependency of the relationship between M. robertsii and maize, we conducted a greenhouse experiment that imposed stress as deficit and excess soil moisture on maize plants which were inoculated or not inoculated with M. robertsii and measured plant growth and defense indicators. Maize height and endophytic root colonization by M. robertsii were positively correlated in the deficit water treatment, but not in the adequate or excess water treatments. The relative expression of ZmLOX1 in the jasmonic acid (JA) biosynthesis pathway was significantly greater in M. robertsii-inoculated than in non-inoculated plants, but water treatment had no effect. There was significant interaction between M. robertsii and water treatments on foliar concentrations of JA and jasmonoyl isoleucine (JA-ILE), suggesting that water stress impacts M. robertsii as a modulator of plant defense. Water stress, but not inoculation with M. robertsii, had a significant effect on the expression of MYB (p = 0.021) and foliar concentrations of abscisic acid (p<0.001), two signaling molecules associated with abiotic stress response. This study contributes toward understanding the highly sophisticated stress response signaling network and context dependency of endophytic mutualisms in crops.


Asunto(s)
Metarhizium , Zea mays , Deshidratación , Metarhizium/fisiología , Productos Agrícolas
14.
Heliyon ; 9(9): e19600, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37809801

RESUMEN

The Pleurotus ostreatus mushroom, commonly referred to as the oyster mushroom, is a widely consumed edible mushroom that grows in clusters on dead or dying trees. In addition to its culinary uses, research has found that the mushroom may also have potential medicinal properties. The current study investigated the potential use of a fungal extract from P. ostreatus as a natural acaricide against Rhipicephalus microplus, a major vector of economically significant infections and one of the most significant bovine ectoparasites. The study used the adult immersion test (AIT) and the larvae packet test (LPT) to evaluate the effectiveness of the extract against ticks. To evaluate the reproductive effect of the fungal extract on the reproduction of R. microplus engorged females, the eggs were tested for weight and egg-laying index. The results of the study showed that P. ostreatus extract had a significant acaricidal effect, with a 40 mg/mL concentration causing 89 ± 2.64% mortality in R. microplus larvae compared to the 91.00 ± 3.60% mortality by the positive control at 48 h interval. Whereas in the AIT, the extract inhibited 39.86 ± 4.13% of oviposition. The study also used in silico approach to further examine the binding mechanisms of the compounds in the fungal extract to the target protein R. microplus Triosephosphate isomerase RmTIM, using molecular docking in AutoDock Vina software. Docking scores of -8.3, -7.7 and -6.9 kcal/mol, respectively, showed that rutin, naringin and myricitin had significant interactions with the active site residues of the target protein. Our results suggest that P. ostreatus extract may be a potential alternative to traditional acaricides for controlling R. microplus in livestock.

15.
World J Microbiol Biotechnol ; 39(12): 345, 2023 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-37843704

RESUMEN

Macroalgae has the potential to be a precious resource in food, pharmaceutical, and nutraceutical industries. Therefore, the present study was carried out to identify and quantify the phyco-chemicals and to assess the nutritional profile, antimicrobial, antioxidant, and anti-diabetic properties of Nitella hyalina extracts. Nutritional composition revealed0.05 ± 2.40% ash content, followed by crude protein (24.66 ± 0.95%), crude fat (17.66 ± 1.42%), crude fiber (2.17 ± 0.91%), moisture content (15.46 ± 0.48%) and calculated energy value (173.50 ± 2.90 Kcal/100 g). 23 compounds were identified through GC-MS analysis in ethyl acetate extract, with primary compounds being Palmitic acid, methyl ester, (Z)-9-Hexadecenoic acid, methyl ester, and Methyl tetra decanoate. Whereas 15 compounds were identified in n-butanol extract, with the major compounds being Tetra decanoic acid, 9-hexadecanoic acid, Methyl pentopyranoside, and undecane. FT-IR spectroscopy confirmed the presence of alcoholic phenol, saturated aliphatic compounds, lipids, carboxylic acid, carbonyl, aromatic components, amine, alkyl halides, alkene, and halogen compounds. Moreover, n-butanol contains 1.663 ± 0.768 mg GAE/g, of total phenolic contents (TPC,) and 2.050 ± 0.143 QE/g of total flavonoid contents (TFC), followed by ethyl acetate extract, i.e. 1.043 ± 0.961 mg GAE/g and 1.730 ± 0.311 mg QE/g respectively. Anti-radical scavenging effect in a range of 34.55-46.35% and 35.39-41.79% was measured for n-butanol and ethyl acetate extracts, respectively. Antimicrobial results declared that n-butanol extract had the highest growth inhibitory effect, followed by ethyl acetate extract. Pseudomonas aeruginosa was reported to be the most susceptible strain, followed by Staphylococcus aureus and Escherichia coli, while Candida albicans showed the least inhibition at all concentrations. In-vivo hypoglycemic study revealed that both extracts exhibited dose-dependent activity. Significant hypoglycemic activity was observed at a dose of 300 mg/kg- 1 after 6 h i.e. 241.50 ± 2.88, followed by doses of 200 and 100 mg/kg- 1 (245.17 ± 3.43 and 250.67 ± 7.45, respectively) for n-butanol extract. In conclusion, the macroalgae demonstrated potency concerning antioxidant, antimicrobial, and hypoglycemic properties.


Asunto(s)
Antiinfecciosos , Nitella , Antioxidantes/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Hipoglucemiantes/farmacología , Espectroscopía Infrarroja por Transformada de Fourier , 1-Butanol , Antiinfecciosos/farmacología , Antiinfecciosos/química , Ésteres
16.
Int J Mol Sci ; 24(19)2023 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-37834060

RESUMEN

GM2 gangliosidoses are a group of neurodegenerative lysosomal storage disorders that are characterized by the accumulation of GM2 gangliosides (GM2), leading to rapid neurological decline and death. The hydrolysis of GM2 requires the specific synthesis, processing, and combination of products of three genes-HEXA, HEXB, and GM2A-within the cell's lysosomes. Mutations in these genes result in Tay-Sachs disease, Sandhoff disease, or AB-variant GM2 gangliosidosis (ABGM2), respectively. ABGM2, the rarest of the three types, is characterized by a mutation in the GM2A gene, which encodes the GM2 activator (GM2A) protein. Being a monogenic disease, gene therapy is a plausible and likely effective method of treatment for ABGM2. This study aimed at assessing the effects of administering a one-time intravenous treatment of single-stranded Adeno-associated virus serotype 9 (ssAAV9)-GM2A viral vector at a dose of 1 × 1014 vector genomes (vg) per kilogram per mouse in an ABGM2 mouse model (Gm2a-/-). ssAAV9-GM2A was administered at 1-day (neonatal) or 6-weeks of age (adult-stage). The results demonstrated that, in comparison to Gm2a-/- mice that received a vehicle injection, the treated mice had reduced GM2 accumulation within the central nervous system and had long-term persistence of vector genomes in the brain and liver. This proof-of-concept study is a step forward towards the development of a clinically therapeutic approach for the treatment of patients with ABGM2.


Asunto(s)
Gangliosidosis GM2 , Enfermedad de Tay-Sachs , Humanos , Animales , Ratones , Dependovirus/genética , Serogrupo , Enfermedad de Tay-Sachs/terapia , Gangliosidosis GM2/genética , Gangliosidosis GM2/terapia , Proteína Activadora de G (M2)/genética , Terapia Genética
17.
Front Biosci (Landmark Ed) ; 28(8): 184, 2023 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-37664939

RESUMEN

BACKGROUND: A previously unstudied medicinal plant, Leucophyllum frutescens (Berland.) I.M. Johnst. (Scrophulariaceae) was investigated to evaluate its potential in preventing and treating neurodegenerative diseases, including Alzheimer's disease. METHODS: Methanolic leaf extract (MELE) and its fractions (HELE, CHLE, and BULE) were evaluated for their polyphenolic content and antioxidant activity by five different methods, including in vitro enzyme inhibition assays, which are clinically linked to neurodegenerative diseases. The potentially active n-butanol fraction (BULE) was further evaluated for its neuroprotective effects using an albino rat animal model and phytoconstituents profiling using Liquid chromatography with tandem mass spectrometry (LC-MS/MS), and in silico molecular docking by Maestro® Schrödinger. RESULTS: The n-butanol fraction (BULE) in the hydroalcoholic leaf extract exhibited the highest total phenolic content (230.435 ± 1.575 mg gallic acid equivalent gm-1± SD). The chloroform leaf extract exhibited the highest total flavonoid content (293.343 ± 3.756 mg quercetin equivalent gm-1± SD) as well as the highest antioxidant content, which was equivalent to Trolox, with five assay methods. Similarly, the chloroform and n-butanol fractions from the hydroalcoholic leaf extract significantly inhibited human acetylcholinesterase and butyrylcholinesterase with their IC50 values of 12.14 ± 0.85 and 129.73 ± 1.14 µg∙mL-1, respectively. The in vivo study revealed that BULE exhibited a significant neuroprotective effect at doses of 200 and 400 mg/kg/day in an aluminum chloride-induced neurodegenerative albino rat model. The LC-MS/MS analysis of BULE tentatively confirmed the presence of biologically active secondary metabolites, such as theobromine, propyl gallate, quercetin-3-O-glucoside, myricetin-3-acetylrhamnoside, isoquercitrin-6'-O-malonate, diosmetin-7-O-glucuronide-3'-O-pentose, pinoresinol diglucoside, asarinin, eridictoyl, epigallocatechin, methyl gallate derivative, and eudesmin. The results from the computational molecular docking of the identified secondary metabolites revealed that diosmetin-7-O-glucuronide-3'-O-pentose had the highest binding affinity to human butyrylcholinesterase, while isoquercetin-6'-O-malonate had the highest to human acetylcholinesterase, and pinoresinol diglucoside to human salivary alpha-amylase. CONCLUSIONS: The present study concluded a need for further exploration into this medicinal plant, including the isolation of the bioactive compounds responsible for its neuroprotective effects.


Asunto(s)
Fármacos Neuroprotectores , Scrophulariaceae , Ratas , Animales , Humanos , Antioxidantes/farmacología , Neuroprotección , Fármacos Neuroprotectores/farmacología , Acetilcolinesterasa , Cloruro de Aluminio , Butirilcolinesterasa , 1-Butanol , Cloroformo , Cromatografía Liquida , Glucurónidos , Simulación del Acoplamiento Molecular , Espectrometría de Masas en Tándem , Hipocampo , Extractos Vegetales/farmacología
18.
Pak J Pharm Sci ; 36(2(Special)): 673-679, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37548208

RESUMEN

Aqueous methanol extracts of Sarcococca saligna leaves and roots were used in this work to explore its phytochemical contents, antioxidant, enzyme inhibition and antibacterial activities. Total phenolic contents were found to be in higher concentrations then total flavonoids contents in aqueous methanolic extracts of leaves. Antioxidant activity was performed using DPPH radical scavenging assay. In our findings both leaves and roots extracts were found to show substantial antioxidant potential. Aqueous methanolic extracts of both the leaves and roots gave significant inhibition against butyryl cholinesterase whereas against acetyl cholinesterase extracts of roots gave significant inhibition. The results were compared with the standard drug Eserine. The aqueous methanolic extract of leaves, roots and crude saponins isolated from leaf extracts gave moderate to significant antibacterial activity against the tested bacterial strains using agar disc diffusion method. According to the conclusions, S. saligna possesses significant antioxidant, enzyme inhibition, and antibacterial activities. Hence it is assumed that S. saligna has the potential to be used in the discovery and development of new bioactive compounds.


Asunto(s)
Antioxidantes , Extractos Vegetales , Extractos Vegetales/farmacología , Extractos Vegetales/química , Colinesterasas , Antibacterianos , Fitoquímicos/farmacología , Flavonoides/química
19.
Spectrochim Acta A Mol Biomol Spectrosc ; 302: 123091, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37453386

RESUMEN

The substantial optical features of perovskite quantum dots (PQD) lead to rapid growth in the investigation of their surface and lattice doping for optoelectronic and biochemical sensor advancements. Herein, we have used the surface ligand crafting model of PQD by ammonia and its optimum response to recognise ammonia in the sensing cellulose paper. The PQD with acetyl amine and octanoic acid capped were synthesized and entrapped in zeolites imidazole framework to delay the instant quenching and envisaged response to ammonia with high sensitivity. The hybrid perovskite quantum dots and Zeolite imidazolate framework-8 (PQD@ZIF-8) materials were further immersed in cellulose paper for solid-state sensor fabrication for the detection of ammonia by naked-eye and a Xiaomi Note-5 mobile camera. The ammonia was measured with high sensitivity at ambient conditions, with a detection limit of 16 ppm and a linear detection range of 1 to 500 ppm. This research provides a new platform for designing sensor selectivity and sensitivity, which could be used to further develop fluorescent nanomaterials-based sensors for small molecule detection.

20.
Pak J Med Sci ; 39(4): 1091-1094, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37492336

RESUMEN

Objective: To find out the prevalence of diabetes mellitus in patients undergoing coronary artery bypass grafting (CABG). Methods: This retrospective study was conducted in Northwest General Hospital and Research center Hayatabad, Peshawar over a duration of 15 months (December 2020 - March 2022). Every patient was tested through regular laboratory investigations. Diabetes mellitus was established according to WHO standards of fasting plasma glucose >126 mg/dl or two hours postprandial glucose level of 200 mg/dl. Data were analyzed using SPSS. Mean and standard deviation was used for quantitative data. Frequency and percentages were used for qualitative data. Shapiro Wilk's test was done to find the normality of the data. Results: Out of a total of 360 candidates, 129 (36%) individuals were non-diabetic and 231 (64%) candidates were diabetic. Among the diabetic patients, 64 (28%) were female and 167 (72%) were males with a ratio of 1:2.6 respectively. Conclusion: Prevalence of diabetes was 64% among the CABG population. Since the prevalence of diabetes can significantly affect the outcomes of people undergoing CABG, it is essential to generate awareness regarding diabetes among healthcare workers as well as the general population. More extensive research is needed to be carried by various health care centers to figure out the prevalence of diabetes mellitus in cardiac surgery patients.

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