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1.
J Mech Behav Biomed Mater ; 157: 106629, 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38889531

RESUMEN

In this paper, the Ti6Al4V alloy surface was modified via ceramic conversion treatment (CCT) with or without a pre-deposited silver layer. After characterizing the surface morphologies, microstructure and phase constituents of the ceramic oxide layer formed at 620 °C, we investigated the surface hardness and the cross-sectional nano-hardness profile under the oxide layer. The static load-bearing capacity of the oxide layers was examined by applying discrete loads via a Vickers indenter and observing the indentations. A scratch test was used to evaluate the load-bearing capacity and the adhesion/cohesion of the oxide layers. The wettability of the surface changed due to the incorporation of silver and the change of surface morphology. Reciprocating friction and wear test was used to assess the tribological properties. Small and dispersed silver nanoparticles and clusters were found in the oxide layer of the Ag pre-deposited Ti6Al4V samples, and they had much better tribological properties in terms of reduced coefficient of friction and wear volume. With the assistance of silver, the efficiency of the CCT was significantly improved.

2.
JMIR Med Inform ; 12: e62757, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38838306

RESUMEN

[This corrects the article DOI: 10.2196/44892.].

3.
Science ; 384(6701): eadk5382, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38870290

RESUMEN

Polycystic ovary syndrome (PCOS), a prevalent reproductive disorder in women of reproductive age, features androgen excess, ovulatory dysfunction, and polycystic ovaries. Despite its high prevalence, specific pharmacologic intervention for PCOS is challenging. In this study, we identified artemisinins as anti-PCOS agents. Our finding demonstrated the efficacy of artemisinin derivatives in alleviating PCOS symptoms in both rodent models and human patients, curbing hyperandrogenemia through suppression of ovarian androgen synthesis. Artemisinins promoted cytochrome P450 family 11 subfamily A member 1 (CYP11A1) protein degradation to block androgen overproduction. Mechanistically, artemisinins directly targeted lon peptidase 1 (LONP1), enhanced LONP1-CYP11A1 interaction, and facilitated LONP1-catalyzed CYP11A1 degradation. Overexpression of LONP1 replicated the androgen-lowering effect of artemisinins. Our data suggest that artemisinin application is a promising approach for treating PCOS and highlight the crucial role of the LONP1-CYP11A1 interaction in controlling hyperandrogenism and PCOS occurrence.


Asunto(s)
Proteasas ATP-Dependientes , Artemisininas , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol , Proteínas Mitocondriales , Síndrome del Ovario Poliquístico , Animales , Femenino , Humanos , Ratones , Ratas , Andrógenos/metabolismo , Artemisininas/uso terapéutico , Artemisininas/farmacología , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/metabolismo , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/genética , Modelos Animales de Enfermedad , Hiperandrogenismo/tratamiento farmacológico , Hiperandrogenismo/metabolismo , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Ovario/efectos de los fármacos , Ovario/metabolismo , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Proteolisis , Ratones Endogámicos C57BL , Adulto Joven , Adulto , Ratas Sprague-Dawley , Proteasas ATP-Dependientes/genética , Proteasas ATP-Dependientes/metabolismo
4.
Adv Healthc Mater ; : e2400474, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38875525

RESUMEN

Ferroptosis induction is particularly promising for cancer therapy when the apoptosis pathway is compromised. Current strategies in nanomedicine for inducing ferroptosis primarily focus on promoting the accumulation of reactive oxygen species (ROS). However, the presence of intracellular antioxidants, such as nuclear factor erythroid 2-related factor 2 (Nrf2), can limit the effectiveness of such therapy by activating detoxification systems and eliminating ROS. To overcome this challenge, a simple one-step strategy for the construction of Mn2+-aloe-emodin (AE) nanoscale coordination polymers (MAP NPs) with ultrahigh loading capacity, followed by the modification of polyvinyl pyrrolidone (PVP), was developed. In the tumour microenvironment (TME), these NPs degraded and released AE and Mn(II), facilitating the generation of ROS and Mn(IV) through a Fenton-like reaction between H2O2 and Mn(II). Mn(IV) subsequently interacted with glutathione (GSH) to induce a cyclic catalytic effect, and the depletion of GSH diminished the activation of glutathione-dependent peroxidase 4 (GPX4). Furthermore, AE inhibited the activity of Nrf2 and depleted GSH, thereby synergistically enhancing antitumour efficacy. Our study demonstrated that MAP NPs effectively generate a robust ROS storm within tumour cells, suggesting that high-performance ferroptosis therapy is effective. Additionally, the inclusion of Mn(II) in the MAP NPs enabled real-time monitoring of therapeutic efficacy via magnetic resonance T1-weighted contrast imaging. This article is protected by copyright. All rights reserved.

5.
Materials (Basel) ; 17(11)2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38893889

RESUMEN

Low friction and high wear resistance are critical properties for sliding bearings. In this research, advanced Cu/GO nanocomposite coatings have been developed by a brush plating method to improve the tribological performance of brass-based sliding bearings. A series of brush plating studies under voltages from 2 to 6 V with different GO concentrations (0.2-0.8 g/L) was conducted, and the coating microstructures were characterised by SEM, EDX, GDOES and XRD and the tribological behaviour of the Cu/GO composite coatings were evaluated using dry ball-on-plane tribological tests The experimental results have demonstrated that GO can be successfully introduced into the whole composite coating layer; the Cu/GO composite coatings can reduce the friction of brass and increase its wear resistance by two orders of magnitude, mainly due to the self-lubricating GO added into the coatings.

6.
Small ; : e2402845, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38895955

RESUMEN

Metal chalcogenides as an ideal family of anode materials demonstrate a high theoretical specific capacity for potassium ion batteries (PIBs), but the huge volume variance and poor cyclic stability hinder their practical applications. In this study, a design of a stress self-adaptive structure with ultrafine SnSe nanoparticles embedded in carbon nanofiber (SnSe@CNF) via the electrospinning technology is presented. Such an architecture delivers a record high specific capacity (272 mAh g-1 at 50 mA g-1) and high-rate performance (125 mAh g-1 at 1 A g-1) as a PIB anode. It is decoded that the fundamental understanding for this great performance is that the ultrafine SnSe particles enhance the full utilization of the active material and achieve stress relief as the stored strain energy from cycling is insufficient to drive crack propagation and thus alleviates the intrinsic chemo-mechanical degradation of metal chalcogenides.

7.
Front Plant Sci ; 15: 1344895, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38887465

RESUMEN

Edamame (Glycine max (L.) Merr.), a specialty soybean prized for its nutritional value and taste, has witnessed a surge in demand within the U.S. However, subpar seedling stands have hindered its production potential, necessitating increased inputs for farmers. This study aims to uncover potential physiological factors contributing to low seedling emergence in edamame. We conducted comprehensive assessments on thirteen prominent edamame genotypes alongside two food-grade and two grain-type soybean genotypes, focusing on germination and emergence speed in both laboratory and field settings. Additionally, we employed single electrical conductivity tests and identified and quantified seed leachate components to distinguish among soybean types. Furthermore, using a LabField™ simulation table, we examined seed emergence across a wide soil temperature range (5°C to 45°C) for edamame and other soybean types. All seeds were produced under the same environmental conditions, harvested in Fall 2020, and stored under uniform conditions to minimize quality variations. Our findings revealed minimal divergence in emergence percentages among the seventeen genotypes, with over 95% germination and emergence in laboratory conditions and over 70% emergence in the field. Nonetheless, edamame genotypes typically exhibited slower germination speeds and higher leachate exudates containing higher soluble sugars and amino acids. Seed size did not significantly impact total emergence but was negatively correlated with germination and emergence speed, although this effect could be mitigated under complex field conditions. Furthermore, this study proposed differences that distinguish edamame from other soybean types regarding ideal and base temperatures, as well as thermal time. The finds offer valuable insights into edamame establishment, potentially paving the way for supporting local edamame production in the U.S.

8.
J Hum Genet ; 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38880818

RESUMEN

Variants in voltage-gated sodium channel (VGSC) genes are implicated in seizures, epilepsy, and neurodevelopmental disorders, constituting a significant aspect of hereditary epilepsy in the Chinese population. Through retrospective analysis utilizing next-generation sequencing (NGS), we examined the genotypes and phenotypes of VGSC-related epilepsy cases from a cohort of 691 epilepsy subjects. Our findings revealed that 5.1% of subjects harbored VGSC variants, specifically 22 with SCN1A, 9 with SCN2A, 1 with SCN8A, and 3 with SCN1B variants; no SCN3A variants were detected. Among these, 14 variants were previously reported, while 21 were newly identified. SCN1A variant carriers predominantly presented with Dravet Syndrome (DS) and Genetic Epilepsy with Febrile Seizures Plus (GEFS + ), featuring a heightened sensitivity to fever-induced seizures. Statistically significant disparities emerged between the SCN1A-DS and SCN1A-GEFS+ groups concerning seizure onset and genetic diagnosis age, incidence of status epilepticus, mental retardation, anti-seizure medication (ASM) responsiveness, and familial history. Notably, subjects with SCN1A variants affecting the protein's pore region experienced more frequent cluster seizures. All SCN2A variants were of de novo origin, and 88.9% of individuals with SCN2A variations exhibited cluster seizures. This research reveals a significant association between variations in VGSC-related genes and the clinical phenotype diversity of epilepsy subjects in China, emphasizing the pivotal role of NGS screening in establishing accurate disease diagnoses and guiding the selection of ASM.

9.
Vet Parasitol ; 330: 110237, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38878462

RESUMEN

Cryptosporidium parvum is an important zoonotic pathogen that is studied worldwide. MicroRNAs (miRNAs) act as post-transcriptional regulators and may play a key role in modulating host epithelial responses following Cryptosporidium infection. Our previous study has shown that C. parvum downregulates the expression of miR-181d through the p50-dependent TLRs/NF-κB pathway. However, the mechanism by which miR-181d regulates host cells in response to C. parvum infection remains unclear. The present study found that miR-181d downregulation inhibited cell apoptosis and increased parasite burden in HCT-8 cells after C. parvum infection. Bioinformatics analysis and luciferase reporter assays have shown that BCL2 was a target gene for miR-181d. Moreover, BCL2 overexpression and miR-181d downregulation had similar results. To further investigate the mechanism by which miR-181d regulated HCT-8 cell apoptosis during C. parvum infection, the expression of molecules involved in the intrinsic apoptosis pathway was detected. Bax, caspase-9, and caspase-3 expression was decreased at 4, 8, 12, and 24 hpi and upregulated at 36 and 48 hpi. Interfering with the expression of miR-181d or BCL2 significantly affected the expression of molecules in the intrinsic apoptosis pathway. These data indicated that miR-181d targeted BCL2 to regulate HCT-8 cell apoptosis and parasite burden in response to C. parvum infection via the intrinsic apoptosis pathway. These results allowed us to further understand the regulatory mechanisms of host miRNAs during Cryptosporidium infection, and provided a theoretical foundation for the design and development of anti-cryptosporidiosis drugs.

10.
Food Funct ; 15(12): 6383-6394, 2024 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-38819120

RESUMEN

Background & aims: Macronutrients are the main part of the human diet and can affect multiple health outcomes. Nevertheless, associations between dietary macronutrient quality and asthenozoospermia risk have not been reported to date. Thus, this study aimed to be the first to explore the associations between macronutrient quality and asthenozoospermia risk using the novel multidimensional macronutrient quality index (MQI). Methods: A case-control study was conducted at infertility clinics of Shengjing Hospital of China Medical University during June and December 2020, including 552 asthenozoospermia cases and 585 normozoospermia controls. Data on diet were collected using a validated food frequency questionnaire. MQI was estimated according to the carbohydrate quality index (CQI), fat quality index (FQI), and protein quality index (PQI). Binary logistic regression models were performed to calculate the odds ratio (OR) with a 95% confidence interval (CI). Subgroup and interaction analyses were performed based on age, body mass index, physical activity, smoking, drinking, and education level. Dose-response relationships were evaluated by restricted cubic splines. Sensitivity analyses were performed in two ways. First, participants with a dietary change were excluded to lower potential reverse causation. Then, we used the healthy plate protein source quality index instead of PQI to redefine MQI. Results: No statistically significant association was observed between dietary MQI and asthenozoospermia risk (OR = 1.24, 95% CI: 0.88-1.73). The sub-indices of MQI, CQI, FQI, and PQI, failed to be identified as having a statistically significant association with asthenozoospermia risk (OR = 1.35, 95% CI: 0.92-1.97 for CQI; OR = 1.13, 95% CI: 0.84-1.53 for FQI; OR = 1.28, 95% CI: 0.92-1.78 for PQI). However, CQI showed a positive association with the risk of asthenozoospermia among non-drinkers (Ptrend < 0.05) and highly educated participants (OR = 1.82, 95% CI: 1.13-2.94; Ptrend < 0.05). Additionally, there was a multiplicative interaction between CQI and education level for asthenozoospermia risk (P < 0.05). Conclusions: Our findings demonstrated no association of MQI and its sub-indices with asthenozoospermia risk except for CQI. Although our findings are mostly non-significant, they contribute novel knowledge to this research field and lay the foundation for future studies.


Asunto(s)
Astenozoospermia , Dieta , Nutrientes , Humanos , Masculino , Estudios de Casos y Controles , Adulto , China/epidemiología , Nutrientes/análisis , Factores de Riesgo , Índice de Masa Corporal
11.
J Cancer ; 15(10): 3173-3182, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38706892

RESUMEN

Oral squamous cell carcinoma (OSCC) is the most common malignant head and neck carcinoma type. Myeloid cell leukemia-1 (MCL-1), an anti-apoptotic BCL-1 protein, has been verified to be among the most highly upregulated pathologic proteins in human cancers linked to tumor relapse, poor prognosis and therapeutic resistance. Herein, therapeutic targeting MCL-1 is an attractive focus for cancer treatment. The present study found that butein, a potential phytochemical compound, exerted profound antitumor effects on OSCC cells. Butein treatment significantly inhibited cell viability, proliferation capacity and colony formation ability, and activated cell apoptotic process. Further potential mechanism investigation showed that promoting MCL-1 ubiquitination and degradation is the major reason for butein-mediated OSCC cell cytotoxicity. Our results uncovered that butein could facilitate E3 ligase FBW7 combined with MCL-1, which contributed to an increase in the ubiquitination of MCL-1 Ub-K48 and degradation. The results of both in vitro cell experiments and in vivo xenograft models imply a critical antitumor function of butein with the well-tolerated feature, and it might be an attractive and promising agent for OSCC treatment.

12.
Heliyon ; 10(9): e29497, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38699007

RESUMEN

Objective: Diabetic retinopathy is one of the major complications of diabetes. In this study, a diabetic retinopathy risk prediction model integrating machine learning models and SHAP was established to increase the accuracy of risk prediction for diabetic retinopathy, explain the rationality of the findings from model prediction and improve the reliability of prediction results. Methods: Data were preprocessed for missing values and outliers, features selected through information gain, a diabetic retinopathy risk prediction model established using the CatBoost and the outputs of the mode interpreted using the SHAP model. Results: One thousand early warning data of diabetes complications derived from diabetes complication early warning dataset from the National Clinical Medical Sciences Data Center were used in this study. The CatBoost-based model for diabetic retinopathy prediction performed the best in the comparative model test. ALB_CR, HbA1c, UPR_24, NEPHROPATHY and SCR were positively correlated with diabetic retinopathy, while CP, HB, ALB, DBILI and CRP were negatively correlated with diabetic retinopathy. The relationships between HEIGHT, WEIGHT and ESR characteristics and diabetic retinopathy were not significant. Conclusion: The risk factors for diabetic retinopathy include poor renal function, elevated blood glucose level, liver disease, hematonosis and dysarteriotony, among others. Diabetic retinopathy can be prevented by monitoring and effectively controlling relevant indices. In this study, the influence relationships between the features were also analyzed to further explore the potential factors of diabetic retinopathy, which can provide new methods and new ideas for the early prevention and clinical diagnosis of subsequent diabetic retinopathy.

13.
J Hazard Mater ; 472: 134556, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38735187

RESUMEN

BACKGROUND: Although evidence on the association between per- and polyfluoroalkyl substances (PFASs) and human health outcomes has grown exponentially, specific health outcomes and their potential associations with PFASs have not been conclusively evaluated. METHODS: We conducted a comprehensive search through the databases of PubMed, Embase, and Web of Science from inception to February 29, 2024, to identify systematic reviews with meta-analyses of observational studies examining the associations between the PFASs and multiple health outcomes. The quality of included studies was evaluated using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool, and credibility of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. The protocol of this umbrella review (UR) had been registered in PROSPERO (CRD 42023480817). RESULTS: The UR identified 157 meta-analyses from 29 articles. Using the AMSTAR measurement tool, all articles were categorized as of moderate-to-high quality. Based on the GRADE assessment, significant associations between specific types of PFASs and low birth weight, tetanus vaccine response, and triglyceride levels showed high certainty of evidence. Moreover, moderate certainty of evidence with statistical significance was observed between PFASs and health outcomes including lower BMI z-score in infancy, poor sperm progressive motility, and decreased risk of preterm birth as well as preeclampsia. Fifty-two (33%) associations (e.g., PFASs and gestational hypertension, cardiovascular disease, etc) presented low certainty evidence. Additionally, eighty-five (55%) associations (e.g., PFASs with infertility, lipid metabolism, etc) presented very low certainty evidence. CONCLUSION: High certainty of evidence supported that certain PFASs were associated with the incidence of low birth weight, low efficiency of the tetanus vaccine, and low triglyceride levels.


Asunto(s)
Fluorocarburos , Revisiones Sistemáticas como Asunto , Humanos , Embarazo , Estudios Observacionales como Asunto , Metaanálisis como Asunto , Recién Nacido de Bajo Peso , Femenino , Contaminantes Ambientales , Toxoide Tetánico , Triglicéridos/sangre
14.
Thromb Haemost ; 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38744425

RESUMEN

The consensus guidelines of the Geriatric Society of Chinese Medical Association (GSCMA) on the management of atrial fibrillation (AF) in the elderly was first published in 2011 and updated in 2016, with endorsement by Chinese Society of Geriatric Health Medicine (CSGHM). Since then, many important studies regarding the screening and treatment in the elderly population have been reported, necessitating this updated expert consensus guidelines. The writing committee members comprehensively reviewed updated evidence pertaining to elderly patients with AF, and formulated this 2024 update. The highlighted issues focused on the following: screening for AF, geriatric comprehensive assessment, use of the Atrial fibrillation Better Care (ABC) pathway for the elderly patients, and special clinical settings related to elderly patients with AF. New recommendations addressing smart technology facilitated AF screening, ABC pathway based management and optimal anticoagulation were developed, with a focus on the elderly.

15.
Mol Brain ; 17(1): 23, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750560

RESUMEN

This study aimed to unveil the central mechanism of moxibustion treating chronic inflammatory visceral pain (CIVP) from the angle of circRNA-miRNA-mRNA networks in the spinal cord. The rat CIVP model was established using a mixture of 5% (w/v) 2,4,6-trinitrobenzene sulfonic acid and 50% ethanol at a volume ratio of 2:1 via enema. Rats in the moxibustion group received herb-partitioned moxibustion at Tianshu (ST25, bilateral) and Qihai (CV6) points. The abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL) were adopted for pain behavior observation and pain sensitivity assessment. The circRNA, miRNA, and mRNA expression profiles were detected using the high-throughput sequencing technique. Relevant databases and bioinformatics analysis methods were used to screen for differentially expressed (DE) RNAs and build a circRNA-miRNA-mRNA (competing endogenous RNA) ceRNA regulatory network. The real-time quantitative PCR was employed to verify the sequencing result. CIVP rat models had a significantly higher AWR and lower TWL and MWT than normal rats. Between normal and model rats, there were 103 DE-circRNAs, 16 DE-miRNAs, and 397 DE-mRNAs in the spinal cord. Compared with the model group, the moxibustion group had a lower AWR and higher TWL and MWT; between these two groups, there were 118 DE-circRNAs, 15 DE-miRNAs, and 804 DE-mRNAs in the spinal cord. Two ceRNA networks were chosen to be verified. As a result, moxibustion's analgesic effect on visceral pain in CIVP rats may be associated with regulating the circRNA_02767/rno-miR-483-3p/Gfap network in the spinal cord and improving central sensitization.


Asunto(s)
Redes Reguladoras de Genes , MicroARNs , Moxibustión , ARN Circular , ARN Mensajero , Ratas Sprague-Dawley , Médula Espinal , Dolor Visceral , Animales , Moxibustión/métodos , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Médula Espinal/metabolismo , Médula Espinal/patología , Dolor Visceral/genética , Dolor Visceral/terapia , Masculino , Inflamación/genética , Inflamación/patología , Dolor Crónico/terapia , Dolor Crónico/genética , Ratas , Regulación de la Expresión Génica
16.
Am J Chin Med ; 52(3): 865-884, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38790085

RESUMEN

Ovarian cancer is a common, highly lethal tumor. Herein, we reported that S-phase kinase-associated protein 2 (Skp2) is essential for the growth and aerobic glycolysis of ovarian cancer cells. Skp2 was upregulated in ovarian cancer tissues and associated with poor clinical outcomes. Using a customized natural product library screening, we found that xanthohumol inhibited aerobic glycolysis and cell viability of ovarian cancer cells. Xanthohumol facilitated the interaction between E3 ligase Cdh1 and Skp2 and promoted the Ub-K48-linked polyubiquitination of Skp2 and degradation. Cdh1 depletion reversed xanthohumol-induced Skp2 downregulation, enhancing HK2 expression and glycolysis in ovarian cancer cells. Finally, a xenograft tumor model was employed to examine the antitumor efficacy of xanthohumol in vivo. Collectively, we discovered that xanthohumol promotes the binding between Skp2 and Cdh1 to suppress the Skp2/AKT/HK2 signal pathway and exhibits potential antitumor activity for ovarian cancer cells.


Asunto(s)
Flavonoides , Glucólisis , Neoplasias Ováricas , Propiofenonas , Proteínas Quinasas Asociadas a Fase-S , Ubiquitinación , Propiofenonas/farmacología , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Proteínas Quinasas Asociadas a Fase-S/genética , Flavonoides/farmacología , Femenino , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/metabolismo , Glucólisis/efectos de los fármacos , Animales , Transducción de Señal/efectos de los fármacos , Cadherinas/metabolismo , Carcinogénesis/efectos de los fármacos , Antígenos CD/metabolismo , Hexoquinasa/metabolismo , Línea Celular Tumoral , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratones , Fitoterapia , Ratones Desnudos , Antineoplásicos Fitogénicos/farmacología
17.
Biochem Biophys Res Commun ; 721: 150130, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-38761750

RESUMEN

Apigenin (API) is a natural flavonoid compound with antioxidant, anti fibrotic, anti-inflammatory and other effects, but there is limited research on the effect of API on liver fibrosis. This study aims to explore the effect and potential mechanism of API on liver fibrosis induced by CCl4 in mice. The results indicate that API reduces oxidative stress levels, inhibits hepatic stellate cell (HSC) activation, and exerts anti liver fibrosis effects by regulating the PKM2-HIF-1α pathway. We observed that API alleviated liver tissue pathological damage and collagen deposition in CCl4 induced mouse liver fibrosis model, promoting the recovery of liver function in mice with liver fibrosis. In addition, the API inhibits the transition of Pyruvate kinase isozyme type M2 (PKM2) from dimer to tetramer formation by regulating the EGFR-MEK1/2-ERK1/2 pathway, thereby preventing dimer from entering the nucleus and blocking PKM2-HIF-1α access. This change leads to a decrease in malondialdehyde (MDA) and Catalase (CAT) levels and an increase in glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) levels, as well as total antioxidant capacity (T-AOC) in the liver of liver fibrosis mice. At the same time, API downregulated the expression of α-smooth muscle actin (α-SMA), Vimentin and Desmin in the liver tissue of mice with liver fibrosis, inhibited the activation of HSC, and reduced collagen deposition. These results indicate that API can inhibit HSC activation and alleviate CCl4 induced liver fibrosis by inhibiting the PKM2-HIF-1α pathway and reducing oxidative stress, laying an important foundation for the development and clinical application of API as a novel drug for treating liver fibrosis.


Asunto(s)
Apigenina , Subunidad alfa del Factor 1 Inducible por Hipoxia , Cirrosis Hepática , Estrés Oxidativo , Animales , Estrés Oxidativo/efectos de los fármacos , Apigenina/farmacología , Apigenina/uso terapéutico , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Cirrosis Hepática/metabolismo , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/patología , Ratones , Masculino , Piruvato Quinasa/metabolismo , Ratones Endogámicos C57BL , Tetracloruro de Carbono/toxicidad , Células Estrelladas Hepáticas/metabolismo , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/patología , Proteínas de Unión a Hormona Tiroide , Hígado/metabolismo , Hígado/efectos de los fármacos , Hígado/patología , Hormonas Tiroideas/metabolismo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Receptores ErbB
18.
Asia Pac J Clin Nutr ; 33(2): 272-282, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38794985

RESUMEN

BACKGROUND AND OBJECTIVES: To elucidate the role of dietary fats on the relationship between mild cognitive impairment and sarcopenia and help identifying and preventing the decline of cognitive and muscle function in elderly individuals. METHODS AND STUDY DESIGN: The study conducted involving a group of 1812 individuals between the ages of 61 and 92. Body composition and BMR were assessed by bioelectrical impedance analysis. Cognitive function and dietary nutrition were evaluated by neuropsychological assessments and questionnaire of food intake frequency. Lipidomics analysis was performed using UHPLC-Qtrap-MS/MS. RESULTS: MCI and SA are mutual influencing factors, lower intake of MUFA, PUFA and higher intake of fat was associated with cognitive dysfunction and/or SA (p < 0.05). PUFA was important for MCI combined with SA (Compared with Q1, Q4 OR: 0.176, 95%CI: 0.058,0.533). Lipidomics analysis revealed that triacylglycerol (TAG) contain more carbon chains with saturated double bonds may be closely related to cognitive impairment and the progression of SA (p < 0.05). While, DAG with carbon chains of unsaturated double bonds is opposite. CONCLUSIONS: Insufficient intake of unsaturated fatty acids was associated with the development of cognitive decline and the progression of SA. MUFA affecting muscle health, fats and PUFA has a greater impact on MCI combined with SA. Less MUFA intake and increasing saturated double-bonded fatty acid intake might be the key factors on promoting cognitive impairment and SA in the elderly. They have the potential to serve as prospective biomarkers indicating a higher risk of cognitive decline and/or SA in the elderly population.


Asunto(s)
Cognición , Disfunción Cognitiva , Grasas de la Dieta , Sarcopenia , Humanos , Sarcopenia/prevención & control , Anciano , Masculino , Femenino , Anciano de 80 o más Años , Grasas de la Dieta/administración & dosificación , Disfunción Cognitiva/prevención & control , Persona de Mediana Edad , Composición Corporal
19.
JAMA ; 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38819983

RESUMEN

Importance: Obesity has become a global public health concern and China has the largest number of affected people worldwide. Objective: To assess the efficacy and safety of treatment with tirzepatide for weight reduction in Chinese adults with obesity or overweight and weight-related comorbidities. Design, Setting, and Participants: This randomized, double-blind, placebo-controlled, phase 3 clinical trial conducted at 29 centers in China from September 2021 to December 2022 included Chinese adults (aged ≥18 years) with a body mass index (BMI) greater than or equal to 28 or greater than or equal to 24 and at least 1 weight-related comorbidity, excluding diabetes. Interventions: Participants were randomly assigned (1:1:1) to receive once-weekly, subcutaneous 10-mg (n = 70) or 15-mg (n = 71) tirzepatide or placebo (n = 69), plus a lifestyle intervention, for 52 weeks. Main Outcomes and Measures: Co-primary end points were the percent change in body weight from baseline and weight reduction of at least 5% at week 52. Efficacy and safety analyses were performed on an intention-to-treat population. Results: Of 210 randomized participants (103 [49.0%] female; mean [SD] age, 36.1 [9.1] years; body weight, 91.8 [16.0] kg; BMI, 32.3 [3.8]), 201 (95.7%) completed the trial. The mean change in body weight at week 52 was -13.6% (95% CI, -15.8% to -11.4%) with tirzepatide 10 mg, -17.5% (95% CI, -19.7% to -15.3%) with tirzepatide 15 mg, and -2.3% with placebo (difference between 10 mg and placebo, -11.3% [95% CI, -14.3% to -8.3%; P < .001]; difference between 15 mg and placebo, -15.1% [95% CI, -18.2% to -12.1%; P < .001]). The percentage of participants achieving body weight reductions of 5% or greater was 87.7% with tirzepatide 10 mg, 85.8% with tirzepatide 15 mg, and 29.3% with placebo (P < .001 for comparisons with placebo). The most frequent treatment-emergent adverse events with tirzepatide were gastrointestinal. Most were mild to moderate in severity, with few events leading to treatment discontinuation (<5%). Conclusions and Relevance: In Chinese adults with obesity or overweight, once-weekly treatment with tirzepatide 10 mg or 15 mg resulted in statistically significant and clinically meaningful weight reduction with an acceptable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT05024032.

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