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1.
Artigo em Inglês | MEDLINE | ID: mdl-38366319

RESUMO

Comprehending the spatial-temporal characteristics, contributions, and evolution of driving factors in agricultural non-CO2 greenhouse gas (GHG) emissions at a macro level is pivotal in pursuing temperature control objectives and achieving China's strategic goals related to carbon peak and carbon neutrality. This study employs the Intergovernmental Panel on Climate Change (IPCC) carbon emissions coefficient method to comprehensively evaluate agricultural non-CO2 GHG emissions at the provincial level. Subsequently, the contributions and spatial-temporal evolution of six driving factors derived from the Kaya identity were quantitatively explored using the Logarithmic Mean Divisia Index (LMDI) and Geographical and Temporal Weighted Regression (GTWR) methods. The results revealed that the distribution of agricultural non-CO2 GHG emissions is shifting from the central provinces to the northwest regions. Moreover, the dominant driving factors of agricultural non-CO2 GHG emissions were primarily economic factor (EDL) with positive impact (cumulative promotion is 2939.61 million metric tons (Mt)), alongside agricultural production efficiency factor (EI) with negative impact (cumulative reduction is 2208.98 Mt). Influence of EDL diminished in the eastern coastal regions but significantly impacted underdeveloped regions such as the northwest and southwest. In the eastern coastal regions, EI gradually became the absolute dominant driver, demonstrating a rapid reduction effect. Additionally, a declining birth rate and rural-to-urban population migration have significantly amplified the driving effects of the population factor (RP) at a national scale. These findings, in conjunction with the disparities in geographic and socioeconomic development among provinces, can serve as a guiding framework for the development of a region-specific roadmap aimed at reducing agricultural non-CO2 GHG emissions.

2.
Int Immunopharmacol ; 130: 111675, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38377852

RESUMO

The aim of our research was to investigate the effects of Bacillus amyloliquefaciens SC06 on growth performance, immune status, intestinal stem cells (ISC) proliferation and differentiation, and gut microbiota in weaned piglets. Twelve piglets (male, 21 days old, 6.11 ± 0.12 kg) were randomly allocated to CON and SC06 (1 × 108 cfu/kg to diet) groups. This experiment lasted three weeks. Our results showed that SC06 increased (P < 0.05) growth performance and reduced the diarrhea rate in weaned piglets. In addition, SC06 increased intestinal morphology and interleukin (IL)-10 levels, and decreased (P < 0.01) necrosis factor (TNF-α) levels in jejunum and serum. Moreover, weaning piglets fed SC06 had a better balance of colonic microbiota, with an increase in the abundance of Lactobacillus. Furthermore, SC06 enhanced ISCs proliferation and induced its differentiation to goblet cells via activating wnt/ß-catenin pathway in weaned piglets and intestinal organoid. Taken together, SC06 supplementation improved the growth performance and decreased inflammatory response of piglets by modulating intestinal microbiota, thereby accelerating ISC proliferation and differentiation and promoting epithelial barrier healing.

4.
Artigo em Inglês | MEDLINE | ID: mdl-38330582

RESUMO

Objective: To investigate magnetic resonance longitudinal relaxation time quantitative imaging (T1rho) and transverse relaxation time quantitative imaging (T2 mapping) techniques in evaluating cartilage damage in middle-aged and elderly patients with knee osteoarthritis (OA). Methods: To carry out this investigation, the researchers enrolled 65 OA patients subjects for the study. These patients were divided into 2 groups based on the severity of their OA. Thirty healthy individuals were included as the control group. All study participants underwent magnetic resonance T1rho and T2 mapping scans. OA patient scores and values from the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), T2, and a T1rho MRI measurement indicating potential early indication of bone and joint diseases from each cartilage area were compared among the OA patients as well as the control group. Pearson correlation analysis was used to examine the relationships between T2 and T1rho values and WOMAC scores. Results: The WOMAC scores in the mild OA group were lower than the severe OA group (P < .05). There were no significant differences in T2 and T1rho values of lateral tibial cartilage among the 3 groups (P > .05). On the other hand, the T2 and T1rho values of medial femoral, lateral femoral, and medial tibial cartilage areas increased progressively in the control, mild OA, and severe OA groups (P < .05). A Pearson analysis found a positive correlation between the T2 values of medial, lateral, and medial tibial cartilages and the WOMAC scores. Similarly, the T1rho values of these cartilage areas were also positively correlated with the WOMAC scores. Conclusion: Magnetic resonance T1rho and T2 mapping offer good evaluation value for assessing cartilage injury in middle-aged and elderly patients with knee OA. The values obtained from T1rho and T2 mapping in various areas of the cartilage show a positive correlation with WOMAC scores.

5.
Lancet ; 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38330980

RESUMO

BACKGROUND: Introduced in 1992, intracytoplasmic sperm injection (ICSI) was initially indicated for severe male infertility; however, its use has since been expanded to non-severe male infertility. We aimed to compare the efficacy and safety of ICSI versus conventional in-vitro fertilisation (IVF) in couples with infertility with non-severe male factor. METHODS: We conducted an investigator-initiated, multicentre, open-label, randomised controlled trial in ten reproductive medicine centres across China. Couples with infertility with non-severe male factor without a history of poor fertilisation were randomly assigned (1:1) to undergo either ICSI or conventional IVF. The primary outcome was live birth after first embryo transfer. We performed the primary analysis in the intention-to-treat population using log-binomial regression models for categorical outcomes or linear regression models for continuous outcomes, adjusting for centre. This trial is registered with Clinicaltrials.gov, NCT03298633, and is completed. FINDINGS: Between April 4, 2018, and Nov 15, 2021, 3879 couples were screened, of whom 2387 (61·5%) couples were randomly assigned (1184 [49·6%] to the ICSI group and 1203 [50·4%] to the conventional IVF group). After excluding couples who were ineligible, randomised twice, or withdrew consent, 1154 (97·5%) in the ICSI group and 1175 (97·7%) in the conventional IVF group were included in the primary analysis. Live birth after first embryo transfer occurred in 390 (33·8%) couples in the ICSI group and in 430 (36·6%) couples in the conventional IVF group (adjusted risk ratio [RR] 0·92 [95% CI 0·83-1·03]; p=0·16). Two (0·2%) neonatal deaths were reported in the ICSI group and one (0·1%) in the conventional IVF group. INTERPRETATION: In couples with infertility with non-severe male factor, ICSI did not improve live birth rate compared with conventional IVF. Given that ICSI is an invasive procedure associated with additional costs and potential increased risks to offspring health, routine use is not recommended in this population. FUNDING: National Natural Science Foundation of China, National Key Research and Development Program, Beijing Municipal Science & Technology Commission, and Peking University Third Hospital.

6.
J Cancer Res Clin Oncol ; 150(2): 72, 2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38305910

RESUMO

PURPOSE: This systematic review and meta-analysis aimed to identify whether E-health interventions effectively improve physical activity (PA) in cancer survivors. METHODS: PubMed, Web of Science, and Cochrane Library databases were searched from inception to October 21, 2023. Randomized controlled trials reporting the effect of E-health interventions on PA among cancer survivors were included. Random-effect models were used to calculate standardized mean differences (SMD) and the 95% confidence interval (CI). RESULTS: In total, 15 trials with 2,291 cancer survivors were included in this meta-analysis. The results showed that E-health interventions improved moderate to vigorous physical activity (MVPA) among cancer survivors (SMD = 0.26, 95% CI 0.08, 0.43, N = 8, p < 0.001, I2 = 37%), as well as moderate physical activity (MPA) (SMD = 0.22, 95% CI 0.05, 0.38, N = 9, p < 0.001, I2 = 28%) and vigorous physical activity (VPA) (SMD = 0.34, 95% CI 0.15, 0.54, N = 6, p < 0.001, I2 = 11%). CONCLUSION: E-health interventions are effective at promoting PA among cancer survivors. As current research primarily focuses on immediate post-intervention measurements with limited follow-up data, further investigation is required to explore the long-term effects of E-health interventions on PA.


Assuntos
Sobreviventes de Câncer , Neoplasias , Telemedicina , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Exercício Físico , Neoplasias/terapia
7.
Asia Pac J Ophthalmol (Phila) ; 13(1): 100033, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38383075

RESUMO

PURPOSE: To investigate the effectiveness and safety of phacogoniotomy versus phacotrabeculectomy (PVP) among patients with advanced primary angle-closure glaucoma (PACG) and cataracts. DESIGN: Multicenter, randomized controlled, non-inferiority trial. METHODS: A total of 124 patients (124 eyes) with advanced PACG and cataracts were enrolled, with 65 in the phacogoniotomy group and 59 in the phacotrabeculectomy group. Patients were followed up for 12 months with standardized evaluations. The primary outcome was the reduction in intraocular pressure (IOP) from baseline to 12 months postoperatively, of which a non-inferiority margin of 4 mmHg was evaluated. Secondary outcomes included the cumulative surgical success rate, postoperative complications, and changes in the number of glaucoma medications. RESULTS: After 12 months, phacogoniotomy demonstrated non-inferiority to phacotrabeculectomy in terms of IOP reduction, with mean IOP reductions of - 26.1 mmHg and - 25.7 mmHg (P = 0.383), respectively, from baseline values of around 40 mmHg. Both groups experienced a significant reduction in the mean number of medications used postoperatively (P < 0.001). The cumulative success rate was comparable between the groups (P = 0.890). However, phacogoniotomy had a lower rate of postoperative complications and interventions (12.3% and 4.6%) compared to phacotrabeculectomy (23.7% and 20.3% respectively). The phacogoniotomy group reported shorter surgery time (22.1 ± 6.5 vs. 38.8 ± 11.1 min; P = 0.030) and higher quality of life (EQ-5D-5 L) improvement at 12 months (7.0 ± 11.5 vs. 3.0 ± 12.9, P = 0.010) than the phacotrabeculectomy group. CONCLUSIONS: Phacogoniotomy was non-inferior to phacotrabeculectomy in terms of IOP reduction for advanced PACG and cataracts. Additionally, phacogoniotomy provided a shorter surgical time, lower postoperative complication rate, fewer postoperative interventions, and better postoperative quality of life.


Assuntos
Catarata , Glaucoma de Ângulo Fechado , Facoemulsificação , Trabeculectomia , Humanos , Glaucoma de Ângulo Fechado/complicações , Glaucoma de Ângulo Fechado/cirurgia , Qualidade de Vida , Catarata/complicações , Pressão Intraocular , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento
9.
iScience ; 27(2): 108851, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38318387

RESUMO

The efficacy of COVID-19 vaccination relies on the induction of neutralizing antibodies, which can vary among vaccine recipients. In this study, we investigated the potential factors affecting the neutralizing antibody response by combining plasma and urine proteomics and gut microbiota analysis. We found that activation of the LXR/FXR pathway in plasma was associated with the production of ACE2-RBD-inhibiting antibodies, while urine proteins related to complement system, acute phase response signaling, LXR/FXR, and STAT3 pathways were correlated with neutralizing antibody production. Moreover, we observed a correlation between the gut microbiota and plasma and urine proteins, as well as the vaccination response. Based on the above data, we built a predictive model for vaccination response (AUC = 0.85). Our study provides insights into characteristic plasma and urine proteins and gut microbiota associated with the ACE2-RBD-inhibiting antibodies, which could benefit our understanding of the host response to COVID-19 vaccination.

11.
Pediatr Infect Dis J ; 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38359358

RESUMO

BACKGROUND: Continuous infusion vancomycin (CIV) may benefit children who are unable to achieve therapeutic concentrations with intermittent vancomycin dosing and may facilitate outpatient administration by alleviating the burden of frequent dosing intervals. Previous studies have used variable dosing regimens and steady-state concentration goals. The purpose of this study was to evaluate the total daily dose (TDD) of CIV required to achieve therapeutic steady-state concentrations of 15-25 µg/mL in pediatric hematology/oncology patients. METHODS: A single-center retrospective study was performed for patients treated with CIV from January 2017 to June 2019. The primary outcome was the TDD required to achieve therapeutic steady-state concentrations on CIV. Secondary outcomes included time to reach therapeutic steady-state concentrations, CIV indications and adverse events associated with CIV. RESULTS: Data were collected for 71 courses of CIV in 60 patients. Median patient age was 4 years (range: 0.4-20 years). The median TDD required to achieve initial therapeutic concentrations was 50.3 mg/kg/d (interquartile range: 38.8-59.2) and was further divided into age-based cohorts. TDD in mg/kg was significantly lower in the older cohort (P < 0.001), but there was no statistically significant difference between age-based cohorts with TDD in mg/m2 (P = 0.97). Median time to achieve first therapeutic concentration was 19.3 hours (range: 8.6-72.3 hours). The most common indication for CIV was ease of outpatient administration (69.0%). Acute kidney injury incidence was minimal (4.2%). CONCLUSIONS: CIV is associated with rapid attainment of target concentrations in pediatric hematology/oncology patients and is safe and well tolerated.

12.
BMC Med ; 22(1): 56, 2024 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317226

RESUMO

BACKGROUND: A comprehensive overview of artificial intelligence (AI) for cardiovascular disease (CVD) prediction and a screening tool of AI models (AI-Ms) for independent external validation are lacking. This systematic review aims to identify, describe, and appraise AI-Ms of CVD prediction in the general and special populations and develop a new independent validation score (IVS) for AI-Ms replicability evaluation. METHODS: PubMed, Web of Science, Embase, and IEEE library were searched up to July 2021. Data extraction and analysis were performed for the populations, distribution, predictors, algorithms, etc. The risk of bias was evaluated with the prediction risk of bias assessment tool (PROBAST). Subsequently, we designed IVS for model replicability evaluation with five steps in five items, including transparency of algorithms, performance of models, feasibility of reproduction, risk of reproduction, and clinical implication, respectively. The review is registered in PROSPERO (No. CRD42021271789). RESULTS: In 20,887 screened references, 79 articles (82.5% in 2017-2021) were included, which contained 114 datasets (67 in Europe and North America, but 0 in Africa). We identified 486 AI-Ms, of which the majority were in development (n = 380), but none of them had undergone independent external validation. A total of 66 idiographic algorithms were found; however, 36.4% were used only once and only 39.4% over three times. A large number of different predictors (range 5-52,000, median 21) and large-span sample size (range 80-3,660,000, median 4466) were observed. All models were at high risk of bias according to PROBAST, primarily due to the incorrect use of statistical methods. IVS analysis confirmed only 10 models as "recommended"; however, 281 and 187 were "not recommended" and "warning," respectively. CONCLUSION: AI has led the digital revolution in the field of CVD prediction, but is still in the early stage of development as the defects of research design, report, and evaluation systems. The IVS we developed may contribute to independent external validation and the development of this field.


Assuntos
Inteligência Artificial , Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Algoritmos , África , Europa (Continente)
13.
J Med Virol ; 96(2): e29447, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38305064

RESUMO

With the emergence of the Omicron variant, the number of pediatric Coronavirus Disease 2019 (COVID-19) cases requiring hospitalization and developing severe or critical illness has significantly increased. Machine learning and multivariate logistic regression analysis were used to predict risk factors and develop prognostic models for severe COVID-19 in hospitalized children with the Omicron variant in this study. Of the 544 hospitalized children including 243 and 301 in the mild and severe groups, respectively. Fever (92.3%) was the most common symptom, followed by cough (79.4%), convulsions (36.8%), and vomiting (23.2%). The multivariate logistic regression analysis showed that age (1-3 years old, odds ratio (OR): 3.193, 95% confidence interval (CI): 1.778-5.733], comorbidity (OR: 1.993, 95% CI:1.154-3.443), cough (OR: 0.409, 95% CI:0.236-0.709), and baseline neutrophil-to-lymphocyte ratio (OR: 1.108, 95% CI: 1.023-1.200), lactate dehydrogenase (OR: 1.993, 95% CI: 1.154-3.443), blood urea nitrogen (OR: 1.002, 95% CI: 1.000-1.003) and total bilirubin (OR: 1.178, 95% CI: 1.005-3.381) were independent risk factors for severe COVID-19. The area under the curve (AUC) of the prediction models constructed by multivariate logistic regression analysis and machine learning (RandomForest + TomekLinks) were 0.7770 and 0.8590, respectively. The top 10 most important variables of random forest variables were selected to build a prediction model, with an AUC of 0.8210. Compared with multivariate logistic regression, machine learning models could more accurately predict severe COVID-19 in children with Omicron variant infection.


Assuntos
COVID-19 , Criança Hospitalizada , Humanos , Criança , Lactente , Pré-Escolar , COVID-19/diagnóstico , Modelos Logísticos , SARS-CoV-2 , Tosse , Aprendizado de Máquina , Estudos Retrospectivos
14.
BMC Urol ; 24(1): 47, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38389059

RESUMO

BACKGROUND: Some studies have suggested that hepatitis B virus (HBV) infection had a negative association with semen quality, but the conclusions have been inconsistent. The purpose of our study was to systematically assess the association between HBV infection and semen parameters. METHODS: We searched electronic databases for studies published from January 1980 to August 2023. Eleven studies were included in the analysis. Primary outcomes were semen volume, sperm concentration, sperm morphology, sperm motility and sperm progressive motility. We also conducted a subgroup analysis between China and other countries. RESULT: Compared with the semen quality of HBV-negative men, HBV infection had a negative association with semen volume (MD: -0.20 mL, 95%CI: -0.32 to - 0.09, P = 0.0004), sperm concentration (MD: -4.46 × 106/mL, 95%CI: -7.09 to - 1.84, P = 0.0009), sperm morphology (MD: -2.49%, 95%CI: -4.35 to - 0.64, P = 0.008), sperm motility (MD: -6.85%, 95%CI: -11.53 to - 2.18, P = 0.004), and sperm progressive motility (MD: -6.63%, 95%CI: -10.24 to - 3.02, P = 0.0003). However, HBV infection had no significant association with total sperm count (MD: -31.50 × 106, 95%CI: -74.11 to 11.10, P = 0.15). The association between HBV and semen quality were inconsistent between the subgroups. CONCLUSION: HBV infection had a negative association with sperm concentration, motility, morphology, and semen volume. However, The association between HBV and total sperm count remain unclear. This metaanalysis suggests that we should pay attention to the adverse effect of HBV on sperm quality, and several studies have reported the relevant mechanisms. But due to the significant heterogeneity among studies on some semen parameters, further large and well-designed researches are needed before introducing clinical management recommendations.

16.
J Transl Med ; 22(1): 98, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263117

RESUMO

BACKGROUND: Interindividual variation characterizes the relief experienced by constipation-predominant irritable bowel syndrome (IBS-C) patients following linaclotide treatment. Complex bidirectional interactions occur between the gut microbiota and various clinical drugs. To date, no established evidence has elucidated the interactions between the gut microbiota and linaclotide. We aimed to explore the impact of linaclotide on the gut microbiota and identify critical bacterial genera that might participate in linaclotide efficacy. METHODS: IBS-C patients were administered a daily linaclotide dose of 290 µg over six weeks, and their symptoms were then recorded during a four-week posttreatment observational period. Pre- and posttreatment fecal samples were collected for 16S rRNA sequencing to assess alterations in the gut microbiota composition. Additionally, targeted metabolomics analysis was performed for the measurement of short-chain fatty acid (SCFA) concentrations. RESULTS: Approximately 43.3% of patients met the FDA responder endpoint after taking linaclotide for 6 weeks, and 85% of patients reported some relief from abdominal pain and constipation. Linaclotide considerably modified the gut microbiome and SCFA metabolism. Notably, the higher efficacy of linaclotide was associated with enrichment of the Blautia genus, and the abundance of Blautia after linaclotide treatment was higher than that in healthy volunteers. Intriguingly, a positive correlation was found for the Blautia abundance and SCFA concentrations with improvements in clinical symptoms among IBS-C patients. CONCLUSION: The gut microbiota, especially the genus Blautia, may serve as a significant predictive microbe for symptom relief in IBS-C patients receiving linaclotide treatment. TRIAL REGISTRATION: This trial was registered with the Chinese Clinical Trial Registry (Chictr.org.cn, ChiCTR1900027934).


Assuntos
Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Peptídeos , Humanos , Estudos Prospectivos , RNA Ribossômico 16S , Constipação Intestinal
17.
J Orthop Surg Res ; 19(1): 69, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38225652

RESUMO

BACKGROUND AND OBJECTIVES: In anterior cruciate ligament reconstruction, the strength of the graft was found to be unsatisfactory usually the anterior half of the peroneus longus tendon was taken for supplementation, but the effect on foot and ankle function and gait in the donor area is unclear. This study aims to explore the changes in the ankle and gait after using the harvested anterior half of the peroneus longus tendon as a reconstruction graft for the anterior cruciate ligament. METHODS: A total of 20 patients, 6 males and 14 females, aged 18 to 44 years, with unilateral anterior cruciate ligament injuries, underwent reconstruction using the harvested anterior half of the peroneus longus tendon as a graft between June 2021 and December 2021. The part on which the anterior half of the peroneus longus tendon was harvested was considered the experimental group, while the contralateral foot was the control group. At the 6-month follow-up, the Lysholm knee score, AOFAS ankle score, and gait-related data (foot length, arch index, arch volume, arch volume index, and gait cycle parameters: percentage of time in each gait phase, step frequency, step length, foot strike angle, and push-off angle) were assessed using a 3D foot scanner and wearable sensors for both groups. RESULTS: All 20 patients completed the six-month follow-up. There were no statistically significant differences between the experimental and control groups regarding knee scores, ankle scores, foot length, arch index, arch volume, arch volume index, step frequency, and step length (P > 0.05). However, there were statistically significant differences between the experimental and control groups in terms of the gait cycle parameters, including the percentage of time in the stance, mid-stance, and push-off phases, as well as foot strike angle and push-off angle (P < 0.05). CONCLUSION: Through our study of the surgical experimental group we have shown that harvesting the anterior half of the peroneus longus tendon does not affect foot morphology and gait parameters; however, it does impact the gait cycle.


Assuntos
Lesões do Ligamento Cruzado Anterior , Tendões , Masculino , Feminino , Humanos , Transplante Autólogo , Tendões/transplante , Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/cirurgia , Articulação do Joelho
19.
PLoS Biol ; 22(1): e3002470, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38206965

RESUMO

The bridging integrator 1 (BIN1) gene is an important risk locus for late-onset Alzheimer's disease (AD). BIN1 protein has been reported to mediate tau pathology, but the underlying molecular mechanisms remain elusive. Here, we show that neuronal BIN1 is cleaved by the cysteine protease legumain at residues N277 and N288. The legumain-generated BIN1 (1-277) fragment is detected in brain tissues from AD patients and tau P301S transgenic mice. This fragment interacts with tau and accelerates its aggregation. Furthermore, the BIN1 (1-277) fragment promotes the propagation of tau aggregates by enhancing clathrin-mediated endocytosis (CME). Overexpression of the BIN1 (1-277) fragment in tau P301S mice facilitates the propagation of tau pathology, inducing cognitive deficits, while overexpression of mutant BIN1 that blocks its cleavage by legumain halts tau propagation. Furthermore, blocking the cleavage of endogenous BIN1 using the CRISPR/Cas9 gene-editing tool ameliorates tau pathology and behavioral deficits. Our results demonstrate that the legumain-mediated cleavage of BIN1 plays a key role in the progression of tau pathology. Inhibition of legumain-mediated BIN1 cleavage may be a promising therapeutic strategy for treating AD.


Assuntos
Doença de Alzheimer , Animais , Humanos , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Doença de Alzheimer/patologia , Encéfalo/metabolismo , Clatrina/metabolismo , Endocitose , Camundongos Transgênicos , Proteínas tau/genética , Proteínas tau/metabolismo
20.
BMC Cardiovasc Disord ; 24(1): 18, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172711

RESUMO

OBJECTIVE: Many studies have found that miR-26a-5p plays an essential role in the progression of pathological cardiac hypertrophy, however, there is still no evidence on whether miR-26a-5p is related to the activation of autophagy and NLRP3 inflammasome. And the mechanism of miR-26a-5p and NLRP3 inflammasome aggravating pathological cardiac hypertrophy remain unclear. METHODS: Cardiomyocytes were treated with 200µM PE to induce cardiac hypertrophy and intervened with 10mM NLRP3 inhibitor INF39. In addition, we also used the MiR-26a-5p mimic and inhibitor to transfect PE-induced cardiac hypertrophy. RT-qPCR and western blotting were used to detect the expressions of miR-26a-5p, NLRP3, ASC and Caspase-1 in each group, and we used α-SMA immunofluorescence to detect the change of cardiomyocyte area. The expression levels of autophagy proteins LC3, beclin-1 and p62 were detected by western blotting. Finally, we induced the SD rat cardiac hypertrophy model through aortic constriction (TAC) surgery. In the experimental group, rats were intervened with MiR-26a-5p mimic, MiR-26a-5p inhibitor, autophagy inhibitor 3-MA, and autophagy activator Rapamycin. RESULTS: In cell experiments, we observed that the expression of miR-26a-5p was associated with cardiomyocyte hypertrophy and increased surface area. Furthermore, miR-26a-5p facilitated autophagy and activated the NLRP3 inflammasome pathway, which caused changes in the expression of genes and proteins including LC3, beclin-1, p62, ACS, NLRP3, and Caspase-1. We discovered similar outcomes in the TAC rat model, where miR-26a-5p expression corresponded with cardiomyocyte enlargement and fibrosis in the cardiac interstitial and perivascular regions. In conclusion, miR-26a-5p has the potential to regulate autophagy and activate the NLRP3 inflammasome, contributing to the development of cardiomyocyte hypertrophy. CONCLUSION: Our study found a relationship between the expression of miR-26a-5p and cardiomyocyte hypertrophy. The mechanism behind this relationship appears to involve the activation of the NLRP3 inflammasome pathway, which is caused by miR-26a-5p promoting autophagy. Targeting the expression of miR-26a-5p, as well as inhibiting the activation of autophagy and the NLRP3 inflammasome pathway, could offer additional treatments for pathological cardiac hypertrophy.


Assuntos
Cardiopatias Congênitas , MicroRNAs , Ratos , Animais , Inflamassomos/genética , Inflamassomos/metabolismo , Miócitos Cardíacos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína Beclina-1/metabolismo , Ratos Sprague-Dawley , MicroRNAs/genética , MicroRNAs/metabolismo , Cardiopatias Congênitas/metabolismo , Cardiomegalia/genética , Autofagia , Caspases/metabolismo
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