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1.
Front Psychol ; 15: 1307393, 2024.
Article de Anglais | MEDLINE | ID: mdl-38966732

RÉSUMÉ

Introduction: While adversity can bring great challenges to individuals' life and work, many people also find ways to make positive changes and adapt to these difficult circumstances. Individuals tend to make social comparisons more frequently and intensely when faced with adversity or high stress. The study attempts to examine the influence mechanism of downward social comparison on individual adversarial growth. Methods: By collecting data from 353 Chinese who have experienced adversities in the past 3 years, the study validates the dual mediating model of gratitude and self-acceptance and explores the moderating effect of interpersonal sensitivity. Results: The findings indicate that: downward social comparison can increase the occurrence of adversarial growth by enhancing individuals' self-acceptance and gratitude. Compared to individuals with low interpersonal sensitivity, individuals with high interpersonal sensitivity are more likely to facilitate the occurrence of adversarial growth through self-acceptance and gratitude due to downward social comparison. Discussion: In the face of adversity, individuals can regain self-confidence and respond positively by comparing themselves to people in worse situations than themselves. In particular, individuals with higher interpersonal sensitivity are more likely to benefit from downward social comparisons and grow from adversity.

2.
Front Psychol ; 15: 1353271, 2024.
Article de Anglais | MEDLINE | ID: mdl-38966737

RÉSUMÉ

Studies documenting and seeking to understand the mindset effect have yielded mixed and inconclusive findings. The present study sought to address the research question pertaining to the mindset effect on creative thinking and its underlying mechanism from the perspectives of social cognitive theory and mindset theory, which postulate a motivational mechanism underlying the mindset-creativity link. Specifically, this study aimed to examine the mediating role of creativity motivation in the effects of growth and fixed creative mindsets on creative thinking. A convenience sample of 948 college students from three universities in Hong Kong participated in the study. Creative mindset, creativity motivation, and creative thinking were assessed using the Chinese version of the Creative Mindset Scale, the Creativity Motivation Scale, and the Test for Creative Thinking-Drawing Production (TCT-DP), respectively. Lending support to the perspectives of social cognitive and mindset theories, the results of mediation analyses conducted using Preacher and Hayes's bootstrapping approach indicated that creativity motivation had partial mediating effects on the positive and negative roles of growth and fixed mindsets, respectively, in creative thinking. Enriching the research on the motivation mechanism underlying the impacts of creative mindsets on creative thinking, the results further illustrated that creativity motivation has a stronger mediating effect on the impact of growth creative mindset on creative thinking than on that of fixed creative mindset. The possible theoretical and educational implications of the findings of this research are discussed.

3.
Diabetes Care ; 2024 Jul 05.
Article de Anglais | MEDLINE | ID: mdl-38968411

RÉSUMÉ

OBJECTIVE: To investigate associations of plasma glycated albumin (GA) concentrations in early and midpregnancy with gestational diabetes mellitus (GDM) risk. RESEARCH DESIGN AND METHODS: We measured GA concentrations using blood samples collected at 10-14 and 15-26 weeks' gestation (GW) in 107 GDM case subjects and 214 control subjects from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Study. We performed generalized linear mixed-effect regression to test the mean GA difference between GDM case subjects and control subjects and conditional logistic regression to assess prospective associations between GA concentrations and GDM risk. RESULTS: At 15-26 GW, mean GA was lower in GDM case subjects than control subjects (mean 11.90% [95% CI 6.42-32.76] vs. 12.46% [8.45-38.35], adjusted P value for difference = 0.004). Consistently, women with higher GA concentrations tended to have a lower GDM risk, although the associations were not statistically significant. CONCLUSIONS: This study suggests that GA concentrations in midpregnancy might be lower in women who later develop GDM. Further studies are needed to identify the mechanism.

4.
Environ Geochem Health ; 46(8): 282, 2024 Jul 04.
Article de Anglais | MEDLINE | ID: mdl-38963450

RÉSUMÉ

Polycyclic aromatic hydrocarbons (PAHs) are a class of persistent organic pollutants with carcinogenic, mutagenic and teratogenic effects. The white-rot fungi in the fungal group have significant degradation ability for high molecular weight organic pollutants. However, exogenous fungi are easily antagonized by indigenous microorganisms. Low molecular weight organic acids, a small molecular organic matter secreted by plants, can provide carbon sources for soil microorganisms. Combining organic acids with white rot fungi may improve the nutritional environment of fungi. In this study, immobilized Trametes versicolor was used to degrade benzo[a]pyrene in soil, and its effect on removing benzo[a]pyrene in soil mediated by different low molecular weight organic acids was investigated. The results showed that when the degradation was 35 days, the removal effect of the experimental group with citric acid was the best, reaching 43.7%. The degradation effect of Trametes versicolor on benzo[a]pyrene was further investigated in the liquid medium when citric acid was added, and the effects of citric acid on the biomass, extracellular protein concentration and laccase activity of Trametes versicolor were investigated by controlling different concentrations of citric acid. In general, citric acid can act as a carbon source for Trametes versicolor and promote its extracellular protein secretion and laccase activity, thereby accelerating the mineralization of benzo[a]pyrene by Trametes versicolor. Therefore, citric acid can be used as a biostimulant in the remediation of PAHs contaminated soil with Trametes versicolor.


Sujet(s)
Benzo[a]pyrène , Dépollution biologique de l'environnement , Acide citrique , Polluants du sol , Benzo[a]pyrène/toxicité , Benzo[a]pyrène/métabolisme , Acide citrique/métabolisme , Polluants du sol/métabolisme , Polluants du sol/toxicité , Laccase/métabolisme , Microbiologie du sol , Polyporaceae/métabolisme , Trametes/métabolisme , Biomasse
5.
Drug Deliv ; 31(1): 2372269, 2024 Dec.
Article de Anglais | MEDLINE | ID: mdl-38956885

RÉSUMÉ

Acne is a common chronic inflammatory disorder of the sebaceous gland in the hair follicle. Commonly used external medications cause skin irritation, and the transdermal capacity is weak, making it difficult to penetrate the cuticle skin barrier. Hair follicles can aid in the breakdown of this barrier. As nanomaterials progress, polymer-based nanocarriers are routinely used for hair follicle drug delivery to treat acne and other skin issues. Based on the physiological and anatomical characteristics of hair follicles, this paper discusses factors affecting hair follicle delivery by polymer nanocarriers, summarizes the common combination technology to improve the targeting of hair follicles by carriers, and finally reviews the most recent research progress of different polymer nanodrug-delivery systems for the treatment of acne by targeting hair follicles.


Sujet(s)
Acné juvénile , Vecteurs de médicaments , Follicule pileux , Polymères , Follicule pileux/effets des médicaments et des substances chimiques , Follicule pileux/métabolisme , Acné juvénile/traitement médicamenteux , Humains , Polymères/composition chimique , Vecteurs de médicaments/composition chimique , Systèmes de délivrance de médicaments/méthodes , Nanoparticules , Administration par voie cutanée , Animaux , Système d'administration de médicaments à base de nanoparticules/composition chimique
6.
Article de Anglais | MEDLINE | ID: mdl-38950354

RÉSUMÉ

PURPOSE: To elucidate the underlying motivations, experiential dimensions, and cognitive perceptions in adolescents with depression and non-suicidal self-injury (NSSI). METHOD: A descriptive qualitative design was used. Participants were 18 Chinese adolescents with depression and NSSI. Conventional content analysis was used for data analysis. RESULTS: Three primary themes and 11 subthemes were identified: Triggers of NSSI (personal, family, school, and social factors); Experiencing Emotional Complexity in NSSI Implementation (mitigating psychological distress, awakening a sense of existential life, generating secondary negative emotions, stimulating reflections on life and death); and Perceptions and Understandings of NSSI are Diverse (NSSI as a form of seeking validation or approval, an addictive behavior, a means to attain a sense of control, and unacceptable behavior). CONCLUSION: Although nursing staff should provide comprehensive treatment and psychological support, efforts should also be made to strengthen caregiving skills of family members, thereby promoting overall physical and mental health of adolescents. [Journal of Psychosocial Nursing and Mental Health Services, xx(x), xx-xx.].

7.
Adv Sci (Weinh) ; : e2404313, 2024 Jul 01.
Article de Anglais | MEDLINE | ID: mdl-38952047

RÉSUMÉ

Bacillus subtilis is an industrially important microorganism that is often used as a microbial cell factory for the production of recombinant proteins due to its food safety, rapid growth, and powerful secretory capacity. However, the lack of data on functional genes related to recombinant protein production has hindered the further development of B. subtilis cell factories. Here, a strategy combining genome-wide CRISPRi screening and targeted CRISPRa activation to enhance recombinant protein expression is proposed. First, a CRISPRi library covering a total of 4225 coding genes (99.7%) in the B. subtilis genome and built the corresponding high-throughput screening methods is constructed. Twelve key genes for recombinant protein expression are identified, including targets without relevant functional annotations. Meanwhile, the transcription of recombinant protein genes by CRISPRa is up-regulated. These screened or selected genes can be easily applied to metabolic engineering by constructing sgRNA arrays. The relationship between differential pathways and recombinant protein expression in engineered strains by transcriptome analysis is also revealed. High-density fermentation and generalisability validation results prove the reliability of the strategy. This method can be extended to other industrial hosts to support functional gene annotation and the design of novel cell factories.

8.
World J Gastrointest Surg ; 16(6): 1749-1755, 2024 Jun 27.
Article de Anglais | MEDLINE | ID: mdl-38983316

RÉSUMÉ

BACKGROUND: Intestinal colic is a common complication in patients who have undergone radical surgery for colorectal cancer. Traditional Chinese medicine has advantages, including safety and stability, for the treatment of intestinal colic. Lamp irradiation for abdominal ironing has been applied in the treatment of many gastrointestinal diseases. Purple gromwell oil has the effects of clearing heat, cooling blood, reducing swelling, and relieving pain. AIM: To investigate the impact of lamp irradiation combined with purple gromwell oil gauze on ameliorating intestinal colic in patients after radical surgery for colorectal cancer. METHODS: A total of 120 patients who experienced postoperative intestinal colic complications after radical surgery for colorectal cancer and who were admitted to Foshan Traditional Chinese Medicine Hospital between June 2019 and March 2023 were enrolled as study subjects. The patients were divided into a control group (60 patients) and an observation group (60 patients) based on treatment method. The control group was treated with lamp irradiation, while the observation group was treated with lamp irradiation and external application of purple gromwell oil gauze. The clinical efficacy, Numeric Rating Scale (NRS) score, duration of symptoms, and rate of adverse reaction occurrence were further compared between the two groups. RESULTS: The general effective rate in the observation group was 95.00%, which was significantly higher than that in the control group (86.67%, P < 0.05). Before treatment, there was no significant difference in the duration of symptoms between the groups (P > 0.05). After 1, 2, 3, and 4 d of treatment, the duration of symptoms in both groups were decreased, and the duration in the observation group was significantly lower than that in the control group (96.54 ± 9.57 vs 110.45 ± 11.23, 87.26 ± 12.07 vs 104.44 ± 11.68, 80.45 ± 16.21 vs 99.44 ± 14.95, 73.18 ± 15.58 vs 92.17 ± 14.20; P < 0.05). After 1, 3, 5, and 7 d of treatment, the NRS scores in both groups were decreased, and the NRS scores in the observation group were significantly lower than those in the control group (3.56 ± 0.41 vs 4.04 ± 0.58, 3.07 ± 0.67 vs 3.74 ± 1.02, 2.52 ± 0.76 vs 3.43 ± 0.85, 2.03 ± 0.58 vs 3.03 ± 0.82; P < 0.05). There was no significant difference in the rate of adverse reaction occurrence between the groups (P > 0.05). CONCLUSION: The use of lamp irradiation combined with purple gromwell oil gauze in patients with intestinal colic after radical surgery for colorectal cancer can reduce symptom duration, alleviate intestinal colic, and improve treatment efficacy, and this approach is safe. It is worth promoting the use of this treatment in clinical practice.

9.
iScience ; 27(6): 110127, 2024 Jun 21.
Article de Anglais | MEDLINE | ID: mdl-38966571

RÉSUMÉ

Identifying the atlas of immune cells from coronary sinus circulation (CSC) of patients with persistent atrial fibrillation (PerAF) may provide new insights into the role of immune cells in the progression of AF. Single-cell sequencing revealed substantial alterations in immune cells from CSCs of patients with PerAF, especially a markedly elevated abundance of T cells, after which we identified a T cell subset: FGFBP2(+)TRDC(-)CD4(-) T cells (Ftc-T cells), which can promote the proliferation of cardiac fibroblasts (CFs),and the proportion of Ftc-T had a positive linear with AF recurrence post catheter ablation (CA). Moreover, IFI27 was found to be highly enriched in Ftc-T cells and promoted CFs proliferation and collagen expression. Altogether, our findings represent a unique resource providing in-depth insights into the heterogeneity of the immune cell from CSC of patients with PerAF and highlight the potential role of Ftc-T cells and IFI27 for AF progression.

10.
Immun Inflamm Dis ; 12(7): e1282, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38967365

RÉSUMÉ

OBJECTIVE: This study aimed to investigate the expressions of glycemic parameters, lipid profile, and thyroid hormone in type 2 diabetes mellitus (T2DM) patients and their correlation. METHODS: Eighty-four patients with T2DM in our hospital were included as the observation group. The T2DM patients were divided into mild group, moderate group, and severe group according to the fasting plasma glucose (FPG) level. Another 84 healthy subjects in the same period of health examination in our hospital were included as the control group. The levels of glycemic parameters, (HbA1c and FPG), lipid profile (TC, TG, LDL-C, and HDL-C) and thyroid hormone (FT3, TSH, and FT4) were measured by automatic biochemical analyzer. The correlation between glycemic parameters, lipid profile, and thyroid hormone was analyzed by Pearson correlation analysis. RESULTS: The FPG, TC, TG, LDL-C, HbA1c, and TSH levels were significantly elevated, while the HDL-C and FT3 levels were significantly declined in the observation group versus to control group (p < .05). The levels of HbA1c, FPG, TC, LDL-C, and TSH were significantly increased, while the levels of HDL-C and FT3 were decreased in moderate and severe groups, when compared to mild group (p < .05). The levels of HbA1c, FPG, TC, LDL-C and TSH were higher, while the level of FT3 was lower in severe group than those in moderate group (p < .05). Pearson Correlation analysis showed that FT3 level in T2DM patients was positively correlated with FPG, HbAlc, TC, TG, and LDL-C levels (p < .05), but negatively correlated with HDL-C level (p < .05). TSH level was negatively correlated with FPG, HbAlc, TC, TG, and LDL-C levels (p < .05), while positively correlated with HDL-C level. CONCLUSION: The thyroid hormone levels were of clinical significance in evaluating glycolipid metabolism and severity of T2DM. Clinical detection of glycolipid metabolism and thyroid hormone levels in T2DM patients is of great significance for diagnosis, evaluation, and targeted treatment of the disease.


Sujet(s)
Glycémie , Diabète de type 2 , Hémoglobine glyquée , Lipides , Hormones thyroïdiennes , Humains , Diabète de type 2/sang , Mâle , Femelle , Adulte d'âge moyen , Hormones thyroïdiennes/sang , Lipides/sang , Glycémie/analyse , Glycémie/métabolisme , Hémoglobine glyquée/analyse , Hémoglobine glyquée/métabolisme , Sujet âgé , Adulte
11.
Clinics (Sao Paulo) ; 79: 100441, 2024.
Article de Anglais | MEDLINE | ID: mdl-38976936

RÉSUMÉ

OBJECTIVE: This study aimed to identify differentially expressed microRNAs (miRNAs) in exosomes derived from the blood plasma of Rheumatoid Arthritis (RA) patients and explore their clinical significance and biological roles. METHODS: Illumina high-throughput sequencing was employed to measure miRNA expression levels in plasma exosomes, followed by validation using qRT-PCR. The correlation between exosomal miRNAs and disease activity was systematically analyzed. Additionally, the pathogenic effects of RA exosomes were investigated through bioinformatics analysis and in vitro experiments. RESULTS: Significantly reduced levels of exosomal miR-144-3p and miR-30b-5p were observed in RA patients, which were negatively correlated with DAS28 scores and anti-CCP antibody levels. ROC curve analysis showed that miR-144-3p and miR-30b-5p in plasma exosomes could effectively distinguish RA patients from healthy controls, with AUC values of 0.725 and 0.773, respectively. Combining bioinformatics analysis and in vitro experiments, it was demonstrated that plasma exosomes contribute to ongoing autoantibody production in RA by promoting B-cell differentiation and antibody production. CONCLUSION: The present study indicates that plasma exosomes from RA patients may be potentially pathogenic. Exosomal miR-144-3p and miR-30b-5p exhibit significant decreases in RA patients and are associated with disease activity, suggesting their potential as valuable biomarkers for RA.


Sujet(s)
Polyarthrite rhumatoïde , Lymphocytes B , Exosomes , microARN , Humains , Polyarthrite rhumatoïde/sang , Polyarthrite rhumatoïde/génétique , Polyarthrite rhumatoïde/immunologie , microARN/sang , Femelle , Mâle , Adulte d'âge moyen , Lymphocytes B/immunologie , Études cas-témoins , Adulte , Marqueurs biologiques/sang , Courbe ROC , Réaction de polymérisation en chaine en temps réel
12.
Article de Anglais | MEDLINE | ID: mdl-39004591

RÉSUMÉ

BACKGROUND AND AIMS: Iron deficiency is a major public health concern. We aimed to assess the predictive capability of 4 iron metabolism biomarkers for all-cause and cardiovascular disease-specific mortality in U.S. patients with congestive heart failure (CHF). METHODS AND RESULTS: 1904 CHF patients aged ≥20 years were enrolled from NHANES, 1999-2000 to 2017-2018. All analyses were weighted to provide nationally representative estimates. Among 1905 CHF patients, mean age was 71 years, and 1024 (53.8%), 459 (24.1%), 206 (10.8%), and 216 (11.3%) were Non-Hispanic Black, Non-Hispanic White, Hispanic-Mexican American, and Hispanic-Other Hispanic, respectively. During follow-ups, 1080 deaths occurred. Median follow-up time was 5.08 years. Per-unit increase in natural-logarithmic-transformed iron and transferrin saturation decreased all-cause mortality risk separately by 33.0% (adjusted hazard ratio: 0.670, 95% confidence interval: 0.563 to 0.797, P < 0.001) and 32.6% (0.674, 0.495 to 0.917, 0.013), and per-unit increase in transferrin receptor increased mortality risk by 33.7% (1.337, 1.104 to 1.618, 0.004). Two derivates from 3 significant iron biomarkers were generated - transferrin receptor to natural-logarithmic-transformed iron ratio (TRI) and transferrin receptor to natural-logarithmic-transformed transferrin saturation ratio (TRTS), which were significantly associated with all-cause mortality, with per-unit increase corresponding to 2.692- and 1.655-fold increased all-cause mortality risk (P: 0.003 and 0.023). Only iron and TRTS were associated with the significant risk of cardiovascular disease-specific mortality (P: 0.004 and 0.017). CONCLUSIONS: Our findings identified 3 iron metabolism biomarkers that were individually, significantly, and independently associated with all-cause mortality in patients with CHF, and importantly 2 derivates generated exhibited stronger predictive capability.

13.
Anal Chem ; 96(28): 11533-11541, 2024 Jul 16.
Article de Anglais | MEDLINE | ID: mdl-38973171

RÉSUMÉ

In the landscape of biomolecular detection, surface-enhanced Raman spectroscopy (SERS) confronts notable obstacles, particularly in the label-free detection of biomolecules, with glucose and other sugars presenting a quintessential challenge. This study heralds the development of a pioneering SERS substrate, ingeniously engineered through the self-assembly of nanoparticles of diverse sizes (Ag1@Ag2NPs). This configuration strategically induces 'hot spots' within the interstices of nanoparticles, markedly amplifying the detection signal. Rigorous experimental investigations affirm the platform's rapidity, precision, and reproducibility, and the detection limit of this detection method is calculated to be 6.62 pM. Crucially, this methodology facilitates nondestructive glucose detection in simulated samples, including phosphate-buffered saline and urine. Integrating machine learning algorithms with simulated serum samples, the approach adeptly discriminates between hypoglycemic, normoglycemic, and hyperglycemic states. Moreover, the platform's versatility extends to the detection and differentiation of monosaccharides, disaccharides, and methylated glycosides, underscoring its universality and specificity. Comparative Raman spectroscopic analysis of various carbohydrate structures elucidates the unique SERS characteristics pertinent to these molecules. This research signifies a major advance in nonchemical, label-free glucose determination with enhanced sensitivity via SERS, laying a new foundation for its application in precision medicine and advancing structural analysis in the sugar domain.


Sujet(s)
Glucose , Nanoparticules métalliques , Analyse spectrale Raman , Analyse spectrale Raman/méthodes , Nanoparticules métalliques/composition chimique , Glucose/analyse , Humains , Argent/composition chimique , Propriétés de surface , Limite de détection , Glycémie/analyse
14.
J Cancer Res Clin Oncol ; 150(7): 348, 2024 Jul 13.
Article de Anglais | MEDLINE | ID: mdl-39002018

RÉSUMÉ

BACKGROUND & AIMS: Patients with intrahepatic cholangiocarcinoma (iCCA) respond poorly to immune checkpoint blockades (ICBs). In this study, we aimed to dissect the potential mechanisms underlying poor response to ICBs and explore a rational ICB-based combination therapy in iCCA. METHODS: scRNA-seq dataset GSE151530 was analyzed to investigate the differentially expressed genes in malignant cells following ICBs therapy. RNA-seq analysis and western blot assays were performed to examine the upstream and downstream signaling pathways of CD73. Subcutaneous tumor xenograft models were utilized to investigate the impact of CD73 on iCCA growth. Plasmid AKT/NICD-induced spontaneous murine iCCAs were used to explore the therapeutic efficacy of CD73 enzymatic inhibitor AB680 combined with PD-1 blockade. Time-of-flight mass cytometry (CyTOF) was conducted to identify the tumor-infiltrating immune cell populations and their functional changes in murine iCCAs treated with AB680 in combination with PD-1 antibody. RESULTS: scRNA-seq analysis identified elevated CD73 expression in malignant cells in response to ICBs therapy. Mechanistically, ICBs therapy upregulated CD73 expression in malignant cells via TNF-α/NF-κB signaling pathway. In vivo studies revealed that CD73 inhibition suppressed the growth of subcutaneous tumors, and achieved synergistic depression effects with gemcitabine and cisplatin (GC). Adenosine produced by CD73 activates AKT/GSK3ß/ß-catenin signaling axis in iCCA cells. CD73 inhibitor AB680 potentiates anti-tumor efficacy of PD-1 antibody in murine iCCAs. CyTOF analysis showed that AB680 combined with anti-PD-1 therapy promoted the infiltration of CD8+ T, CD4+ T cells, and NK cells in murine iCCAs, while simultaneously decreased the proportions of macrophages and neutrophils. Moreover, AB680 combined with anti-PD-1 significantly upregulated the expression of Granzyme B, Tbet and co-stimulatory molecule ICOS in infiltrating CD8+ T cells. CONCLUSIONS: CD73 inhibitor AB680 limits tumor progression and potentiates therapeutic efficacy of GC chemotherapy or anti-PD-1 treatment in iCCA. AB680 combined with anti-PD-1 therapy effectively elicits anti-tumor immune response.


Sujet(s)
5'-Nucleotidase , Tumeurs des canaux biliaires , Cholangiocarcinome , Inhibiteurs de points de contrôle immunitaires , Récepteur-1 de mort cellulaire programmée , Cholangiocarcinome/traitement médicamenteux , Cholangiocarcinome/anatomopathologie , Cholangiocarcinome/immunologie , Animaux , 5'-Nucleotidase/antagonistes et inhibiteurs , 5'-Nucleotidase/métabolisme , Souris , Tumeurs des canaux biliaires/traitement médicamenteux , Tumeurs des canaux biliaires/anatomopathologie , Tumeurs des canaux biliaires/immunologie , Tumeurs des canaux biliaires/métabolisme , Humains , Inhibiteurs de points de contrôle immunitaires/pharmacologie , Récepteur-1 de mort cellulaire programmée/antagonistes et inhibiteurs , Protéines liées au GPI/antagonistes et inhibiteurs , Protéines liées au GPI/métabolisme , Tests d'activité antitumorale sur modèle de xénogreffe , Lignée cellulaire tumorale , Évolution de la maladie
15.
Cell Death Differ ; 2024 Jul 16.
Article de Anglais | MEDLINE | ID: mdl-39009654

RÉSUMÉ

Dysregulated metabolism, cell death, and inflammation contribute to the development of metabolic dysfunction-associated steatohepatitis (MASH). Pyroptosis, a recently identified form of programmed cell death, is closely linked to inflammation. However, the precise role of pyroptosis, particularly gasdermin-E (GSDME), in MASH development remains unknown. In this study, we observed GSDME cleavage and GSDME-associated interleukin-1ß (IL-1ß)/IL-18 induction in liver tissues of MASH patients and MASH mouse models induced by a choline-deficient high-fat diet (CDHFD) or a high-fat/high-cholesterol diet (HFHC). Compared with wild-type mice, global GSDME knockout mice exhibited reduced liver steatosis, steatohepatitis, fibrosis, endoplasmic reticulum stress, lipotoxicity and mitochondrial dysfunction in CDHFD- or HFHC-induced MASH models. Moreover, GSDME knockout resulted in increased energy expenditure, inhibited intestinal nutrient absorption, and reduced body weight. In the mice with GSDME deficiency, reintroduction of GSDME in myeloid cells-rather than hepatocytes-mimicked the MASH pathologies and metabolic dysfunctions, as well as the changes in the formation of neutrophil extracellular traps and hepatic macrophage/monocyte subclusters. These subclusters included shifts in Tim4+ or CD163+ resident Kupffer cells, Ly6Chi pro-inflammatory monocytes, and Ly6CloCCR2loCX3CR1hi patrolling monocytes. Integrated analyses of RNA sequencing and quantitative proteomics revealed a significant GSDME-dependent reduction in citrullination at the arginine-114 (R114) site of dynamin-related protein 1 (Drp1) during MASH. Mutation of Drp1 at R114 reduced its stability, impaired its ability to redistribute to mitochondria and regulate mitophagy, and ultimately promoted its degradation under MASH stress. GSDME deficiency reversed the de-citrullination of Drp1R114, preserved Drp1 stability, and enhanced mitochondrial function. Our study highlights the role of GSDME in promoting MASH through regulating pyroptosis, Drp1 citrullination-dependent mitochondrial function, and energy balance in the intestine and liver, and suggests that GSDME may be a potential therapeutic target for managing MASH.

16.
Toxicol Res (Camb) ; 13(4): tfae102, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38993483

RÉSUMÉ

Background: Paclitaxel (PTX) is a commonly used as a chemotherapeutic drug for non-small cell lung cancer (NSCLC). Exploring the underlying mechanism of PTX resistance is of great significance for NSCLC treatment. Methods: The expression levels of RNA and protein were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assays. The targeted relationship was confirmed by dual-luciferase reporter assay and RNA-pull down assay. The PTX resistance and cell proliferation were assessed by cell counting kit-8 (CCK-8) assay and 5-Ethynyl-2'-deoxyuridine (EDU) assay, respectively. Cell migration and invasion were analyzed by transwell assays. Cell apoptosis was analyzed by flow cytometry, and cell glycolysis was analyzed using the commercial kits. The role of circular RNA_0076305 (circ_0076305) in regulating the PTX sensitivity in vivo was explored in xenograft tumor model. Results: Circ_0076305 was up-regulated in PTX-resistant NSCLC tissues and cells. Mechanically, circ_0076305 bound to microRNA-936 (miR-936), and miR-936 targeted transmembrane serine protease 4 (TMPRSS4). Circ_0076305 could up-regulate TMPRSS4 expression by sponging miR-936 in NSCLC cells. miR-936 knockdown or TMPRSS4 overexpression reversed the anti-tumor effects of circ_0076305 knockdown in NSCLC cells with PTX treatment. Circ_0076305 silencing increased the PTX sensitivity of xenograft tumors in vivo. Conclusion: Circ_0076305 silencing promoted PTX sensitivity by targeting miR-936/TMPRSS4 axis in NSCLC cells.

17.
World J Clin Cases ; 12(19): 3671-3675, 2024 Jul 06.
Article de Anglais | MEDLINE | ID: mdl-38994317

RÉSUMÉ

This editorial provides insights from a case report by Sun et al published in the World Journal of Clinical Cases. The case report focuses on a case where a multilocular thymic cyst (MTC) was misdiagnosed as a thymic tumor, resulting in an unnecessary surgical procedure. Both MTCs and thymic tumors are rare conditions that heavily rely on radiological imaging for accurate diagnosis. However, the similarity in their imaging presentations can lead to misinterpretation, resulting in unnecessary surgical procedures. Due to the ongoing lack of comprehensive knowledge about MTCs and thymic tumors, we offer a summary of diagnostic techniques documented in recent literature and examine potential causes of misdiagnosis. When computer tomography (CT) values surpass 20 Hounsfield units and display comparable morphology, there is a risk of misdiagnosing MTCs as thymic tumors. Employing various differential diagnostic methods like biopsy, molecular biology, multi-slice CT, CT functional imaging, positron emission tomography/CT molecular functional imaging, magnetic resonance imaging and radiomics, proves advantageous in reducing clinical misdiagnosis. A deeper understanding of these conditions requires increased attention and exploration by healthcare providers. Moreover, the continued advancement and utilization of various diagnostic methods are expected to enhance precise diagnoses, provide appropriate treatment options, and improve the quality of life for patients with thymic tumors and MTCs in the future.

18.
Front Genet ; 15: 1413641, 2024.
Article de Anglais | MEDLINE | ID: mdl-38978873

RÉSUMÉ

Background: Tumor necrosis factor receptor-associated periodic syndrome (TRAPS) is a rare autosomal dominant disorder with a low incidence in Asia. The most frequent clinical manifestations include fever, rash, myalgia, joint pain and abdominal pain. Misdiagnosis rates are high because of the clinical and genetic variability of the disease. The pathogenesis of TRAPS is complex and yet to be fully defined. Early genetic diagnosis is the key to precise treatment. Methods: In this study, a Chinese family with suspected TRAPS were analyzed by genome-wide SNP genotyping, linkage analysis and targeted sequencing for identification of mutations in causative genes. To study the pathogenicity of the identified gene mutation, we performed a conservation analysis of the mutation site and protein structure analysis. Flow cytometry was used to detect TNFRSF1A shedding and quantitative real-time PCR were used to assess the activation of unfolded protein response (UPR) in the mutation carriers and healthy individuals. Results: A typical TRAPS family history, with a pattern of autosomal dominant inheritance, led to the identification of a rare mutation in the TNFRSF1A gene (c.G374A [p.Cys125Tyr]) with unknown significance. The patient responded well to corticosteroids, and long-term therapy with colchicine effectively reduced the inflammatory attacks. No amyloid complications occurred during the 6-year follow-up. In silico protein analysis showed that the mutation site is highly conversed and the mutation prevents the formation of intrachain disulfide bonds in the protein. Despite a normal shedding of the TNFRSF1A protein from stimulated monocytes in the TRAPS patients with p.C125Y mutation, the expression of CHOP and the splicing of XBP1 was significantly higher than healthy controls, suggesting the presence of an activation UPR. Conclusion: This is the first report of a Chinese family with the rare p.C125Y mutation in TNFRSF1A. The p.C125Y mutation does not result in aberrant receptor shedding, but instead is associated with an activated UPR in these TRAPS patients, which may provide new insights into the pathogenesis of this rare mutation in TRAPS.

19.
Nutrients ; 16(13)2024 Jun 21.
Article de Anglais | MEDLINE | ID: mdl-38999734

RÉSUMÉ

Previous studies show that B vitamins and homocysteine (Hcy) may be associated with mental disorders, but the accurate causal relationship remains unclear. This study aimed to elucidate the potential causal relationship of serum B vitamins and Hcy levels with five common mental disorders through a two-sample Mendelian randomization (MR) study. In this MR analysis, 50 single-nucleotide polymorphisms (SNPs)-13 related to folate, 17 to vitamin B6, 8 to vitamin B12 and 12 to Hcy-were obtained from a large-scale Genome-Wide Association Studies (GWAS) database and employed as instrumental variables (IVs). The MR analyses were conducted using the inverse variance weighted (IVW), weighted median (WM), MR-Egger methods and sensitivity analyses were further performed to test the robustness. This MR study found a suggestive causal relationships between serum vitamin B12 levels and the risk of anxiety disorders (odds ratio (OR): 1.34, 95% confidence interval (CI): 1.01-1.78, p = 0.046) and bipolar affective disorders (OR: 1.85, 95% CI: 1.16-2.96, p = 0.010). However, folate, vitamin B6 and Hcy levels may not be causally associated with the risk of mental disorders. In conclusion, this study reveals that elevated serum vitamin B12 levels might suggestively increase the risk of anxiety and bipolar affective disorders, even though horizontal pleiotropy cannot be completely eliminated. The potential implications of our results warrant validation in larger GWAS based on diverse populations.


Sujet(s)
Étude d'association pangénomique , Homocystéine , Analyse de randomisation mendélienne , Troubles mentaux , Polymorphisme de nucléotide simple , Vitamine B12 , Complexe vitaminique B , Humains , Homocystéine/sang , Complexe vitaminique B/sang , Troubles mentaux/sang , Troubles mentaux/génétique , Vitamine B12/sang , Acide folique/sang , Facteurs de risque
20.
Small ; : e2402323, 2024 Jul 02.
Article de Anglais | MEDLINE | ID: mdl-38953346

RÉSUMÉ

Constructing dual-site catalysts consisting of atomically dispersed metal single atoms and metal atomic clusters (MACs) is a promising approach to further boost the catalytic activity for oxygen reduction reaction (ORR). Herein, a porous CoSA-AC@SNC featuring the coexistence of Co single-atom sites (CoN4) and S-coordinated Co atomic clusters (SCo6) in S, N co-doped carbon substrate is successfully synthesized by using porphyrinic metal-organic framework (Co-TPyP MOF) as the precursor. The introduction of the sulfur source creates abundant microstructural defects to anchor Co metal clusters, thus modulating the electronic structure of its surrounding carbon substrate. The synergistic effect between the two types of active sites and structural advantages, in turn, results in high ORR performance of CoSA-AC@SNC with half-wave potential (E1/2) of 0.86 V and Tafel slope of 50.17 mV dec-1. Density functional theory (DFT) calculations also support the synergistic effect between CoN4 and SCo6 by detailing the catalytic mechanism for the improved ORR performance. The as-fabricated Zn-air battery (ZAB) using CoSA-AC@SNC demonstrates impressive peak power density of 174.1 mW cm-2 and charge/discharge durability for 148 h. This work provides a facile synthesis route for dual-site catalysts and can be extended to the development of other efficient atomically dispersed metal-based electrocatalysts.

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