Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 382
Filtrar
1.
Eat Behav ; 54: 101908, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39137484

RESUMEN

OBJECTIVE: People with attentional problems are at increased risk of eating disorders. This paper aimed to systematically review and synthesize the existing evidence on stimulant medication in the management of patients with bulimia nervosa (BN) or anorexia nervosa (AN) with or without comorbid attention deficit hyperactivity disorder (ADHD). METHOD: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A protocol for the review was registered with Open Science Framework (OSF) Registry and critical appraisal of the literature was conducted using Joanna Briggs Institute (JBI) Critical Appraisal Tools. RESULTS: Thirteen articles met inclusion criteria including two quasi-experimental studies, one randomized controlled trial, four case series, and six case reports. 26 cases were included from studies and 32 from case series/reports. Only two cases from a single case report had a diagnosis of AN, while the remainder had BN. Stimulants included methylamphetamine, lisdexamfetamine, methylphenidate, dextroamphetamine sulphate and mixed amphetamine salt. In nearly all cases of BN there were reported reductions in eating disorder symptoms. The rates of adverse effects were high and included weight loss, decreased appetite, tachycardia, dry mouth, fatigue, insomnia, restlessness, nausea, bruxism, headache, palpitations, blood pressure changes, irritability, anxiety, depressed mood, and diaphoresis. CONCLUSION: There is currently insufficient evidence to support the use of stimulant medications to treat symptoms of BN or AN. The authors recommend considering screening patients with BN for ADHD.

2.
Front Mol Biosci ; 11: 1375360, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38962282

RESUMEN

Background: High altitude de-acclimatization (HADA) is gradually becoming a public health concern as millions of individuals of different occupations migrate to high-altitude areas for work due to economic growth in plateau areas. HADA affects people who return to lower elevations after exposure to high altitudes. It causes significant physiological and functional changes that can negatively impact health and even endanger life. However, uncertainties persist about the detailed mechanisms underlying HADA. Methods: We established a population cohort of individuals with HADA and assessed variations in metabolite composition. Plasm samples of four groups, including subjects staying at plain (P) and high altitude (H) as well as subjects suffering from HADA syndrome with almost no reaction (r3) and mild-to-moderate reaction (R3) after returning to plain from high altitude, were collected and analyzed by Liquid Chromatography-Mass Spectrometry metabolomic. Multivariate statistical analyses were used to explore significant differences and potential clinical prospect of metabolites. Result: Although significantly different on current HADAS diagnostic symptom score, there were no differences in 17 usual clinical indices between r3 and R3. Further multivariate analyses showed isolated clustering distribution of the metabolites among the four groups, suggesting significant differences in their metabolic characteristics. Through K-means clustering analysis, we identified 235 metabolites that exhibited patterns of abundance change consistent with phenotype of HADA syndrome. Pathway enrichment analysis indicated a high influence of polyunsaturated fatty acids under high-altitude conditions. We compared the metabolites between R3 and r3 and found 107 metabolites with differential abundance involved in lipid metabolism and oxidation, suggesting their potential role in the regulation of oxidative stress homeostasis. Among them, four metabolites might play a key role in the occurrence of HADA, including 11-beta-hydroxyandrosterone-3-glucuronide, 5-methoxyindoleacetate, 9,10-epoxyoctadecenoic acid, and PysoPC (20:5). Conclusion: We observed the dynamic variation in the metabolic process of HADA. Levels of four metabolites, which might be provoking HADA mediated through lipid metabolism and oxidation, were expected to be explore prospective indices for HADA. Additionally, metabolomics was more efficient in identifying environmental risk factors than clinical examination when dramatic metabolic disturbances underlying the difference in symptoms were detected, providing new insights into the molecular mechanisms of HADAS.

3.
Methods Enzymol ; 700: 275-294, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38971603

RESUMEN

Synthetic model membranes are important tools to elucidate lipid domain and protein interactions due to predefined lipid compositions and characterizable biophysical properties. Here, we introduce a model membrane with multiple lipid bilayers (multi-bilayers) stacked on a mica substrate that is prepared through a spin-coating technique. The spin-coated multi-bilayers are useful in the study of phase separated membranes with a high cholesterol content, mobile lipids, microscopic and reversible phase separation, and easy conjugation with proteins, which make them a good model to study interactions between proteins and membrane domains.


Asunto(s)
Membrana Dobles de Lípidos , Membrana Dobles de Lípidos/química , Membrana Dobles de Lípidos/metabolismo , Proteínas de la Membrana/química , Proteínas de la Membrana/metabolismo , Colesterol/química , Colesterol/metabolismo , Silicatos de Aluminio/química , Microdominios de Membrana/química , Microdominios de Membrana/metabolismo , Unión Proteica
4.
J Am Heart Assoc ; 13(15): e034575, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39023075

RESUMEN

BACKGROUND: Beat-to-beat blood pressure variability (BPV) is based on each heartbeat and represents a dynamic equilibrium process modulated by artery and cardiac involvement of pressure-receptive reflexes. To date, there remains a lack of prospective studies illustrating the clinical value of beat-to-beat BPV within 24 hours of acute ischemic stroke onset. METHODS AND RESULTS: This study prospectively monitored beat-to-beat blood pressure and heart rate in patients with acute ischemic stroke within 24 hours of onset using a noninvasive plethysmograph and calculated beat-to-beat BPV, heart rate variability, and the cross-correlation baroreflex sensitivity. A modified Rankin Scale score of ≥2 at 90 days was defined as an unfavorable prognosis. Multivariate logistic regression was performed, and the nomogram model was developed by adding the beat-to-beat BPV to the traditional model for predicting prognosis. Beat-to-beat BPV increased significantly in the unfavorable outcome group (P<0.05) compared with that in the favorable outcome group, whereas no difference was observed in beat-to-beat heart rate variability and cross-correlation baroreflex sensitivity between both groups (P>0.05). Furthermore, beat-to-beat BPV within 24 hours of acute ischemic stroke onset was independently associated with unfavorable outcome at 90 days (P<0.005). The addition of beat-to-beat BPV to the traditional model for predicting prognosis enhanced the area under the receiver operating characteristic curve from 0.816 to 0.830. CONCLUSIONS: Increased beat-to-beat BPV within 24 hours of acute ischemic stroke onset was independently associated with a poor prognosis at 90 days and may be a potential predictor for discriminating unfavorable prognosis.


Asunto(s)
Barorreflejo , Presión Sanguínea , Frecuencia Cardíaca , Accidente Cerebrovascular Isquémico , Humanos , Masculino , Femenino , Presión Sanguínea/fisiología , Frecuencia Cardíaca/fisiología , Anciano , Accidente Cerebrovascular Isquémico/fisiopatología , Accidente Cerebrovascular Isquémico/diagnóstico , Pronóstico , Barorreflejo/fisiología , Estudios Prospectivos , Persona de Mediana Edad , Factores de Tiempo , Valor Predictivo de las Pruebas , Nomogramas , Pletismografía , Anciano de 80 o más Años , Estado Funcional
5.
J Hazard Mater ; 476: 135125, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39003809

RESUMEN

Young people are consuming large amounts of microplastics (MPs) due to the booming development of the take-out industry. To investigate the association between MPs exposure and obesity, 121 volunteers were divided into high MPs exposure (HME) and low MPs exposure (LME) according to the frequency of take-out food consumption. Fecal samples were collected for MPs detection using Raman spectra analysis, and identification of the gut microbiota was based on 16 S rDNA/ITS, while metabolite analysis was performed by LC-MS/MS. High levels of MPs and body mass index (BMI) were observed in the HME group (P < 0.05). Both the multiple linear regression (MLR) model and the binary logistic regression (BLR) (OR: 1.264, 95 % CI: 1.108-1.441, P < 0.001) analysis showed a positive correlation between MPs content and BMI. Microbial community analysis revealed that Veillonella, Alistipes and Dothideomycotes (pathogenic fungi) increased in HME participants, whereas Faecalibacterium and Coprococcus decreased. Meanwhile, analysis of stool metabolites showed that vancomycin resistance, selenocompound metabolism and drug metabolism pathways were enhanced in HME participants. These findings indicate that frequent consumption of take-out food may elevate the intake of microplastics, consequently modifying the gut microbiota and metabolites of young adults, and could represent a potential risk factor for obesity.


Asunto(s)
Heces , Microbioma Gastrointestinal , Microplásticos , Obesidad , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Obesidad/microbiología , Adulto Joven , Masculino , Femenino , Heces/microbiología , Heces/química , Microplásticos/toxicidad , Adulto , Índice de Masa Corporal
6.
J Magn Reson Imaging ; 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38544434

RESUMEN

BACKGROUND: The fasting-postprandial state remains an underrecognized confounding factor for quantifying cerebral blood flow (CBF) in the cognitive assessment and differential diagnosis of Alzheimer's disease (AD). PURPOSE: To investigate the effects of fasting-postprandial state on arterial spin labeling (ASL)-based CBF in AD patients. STUDY TYPE: Prospective. SUBJECTS: Ninety-two subjects (mean age = 62.5 ± 6.4 years; females 29.3%), including 30 with AD, 32 with mild cognitive impairment (MCI), and 30 healthy controls (HCs). Differential diagnostic models were developed with a 4:1 training to testing set ratio. FIELD STRENGTH/SEQUENCE: 3-T, T1-weighted imaging using gradient echo and pseudocontinuous ASL imaging using turbo spin echo. ASSESSMENT: Two ASL scans were acquired to quantify fasting state and postprandial state regional CBFs based on an automated anatomical labeling atlas. Two-way ANOVA was used to assess the effects of fasting/postprandial state and disease state (AD, MCI, and HC) on regional CBF. Pearson's correlation analysis was conducted between regional CBF and cognitive scores (Mini-Mental State Examination [MMSE] and Montreal Cognitive Assessment [MoCA]). The diagnostic performances of the fasting state, postprandial state, and mixed state (random mixing of the fasting and postprandial state CBF) in differential diagnosis of AD were conducted using support vector machine and logistic regression models. STATISTICAL TESTS: Two-way ANOVA, Pearson's correlation, and area under the curve (AUC) of diagnostic model were performed. P values <0.05 indicated statistical significance. RESULTS: Fasting-state CBF was correlated with cognitive scores in more brain regions (17 vs. 4 [MMSE] and 15 vs. 9 [MoCA]) and had higher absolute correlation coefficients than postprandial-state CBF. In the differential diagnosis of AD patients from MCI patients and HCs, fasting-state CBF outperformed mixed-state CBF, which itself outperformed postprandial-state CBF. DATA CONCLUSION: Compared with postprandial CBF, fasting-state CBF performed better in terms of cognitive score correlations and in differentiating AD patients from MCI patients and HCs. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

7.
Neurocrit Care ; 40(1): 282-291, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36991176

RESUMEN

BACKGROUND: Although abnormal heart rate variability (HRV) is frequently observed in patients with spontaneous intracerebral hemorrhage (ICH), its time course and presentation of different indices remain unclear, and few studies have focused on its association with clinical outcomes. METHODS: We prospectively recruited consecutive patients with spontaneous ICH between June 2014 and June 2021. HRV was evaluated twice during hospitalization (within 7 days and 10-14 days after stroke). Time and frequency domain indices were calculated. A modified Rankin Scale score ≥ 3 at 3 months was defined as a poor outcome. RESULTS: Finally, 122 patients with ICH and 122 age- and sex-matched volunteers were included. Compared with controls, time domain and absolute frequency domain HRV parameters (total power, low frequency [LF], and high frequency [HF]) in the ICH group were significantly decreased within 7 days and 10-14 days. For relative values, normalized LF (LF%) and LF/HF were significantly higher, whereas normalized HF (HF%) was significantly lower, in the patient group than in the control group. Furthermore, LF% and HF% measured at 10-14 days were independently associated with 3-month outcomes. CONCLUSIONS: HRV values were impaired significantly within 14 days after ICH. Furthermore, HRV indices measured 10-14 days after ICH were independently associated with 3-month outcomes.


Asunto(s)
Hemorragia Cerebral , Accidente Cerebrovascular , Humanos , Frecuencia Cardíaca/fisiología , Arritmias Cardíacas , Hospitalización
8.
Chinese Pharmacological Bulletin ; (12): 213-218, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1013583

RESUMEN

As a widely used anti-tumor drug and anti-rheumatic drug in clinic, methotrexate (MTX) has many toxic and side effects, including gastrointestinal mucosa injury, central nervous system injury, liver and kidney function injury, etc. They often bring great trouble to the follow-up treatment of patients. The clarification of the mechanism of MTX toxicity to various organs has become the key to rescue the toxicity. The purpose of the article is to review the toxicity mechanism of MTX in various organs, so as to save the patients from the adverse reactions in clinical treatment.

9.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1039176

RESUMEN

Objective To investigate the influence of individual factors and labor organization factors on work-related musculoskeletal disorders (WMSDs) in automobile manufacturing workers, and to provide a scientific basis for the prevention and treatment of WMSDs in automobile manufacturing workers. Methods In April 2020, 5564 workers in an automobile factory were selected by cluster sampling method. The prevalence of WMSDs was investigated by using the Musculoskeletal Disorders Questionnaire, and the influence of individual factors and labor organization factors on WMSDs was investigated by using generalized estimation equation. Results The prevalence rate of WMSDs was 79.00% (4396/5564), and the prevalence rate of multisite WMSDs was 67.95% (3781/5564). The analysis of generalized estimation equation showed that doing the same job every day (OR= 1.478, P 40 hours per week increased the risk of WMSDs (P< 0.05). Male and adequate rest time were protective factors for WMSDs. The job correlation matrix showed that WMSDs in most parts had a positive correlation. Conclusions The prevalence of multisite WMSDs of workers in automobile manufacturing industry is high, and unreasonable labor organization is the main risk factor of WMSDs. Appropriate work breaks can effectively reduce the risk of WMSDs, and effective intervention measures should be carried out to prevent the occurrence of WMSDs in workers in automobile manufacturing industry. The generalized estimation equation can better analyze the influencing factors of WMSDs.

10.
Chinese Journal of Medical Imaging ; (12): 162-165,167, 2024.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1026368

RESUMEN

Purpose To explore the diagnostic value of beak sign in fetal annular pancreas by analyzing the ultrasonographic features of fetal annular pancreas.Materials and Methods The ultrasound images and clinical data of 13 cases of fetal annular pancreas diagnosed by prenatal ultrasound in Shandong Provincial Maternal and Child Health Hospital from September 2019 to December 2021 and confirmed by surgery after birth were retrospectively analyzed.The degree of duodenal stenosis at the obstruction site was observed,especially whether the angle formed by the intestinal wall could identify the fetal annular pancreas,and the ultrasonic characteristics were summarized and analyzed.Results A total of 13 fetuses with annular pancreas showed double bubble sign,3 cases showed clamp sign,and 7 cases showed beak sign at the end of duodenal dilatation.All the 13 cases underwent surgical treatment after birth,including 2 cases with duodenal atresia and 1 case with atypical intestinal malrotation.All the children had good prognosis after operation.Conclusion By observing the dilated end of duodenum and the relationship with pancreatic head,prenatal ultrasound combined with beak sign and double bubble sign could improve the diagnostic accuracy of fetal annular pancreas,which has significant value in prenatal diagnosis of fetal annular pancreas.

11.
Mol Biol Cell ; 35(3): ar12, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38117594

RESUMEN

Insulin secretion depends on the Ca2+-regulated fusion of granules with the plasma membrane. A recent model of Ca2+-triggered exocytosis in secretory cells proposes that lipids in the plasma membrane couple the calcium sensor Syt1 to the membrane fusion machinery (Kiessling et al., 2018). Specifically, Ca2+-mediated binding of Syt1's C2 domains to the cell membrane shifts the membrane-anchored SNARE syntaxin-1a to a more fusogenic conformation, straightening its juxtamembrane linker. To test this model in live cells and extend it to insulin secretion, we enriched INS1 cells with a panel of lipids with different acyl chain compositions. Fluorescence lifetime measurements demonstrate that cells with more disordered membranes show an increase in fusion efficiency, and vice versa. Experiments with granules purified from INS1 cells and recombinant SNARE proteins reconstituted in supported membranes confirmed that lipid acyl chain composition determines SNARE conformation and that lipid disordering correlates with increased fusion. Addition of Syt1's C2AB domains significantly decreased lipid order in target membranes and increased SNARE-mediated fusion probability. Strikingly, Syt's action on both fusion and lipid order could be partially bypassed by artificially increasing unsaturated phosphatidylserines in the target membrane. Thus, plasma membrane lipids actively participate in coupling Ca2+/synaptotagmin-sensing to the SNARE fusion machinery in cells.


Asunto(s)
Células Secretoras de Insulina , Fusión de Membrana , Lípidos de la Membrana/metabolismo , Proteínas SNARE/metabolismo , Células Secretoras de Insulina/metabolismo , Membrana Celular/metabolismo , Sinaptotagmina I/química , Sinaptotagmina I/metabolismo , Exocitosis , Proteínas Recombinantes/metabolismo , Calcio/metabolismo
12.
J Alzheimers Dis ; 96(2): 669-681, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37840496

RESUMEN

BACKGROUND: Apolipoprotein E (APOE) is the most recognized risk gene for cognitive decline and clinical progression of late-onset Alzheimer's disease (AD); nonetheless, its association with neuropsychiatric symptoms (NPSs) remains inconclusive. OBJECTIVE: To investigate the association of APOE ɛ4 with NPSs and explore nutritional status and cognition as joint mediators of this association. METHODS: Between June 2021 and October 2022, patients with amnestic mild cognitive impairment (aMCI) or AD were recruited from the Chinese Imaging, Biomarkers, and Lifestyle Study. NPSs were assessed using the Neuropsychiatric Inventory, while global cognition and nutritional status were evaluated using the Mini-Mental State Examination (MMSE) and Mini-Nutritional Assessment (MNA), respectively. Simple mediation and multiple chain mediation models were developed to examine the mediating effects of the MNA and MMSE scores on the relationship between APOE ɛ4 and specific neuropsychiatric symptom. RESULTS: Among 310 patients, 229 (73.87%) had NPSs, and 110 (35.48%) carried APOE ɛ4. Patients with APOE ɛ4 were more likely to have hallucinations (p = 0.014), apathy (p = 0.008), and aberrant motor activity (p = 0.018). MNA and MMSE scores mediated the association between APOE ɛ4 and hallucinations (17.97% and 37.13%, respectively), APOE ɛ4 and apathy (30.73% and 57.72%, respectively), and APOE ɛ4 and aberrant motor activity (17.82% and 34.24%), respectively. Chain-mediating effects of MNA and MMSE scores on the association of APOE ɛ4 with hallucinations, apathy, and aberrant motor activity after adjusting for confounding factors were 6.84%, 11.54%, and 6.19%, respectively. CONCLUSION: Nutritional status and cognition jointly mediate the association between APOE ɛ4 and neuropsychiatric symptoms in patients with aMCI or AD.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/psicología , Apolipoproteína E4/genética , Estado Nutricional , Análisis de Mediación , Cognición , Apolipoproteínas E/genética , Disfunción Cognitiva/genética , Alucinaciones
13.
Huan Jing Ke Xue ; 44(9): 5196-5203, 2023 Sep 08.
Artículo en Chino | MEDLINE | ID: mdl-37699837

RESUMEN

To explore the safe utilization technology of farmland polluted by the heavy metals cadmium (Cd) and lead (Pb) and to realize the safe production of agricultural products, a pot experiment was conducted to investigate the effects of two soil passivators and five foliar inhibitors on Cd and Cd-accumulation and quality of lettuce with low Pb and Cd accumulation (KCW). The results showed that different control measures had different effects on the soil pH value of lettuce, and the application of 45 g·m-2biochar-based passivator had the most significant difference in improving the soil pH value, which was increased by 0.8 units compared with that in CK. By using 72 g·m-2 of humic acid passivator yielded notable difference in reducing the soil pH value of lettuce. A reduction of 0.25 units was achieved compared with that in CK. Among all the control measures, the application of 45 g·m-2 biocharcoal-based passivation agent had the best effect on reducing soil available Cd content, which was significantly reduced by 53% compared with that in CK, and the application of 135 g·m-2biocharcoal-based passivation agent had the best effect on reducing soil available Pb content, which was significantly reduced by 64% compared with that in CK. Spraying 0.8% FAK-Zn foliar inhibitor not only had the best control effect on reducing Cd and Pb contents in the edible parts of lettuce, which were significantly reduced by 77% and 60%, respectively, compared with that in CK, but it also significantly reduced Cd and Pb enrichment coefficients and transport coefficients from the root to the edible parts of the lettuce. Different control measures had different effects on the nutritional quality of lettuce, and 0.4% FAK-Zn foliar inhibitor had the best effect on soluble protein. The 0.6% FAK-Zn had the best effect on soluble sugar, and the 0.4% FAK-Zn inhibitor had the best effect on vitamin C content. The application of biocarbon-based passivator could effectively repair lettuce soil polluted by Cd and Pb, whereas the application of FAK-Zn leaf surface inhibitor could effectively inhibit the accumulation, absorption, and transfer of Cd and Pb in lettuce; improve the nutritional quality of lettuce; provide a theoretical basis for safe production of vegetables polluted by heavy metals; and promote the recycling of resources and environment.


Asunto(s)
Cadmio , Lactuca , Plomo , Verduras , Suelo
14.
J Fungi (Basel) ; 9(6)2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37367613

RESUMEN

Arbuscular mycorrhizal fungi (AMF) play key roles in enhancing plant tolerance to heavy metals, and iron (Fe) compounds can reduce the bioavailability of arsenic (As) in soil, thereby alleviating As toxicity. However, there have been limited studies of the synergistic antioxidant mechanisms of AMF (Funneliformis mosseae) and Fe compounds in the alleviation of As toxicity on leaves of maize (Zea mays L.) with low and moderate As contamination. In this study, a pot experiment was conducted with different concentrations of As (0, 25, 50 mgꞏkg-1) and Fe (0, 50 mgꞏkg-1) and AMF treatments. Results showed that under low and moderate As concentrations (As25 and As50), the co-inoculation of AMF and Fe compound significantly increased the biomass of maize stems and roots, phosphorus (P) concentration, and P-to-As uptake ratio. Moreover, the co-inoculation of AMF and Fe compound addition significantly reduced the As concentration in stem and root, malondialdehyde (MDA) content in leaf, and soluble protein and non-protein thiol (NPT) contents in leaf of maize under As25 and As50 treatments. In addition, co-inoculation with AMF and Fe compound addition significantly increased the activities of catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) in the leaves of maize under As25 treatment. Correlation analysis showed that stem biomass and leaf MDA content were very significantly negatively correlated with stem As content, respectively. In conclusion, the results indicated that the co-inoculation of AMF and Fe compound addition can inhibit As uptake and promote P uptake by maize under low and moderate As contamination, thereby mitigating the lipid peroxidation on maize leaves and reducing As toxicity by enhancing the activities of antioxidant enzymes under low As contamination. These findings provide a theoretical basis for the application of AMF and Fe compounds in the restoration of cropland soil contaminated with low and moderate As.

15.
Molecules ; 28(12)2023 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-37375139

RESUMEN

Six compounds including three new benzophenones, selagibenzophenones D-F (1-3), two known selaginellins (4-5) and one known flavonoid (6), were isolated from Selaginella tamariscina. The structures of new compounds were established by 1D-, 2D-NMR and HR-ESI-MS spectral analyses. Compound 1 represents the second example of diarylbenzophenone from natural sources. Compound 2 possesses an unusual biphenyl-bisbenzophenone structure. Their cytotoxicity against human hepatocellular carcinoma HepG2 and SMCC-7721 cells and inhibitory activities on lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 cells were evaluated. Compound 2 showed moderate inhibitory activity against HepG2 and SMCC-7721 cells, and compounds 4 and 5 showed moderate inhibitory activity to HepG2 cells. Compounds 2 and 5 also exhibited inhibitory activities on lipopolysaccharide-induced nitric oxide (NO) production.


Asunto(s)
Selaginellaceae , Humanos , Estructura Molecular , Selaginellaceae/química , Óxido Nítrico , Lipopolisacáridos/farmacología , Benzofenonas/farmacología
16.
Sci Adv ; 9(17): eadf6205, 2023 04 28.
Artículo en Inglés | MEDLINE | ID: mdl-37126554

RESUMEN

During T cell activation, the transmembrane adaptor protein LAT (linker for activation of T cells) forms biomolecular condensates with Grb2 and Sos1, facilitating signaling. LAT has also been associated with cholesterol-rich condensed lipid domains; However, the potential coupling between protein condensation and lipid phase separation and its role in organizing T cell signaling were unknown. Here, we report that LAT/Grb2/Sos1 condensates reconstituted on model membranes can induce and template lipid domains, indicating strong coupling between lipid- and protein-based phase separation. Correspondingly, activation of T cells induces cytoplasmic protein condensates that associate with and stabilize raft-like membrane domains. Inversely, lipid domains nucleate and stabilize LAT protein condensates in both reconstituted and living systems. This coupling of lipid and protein assembly is functionally important, as uncoupling of lipid domains from cytoplasmic protein condensates abrogates T cell activation. Thus, thermodynamic coupling between protein condensates and ordered lipid domains regulates the functional organization of living membranes.


Asunto(s)
Proteínas de la Membrana , Linfocitos T , Linfocitos T/metabolismo , Proteínas de la Membrana/metabolismo , Transducción de Señal , Lípidos
17.
Proc Natl Acad Sci U S A ; 120(10): e2207461120, 2023 03 07.
Artículo en Inglés | MEDLINE | ID: mdl-36848577

RESUMEN

The composition of the plasma membrane (PM) must be tightly controlled despite constant, rapid endocytosis, which requires active, selective recycling of endocytosed membrane components. For many proteins, the mechanisms, pathways, and determinants of this PM recycling remain unknown. We report that association with ordered, lipid-driven membrane microdomains (known as rafts) is sufficient for PM localization of a subset of transmembrane proteins and that abrogation of raft association disrupts their trafficking and leads to degradation in lysosomes. Using orthogonal, genetically encoded probes with tunable raft partitioning, we screened for the trafficking machinery required for efficient recycling of engineered microdomain-associated cargo from endosomes to the PM. Using this screen, we identified the Rab3 family as an important mediator of PM localization of microdomain-associated proteins. Disruption of Rab3 reduced PM localization of raft probes and led to their accumulation in Rab7-positive endosomes, suggesting inefficient recycling. Abrogation of Rab3 function also mislocalized the endogenous raft-associated protein Linker for Activation of T cells (LAT), leading to its intracellular accumulation and reduced T cell activation. These findings reveal a key role for lipid-driven microdomains in endocytic traffic and suggest Rab3 as a mediator of microdomain recycling and PM composition.


Asunto(s)
Endocitosis , Proteínas de la Membrana , Membrana Celular , Movimiento Celular , Lípidos , Proteínas de Unión al GTP rab3/metabolismo
18.
Am J Med Sci ; 365(1): 48-55, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36037989

RESUMEN

BACKGROUND: Intra-abdominal hypertension (IAH) is an important risk factor for organ dysfunction, and it occurs in the early phase of severe acute pancreatitis (SAP). We have reported a novel step-up approach and shown the benefit of performing abdominal paracentesis drainage (APD) ahead of percutaneous catheter drainage (PCD) when treating Patients with SAP with fluid collections. This study aimed to evaluate the efficacy of APD in Patients with SAP complicated with IAH in the early phase. METHODS: In the present study, 206 AP patients complicated with IAH in the early phase were enrolled in hospital between June 2017 and December 2020. The patients were divided into two groups: 109 underwent APD (APD group) and 97 were managed without APD (non-APD group). We retrospectively compared the outcomes of the APD and non-APD groups for IAH treatment. The parameters including mortality, infection, organ failure, inflammatory factors, indications for further interventions, and drainage-related complications were observed. RESULTS: The demographic data and severity scores of the two groups were comparable. The mortality rate was lower in the APD group (3.7%) than in the non-APD group (8.2%). Compared with the non-APD group, the intra-abdominal pressure and laboratory parameters of the APD group decreased more rapidly, and the mean number of failed organs was lower. However, there was no significant difference in incidence of infections between the two groups. CONCLUSIONS: Application of APD is beneficial to AP patients. It significantly attenuated inflammation injury, avoided further interventions, and reduced multiple organ failure.


Asunto(s)
Hipertensión Intraabdominal , Pancreatitis , Humanos , Pancreatitis/complicaciones , Pancreatitis/terapia , Paracentesis/efectos adversos , Hipertensión Intraabdominal/terapia , Hipertensión Intraabdominal/complicaciones , Estudios Retrospectivos , Enfermedad Aguda , Drenaje/efectos adversos
19.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-1045886

RESUMEN

Objective: To investigate the expression change of the Mas1 receptor in the placenta of healthy pregnant women during different gestation periods, analyze the expression level of the Mas1 receptor in the placenta of pre-eclampsia (PE) patients, and its biological function in trophoblast cells. Methods: Placental villous tissues were collected from normal pregnant women in early, mid and late pregnancy. Human trophoblast stem cells were isolated and cultured from early pregnancy villous tissues. The expression of the Mas1 receptor was detected by fluorescence immunoassay and real-time fluorescence quantitative PCR. In a case-control study, patients with full-term PE were selected as the case group and healthy women with full-term pregnancy were selected as the control group. Placental villus tissues were collected from both groups. Immunofluorescence chemistry and immunoprotein blotting were used to study the changes in Mas1 receptor expression in PE. Mas1 receptor agonists and blockers induced HTR8/Svneo cells and BeWo cells, and the effects of the Mas1 receptor on the proliferation and migration of trophoblast cells were detected by the CCK8 proliferation test and scratch test. Results: Eight cases were included in early pregnancy, seven cases in mid-pregnancy and six cases in late pregnancy. Mas1 receptors in normal placental villi tissue were mainly expressed in human trophoblast stem cell membranes and cytoplasm, and the expression of Mas1 receptor mRNA in villi tissue was significantly higher in late pregnancy than in mid-pregnancy. There were 24 cases included in the case group and 12 cases in the control group. Mas1 receptor expression in placental villi was significantly lower in the case group compared to the control group; Activation/inhibition of the Mas1 receptor had no significant effect on the proliferation of HTR8/Svneo cells and BeWo cells. Activated Mas1 receptor had no significant effect on the migration ability of HTR8/Svneo cells. Conclusion: Mas1 receptors are expressed in placental villous tissue and their expression varies with gestation. Mas1 receptor expression is reduced in PE patients, but it does not affect the value-added or migratory function of trophoblast cells.


Asunto(s)
Humanos , Femenino , Embarazo , Placenta , Trofoblastos , Estudios de Casos y Controles , Preeclampsia , Expresión Génica
20.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-995588

RESUMEN

Objective:To observe and investigate the related factors that might affect clinical features of familial exudative vitreoretinopaty (FEVR) patients.Methods:A retrospective chart study. From January 2012 and December 2021, 42 patients with 84 eyes with a diagnosis of FEVR from Department of Ophthalmology, Peking University People's Hospital were included in the study. The patients came from 42 separate families. There were 31 males and 11 females, with an average age of first diagnosis was 16.6±33.7 months. There were 21 patients referred from other hospitals for the fundus disease found in eye screening after birth, 21 patients were first seen in our hospital. There were 4 and 38 premature and full-term infants, respectively. Two patients with a positive family history of FEVR. All patients are FEVR stages 1-5. The wide-angle digital pediatric retinal imaging system after general anesthesia for fluorescein fundus angiography (FFA) examination were performed for patients aged <5 years. If patients ≥ 5 years old, routine FFA examination was performed. Sixty-eight first-degree relatives from 28 families undergo routine fundus examinations and FFA examination. Genetic examination was performed for 26 families, including 26 probands and 57 first-degree relatives. Genetic examination were performed on gene the coreceptor of low density lipoprotein receptor-associated protein 5 ( LRP5), Wnt receptor coiled protein 4 ( FZD4), Norrie disease ( NDP), tetraporin 12 ( TSPAN12), catenin β1 ( CTNNB1) genes known to be involved in FEVR. The clinical features and the genotype of FEVR were observed in relation to the clinical phenotype. Results:Among the 42 patients, 13 patients were first observed by strabismus and nystagmus, with the median age of 12 months. Eight patients were complained non-chasing or vision-related symptoms. Among the 84 eyes, FEVR stage 1 or 2, 3 or 4, and 5 were 50 (59.5%, 50/84), 31 (36.9%, 31/84), and 3 (3.6%, 3/84) eyes, respectively. Among the 23 patients who were > 3 months at first diagnosis, 16 patients had at least one eye severer than stage 3 (69.6%, 16/23). Of the 68 first-degree relatives, 22 (32.4%, 22/68) had FEVR-like changes. Among the 26 families that underwent genetic detection, 13 families (50%, 13/26) of 16 variants of FEVR-related genes were detected, of which 10 mutations of LRP5 gene were the most common. There were 10 families with single gene mutations, including 6, 2 and 2 families of LRP5, FZD4 and CTNNB1 genes, respectively. One family of LRP5 gene mutations were compound heterozygous mutations, 1 family with LRP5 gene mutaition combined with NDP gene mutation, and 1 family with LRP5 and TSPAN12 gene mutation. Among the proband with FEVR pathogenic genes, 6 cases with similiar stage of both eyes, and 7 cases with inconsistent disease stages, and there was no obvious correlation between gene mutations and clinical phenotypes. Conclusion:In addition to the age of first diagnosis, no exact factors affecting the clinical manifestations of FEVR are found, and the association between clinical phenotypic and genetic heterogeneity still needs to be further explored.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA