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1.
Int J Pharm ; : 124748, 2024 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-39317245

RESUMEN

Hypertrophic scar (HS) manifests as abnormal dermal myofibroblast proliferation and excessive collagen deposition, leading to raised scars and significant physical, psychological, and financial burdens for patients. HS is difficult to cure in the clinic and current therapies lead to recurrence, pain, and side effects. In this study, a natural amphiphilic polymer mucin is used to prepare a dissolving microneedle (muMN) that is loaded with oregano essential oil (OEO) for HS therapy. muMN exhibits sufficient skin/scar tissue penetration, quick skin recovery time after removal, good loading of natural essential oil, fast dissolution and detachment from the base layer, and good biocompatibility to applied skin. In the rabbit HS model, OEO@muMN shows a significant reduction in scar thickness, epidermal thickness index, and scar elevation index. OEO@muMN also attenuates the mean collagen area fraction and decreases the number of capillaries in scar tissues. Biochemical Assay reveals that OEO@muMN significantly inhibits the expression of transforming growth factor-ß1 (TGF-ß1) and hydroxyproline (HYP). In summary, this study demonstrates the feasibility and good efficacy of using the anti-proliferative and anti-oxidative OEO for HS treatment. OEO@muMN is an efficient formulation that holds the potential for clinical anti-HS application. muMN is an efficient platform to load and apply essential oils transdermally.

2.
Medicine (Baltimore) ; 103(22): e37825, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-39259062

RESUMEN

BACKGROUND: Gut microbial metabolites such as trimethylamine N-oxide (TMAO) and its precursors, namely betaine, L-carnitine, and choline, have been implicated as risk factors for cardiovascular events and mortality development. Therefore, we aim to perform a systematic review and meta-analysis to assess the validity of these associations. METHODS: MEDLINE and Scopus were queried from their inception to August 2023 to identify studies that quantified estimates of the associations of TMAO with the development of major adverse cardiovascular events (MACE) or death. A random-effects meta-analysis was conducted to pool unadjusted or multivariable-adjusted hazard ratios (HR) and their 95% confidence intervals. The primary endpoint was the risk of MACE and all-cause death. RESULTS: 30 prospective observational studies (n = 48 968) were included in the analysis. Elevated TMAO levels were associated with a significantly greater risk of MACE and all-cause death compared to low TMAO levels (HR: 1.41, 95% CI 1.2-1.54, P < .00001, I2 = 43%) and (HR: 1.55, 95% CI 1.37-1.75, P < .00001, I2 = 46%), respectively. Furthermore, high levels of either L-carnitine or choline were found to significantly increase the risk of MACE. However, no significant difference was seen in MACE in either high or low levels of betaine. CONCLUSION: Elevated concentrations of TMAO were associated with increased risks of MACE and all-cause mortality. High levels of L-carnitine/choline were also significantly associated with an increased risk of MACE. However, no significant difference was found between high or low levels of betaine for the outcome of MACE.


Asunto(s)
Enfermedades Cardiovasculares , Carnitina , Colina , Microbioma Gastrointestinal , Metilaminas , Humanos , Betaína/metabolismo , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/fisiopatología , Carnitina/metabolismo , Colina/metabolismo , Microbioma Gastrointestinal/fisiología , Metilaminas/metabolismo , Factores de Riesgo
3.
Ann Med Surg (Lond) ; 86(9): 5461-5470, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39238980

RESUMEN

Background: Spinal anesthesia is the most preferred method for cesarean section (C-section). This meta-analysis was performed to determine the effect of low and high intrathecal doses of pethidine on the maternal outcomes after C-section. Methods: A systematic search of PubMed, Scopus, Cochrane Library, and Google Scholar was performed. Random-effects meta-analysis was performed to derive odds ratios (ORs) from dichotomous data. Results: Seventeen randomized controlled trials with 1304 C-section patients were included. Patients who had received intrathecal pethidine experienced decreased shivering and intensity of shivering (OR 0.13; P<0.001) and (OR 0.21; P<0.001), respectively. Moreover, vomiting (OR 2.47; P=0.002) and pruritus (OR 5.92; P<0.001) were significantly higher in the pethidine group. There was no statistically significant difference in the incidence of nausea (OR 2.55; P=0.06) and hypotension (OR 0.91; P=0.67). Conclusions: Intrathecal pethidine can effectively decrease shivering, although it increases the risk of vomiting and pruritus. No significant difference was found both in the maternal hypotension and nausea.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39158404

RESUMEN

BACKGROUND: Localized prostate tumors show significant spatial heterogeneity, with regions of high-grade disease adjacent to lower-grade disease. Consequently, prostate cancer biopsies are prone to sampling bias, potentially leading to underestimation of tumor grade. To study the clinical, epidemiologic and molecular hallmarks of this phenomenon, we conducted a prospective study of grade upgrading: differences in detected prostate cancer grade between biopsy and surgery. METHODS: We established a prospective, multi-institutional cohort of men with Grade Group 1 (GG1) prostate cancer on biopsy who underwent radical prostatectomy. Upgrading was defined as detection of GG2+ in the resected tumor. Germline DNA from 192 subjects was subjected to whole-genome sequencing to quantify ancestry, pathogenic variants in DNA damage response genes and polygenic risk. RESULTS: Of 285 men, 67% upgraded at surgery. PSA density and percent of cancer in pre-prostatectomy positive biopsy cores were significantly associated with upgrading. No assessed genetic risk factor was predictive of upgrading, including polygenic risk scores for prostate cancer diagnosis. CONCLUSIONS: In a cohort of low-grade prostate cancer patients, a majority upgraded at radical prostatectomy. PSA density and percent of cancer in pre-prostatectomy positive biopsy cores portended the presence of higher-grade disease, while germline genetics was not informative in this setting. Patients with low-risk prostate cancer, but elevated PSA density or percent cancer in positive biopsy cores, may benefit from repeat biopsy, additional imaging or other approaches to complement active surveillance. IMPACT: Further risk stratification of patients with low-risk prostate cancer may provide useful context for active surveillance decision-making.

5.
Plant Physiol Biochem ; 215: 109057, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39173365

RESUMEN

Strigolactones (SLs) constitute essential phytohormones that control pathogen defense, resilience to phosphate deficiency and abiotic stresses. Furthermore, SLs are released into the soil by roots, especially in conditions in which there is inadequate phosphate or nitrogen available. SLs have the aptitude to stimulate the root parasite plants and symbiotic cooperation with arbuscular mycorrhizal (AM) fungi in rhizosphere. The use of mineral resources, especially phosphorus (P), by host plants is accelerated by AMF, which also improves plant growth and resilience to a series of biotic and abiotic stresses. Thus, these SL treatments that promote rhizobial symbiosis are substitutes for artificial fertilizers and other chemicals, supporting ecologically friendly farming practices. Moreover, SLs have become a fascinating target for abiotic stress adaptation in plants, with an array of uses in sustainable agriculture. In this review, the biological activity has been summarized that SLs as a signaling hormone for AMF symbiosis, nutrient acquisition, and abiotic stress tolerance through interaction with other hormones. Furthermore, the processes behind the alterations in the microbial population caused by SL are clarified, emphasizing the interplay with other signaling mechanisms. This review covers the latest developments in SL studies as well as the properties of SLs on microbial populations, plant hormone transductions, interactions and abiotic stress tolerance.


Asunto(s)
Lactonas , Micorrizas , Estrés Fisiológico , Simbiosis , Micorrizas/fisiología , Simbiosis/fisiología , Lactonas/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Raíces de Plantas/microbiología , Raíces de Plantas/metabolismo , Plantas/metabolismo , Plantas/microbiología
6.
Front Plant Sci ; 15: 1396929, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39135649

RESUMEN

The uneven spatial and temporal distribution of light resources and water scarcity during the grain-filling stage pose significant challenges for sustainable crop production, particularly in the arid areas of the Loess Plateau in Northwest China. This study aims to investigate the combined effects of drought and shading stress on winter wheat growth and its physio-biochemical and antioxidative responses. Wheat plants were subjected to different drought levels- full irrigation (I100), 75% of full irrigation (I75), 50% of full irrigation (I50), and 25% of full irrigation (I25), and shading treatments - 12, 9, 6, 3 and 0 days (SD12, SD9, SD6, SD3, and CK, respectively) during the grain-filling stage. The effects of drought and shading treatments reduced yield in descending order, with the most significant reductions observed in the SD12 and I25 treatments. These treatments decreased grain yield, spikes per plant, 1000-grain weight, and spikelets per spike by 160.67%, 248.13%, 28.22%, and 179.55%, respectively, compared to the CK. Furthermore, MDA content and antioxidant enzyme activities exhibited an ascending trend with reduced irrigation and longer shading durations. The highest values were recorded in the I75 and SD12 treatments, which increased MDA, SOD, POD, and CAT activities by 65.22, 66.79, 65.07 and 58.38%, respectively, compared to the CK. The Pn, E, Gs, and iCO2 exhibited a decreasing trend (318.14, 521.09, 908.77, and 90.85%) with increasing shading duration and decreasing irrigation amount. Drought and shading treatments damage leaf chlorophyll fluorescence, decreasing yield and related physiological and biochemical attributes.

8.
Heliyon ; 10(13): e33752, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39027513

RESUMEN

Today, feeding protein supply according to need in high-yielding lactating cows has become a big challenge. Protein is the most costly bulk constituent of animal diet, and the price of protein sources is increasing steadily, which is different from milk price rising. Therefore, one way for farmers to reduce feed costs is to reduce dietary protein share. Ruminants obtain their amino acids from 2 sources: amino acids from ruminally undegraded protein (RUP) and microbial protein synthesized in the rumen. A key goal in ruminant nutrition strategies, maximizing the use of rumen degradable protein (RDP), is through its efficient conversion into microbial protein. Urea is a supplement and a possible source of non-protein nitrogen (NPN) in ruminants' diets which meets bacteria's ammonia needs. Rumen ammonia sources include protein, peptides, amino acids, and other nitrogen-bearing compounds. As urea, uric acid, nitrate, and possibly nucleic acid are rapidly converted to ammonia, the ammonia reservoir indicates that the ruminal metabolism of ammonia is relatively small. Bacteria in the rumen can obtain between 40 and 95 percent of their nitrogen demand from ammonia, depending on their diet. Using NPN (non-protein nitrogen) as a reliable nitrogen source for ruminants was recognized over 100 years ago. Urea is quickly released in the rumen, its use in the diet is limited due to ammonia toxicity. So, the solution to this problem is that the product in nitrogen release rate from urea changes according to the digestion of fibers in the rumen. In the past, several slow-release products were made and evaluated. Slow-release urea (SRU) sources will also affect microbial growth and livestock performance compared to conventional plant protein sources. Acceptance of SRU sources, depending on their price compared to conventional plant protein ingredients is feasible. Studies has shown that the use of slow-release urea did not have a negative effect on digestibility, rumen parameters, milk production and livestock performance. Single-cell protein (SCP) is an emerging alternative protein source, currently being mainly studied for chicken and aquatic species.Finally, it is concluded that slow release urea can be used in feeding ruminants without any side effects.

9.
Nanoscale Adv ; 6(14): 3668-3679, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38989524

RESUMEN

Water scarcity is an alarming situation across the globe. Several methods have been reported in the literature to minimize the water shortage problem. Sorbent-based atmospheric water harvesting (SBAWH) is considered an energy-efficient, low-cost strategy, and sustainable approach. In the present study, the synthesis of graphene oxide (GO) was carried out using a modified Hummers' method, while the synthesis of MOF-5 and a GO/MOF-5 composite was carried out using a solvothermal approach. The synthesized materials were characterized by X-ray diffraction analysis (XRD), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). The phase composition and crystallinity of all synthesized samples were confirmed by XRD analysis. SEM analysis provided information about the surface morphology of all synthesized samples. The adsorption of water vapors on surfaces of GO, MOF-5, and the GO/MOF-5 composite was evaluated by FTIR analysis. The negative charge was explored by the PZC technique on the surface of all synthesized materials. The water adsorption characteristics of GO, MOF-5, and the GO/MOF-5 composite were evaluated using an atmospheric water harvesting (AWH) plant. The maximum adsorption capacity of 542 mg g-1 was achieved by the MOF at 55% RH (relative humidity), while a low adsorption capacity of the MOF was observed at higher humidity values. This problem was overcome by making a GO/MOF-5 composite. GO imparts structural stability to the MOF-5 structure at higher humidity values. The maximum adsorption capacity of 1137 mg g-1 was achieved by the GO/MOF-5 composite at 75% RH. Several isotherm models, such as Langmuir, Freundlich, and Temkin, were applied to confirm the single-site occupation by water molecules and chemisorption behavior. Several thermodynamic properties were calculated, including isosteric heat (Q st), Gibbs free energy (ΔG), and sorption entropy (ΔS). The overall thermodynamics study confirms that the adsorption process is spontaneous and exothermic. In addition, second-order kinetics confirms that all synthesized material shows chemisorption behavior.

10.
Pest Manag Sci ; 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38924668

RESUMEN

BACKGROUND: Dicer1 plays a crucial role in regulating the development and reproduction of insects. Knockout of Dicer1 causes pupal deformity, low eclosion and low fecundity in Plutella xylostella, but the mechanism behind this phenomenon is not clear. This study aims to identify differentially-expressed genes and miRNAs in the Dicer1-knockout strain (ΔPxDcr-1) and assess their impact on the reproduction and development of P. xylostella. RESULTS: The knockout of Dicer1 affected the expression of genes including the adipokinetic hormone/corazonin-related peptide receptor (PxACPR). The expression of PxACPR was upregulated, and the expression of miR-8514-5p was downregulated in ΔPxDcr-1 of P. xylostella. The dual luciferase reporter assay and pull-down assay showed that miR-8514-5p bound to PxACPR in vitro and in vivo. The expression profiles demonstrated a negative correlation between PxACPR mRNA and miR-8514-5p in different developmental stages of the wild-type strain. Both the miR-8514-5p agomir and double-stranded RNA of ACPR (dsPxACPR) injected into the pre-pupae inhibited the mRNA level of PxACPR, causing high mortality and deformity of pupae, and low fecundity and hatching rate, which were consistent with the phenotype of ΔPxDcr-1. The injection of miR-8514-5p antagomir caused a similar phenotype to the injection of miR-8514-5p agomir. Additionally, the injection of miR-8514-5p antagomir significantly rescued the phenotype caused by dsPxACPR. CONCLUSION: These results indicate that miR-8514-5p affects the development and reproduction of P. xylostella by regulating PxACPR, and the homeostasis of PxACPR expression is essential for the development and reproduction of P. xylostella. © 2024 Society of Chemical Industry.

11.
Comput Biol Med ; 178: 108738, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38870724

RESUMEN

Neisseria meningitidis, commonly known as the meningococcus, leads to substantial illness and death among children and young adults globally, revealing as either epidemic or sporadic meningitis and/or septicemia. In this study, we have designed a novel peptide-based chimeric vaccine candidate against the N. meningitidis strain 331,401 serogroup X. Through rigorous analysis of subtractive genomics, two essential cytoplasmic proteins, namely UPI000012E8E0(UDP-3-O-acyl-GlcNAc deacetylase) and UPI0000ECF4A9(UDP-N-acetylglucosamine acyltransferase) emerged as potential drug targets. Additionally, using reverse vaccinology, the outer membrane protein UPI0001F4D537 (Membrane fusion protein MtrC) identified by subcellular localization and recognized for its known indispensable role in bacterial survival was identified as a novel chimeric vaccine target. Following a careful comparison of MHC-I, MHC-II, T-cell, and B-cell epitopes, three epitopes derived from UPI0001F4D537 were linked with three types of linkers-GGGS, EAAAK, and the essential PADRE-for vaccine construction. This resulted in eight distinct vaccine models (V1-V8). Among them V1 model was selected as the final vaccine construct. It exhibits exceptional immunogenicity, safety, and enhanced antigenicity, with 97.7 % of its residues in the Ramachandran plot's most favored region. Subsequently, the vaccine structure was docked with the TLR4/MD2 complex and six different HLA allele receptors using the HADDOCK server. The docking resulted in the lowest HADDOCK score of 39.3 ± 9.0 for TLR/MD2. Immune stimulation showed a strong immune response, including antibodies creation and the activation of B-cells, T Cytotoxic cells, T Helper cells, Natural Killer cells, and interleukins. Furthermore, the vaccine construct was successfully expressed in the Escherichia coli system by reverse transcription, optimization, and ligation in the pET-28a (+) vector for the expression study. The current study proposes V1 construct has the potential to elicit both cellular and humoral responses, crucial for the developing an epitope-based vaccine against N. meningitidis strain 331,401 serogroup X.


Asunto(s)
Vacunas Meningococicas , Neisseria meningitidis , Neisseria meningitidis/inmunología , Neisseria meningitidis/genética , Humanos , Vacunas Meningococicas/inmunología , Vacunología/métodos , Genómica , Simulación por Computador , Epítopos de Linfocito T/inmunología , Epítopos de Linfocito T/genética , Epítopos de Linfocito T/química , Epítopos de Linfocito B/inmunología , Epítopos de Linfocito B/química , Epítopos de Linfocito B/genética
12.
PLoS One ; 19(6): e0305091, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38900819

RESUMEN

Short and long-term sound-induced stress on daily basis can affect the physiology of avian individuals because they are more susceptible to sound stress in an open environment. OBJECTIVES: An ex-situ study was carried out to determine the impact of noise on physiology and ptilochronology of non-breeding male domesticated quail birds. METHODOLOGY: During 60-days long trial, male quail birds, aged 5-weeks, weighing (c.100gm) were used. Out of 72 experimental birds, 18 birds were assigned to the Control Group (G1) while remaining 54 birds were divided equally into 3 treatment groups: Road Traffic noise (G2), Military activity noise (G3) and Human Activities noise (G4). Birds were housed in standard-sized separate cages (20 ×45 × 20 cm), every bird was kept apart in separate cage in open laboratory under maintained environmental conditions. Millet seeds and water were provided to all the experimental birds ad libitum. Noise originated from several sources of recorded high-intensity music (1125 Hz/ 90 dB), was administered for 5-6 hours per day. Observations were recorded in the morning and afternoon. The experiment was conducted during the non-breeding season from August to October in triplicate. Blood sampling was done after 60 days. RESULTS: According to the current study, noise stress significantly (p<0.05) increased the concentrations of creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, uric acid, cholesterol, triglycerides, total protein, and glucose while a decline in the levels of albumin was seen in treatment birds of G3. While in terms of hematology, total white blood cells count (TWBC), total red blood cells count (TRBC), mean cell volume (MCV) & packed cell volume (PCV) concentrations were raised in blood of treatment birds of G3. In terms of hormones, noise stress significantly (p<0.05) increased the serum concentrations of Corticosterone in G3 while a significant (p<0.05) decline was observed in the concentrations of luteinizing hormone (LH), thyroid stimulating hormone (TSH), and follicle stimulating hormone (FSH) in the same group. Moreover, fault bar formation in G3 was more prominent than others. CONCLUSION: Noise stress can significantly affect serology, hematology, hormonal physiology and ptilochronology in quail birds.


Asunto(s)
Ruido , Animales , Masculino , Ruido/efectos adversos , Estrés Fisiológico , Codorniz/fisiología , Corticosterona/sangre
13.
RSC Adv ; 14(27): 19539-19549, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38895531

RESUMEN

Ascorbic acid plays a pivotal role in the human body. It maintains the robustness, enlargement, and elasticity of the collagen triple helix. However, the abnormal concentration of ascorbic acid causes various diseases, such as scurvy, cardiovascular diseases, gingival bleeding, urinary stones, diarrhea, stomach convulsions, etc. In the present work, an iron-doped hydroxyapatite (HAp@Fe2O3)-based biosensor was developed for the colorimetric detection of ascorbic acid based on a low-cost, biocompatible, and ubiquitous material. Due to the catalytic nature of HAp owing to the acidic and basic moieties within the structure, it was used as a template for HAp@Fe2O3 synthesis. This approach provides an active as well as large surface area for the sensing of ascorbic acid. The synthesized platform was characterized by various techniques, such as UV-Vis, FTIR, SEM, XRD, TGA, EDX, etc. The HAp@Fe2O3 demonstrated inherent peroxidase-like activity in the presence of 3,3',5,5'-tetramethylbenzidine (TMB) oxidized with the assistance of H2O2. It resulted in the color changing to blue-green, and after the addition of ascorbic acid, the color changed to colorless, resulting in the reduction of TMB. To achieve optimal sensing parameters, experimental conditions were optimized. The quantity of HAp@Fe2O3, H2O2, pH, TMB, time, and the concentration of ascorbic acid were fine-tuned. The linear range for the proposed sensor was 0.6-56 µM, along with a limit of detection of 0.16 µM and a limit of quantification of 0.53 µM. The proposed sensor detects ascorbic acid within 75 seconds at room temperature. The proposed platform was also applied to quantitatively check the concentration of ascorbic acid in a physiological solution.

14.
Front Bioeng Biotechnol ; 12: 1364700, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38694624

RESUMEN

Dopamine is one of the most important neurotransmitters and plays a crucial role in various neurological, renal, and cardiovascular systems. However, the abnormal levels of dopamine mainly point to Parkinson's, Alzheimer's, cardiovascular diseases, etc. Hydroxyapatite (HAp), owing to its catalytic nature, nanoporous structure, easy synthesis, and biocompatibility, is a promising matrix material. These characteristics make HAp a material of choice for doping metals such as cobalt. The synthesized cobalt-doped hydroxyapatite (Co-HAp) was used as a colorimetric sensing platform for dopamine. The successful synthesis of the platform was confirmed by characterization with FTIR, SEM, EDX, XRD, TGA, etc. The platform demonstrated intrinsic peroxidase-like activity in the presence of H2O2, resulting in the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB). The proposed sensor detected dopamine in a linear range of 0.9-35 µM, a limit of detection of 0.51 µM, limit of quantification of 1.7 µM, and an R2 of 0.993. The optimization of the proposed sensor was done with different parameters, such as the amount of mimic enzyme, H2O2, pH, TMB concentration, and time. The proposed sensor showed the best response at 5 mg of the mimic enzyme, pH 5, 12 mM TMB, and 8 mM H2O2, with a short response time of only 2 min. The fabricated platform was successfully applied to detect dopamine in physiological solutions.

15.
Clin Cardiol ; 47(5): e24283, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38767042

RESUMEN

BACKGROUND: Semaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, has shown promise in weight management and cardiovascular outcomes in other populations. This study aimed to evaluate the efficacy of semaglutide in heart failure with preserved ejection fraction (HFpEF) patients with obesity. METHODS: A retrospective study analyzed 318 patients with HFpEF, of which 104 received semaglutide and 214 received placebo. Primary endpoints included evaluating changes in exercise capacity and weight management. RESULTS: Semaglutide treatment led to significant improvements in the primary endpoints. Patients in the semaglutide group demonstrated substantial enhancements in exercise capacity, as measured by the 6-min walk distance, compared to the placebo group (mean difference 15.1 meters, 95% CI 5.8 to 24.4, p = 0.002). Additionally, semaglutide resulted in substantial weight loss compared to placebo (mean difference -2.9%, 95% CI -4.1--1.7, p = 0.001). Several secondary endpoints, including reductions in C-reactive protein levels and improvements in other clinical parameters, further supported the efficacy of semaglutide. Adverse events were generally well-tolerated, with no unexpected safety concerns. CONCLUSION: Semaglutide demonstrated significant clinical benefits in HFpEF patients with obesity, as evidenced by improved symptoms, physical function, and weight reduction.


Asunto(s)
Péptidos Similares al Glucagón , Insuficiencia Cardíaca , Obesidad , Volumen Sistólico , Humanos , Péptidos Similares al Glucagón/uso terapéutico , Péptidos Similares al Glucagón/efectos adversos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Masculino , Femenino , Estudios Retrospectivos , Volumen Sistólico/efectos de los fármacos , Obesidad/tratamiento farmacológico , Obesidad/fisiopatología , Obesidad/complicaciones , Resultado del Tratamiento , Anciano , Persona de Mediana Edad , Función Ventricular Izquierda/efectos de los fármacos , Tolerancia al Ejercicio/efectos de los fármacos , Pérdida de Peso/efectos de los fármacos , Receptor del Péptido 1 Similar al Glucagón/agonistas , Factores de Tiempo , Recuperación de la Función
16.
Saudi Pharm J ; 32(6): 102096, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38757071

RESUMEN

The aim of the current study was to explore the potential of human plasma-derived exosomes as versatile carriers for drug delivery by employing various active and passive loading methods. Exosomes were isolated from human plasma using differential centrifugation and ultrafiltration method. Drug loading was achieved by employing sonication and freeze thaw methods, facilitating effective drug encapsulation within exosomes for delivery. Each approach was examined for its effectiveness, loading efficiency and ability to preserve membrane stability. Methotrexate (MTX), a weak acid model drug was loaded at a concentration of 2.2 µM to exosomes underwent characterization using various techniques such as particle size analysis, transmission electron microscopy and drug loading capacity. Human plasma derived exosomes showed a mean size of 162.15 ± 28.21 nm and zeta potential of -30.6 ± 0.71 mV. These exosomes were successfully loaded with MTX demonstrated a better drug encapsulation of 64.538 ± 1.54 % by freeze thaw method in comparison 55.515 ± 1.907 % by sonication. In-vitro drug release displayed 60 % loaded drug released within 72 h by freeze thaw method that was significantly different from that by sonication method i.e., 99 % within 72 h (p value 0.0045). Moreover, cell viability of exosomes loaded by freeze thaw method was significantly higher than that by sonication method (p value 0.0091) suggested that there was membrane disruption by sonication method. In conclusion, this study offers valuable insights into the potential of human plasma-derived exosomes loaded by freeze thaw method suggest as a promising carrier for improved drug loading and maintenance of exosomal membrane integrity.

17.
Environ Sci Pollut Res Int ; 31(23): 34200-34213, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38702484

RESUMEN

Arsenic (As) pollution in cultivated soils poses a significant risk to the sustainable growth of agriculture and jeopardizes food security. However, the mechanisms underlying how zinc (Zn) regulates the toxic effects induced by As in plants remain poorly understood. Hence, this study aimed to explore the potential of ZnO as an effective and environmentally friendly amendment to alleviate As toxicity in rice, thereby addressing the significant risk posed by As pollution in cultivated soils. Through a hydroponic experiment, the study assessed the mitigating effects of different ZnO dosages (Zn5, 5 mg L-1; Zn15, 15 mg L-1; Zn30, 30 mg L-1) on rice seedlings exposed to varying levels of As stress (As0, 0 µM L-1; As25, 25 µM L-1). The findings of the study demonstrate significant improvements in plant height and biomass (shoot and root), with a notable increase of 16-40% observed in the Zn15 treatment, and an even more substantial enhancement of 29-53% observed in the Zn30 treatment under As stress, compared to respective control treatment. Furthermore, in the Zn30 treatment, the shoot and root As contents substantially reduced by 47% and 63%, respectively, relative to the control treatment. The elevated Zn contents in shoots and roots enhanced antioxidant enzyme activities (POD, SOD, and CAT), and decreased MDA contents (13-25%) and H2O2 contents (11-27%), indicating the mitigation of oxidative stress. Moreover, the expression of antioxidant-related genes, OsSOD-Cu/Zn, OsCATA, OsCATB, and OsAPX1 was reduced when rice seedlings were exposed to As stress and significantly enhanced after Zn addition. Overall, the research suggests that ZnO application could effectively mitigate As uptake and toxicity in rice plants cultivated in As-contaminated soils, offering potential solutions for sustainable agriculture and food security.


Asunto(s)
Arsénico , Oryza , Estrés Oxidativo , Contaminantes del Suelo , Óxido de Zinc , Oryza/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Contaminantes del Suelo/toxicidad , Suelo/química , Antioxidantes/metabolismo
18.
Med Image Anal ; 95: 103207, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38776843

RESUMEN

The lack of annotated datasets is a major bottleneck for training new task-specific supervised machine learning models, considering that manual annotation is extremely expensive and time-consuming. To address this problem, we present MONAI Label, a free and open-source framework that facilitates the development of applications based on artificial intelligence (AI) models that aim at reducing the time required to annotate radiology datasets. Through MONAI Label, researchers can develop AI annotation applications focusing on their domain of expertise. It allows researchers to readily deploy their apps as services, which can be made available to clinicians via their preferred user interface. Currently, MONAI Label readily supports locally installed (3D Slicer) and web-based (OHIF) frontends and offers two active learning strategies to facilitate and speed up the training of segmentation algorithms. MONAI Label allows researchers to make incremental improvements to their AI-based annotation application by making them available to other researchers and clinicians alike. Additionally, MONAI Label provides sample AI-based interactive and non-interactive labeling applications, that can be used directly off the shelf, as plug-and-play to any given dataset. Significant reduced annotation times using the interactive model can be observed on two public datasets.


Asunto(s)
Inteligencia Artificial , Imagenología Tridimensional , Humanos , Imagenología Tridimensional/métodos , Algoritmos , Programas Informáticos
19.
Plant J ; 119(2): 861-878, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38761097

RESUMEN

Low phytic acid (lpa) crop is considered as an effective strategy to improve crop nutritional quality, but a substantial decrease in phytic acid (PA) usually has negative effect on agronomic performance and its response to environment adversities. Myo-inositol-3-phosphate synthase (MIPS) is the rate-limiting enzyme in PA biosynthesis pathway, and regarded as the prime target for engineering lpa crop. In this paper, the rice MIPS gene (RINO2) knockout mutants and its wild type were performed to investigate the genotype-dependent alteration in the heat injury-induced spikelet fertility and its underlying mechanism for rice plants being imposed to heat stress at anthesis. Results indicated that RINO2 knockout significantly enhanced the susceptibility of rice spikelet fertility to heat injury, due to the severely exacerbated obstacles in pollen germination and pollen tube growth in pistil for RINO2 knockout under high temperature (HT) at anthesis. The loss of RINO2 function caused a marked reduction in inositol and phosphatidylinositol derivative concentrations in the HT-stressed pollen grains, which resulted in the strikingly lower content of phosphatidylinositol 4,5-diphosphate (PI (4,5) P2) in germinating pollen grain and pollen tube. The insufficient supply of PI (4,5) P2 in the HT-stressed pollen grains disrupted normal Ca2+ gradient in the apical region of pollen tubes and actin filament cytoskeleton in growing pollen tubes. The severely repressed biosynthesis of PI (4,5) P2 was among the regulatory switch steps leading to the impaired pollen germination and deformed pollen tube growth for the HT-stressed pollens of RINO2 knockout mutants.


Asunto(s)
Citoesqueleto de Actina , Germinación , Oryza , Proteínas de Plantas , Oryza/genética , Oryza/crecimiento & desarrollo , Oryza/fisiología , Oryza/metabolismo , Citoesqueleto de Actina/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Polen/crecimiento & desarrollo , Polen/genética , Señalización del Calcio , Tubo Polínico/crecimiento & desarrollo , Tubo Polínico/metabolismo , Tubo Polínico/genética , Calor , Regulación de la Expresión Génica de las Plantas , Respuesta al Choque Térmico , Liasas Intramoleculares/metabolismo , Liasas Intramoleculares/genética , Inositol/metabolismo , Inositol/análogos & derivados
20.
Behav Res Ther ; 178: 104542, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38648683

RESUMEN

Evolutionary theorizing has given rise to the idea that responding to any particular threat may be more mandatory than responding to any particular reward. The present three experiments (total N = 375) sought to provide support for this perspective in an emotion dynamics task in which participants continuously rated their affective state in response to appetitive (reward-related) versus aversive (threat-related) images. Even when equating images for arousal and extremity, several negativity effects (e.g., steeper reactivity slopes in response to aversive images) were found. These negativity effects can serve as an experimental model of threat sensitivity, which should predispose some individuals, more than others, to symptoms related to fear and anxiety. This point was made with respect to sex differences, given that women (relative to men) are diagnosed with anxiety disorders at higher rates. Sex differences were pronounced and extensions of this work, both basic and applied, are proposed.


Asunto(s)
Emociones , Miedo , Humanos , Masculino , Femenino , Adulto Joven , Miedo/psicología , Miedo/fisiología , Emociones/fisiología , Adulto , Caracteres Sexuales , Ansiedad/psicología , Adolescente , Factores Sexuales , Nivel de Alerta/fisiología , Recompensa
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