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1.
BMC Pulm Med ; 24(1): 314, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961405

RESUMEN

BACKGROUND: Massive hemoptysis is characterized by its life-threatening nature, potentially leading to airway obstruction and asphyxia. The objective of this study was to evaluate the clinical effectiveness of combining endobronchial tamponade with bronchial artery embolization (BAE) in the treatment of massive hemoptysis. METHODS: Between March 2018 and March 2022, a total of 67 patients with massive hemoptysis who underwent BAE were divided into two groups: the combination group (n = 26) and the BAE group (n = 41). Technical and clinical success rates were assessed, and adverse events were monitored following the treatment. Blood gas analysis and coagulation function indicators were collected before and after the treatment, and recurrence and survival rates were recorded during the follow-up period. RESULTS: All patients achieved technical success. There were no significant differences in the clinical success rate, recurrence rates at 3 and 6 months, and mortality rates at 3 months, 6 months, and 1 year between the combination group and the BAE group. However, the hemoptysis recurrence rate at 1 year was significantly lower in the combination group compared to the BAE group (15.4% vs. 39.0%, P = 0.039). No serious adverse events were reported in either group. After treatment, the combination group showed higher levels of arterial partial pressure of oxygen (PaO2), oxygenation index (PaO2/FiO2), fibrinogen (FIB), and D-dimer (D-D) compared to the BAE group (P < 0.05). Multivariate regression analysis demonstrated a significant correlation between combined therapy and hemoptysis-free survival. CONCLUSION: Combination therapy, compared to embolization alone, exhibits superior efficacy in improving respiratory function, correcting hypoxia, stopping bleeding, and preventing recurrence. It is considered an effective and safe treatment for massive hemoptysis.


Asunto(s)
Arterias Bronquiales , Embolización Terapéutica , Hemoptisis , Humanos , Hemoptisis/terapia , Hemoptisis/etiología , Embolización Terapéutica/métodos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Resultado del Tratamiento , Estudios Retrospectivos , Terapia Combinada , Adulto , Recurrencia , Broncoscopía/métodos , Análisis de los Gases de la Sangre
2.
Artículo en Inglés | MEDLINE | ID: mdl-38957995

RESUMEN

Background: The objective of this study was to investigate the association between pre-operative body mass index (BMI) and surgical infection in perihilar cholangiocarcinoma (pCCA) patients treated with curative resection. Methods: Consecutive pCCA patients were enrolled from four tertiary hospitals between 2008 and 2022. According to pre-operative BMI, the patients were divided into three groups: low BMI (≤18.4 kg/m2), normal BMI (18.5-24.9 kg/m2), and high BMI (≥25.0 kg/m2). The incidence of surgical infection among the three groups was compared. Multivariable logistic regression models were used to determine the independent risk factors associated with surgical infection. Results: A total of 371 patients were enrolled, including 283 patients (76.3%) in the normal BMI group, 30 patients (8.1%) in the low BMI group, and 58 patients (15.6%) in the high BMI group. The incidence of surgical infection was significantly higher in the patients in the low BMI and high BMI groups than in the normal BMI group. The multivariable logistic regression model showed that low BMI and high BMI were independently associated with the occurrence of surgical infection. Conclusions: The pCCA patients with a normal BMI treated with curative resection could have a lower risk of surgical infection than pCCA patients with an abnormal BMI.

4.
Artículo en Inglés | MEDLINE | ID: mdl-38963167

RESUMEN

OBJECTIVE: The aim of this study was to explore the effect of depression and selective serotonin reuptake inhibitors on implant osseointegration and bone healing. METHODS: Forty-eight 6- to 8-week-old SPF Sprague-Dawley male rats were randomly divided into four groups: the Control group, the Fluoxetine group, the Depression group and the De&Flu group. The rats in the Depression group and the De&Flu group were subjected to a depression modelling process, and the rats in the Control group and the Fluoxetine group were raised normally. Then, a titanium implant was placed in the right tibia of each rat. In the Fluoxetine group and De&Flu group, fluoxetine was injected subcutaneously daily, while subcutaneously injecting physiological saline in the Control group and Depression group. Collecting serum from the rats used for ELISA. The surgical area was cut for microcomputed tomography and histology observation. RESULTS: After 12 weeks, bone mineral density was lower in the De&Flu group than in the Control group, Depression group and Fluoxetine group. Bone mineral density was also lower in the Depression group and the Fluoxetine group than in the Control group. The percentage of bone-implant contact (BIC%) in De&Flu rats was lower than in the Control, Depression and Fluoxetine groups. The BIC% in the Depression group and the Fluoxetine group was lower than in the Control group. CONCLUSIONS: Depression and fluoxetine negatively affect bone density and implant osseointegration independently, and this damaging effect is exacerbated when both factors are present. The mechanism may be related to the dysregulation of the hypothalamic-pituitary-adrenal axis and inflammation in the body.

5.
J Burn Care Res ; 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38970564

RESUMEN

To investigate the effect of an enhanced rehabilitation program on upper limb function in patients with abdominal pedicle flap surgery, we retrospectively analyzed 70 patients received abdominal pedicled flap surgery between 2017 and 2022. Patients were categorized into the traditional rehabilitation group (rehabilitation initiated after the stage Ⅱ pedicle dissection of the abdominal pedicle flap) and the enhanced rehabilitation group (rehabilitation initiated on the first day following the stage Ⅰ abdominal pedicle flap surgery). All the patients received identical rehabilitation protocols. PROM, ADL, FIM, and MMT were assessed at five days and one month following the stage Ⅱ surgery. The main causes of injury were electrical burns in both groups. The hospital stay of patients in the enhanced group was significantly shorter than the traditional group. One month assessment indicated both groups showed significant improvements in the PROM of shoulder flexion, abduction, and elbow extension compared to the five days assessment. Notably, at five days assessment, the enhanced group had significantly higher PROM in shoulder abduction and elbow extension compared to the traditional group. Furthermore, the enhanced group continued to exhibit higher PROM in shoulder flexion and abduction than the traditional group at one month assessment. At one month assessment, a significant increase was observed in the ADL, FIM, and MMT of both groups compared to the five days. The study indicated the enhanced rehabilitation program immediately following the stage Ⅰ surgery can effectively improve the PROM of the shoulder and elbow and reduce the length of hospital stay for patients.

6.
Sci Data ; 11(1): 776, 2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39003298

RESUMEN

Fructus hippophae (Hippophae rhamnoides spp. mongolica×Hippophae rhamnoides sinensis), a hybrid variety of sea buckthorn that Hippophae rhamnoides spp. mongolica serves as the female parent and Hippophae rhamnoides sinensis serves as the male parent, is a traditional plant with great potentials of economic and medical values. Herein, we gained a chromosome-level genome of Fructus hippophae about 918.59 Mb, with the scaffolds N50 reaching 83.65 Mb. Then, we anchored 440 contigs with 97.17% of the total genome sequences onto 12 pseudochromosomes. Next, de-novo, homology and transcriptome assembly strategies were adopted for gene structure prediction. This predicted 36475 protein-coding genes, of which 36226 genes could be functionally annotated. Simultaneously, various strategies were used for quality assessment, both the complete BUSCO value (98.80%) and the mapping rate indicated the high assembly quality. Repetitive elements, which occupied 63.68% of the genome, and 1483600 bp of non-coding RNA were annotated. Here, we provide genomic information on female plants of a popular variety, which can provide data for pan-genomic construction of sea buckthorn and for the resolution of the mechanism of sex differentiation.


Asunto(s)
Cromosomas de las Plantas , Genoma de Planta , Hippophae , Hippophae/genética , Cromosomas de las Plantas/genética , Transcriptoma , Anotación de Secuencia Molecular
7.
Andrology ; 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38958226

RESUMEN

BACKGROUND: Despite cryptorchidism being a common genital abnormality in male newborns with significant prevalence variations globally, there is a notable scarcity of epidemiological data on this condition in China. OBJECTIVE: This study aimed to delineate the prevalence pattern of cryptorchidism in Chinese population over the past 15 years using nationwide surveillance data. MATERIALS AND METHODS: Data from the China National Population-based Birth Defects Surveillance System (2007-2021) were analyzed to calculate the prevalence rates of cryptorchidism, stratified by birth year, maternal age, maternal residence, and geographic region. Adjusted prevalence rate ratios were computed using Poisson regression, while trends in prevalence and average annual percent change (AAPC) were assessed using the joinpoint regression model. RESULTS: During the study period, a total of 1,833 cases of cryptorchidism were identified among 2,565,964 full-term male births, resulting in prevalence rates of 7.14, 5.60, and 1.54 per 10,000 births for overall, isolated, and associated cryptorchidism, respectively. The overall prevalence increased from 3.86 to 11.20 per 10,000 births, with an AAPC of 7.9% (95% confidence interval: 5.5-11.0). Significant variations were observed across maternal age (< 20 years, 7.62/10,000; 20-24 years, 6.14/10,000; 25-29 years, 6.96/10,000; 30-34 years, 7.48/10,000; ≥35 years, 9.22/10,000), maternal residence (urban vs. rural, 10.99/10,000 vs. 2.86/10,000), and geographic region (eastern, 12.38/10,000; central, 2.36/10,000; western, 2.63/10,000). Approximately one-third of cryptorchidism cases were bilaterally, while two-thirds were unilateral. Commonly observed associated abnormalities included congenital hydrocele testis, as well as anomalies in the genital organs, circulatory system, and musculoskeletal system. CONCLUSION: Despite lower rates compared to other countries, the increasing trend in prevalence of cryptorchidism necessitates further investigation and intervention.

8.
Cancer Immunol Immunother ; 73(9): 182, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38967817

RESUMEN

BACKGROUND: The long-term survival benefit of immune checkpoint inhibitors (ICIs) in neoadjuvant and adjuvant settings is unclear for colorectal cancers (CRC) and gastric cancers (GC) with deficiency of mismatch repair (dMMR) or microsatellite instability-high (MSI-H). METHODS: This retrospective study enrolled patients with dMMR/MSI-H CRC and GC who received at least one dose of neoadjuvant ICIs (neoadjuvant cohort, NAC) or adjuvant ICIs (adjuvant cohort, AC) at 17 centers in China. Patients with stage IV disease were also eligible if all tumor lesions were radically resectable. RESULTS: In NAC (n = 124), objective response rates were 75.7% and 55.4%, respectively, in CRC and GC, and pathological complete response rates were 73.4% and 47.7%, respectively. The 3-year disease-free survival (DFS) and overall survival (OS) rates were 96% (95%CI 90-100%) and 100% for CRC (median follow-up [mFU] 29.4 months), respectively, and were 84% (72-96%) and 93% (85-100%) for GC (mFU 33.0 months), respectively. In AC (n = 48), the 3-year DFS and OS rates were 94% (84-100%) and 100% for CRC (mFU 35.5 months), respectively, and were 92% (82-100%) and 96% (88-100%) for GC (mFU 40.4 months), respectively. Among the seven patients with distant relapse, four received dual blockade of PD1 and CTLA4 combined with or without chemo- and targeted drugs, with three partial response and one progressive disease. CONCLUSION: With a relatively long follow-up, this study demonstrated that neoadjuvant and adjuvant ICIs might be both associated with promising DFS and OS in dMMR/MSI-H CRC and GC, which should be confirmed in further randomized clinical trials.


Asunto(s)
Neoplasias Colorrectales , Inhibidores de Puntos de Control Inmunológico , Inestabilidad de Microsatélites , Terapia Neoadyuvante , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Femenino , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Masculino , Terapia Neoadyuvante/métodos , Persona de Mediana Edad , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Estudios Retrospectivos , Anciano , Adulto , Reparación de la Incompatibilidad de ADN , Quimioterapia Adyuvante/métodos , Estudios de Seguimiento
9.
Artículo en Inglés | MEDLINE | ID: mdl-38936270

RESUMEN

BACKGROUND: Due to the close correlation between choline, L-carnitine, betaine and their intestinal microbial metabolites, including trimethylamine (TMA) and trimethylamine N-oxide (TMAO), and creatinine, there has been an increasing interest in the study of these compounds in vivo. METHODS: In this study, a rapid stable isotope dilution (SID)-UHPLC-MS/MS method was developed for the simultaneous determination of choline, L-carnitine, betaine, TMA, TMAO and creatinine in plasma, liver and feces of rats. The method was validated using quality control (QC) samples spiked at low, medium and high levels. Second, we applied the method to quantify the effects of Rosa Roxburghii Tratt juice (RRTJ) on plasma, liver, and fecal levels of choline, L-carnitine, betaine, TMA, TMAO, and creatinine in high-fat diet-induced hyperlipidemic rats, demonstrating the utility of the method. RESULTS: The limits of detection (LOD) were 0.04-0.027 µM and the limits of quantification (LOQ) were 0.009-0.094 µM. The linear ranges for each metabolite in plasma were choline1.50-96 µM; L-carnitine: 2-128 µM; betaine: 3-192 µM; TMA: 0.01-40.96 µM; TMAO: 0.06-61.44 µM and creatinine: 1-64 µM (R2 ≥ 0.9954). The linear ranges for each metabolite in liver were Choline: 12-768 µM; L-carnitine: 1.5-96 µM; betaine: 10-640 µM; TMA: 0.5-32 µM; TMAO: 0.02-81.92 µM and creatinine: 0.2-204.8 µM (R2 ≥ 0.9938). The linear ranges for each metabolite in feces were choline: 1.5-96 µM; L-carnitine: 0.01-40.96 µM; Betaine: 1.5-96 µM; TMA: 1-64 µM; TMAO: 0.02-81.92 µM and Creatinine: 0.02-81.92 µM (R2 ≥ 0.998). The intra-day and inter-day coefficients of variation were < 8 % for all analytes. The samples were stabilized after multiple freeze-thaw cycles (3 freeze-thaw cycles), 24 h at room temperature, 24 h at 4 °C and 20 days at -80 °C. The samples were stable. The average recovery was 89 %-99 %. This method was used to quantify TMAO and its related metabolites and creatinine levels in hyperlipidemic rats. The results showed that high-fat diet led to the disorder of TMAO and its related metabolites and creatinine in rats, which was effectively improved after the intervention of Rosa Roxburghii Tratt juice(RRTJ). CONCLUSIONS: A method for the determination of choline, L-carnitine, betaine, TMA, TMAO and creatinine in plasma, liver and feces samples was established, which is simple, time-saving, high precision, accuracy and recovery.

10.
Biomacromolecules ; 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38935055

RESUMEN

Postoperative tissue adhesion and poor tendon healing are major clinical problems associated with tendon surgery. To avoid postoperative adhesion and promote tendon healing, we developed and synthesized a membrane to wrap the surgical site after tendon suturing. The bilayer-structured porous membrane comprised an outer layer [1,4-butanediol diglycidyl ether cross-linked with carboxymethyl cellulose (CX)] and an inner layer [1,4-butanediol diglycidyl ether cross-linked with Bletilla striata polysaccharides and carboxymethyl cellulose (CXB)]. The morphology, chemical functional groups, and membrane structure were determined. In vitro experiments revealed that the CX/CXB membrane demonstrated good biosafety and biodegradability, promoted tenocyte proliferation and migration, and exhibited low cell attachment and anti-inflammatory effects. Furthermore, in in vivo animal study, the CX/CXB membrane effectively reduced postoperative tendon-peripheral tissue adhesion and improved tendon repair, downregulating inflammatory cytokines in the tendon tissue at the surgical site, which ultimately increased tendon strength by 54% after 4 weeks.

11.
World J Surg Oncol ; 22(1): 161, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38907218

RESUMEN

BACKGROUND: Additional resection for invasive cancer at perihilar cholangiocarcinoma (pCCA) resection margins has become a consensus. However, controversy still exists regarding whether additional resection is necessary for residual biliary intraepithelial neoplasia (BilIN). METHOD: Consecutive patients with pCCA from two hospitals were enrolled. The incidence and pattern of resection margin BilIN were summarized. Prognosis between patients with negative margins (R0) and BilIN margins were analyzed. Cox regression with a forest plot was used to identify independent risk factors associated with overall survival (OS) and recurrence-free survival (RFS). Subgroup analysis was performed based on BilIN features and tumor characteristics. RESULTS: 306 pCCA patients receiving curative resection were included. 255 had R0 margins and 51 had BilIN margins. There was no significant difference in OS (P = 0.264) or RFS (P = 0.149) between the two group. Specifically, 19 patients with BilIN at distal bile ducts and 32 at proximal bile ducts. 42 patients showed low-grade BilIN, and 9 showed high-grade. Further analysis revealed no significant difference in long-term survival between different locations (P = 0.354), or between different grades (P = 0.772). Portal vein invasion, poor differentiation and lymph node metastasis were considered independent risk factors for OS and RFS, while BilIN was not. Subgroup analysis showed no significant difference in long-term survival between the lymph node metastasis subgroup, or between the portal vein invasion subgroup. CONCLUSION: For pCCA patients underwent curative resection, residual BilIN at resection margin is acceptable. Additional resection is not necessary for such patients to achieve absolute R0 margin.


Asunto(s)
Neoplasias de los Conductos Biliares , Tumor de Klatskin , Márgenes de Escisión , Humanos , Masculino , Femenino , Neoplasias de los Conductos Biliares/cirugía , Neoplasias de los Conductos Biliares/patología , Neoplasias de los Conductos Biliares/mortalidad , Estudios Retrospectivos , Tumor de Klatskin/cirugía , Tumor de Klatskin/patología , Tumor de Klatskin/mortalidad , Persona de Mediana Edad , Anciano , Pronóstico , Estudios de Seguimiento , Tasa de Supervivencia , Carcinoma in Situ/cirugía , Carcinoma in Situ/patología , Neoplasia Residual/patología , Neoplasia Residual/cirugía , Adulto , Transformación Celular Neoplásica/patología , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Recurrencia Local de Neoplasia/epidemiología , Hepatectomía/métodos , Hepatectomía/mortalidad , Anciano de 80 o más Años
12.
J Mater Chem B ; 12(28): 6774-6804, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38920094

RESUMEN

In the last few decades, tear-based biosensors for continuous glucose monitoring (CGM) have provided new avenues for the diagnosis of diabetes. The tear CGMs constructed from nanomaterials have been extensively demonstrated by various research activities in this field and are gradually witnessing their most prosperous period. A timely and comprehensive review of the development of tear CGMs in a compartmentalized manner from a nanomaterials perspective would greatly broaden this area of research. However, to our knowledge, there is a lack of specialized reviews and comprehensive cohesive reports in this area. First, this paper describes the principles and development of electrochemical glucose sensors. Then, a comprehensive summary of various advanced nanomaterials recently reported for potential applications and construction strategies in tear CGMs is presented in a compartmentalized manner, focusing on sensing properties. Finally, the challenges, strategies, and perspectives used to design tear CGM materials are emphasized, providing valuable insights and guidance for the construction of tear CGMs from nanomaterials in the future.


Asunto(s)
Técnicas Biosensibles , Técnicas Electroquímicas , Nanoestructuras , Lágrimas , Dispositivos Electrónicos Vestibles , Nanoestructuras/química , Humanos , Lágrimas/química , Glucosa/análisis
14.
J Hazard Mater ; 472: 134503, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38718509

RESUMEN

Research on the association between maternal PM2.5 exposure and hypospadias risk in male offspring, particularly in highly polluted areas, has been limited and inconsistent. This study leveraged data from China's National Population-based Birth Defects Surveillance System spanning the years 2013 to 2019, and employed sophisticated machine learning models to estimate daily PM2.5 levels and other pollutants for mothers at a 1-km resolution and a 6-km buffer surrounding maternal residences. Multivariate logistic regression analyses were performed to evaluate the relationship between PM2.5 exposure and hypospadias risk. For sensitivity analyses, stratification analysis was conducted, and models for one-pollutant and two-pollutants, as well as distributed lag nonlinear models, were constructed. Of the 1194,431 boys studied, 1153 cases of hypospadias were identified. A 10 µg/m3 increase in maternal PM2.5 exposure during preconception and the first trimester was associated with an elevated risk of isolated hypospadias, with Odds Ratios (ORs) of 1.102 (95% CI: 1.023-1.188) and 1.089 (95% CI: 1.007-1.177) at the 1-km grid, and 1.122 (95% CI: 1.034-1.218) and 1.143 (95% CI: 1.048-1.246) within the 6-km buffer. Higher quartiles of PM2.5 exposure were associated with increased odds ratios compared to the lowest quartile. These findings highlight a significant association between PM2.5 exposure during the critical conception period and an elevated risk of isolated hypospadias in children, emphasizing the need for targeted interventions to reduce PM2.5 exposure among expectant mothers.


Asunto(s)
Contaminantes Atmosféricos , Hipospadias , Exposición Materna , Material Particulado , Hipospadias/epidemiología , Humanos , Material Particulado/análisis , Femenino , Masculino , Exposición Materna/efectos adversos , China/epidemiología , Embarazo , Adulto , Contaminantes Atmosféricos/análisis , Efectos Tardíos de la Exposición Prenatal/epidemiología , Recién Nacido , Pueblos del Este de Asia
15.
Environ Sci Pollut Res Int ; 31(24): 35149-35160, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38727972

RESUMEN

An association between green space exposure and preterm birth has been reported. However, evidence on the joint effects of air pollutant and green space exposure on preterm birth from nationwide research is limited in China. Based on a nationwide cohort, this study aims to explore the effect of green space exposure on preterm birth and analyze the joint effects of green space and air pollutant. Logistic regression models were developed to analyze the effects of green space exposure, and interaction effects were evaluated by adding interaction terms between green space and air pollutants. From 2013 to 2019, this study included 2,294,188 records of newborn births, of which 82,921 were preterm births. The results show that for buffer zones with 250 m, 500 m, 1000 m, and 1500 m, every 0.1 unit increase in NDVI exposure was associated with a decrease in the risk of preterm birth by 5.5% (95% CI: 4.6-6.4%), 5.8% (95% CI: 4.9-6.6%), 6.1% (95% CI: 5.3-7.0%), and 5.6% (95% CI: 4.7-6.5%), respectively. Under high-level exposure to air pollutants, high-level NDVI exposure was more strongly negatively correlated with preterm birth than low-level NDVI exposure. High-level green space exposure might mitigate the adverse effect of air pollutants on preterm birth by promoting physical activity, reducing stress, and adsorbing pollutants. Further investigation is needed to explore how green space and air pollution interact and affect preterm birth, in order to improve risk management and provide a reference for newborn health.


Asunto(s)
Contaminantes Atmosféricos , Nacimiento Prematuro , Nacimiento Prematuro/epidemiología , China , Humanos , Contaminación del Aire , Exposición a Riesgos Ambientales , Femenino , Recién Nacido , Embarazo
16.
Free Radic Biol Med ; 220: 139-153, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38705495

RESUMEN

Epigenetic changes are important considerations for degenerative diseases. DNA methylation regulates crucial genes by epigenetic mechanism, impacting cell function and fate. DNA presents hypermethylation in degenerated nucleus pulposus (NP) tissue, but its role in intervertebral disc degeneration (IVDD) remains elusive. This study aimed to demonstrate that methyltransferase mediated hypermethylation was responsible for IVDD by integrative bioinformatics and experimental verification. Methyltransferase DNMT3B was highly expressed in severely degenerated NP tissue (involving human and rats) and in-vitro degenerated human NP cells (NPCs). Bioinformatics elucidated that hypermethylated genes were enriched in oxidative stress and ferroptosis, and the ferroptosis suppressor gene SLC40A1 was identified with lower expression and higher methylation in severely degenerated human NP tissue. Cell culture using human NPCs showed that DNMT3B induced ferroptosis and oxidative stress in NPCs by downregulating SLC40A1, promoting a degenerative cell phenotype. An in-vivo rat IVDD model showed that DNA methyltransferase inhibitor 5-AZA alleviated puncture-induced IVDD. Taken together, DNA methyltransferase DNMT3B aggravates ferroptosis and oxidative stress in NPCs via regulating SLC40A1. Epigenetic mechanism within DNA methylation is a promising therapeutic biomarker for IVDD.


Asunto(s)
ADN (Citosina-5-)-Metiltransferasas , Metilación de ADN , ADN Metiltransferasa 3B , Ferroptosis , Degeneración del Disco Intervertebral , Núcleo Pulposo , Estrés Oxidativo , Adulto , Animales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ratas , Azacitidina/farmacología , Modelos Animales de Enfermedad , ADN (Citosina-5-)-Metiltransferasas/genética , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Epigénesis Genética , Ferroptosis/genética , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/patología , Degeneración del Disco Intervertebral/metabolismo , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patología , Ratas Sprague-Dawley , Regulación hacia Arriba
17.
Nutrients ; 16(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38732622

RESUMEN

Acute lung injury, a fatal condition characterized by a high mortality rate, necessitates urgent exploration of treatment modalities. Utilizing UHPLS-Q-Exactive Orbitrap/MS, our study scrutinized the active constituents present in Rosa roxburghii-fermented juice (RRFJ) while also assessing its protective efficacy against LPS-induced ALI in mice through lung histopathological analysis, cytokine profiling, and oxidative stress assessment. The protective mechanism of RRFJ against ALI in mice was elucidated utilizing metabolomics, network pharmacology, and molecular docking methodologies. Our experimental findings demonstrate that RRFJ markedly ameliorates pathological injuries in ALI-afflicted mice, mitigates systemic inflammation and oxidative stress, enhances energy metabolism, and restores dysregulated amino acid and arachidonic acid metabolic pathways. This study indicates that RRFJ can serve as a functional food for adjuvant treatment of ALI.


Asunto(s)
Lesión Pulmonar Aguda , Jugos de Frutas y Vegetales , Lipopolisacáridos , Metabolómica , Estrés Oxidativo , Rosa , Animales , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/prevención & control , Rosa/química , Metabolómica/métodos , Ratones , Masculino , Estrés Oxidativo/efectos de los fármacos , Farmacología en Red , Fermentación , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , Modelos Animales de Enfermedad , Simulación del Acoplamiento Molecular , Extractos Vegetales/farmacología , Citocinas/metabolismo , Metabolismo Energético/efectos de los fármacos
18.
EBioMedicine ; 104: 105165, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38776596

RESUMEN

BACKGROUND: Understanding the impact of CYP2D6 metabolism on paroxetine, a widely used antidepressant, is essential for precision dosing. METHODS: We conducted an 8-week, multi-center, single-drug, 2-week wash period prospective cohort study in 921 Chinese Han patients with depressive or anxiety disorders (ChiCTR2000038462). We performed CYP2D6 genotyping (single nucleotide variant and copy number variant) to derive the CYP2D6 activity score and evaluated paroxetine treatment outcomes including steady-state concentration, treatment efficacy, and adverse reaction. CYP2D6 metabolizer status was categorized into poor metabolizers (PMs), intermediate metabolizers (IMs), extensive metabolizers (EMs), and ultrarapid metabolizers (UMs). The influence of CYP2D6 metabolic phenotype on paroxetine treatment outcomes was examined using multiple regression analysis and cross-ethnic meta-analysis. The therapeutic reference range of paroxetine was estimated by receiver operating characteristic (ROC) analyses. FINDINGS: After adjusting for demographic factors, the steady-state concentrations of paroxetine in PMs, IMs, and UMs were 2.50, 1.12, and 0.39 times that of EMs, with PM and UM effects being statistically significant (multiple linear regression, P = 0.03 and P = 0.04). Sex and ethnicity influenced the comparison between IMs and EMs. Moreover, poor efficacy of paroxetine was associated with UM, and a higher risk of developing adverse reactions was associated with lower CYP2D6 activity score. Lastly, cross-ethnic meta-analysis suggested dose adjustments for PMs, IMs, EMs, and UMs in the East Asian population to be 35%, 40%, 143%, and 241% of the manufacturer's recommended dose, and 62%, 68%, 131%, and 159% in the non-East Asian population. INTERPRETATION: Our findings advocate for precision dosing based on the CYP2D6 metabolic phenotype, with sex and ethnicity being crucial considerations in this approach. FUNDING: National Natural Science Foundation of China; Academy of Medical Sciences Research Unit.


Asunto(s)
Trastornos de Ansiedad , Citocromo P-450 CYP2D6 , Paroxetina , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos de Ansiedad/tratamiento farmacológico , Trastornos de Ansiedad/genética , China , Citocromo P-450 CYP2D6/genética , Citocromo P-450 CYP2D6/metabolismo , Trastorno Depresivo/tratamiento farmacológico , Trastorno Depresivo/genética , Pueblos del Este de Asia , Genotipo , Paroxetina/administración & dosificación , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , Resultado del Tratamiento
19.
FEBS Open Bio ; 14(7): 1101-1115, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38710658

RESUMEN

Heart failure with preserved ejection fraction (HFpEF) is one of the major subtypes of heart failure (HF) and no effective treatments for this common disease exist to date. Cardiac fibrosis is central to the pathology of HF and a potential avenue for the treatment of HFpEF. To explore key fibrosis-related genes and pathways in the pathophysiological process of HFpEF, a mouse model of HFpEF was constructed. The relevant gene expression profiles were downloaded from the Gene Expression Omnibus database, and single-sample Gene Set Enrichment Analysis (ssGSEA) was performed targeting fibrosis-related pathways to explore differentially expressed genes (DEGs) in healthy control and HFpEF heart tissues with cross-tabulation analysis of fibrosis-related genes. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the identified fibrosis-related genes. The two most significant DEGs were selected, and further validation was conducted in HFpEF mice. The results indicated that myocardial fibrosis was significantly upregulated in HFpEF mice compared to healthy controls, while the ssGSEA results revealed significant differences in the enrichment of nine fibrosis-related pathways in HFpEF myocardial tissue, with 112 out of 798 DEGs being related to fibrosis. The in vivo results demonstrated that expression levels of resistin-like molecule gamma (Relmg) and adenylate cyclase 1 (Adcy1) in the heart tissues of HFpEF mice were significantly higher and lower, respectively, compared to healthy controls. Taken together, these results suggest that Relmg and Acdy1 as well as the fibrosis process may be potential targets for HFpEF treatment.


Asunto(s)
Adenilil Ciclasas , Fibrosis , Insuficiencia Cardíaca , Animales , Ratones , Fibrosis/genética , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/patología , Adenilil Ciclasas/metabolismo , Adenilil Ciclasas/genética , Miocardio/metabolismo , Miocardio/patología , Masculino , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Ratones Endogámicos C57BL
20.
PLoS One ; 19(4): e0301434, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38573953

RESUMEN

Falling nets are a type of fishing gear that appeared and developed rapidly in the northern of South China Sea in the early 1990s. We have developed Light-emitting diode (LED) fishing lamps to replace metal halide (MH) lamps that reduce fuel consumption without reducing the catches. We conducted marine light-fishing experiments in the northern South China Sea during September 20 to 26, 2019 and August 29 to 31, 2021. The results in the first fishing experiment show that there is no significant change in catch of the falling-net fishing vessel when the white LED lamps (with a total power of 36 kW) were used instead of MH lamps (with a total power of 120 kW). Coleoidea catches of the falling-net fishing vessel increased significantly when white LED lamps (with a total power of 36 kW) and cyan LED lamps (with a total power of 6.0 kW) were used. The results in the second fishing experiment show that the total weight of catches of the cyan LED fishing lamps is more than that of the white LED fishing lamps, and the cyan LED light can attract Penaeus merguiensis, Thryssa dussumieri and Sardinella zunasi more effectively than the white LED light.


Asunto(s)
Cefalópodos , Caza , Animales , Explotaciones Pesqueras , China
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