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1.
Food Chem ; 462: 140987, 2025 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-39217748

RESUMEN

This study aimed to investigate the textural changes of cooked germinated brown rice (GBR) during freeze-thaw treatment and propose a strategy for enhancing its texture using magnetic field (MF). Seven freeze-thaw cycles exhibited more pronounced effects compared to 7 days of freezing, resulting in increases in GBR hardness by 85.59 %-164.36 % and decreases in stickiness by 10.34 %-43.55 %. Water loss, structural damage of GBR flour, and starch retrogradation contributed to the deterioration of texture. MF mitigated these effects by inhibiting the transformation of bound water into free water, reducing water loss by 0.39 %-0.57 %, and shortening the phase transition period by 2.0-21.5 min, thereby diminishing structural damage to GBR flour and hindering starch retrogradation. Following MF treatment (5 mT), GBR hardness decreased by 21.00 %, while stickiness increased by 45.71 %. This study elucidates the mechanisms through which MF enhances the texture, offering theoretical insights for the industrial production of high-quality frozen rice products.


Asunto(s)
Culinaria , Congelación , Germinación , Campos Magnéticos , Oryza , Oryza/química , Oryza/crecimiento & desarrollo , Oryza/metabolismo , Harina/análisis , Almidón/química , Almidón/metabolismo , Agua/química , Dureza , Manipulación de Alimentos , Semillas/química , Semillas/crecimiento & desarrollo
2.
J Ethnopharmacol ; 336: 118722, 2025 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-39182704

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Triptolide is a major bioactive and toxic ingredient isolated from the traditional Chinese herb Tripterygium wilfordii (T. wilfordii) Hook F. It exhibits potent antitumor, immunosuppressive, and anti-inflammatory biological activities; however, its clinical application is hindered by severe systemic toxicity. Two preparations of T. wilfordii, including T. wilfordii glycoside tablets and T. wilfordii tablets, containing triptolide, are commonly used in clinical practice. However, their adverse side effects, particularly hepatotoxicity, limit their safe use. Therefore, it is crucial to discover potent and specific detoxification medicines for triptolide. AIM OF THE STUDY: This study aimed to investigate the detoxification effects and potential mechanism of action of spironolactone on triptolide-induced hepatotoxicity to provide a potential detoxifying strategy for triptolide, thereby promoting the safe applications of T. wilfordii preparations in clinical settings. MATERIALS AND METHODS: Cell viability was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and crystal violet staining. Nuclear fragmentation was visualized using 4',6-diamidino-2-phenylindole (DAPI) staining, and protein expression was analyzed by Western blotting. The inhibitory effect of spironolactone on triptolide-induced hepatotoxicity was evaluated by examining the effects of spironolactone on serum alanine aminotransferase and aspartate aminotransferase levels, as well as liver pathology in a mouse model of triptolide-induced acute hepatotoxicity. Furthermore, a survival assay was performed to investigate the effects of spironolactone on the survival rate of mice exposed to a lethal dose of triptolide. The effect of spironolactone on triptolide-induced global transcriptional repression was assessed through 5-ethynyl uridine staining. RESULTS: Triptolide treatment decreased the cell viability, increased the nuclear fragmentation and the cleaved caspase-3 levels in both hepatoma cells and hepatocytes. It also increased the alanine aminotransferase and aspartate aminotransferase levels, induced the hepatocyte swelling and necrosis, and led to seven deaths out of 11 mice. The above effects could be mitigated by pretreatment with spironolactone. Additionally, molecular mechanism exploration unveiled that spironolactone inhibited triptolide-induced DNA-directed RNA polymerase II subunit RPB1 degradation, consequently increased the fluorescence intensity of 5-ethynyl uridine staining for nascent RNA. CONCLUSIONS: This study shows that spironolactone exhibits a potent detoxification role against triptolide hepatotoxicity, through inhibition of RPB1 degradation induced by triptolide and, in turn, retardation of global transcriptional inhibition in affected cells. These findings suggest a potential detoxification strategy for triptolide that may contribute to the safe use of T. wilfordii preparations.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Diterpenos , Compuestos Epoxi , Fenantrenos , Espironolactona , Compuestos Epoxi/toxicidad , Fenantrenos/toxicidad , Fenantrenos/farmacología , Diterpenos/farmacología , Diterpenos/toxicidad , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Ratones , Espironolactona/farmacología , Masculino , Humanos , Supervivencia Celular/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Células Hep G2
3.
Artículo en Inglés | MEDLINE | ID: mdl-39379652

RESUMEN

Lignocellulosic biomass offers substantial potential as an ideal feedstock for dark fermentative hydrogen production due to its sustainability and cost-effectiveness. The current study examined the influence of furfural on fermentative hydrogen production using lignocellulosic hydrolysate in the presence of furfural. Synthetic lignocellulosic hydrolysate, consisting primarily of 76% xylose, 10% glucose, 9% arabinose, and a mixture of other sugars such as galactose and mannose (85% pentose sugars and 15% hexose sugars), was employed as the substrate. Various substrate concentrations ranging from 2 to 32 g/L were tested, along with furfural concentrations of 0, 1, and 2 g/L. The investigation aimed to assess the effects of initial substrate concentration, initial furfural concentration, furfural-to-biomass ratio (F/B), and furfural-to-substrate ratio (F/S) on biohydrogen production yields. The maximum specific substrate utilization rates at different substrate concentrations were effectively characterized using Haldane's substrate inhibition model. Among the tested concentrations, the 16 g/L emerged as the optimal substrate concentration. The initial furfural concentration was identified as the most significant parameter impacting biohydrogen production, with complete inhibition observed at a furfural concentration of 2 g/L. Higher F/S ratios at substrate concentrations ranging from 2 to 16 g/L resulted in reduced maximum specific hydrogen production rates (MSHPR) and hydrogen yields. Substrate inhibition was observed at 24 g/L and 32 g/L. Lactate was the predominant metabolite in all batches containing 2-g/L furfural, as well as in batches with 1-g/L furfural and substrate concentrations of 24 and 32 g/L. Furfural at a concentration of 1 g/L was not inhibitory in any of the batches. Overall, the mixed cultures in this study could efficiently produce hydrogen from lignocellulosic hydrolysates and degrade furfural, providing new insights into fermentative hydrogen-producing bacteria with furfural tolerance.

4.
Curr Top Med Chem ; 2024 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-39350415

RESUMEN

AIMS: The aim of the current study was to explore the anti-diabetic potential of Ochradenus aucheri Boiss (O. aucheri). METHOD: All the fractions of O. aucheri were evaluated for α-glucosidase inhibition, followed by bioassay-guided isolation which resulted in a new sesquiterpenoid, as a potential α-glucosidase inhibitor. RESULTS: The preliminary screening showed that all the fractions including n-hexane (38.0 ± 1.38 µg/mL), dichloromethane (92.6 ± 6.18 µg/mL), ethyl acetate (29.2 ± 0.51 µg/mL) and n-butanol (361.8 ± 5.80 µg/mL) displayed significant α-glucosidase inhibitory activity. The activity-directed fractionation and purification of ethyl acetate fraction led to the isolation of one new sesquiterpenoid, Jardenol (1), and two known metabolites: ß-stitosterol-3-O-ß-D-glucopyranoside (2) and ß-Sitosterol (3). To the best of our knowledge, these metabolites have not been isolated from this plant previously. The structure of the new metabolite 1 was confirmed through 1D and 2D NMR spectroscopy, and MS analysis. Compound 1 showed significant α-glucosidase inhibition with an IC50 value of 138.2 ± 2.43 µg/mL as compared to positive control acarbose (IC50 = 942.0 ± 0.60 µg/mL). Additionally, in-silico docking was employed to predict the binding mechanism of compound 1 in the active site of the target enzyme, α-glucosidase. The docking results suggested that the compound forms strong interactions at the catalytic site of α-glucosidase. CONCLUSION: The results of the present study indicated that the newly purified secondary metabolite, Jardenol, can be a promising anti-diabetic compound.

5.
J Agric Food Chem ; 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39352105

RESUMEN

Amino acids are necessary for life, and many must be consumed because they cannot be endogenously synthesized. Typically, we eat them as proteins and peptides, which have little taste. However, we also directly ingest free amino acids, several of which are aversive because they elicit bitterness. This bitterness often prevents many patient populations from taking formulas and supplements containing free amino acids. Here, we characterize which amino acids are the most bitter, their concentration-intensity functions, and individual differences in bitterness perception, and we explore how sodium salts suppress the bitterness of amino acids. We found that the essential amino acids comprise the most bitter stimuli, with six of them conveying the most bitterness. Clustering and correlating amino acids by individual differences in bitterness perception show that there are approximately four groupings of amino acids and suggest that within these clusters, amino acids may be activating the same or overlapping TAS2Rs. We also show that bitterness can be largely suppressed by sodium salts for 5 of the 6 most bitter amino acids. These results hold promise for managing the bitter taste of nutritional supplements that contain amino acids and improving compliance.

6.
Chemistry ; : e202403035, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39354660

RESUMEN

Achieving food sustainability is one of the biggest challenges in the new millennium. Plant factory cultivation systems provide an alternative for food sustainability, while they often suffer from algal blooms. The overuse of conventional algaecides has caused significant environmental pollution and concerns about food security. Here, we design a nanoenabled metal-organic algaecide that is self-assembled from natural polyphenols and two functional metal ions for providing shading effects and delivering active ingredients synergistically to suppress algal blooms. Black wattle tannin (BWT) and Fe3+ ions are utilized to develop self-assembled FeBWT nanoalgaecides with significant shading effects for decreasing light transmission (up to 97%) and effectively inhibiting algal photosynthesis. Further, the FeBWT is functionalized with Cu2+ ions (bimetallic Cu/FeBWT) to target the algal cells and release Cu2+ ions via phenolic-mediated cell surface interactions, thus enhancing the inhibition efficiency. Importantly, the biosafety of Cu/FeBWT is demonstrated through toxicity tests on zebrafish and NIH3T3 cells. In our real-world field test, the Cu/FeBWT demonstrates high algal inhibition performance (> 95%, over 30 days), and enhances the accumulation of food nutrients in model plant lettuces. Collectively, the supramolecular metal-organic nanoalgaecide provides a promise for nanoagrochemical application and promoting food sustainability and security.

7.
J Agric Food Chem ; 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39356107

RESUMEN

The biosynthesis of amino acid derivatives of animal origin in plants represents a promising frontier in synthetic biology, offering a sustainable and eco-friendly approach to enhancing the nutritional value of plant-based diets. This study leverages the versatile capabilities of Nicotiana benthamiana as a transient expression system to test a synthetic modular framework for the production of creatine, carnosine, and taurine-compounds typically absent in plants but essential for human health. By designing and stacking specialized synthetic modules, we successfully redirected the plant metabolic flux toward the synthesis of these amino acid derivatives of animal origin. Our results revealed the expression of a standalone creatine module resulted in the production of 2.3 µg/g fresh weight of creatine in N. benthamiana leaves. Integrating two modules significantly carnosine yield increased by 3.8-fold and minimized the impact on plant amino acid metabolism compared to individual module application. Unexpectedly, introducing the taurine module caused a feedback-like inhibition of plant cysteine biosynthesis, revealing complex metabolic adjustments that can occur when introducing foreign pathways. Our findings underline the potential for employing plants as biofactories for the sustainable production of essential nutrients of animal origin.

8.
Prep Biochem Biotechnol ; : 1-10, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39356798

RESUMEN

This study investigated the ultrasound-assisted extraction (UAE) techniques used to enhance the polyphenols and antioxidants of mango peel extract (MPE). Additionally, it explored the bacteriostatic activity of MPE against various microorganisms. The UAE method was optimized using response surface methodology (RSM) at different times, temperatures, and ratios, with optimal conditions found to be 35 minutes, 45 °C, and a 1:35 ratio. The optimized yield results for total polyphenol content (TPC) were 17.33 ± 1.57 mg GAE/g, total flavonoid content (TFC) was 12.14 ± 0.29 mg QE/g, and radical scavenging activity (RSA) was 72.11 ± 2.19%. These response models were extremely significant with p-values less than 0.05. MPE showed selective effectiveness against Bacillus cereus, Geobacillus stearothermophilus, and Escherichia coli (E. coli). The results highlight the potential of mango peel as a sustainable source of bioactive compounds, contributing to waste reduction in the food industry and the development of natural antimicrobial agents. This study contributes to further research on the application of MPE in processed foods.

9.
Front Psychol ; 15: 1346896, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39380755

RESUMEN

Objective: This study was to investigate the developmental characteristics of executive function (EF) in obese adolescents and the time-course effects of a 14-week exercise intervention combining aerobic exercise and resistance training on EF in this population. Methods: The experimental group of 28 obese junior high school students participated in the exercise intervention combining aerobic exercise and resistance training, while the control group of 24 healthy weight junior high school students engaged in the regular recess exercise. EF, including inhibition, working memory, and cognitive flexibility, was assessed 1 week prior to the exercise intervention and at 12 and 14 weeks post-intervention. Changes in EF sub-functions in both groups at different time points during the exercise intervention were analyzed. Results: The findings revealed that obese junior high school students exhibited lower levels of inhibition (p = 0.003, Cohen's d = 0.848) and cognitive flexibility (p = 0.013, Cohen's d = 0.706) compared to their healthy weight peers. The exercise intervention combining aerobic exercise and resistance training led to significant improvements in EF among obese junior high school students, with inhibition (p < 0.01, Cohen's d = 0.713; p = 0.003, Cohen's d = 0.683) and cognitive flexibility (p = 0.001, Cohen's d = 0.797; p < 0.01, Cohen's d = 0.890) showing significant improvement at 12 and 14 weeks post-intervention, and working memory demonstrating significant improvement at 14 weeks (p = 0.004, Cohen's d = 0.710). No significant differences were observed in EF over time in healthy weight junior high school students. Conclusion: Obese adolescents had impaired EF, as evidenced by low levels of the inhibition and cognitive flexibility compared to healthy weight adolescents. The exercise intervention combining aerobic exercise and resistance training had a positive effect on EF of obese adolescents. The time-course effects of the intervention on improvements in inhibition, working memory, and cognitive flexibility varied with intervention duration in obese adolescents, with significant changes in inhibition and cognitive flexibility observed at 12 weeks and significant changes in working memory at 14 weeks.

10.
Front Pharmacol ; 15: 1463864, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39380909

RESUMEN

Introduction: Due to its remarkable anti-inflammatory pharmacological activity, Farfarae Flos has gained extensive usage in the treatment of various inflammatory diseases such as bronchitis, pneumonia, prostatitis and colitis. And Farfarae Flos come in two color types depending on the color of the flowers: yellowish-white (YW), and purplish-red (PR). However, the difference in anti-inflammatory activity and metabolic profiles between the two flower colors remains unexplored. Methods: This study aims to explore the difference in the anti-inflammatory potential between YW and PR variants of Farfarae Flos and unravel the mechanisms responsible for the observed differences in anti-inflammatory activity through an integrated approach encompassing untargeted metabolomics and in vivo/vitro experimental studies. Initially, we verified the contrasting effects of YW and PR on the inhibition of the inflammatory factors interleukin-6 (IL-6) and nitric oxide (NO) by utilizing an in vitro RAW 264.7 cell inflammation model. Subsequently, a comprehensive evaluation of the systemic inhibitory capacity of YW and PR on IL-6, Interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) was conducted using a validated whole-body mouse model, followed by the analysis of inflammatory factors and histological examination of collected serum, liver, and spleen after 7 days. Furthermore, non-targeted metabolomics profiling was employed to analyze the metabolite profiles of Farfarae Flos with different colors, and quantitative analysis was conducted to identify differential metabolites between YW and PR. The correlation between the anti-inflammatory activities of differentially accumulated metabolites (DAMs) and Farfarae Flos was investigated, resulting in the identification of 48 compounds exhibiting significant anti-inflammatory activity. Additionally, KEGG pathway enrichment analysis was performed to elucidate the underlying mechanisms. Results: Our findings demonstrate that both YW and PR possess anti-inflammatory abilities, with PR exhibiting significantly superior efficacy. The integration of in vivo/vitro experiments and non-targeted metabolomics confirmed the exceptional anti-inflammatory potential of PR and solidified its classification as the "purplish-red better" of Farfarae Flos. Discussion: This study provides valuable insights into the breeding and medical transformation of Farfarae Flos varieties, along with a scientific basis for the establishment of quality standards and the development of new drugs utilizing Farfarae Flos.

11.
ACS Synth Biol ; 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39383016

RESUMEN

l-Threonine, an essential amino acid, is widely used in various industries, with an annually growing demand. However, the present Corynebacterium glutamicum strains are difficult to achieve industrialization of l-threonine due to low yield and purity. In this study, we engineered an l-isoleucine-producing C. glutamicum WM001 to efficiently produce l-threonine by finely regulating the carbon flux. First, the threonine dehydratase in WM001 was mutated to lower the level of l-isoleucine production, then the homoserine dehydrogenase and aspartate kinase were mutated to release the feedback inhibition of l-threonine, and the resulting strain TWZ006 produced 14.2 g/L l-threonine. Subsequently, aspartate ammonia-lyase and aspartate transaminase were overexpressed to accumulate the precursor l-aspartate. Next, phosphoenolpyruvate carboxylase, pyruvate carboxylase and pyruvate kinase were overexpressed, and phosphoenolpyruvate carboxykinase, oxaloacetate decarboxylase were inactivated to fine-regulate the carbon flux among oxaloacetate, pyruvate and phosphoenolpyruvate. The resulting strain TWZ017 produced 21.5 g/L l-threonine. Finally, dihydrodipicolinate synthase was mutated with strong allosteric inhibition from l-lysine to significantly decrease byproducts accumulation, l-threonine export was optimized, and the final engineered strain TWZ024/pXTuf-thrE produced 78.3 g/L of l-threonine with the yield of 0.33 g/g glucose and the productivity of 0.82 g/L/h in a 7 L bioreactor. To the best of our knowledge, this represents the highest l-threonine production in C. glutamicum, providing possibilities for industrial-scale production.

12.
Mol Cell ; 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39383878

RESUMEN

Poly (ADP-ribose) polymerase (PARP) 1 and 2 enzymatic inhibitors (PARPi) are promising cancer treatments. But recently, their use has been hindered by unexplained severe anemia and treatment-related leukemia. In addition to enzymatic inhibition, PARPi also trap PARP1 and 2 at DNA lesions. Here we report that, unlike Parp2-/- mice, which develop normally, mice expressing catalytically inactive Parp2 (E534A and Parp2EA/EA) succumb to Tp53- and Chk2-dependent erythropoietic failure in utero, mirroring Lig1-/- mice. While DNA damage mainly activates PARP1, we demonstrate that DNA replication activates PARP2 robustly. PARP2 is selectively recruited and activated by 5'-phosphorylated nicks (5'p-nicks), including those between Okazaki fragments, resolved by ligase 1 (Lig1) and Lig3. Inactive PARP2, but not its active form or absence, impedes Lig1- and Lig3-mediated ligation, causing dose-dependent replication fork collapse, which is detrimental to erythroblasts with ultra-fast forks. This PARylation-dependent structural function of PARP2 at 5'p-nicks explains the detrimental effects of PARP2 inactivation on erythropoiesis, shedding light on PARPi-induced anemia and the selection for TP53/CHK2 loss.

13.
Fungal Biol ; 128(7): 2190-2196, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39384288

RESUMEN

Heavy metal Cd2+ can easily be accumulated by fungi, causing significant stress, with the fungal cell membrane being one of the primary targets. However, the understanding of the mechanisms behind this stress remains limited. This study investigated the changes in membrane lipid molecules of Pleurotus ostreatus mycelia under Cd2+ stress and the antagonistic effect of Ca2+ on this stress. Cd2+ in the growth media significantly inhibited mycelial growth, with increasing intensity at higher concentrations. The addition of Ca2+ mitigated this Cd2+-induced growth inhibition. Lipidomic analysis showed that Cd2+ reduced membrane lipid content and altered lipid composition, while Ca2+ counteracted these changes. The effects of both Cd2+ and Ca2+ on lipids are dose dependent and phosphatidylethanolamine appeared most affected. Cd2+ also caused a phosphatidylcholine/phosphatidylethanolamine ratio increase at high concentrations, but Ca2+ helped maintain normal levels. The acyl chain length and unsaturation of lipids remained unaffected, suggesting Cd2+ doesn't alter acyl chain structure of lipids. These findings suggest that Cd2+ may affect the growth of mycelia by inhibiting the synthesis of membrane lipids, particular the synthesis of phosphatidylethanolamine, providing novel insights into the mechanisms of Cd2+ stress in fungi and the role of Ca2+ in mitigating the stress.


Asunto(s)
Cadmio , Calcio , Micelio , Fosfatidiletanolaminas , Pleurotus , Pleurotus/crecimiento & desarrollo , Pleurotus/metabolismo , Pleurotus/efectos de los fármacos , Fosfatidiletanolaminas/metabolismo , Cadmio/metabolismo , Cadmio/farmacología , Micelio/crecimiento & desarrollo , Micelio/efectos de los fármacos , Micelio/metabolismo , Calcio/metabolismo , Lípidos de la Membrana/metabolismo , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Membrana Celular/química , Medios de Cultivo/química
14.
Nano Lett ; 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39352880

RESUMEN

The accumulation of abnormal protein deposits known as amyloid-ß (Aß) plaques contributes to the development and progression of Alzheimer's disease. Aggregated Aß exacerbates oxidative stress by stimulating the production of reactive oxygen species (ROS) in a detrimental feedback loop. 8-Hydroxyquinoline (8-HQ) is recognized for its ability to inhibit or reverse Aß aggregation and reduce neurotoxicity. Here, an 8-HQ-based polymer, DHQ, was developed to combat Aß-mediated neurotoxicity by delivering an antioxidant enzyme. DHQ efficiently delivers superoxide dismutase into targeted cells, thereby downregulating the intracellular ROS level. Additionally, the polymer effectively inhibits the fibrillization of three proteins involved in fibrosis, ß-lactoglobulin (BLG), insulin, and Aß1-40, at nanomolar concentrations. Cell culture models demonstrated that DHQ reduces ROS levels induced by Aß1-40 aggregation, rescuing cell viability and preventing apoptosis. Intracellular delivery of SOD further enhanced the ability to maintain the ROS homeostasis. This polymer offers a multifaceted approach to treating diseases associated with amyloidosis.

15.
Front Pharmacol ; 15: 1401103, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39355774

RESUMEN

Background: While Sodium-glucose cotransporter 2 (SGLT2) inhibitors are effective in managing diabetes and reducing cardiovascular risk, concerns about their association with lower limb complications, including, osteomyelitis, ulcers, and peripheral artery disease (PAD), persist. This study employs Mendelian Randomization (MR) to assess the causal relationship between SGLT2 inhibitors and these lower limb safety outcomes. Methods: A two-sample drug-target MR approach was used, complemented by a one-sample MR and genetic association analysis. Six SNPs were selected as instrumental variables to proxy the effect of SGLT2 inhibition. Primary outcomes were major limb safety outcomes, including osteomyelitis, lower limb ulcers, PAD, and cellulitis. The primary analytical method was the generalized inverse variance-weighted (IVW) approach, along with several sensitivity analyses. Results: The MR analysis indicated no significant causal association between genetically proxied SGLT2 inhibition and most of the studied lower limb safety outcomes. However, a significant association with PAD was observed, necessitating careful interpretation due to discrepancies between IVW and MR-Egger results. Sensitivity analyses supported these findings, showing little evidence of heterogeneity or directional pleiotropy. Conclusion: This study suggests that SGLT2 inhibitors may not be significantly associated with an increased risk of most lower limb safety outcomes, including osteomyelitis, lower limb ulcers, and cellulitis, in patients with type 2 diabetes. However, the complex relationship with PAD highlights the need for further research. These findings contribute to the understanding of the safety profile of SGLT2 inhibitors, supporting their continued use in diabetes management while underlining the importance of continuous safety monitoring.

16.
Curr Res Insect Sci ; 6: 100096, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39386116

RESUMEN

Blacklegged tick, Ixodes scapularis Say (Arachnida: Ixodidae), is a growing health concern for humans as vectors the causative agent of Lyme disease, Borrelia burgdorferi, and many other pathogens. Given the potential health threat I. scapularis entails, and the need to find effective strategies to prevent tick bites, it is pivotal to understand the chemosensory system of ticks and their host-seeking behaviour when exposed to repellents. In this study, we investigated whether the exposure to synthetic and plant-derived repellents impairs the ability of I. scapularis to detect attractants and host volatiles (butyric acid), and ultimately how these repellents interfere with host-seeking behaviour in both wild and lab-reared ticks. Furthermore, we screened wild ticks used in electrophysiology and Y-tube behavioural assays for presence of pathogens (Borrelia, Anaplasma, and Babesia) to evaluate if the bacterial infection status would affect the detection of butyric acid under the exposure to repellents. We determined that the exposure to DEET, lemongrass essential oil, citral, and geraniol significantly inhibited the ability of both lab-reared and wild adult female I. scapularis to detect and respond to butyric acid. We found that tick infection status does not significantly impact host-seeking behaviour in adult female I. scapularis. The knowledge gained from our study contributes to advance our understanding of host-seeking behaviour in ticks and the impact that the exposure to repellent has on the tick chemosensory system. These findings will be important for elucidating the mechanism of repellence in ticks and for the development of effective tick repellent management tools.

17.
BMC Gastroenterol ; 24(1): 349, 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39367371

RESUMEN

OBJECTIVE: To evaluate the effectiveness and safety of tofacitinib in patients with ulcerative colitis (UC) in clinical practice in Lebanon. DESIGN: This was a retrospective cross-sectional study. The data were collected from hospital records. Patients with moderate to severe UC treated with tofacitinib between 2018 and 2021 were included. Patients' demographics, disease-specific characteristics, clinical assessment at three time points (8, 26, and 52 weeks), endoscopic evaluation at 24 weeks, and adverse events were collected. RESULTS: A total of 60 UC patients with a mean duration of disease of 7.9 ± 4.7 years were enrolled. 61.7% of patients had extensive disease, and 58.3% had received ≥ 1 biologic prior to tofacitinib. Clinical remission was reported in 25, 34, and 31 patients (41.7%, 56.7%, and 56.4%) at 8, 26, and 52 weeks respectively. Endoscopic remission (endoscopic Mayo score 0 or 1) was observed in 58.3% of patients at 52 weeks. About one-third of patients (31.7%) stopped tofacitinib at one year, primarily for lack of efficacy or loss of response, with no significant difference between biologics-naïve and experienced patients (24% vs. 37.1% respectively). No serious adverse events or deaths were reported. Adverse events were reported in 3 patients (5.0%) - one C. difficile infection, one case of reversible lymphopenia, and one case of facial acne. No serious adverse events or deaths were noted. On multivariate analysis, biologic-naïve status and reduction or normalization of CRP were associated with clinical remission (OR = 10.87, 95% CI = 1.57, 100, and OR = 78.47, 95% CI = 2.09, 2940.32 respectively), while reduction or normalization of CRP was associated with endoscopic remission at 1 year (OR = 19.03, 95% CI = 1.64, 221.09). CONCLUSION: Tofacitinib was effective in the treatment of moderately severe ulcerative colitis in this real-world cohort in Lebanon. Further, the predictors associated with clinical and endoscopic remissions were found to be biologic-naïve status and reduction in CRP. Observed AEs were consistent with the known safety profile. One of the major limitations of this study is the smaller sample size and the retrospective nature of the study.


Asunto(s)
Colitis Ulcerosa , Piperidinas , Pirimidinas , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Pirimidinas/uso terapéutico , Pirimidinas/efectos adversos , Piperidinas/uso terapéutico , Piperidinas/efectos adversos , Masculino , Femenino , Estudios Retrospectivos , Líbano , Adulto , Estudios Transversales , Persona de Mediana Edad , Resultado del Tratamiento , Inducción de Remisión , Índice de Severidad de la Enfermedad , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos
18.
Dev Cogn Neurosci ; 70: 101454, 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39357147

RESUMEN

Cognitive control processes likely influence the extent to which adolescents can successfully regulate their emotions. This study examined whether individual differences in affective inhibition and heart rate variability (HRV), as a peripheral index of cognitive control, moderated the association between momentary emotion regulation and negative affect (NA). Ecological Momentary Assessments (EMA) over 14 days were obtained in 235 adolescents (Mage = 13.48 years; 106 females). At each assessment, participants reported their current NA and the extent to which they used cognitive reappraisal and rumination. Moreover, at three time points (approximately 1 year, 6 months, and just before the EMA), affective inhibition was assessed using an affective go/no-go task and HRV was recorded at rest. Results indicate that adolescents with lower affective inhibition reported lower average levels of daily rumination. However, affective inhibition did not moderate the association between either daily cognitive reappraisal or rumination and momentary NA. Consistent with hypotheses, the association between momentary rumination and NA was weaker in adolescents showing higher levels of resting HRV. Overall, findings may underscore the importance of interventions targeting HRV as a malleable factor for enhancing adolescents' affective well-being.

19.
J Colloid Interface Sci ; 679(Pt A): 64-74, 2024 Sep 29.
Artículo en Inglés | MEDLINE | ID: mdl-39357227

RESUMEN

The stability and high-dose addition of carbon dots in corrosion and scale inhibition are obstacles to their commercial application. Herein, we report a new type of functional CDs (PEI-CDA) based on Angelica residue and polyethyleneimine (PEI), which can remarkably boost the performance of corrosion and scale inhibition, while expending the application of traditional Chinese medicine waste residue. At 303.15 K, the corrosion inhibition efficiency of PEI-CDA for carbon steel in 1.0 M HCl medium was tested by weight loss method and electrochemical method and reached over 93 %, which is significantly better than that of CDA (83 %) under the same conditions. And its corrosion inhibition efficiency can still remain stable after 15 h. The ultra-low dose (5 mg·L-1) PEI-CDA has excellent anti-corrosion protection effect on carbon steel due to its ability to form a dense and well-organized adsorption film covering on the carbon steel surface, whose adsorption includes two types of chemical and physical adsorption, and follows the Langmuir adsorption model. Furthermore, static methods display that the CaSO4 scale inhibition efficiency of PEI-CDA is up to 100 % when its dosage is 100 mg·L-1. Analysis of the generated CaSO4 scale shows that the addition of PEI-CDA causes lattice distortion, chelation, and dispersion of scale. In addition, the fluorescence spectra imply that PEI-CDA can be expected to on-line detection of its residual content in the water system. The results demonstrate that PEI-CDA possesses significant potential in green inhibitors and the comprehensive utilization of waste resources.

20.
Child Neuropsychol ; : 1-18, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39359060

RESUMEN

The Hayling Completion Sentence Test (HSCT) is dedicated to assess inhibition of the dominant response and includes two conditions, an automatic condition in which the participants are asked to complete sentences properly and an inhibition condition in which the participants were asked to produce a word completely unrelated to the sentence. The aim of our study was 1) to adapt, 2) to evaluate the psychometric properties and 3) to standardize the HSCT into a French-school-aged pediatric population. We developed the Child-Hayling Test, a child adaptation of the adult French version of the HSCT. The reliability and validity of the Child-Hayling Test were then evaluated in a sample of 134 children aged 6-11 years. In the inhibition condition, children had lower response latency, as they get older. No effect of gender was observed. Reliability indices were low to moderate. Concerning the convergent and divergent validity, response latencies in the Child-Hayling Test correlated with latency scores in the Barre-Joe inhibition test, whereas the Child-Hayling Test scores were not related to children's lexical abilities. The Child-Hayling Test was then administered to 393 typically developing 6- to 11-year-old children. Normative data were calculated in the inhibition condition using a regression-based approach. Regression equations to calculate Z scores are provided for clinical use. In addition, we proposed a clear guideline on how to score children's inhibition responses. The Child-Hayling Test provides a useful tool for assessing prepotent response inhibition in children and can be recommended for use in clinical research and practice.

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