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1.
Liver Int ; 2024 Jul 04.
Article de Anglais | MEDLINE | ID: mdl-38963299

RÉSUMÉ

BACKGROUND AND AIMS: Lifestyle intervention is the mainstay of therapy for metabolic dysfunction-associated steatohepatitis (MASH), and liver fibrosis is a key consequence of MASH that predicts adverse clinical outcomes. The placebo response plays a pivotal role in the outcome of MASH clinical trials. Second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) microscopy with artificial intelligence analyses can provide an automated quantitative assessment of fibrosis features on a continuous scale called qFibrosis. In this exploratory study, we used this approach to gain insight into the effect of lifestyle intervention-induced fibrosis changes in MASH. METHODS: We examined unstained sections from paired liver biopsies (baseline and end-of-intervention) from MASH individuals who had received either routine lifestyle intervention (RLI) (n = 35) or strengthened lifestyle intervention (SLI) (n = 17). We quantified liver fibrosis with qFibrosis in the portal tract, periportal, transitional, pericentral, and central vein regions. RESULTS: About 20% (7/35) and 65% (11/17) of patients had fibrosis regression in the RLI and SLI groups, respectively. Liver fibrosis tended towards no change or regression after each lifestyle intervention, and this phenomenon was more prominent in the SLI group. SLI-induced liver fibrosis regression was concentrated in the periportal region. CONCLUSION: Using digital pathology, we could detect a more pronounced fibrosis regression with SLI, mainly in the periportal region. With changes in fibrosis area in the periportal region, we could differentiate RLI and SLI patients in the placebo group in the MASH clinical trial. Digital pathology provides new insight into lifestyle-induced fibrosis regression and placebo responses, which is not captured by conventional histological staging.

2.
BMC Genomics ; 25(1): 666, 2024 Jul 03.
Article de Anglais | MEDLINE | ID: mdl-38961329

RÉSUMÉ

BACKGROUND: Pruning is an important cultivation management option that has important effects on peach yield and quality. However, the effects of pruning on the overall genetic and metabolic changes in peach leaves and fruits are poorly understood. RESULTS: The transcriptomic and metabolomic profiles of leaves and fruits from trees subjected to pruning and unpruning treatments were measured. A total of 20,633 genes and 622 metabolites were detected. Compared with those in the control, 1,127 differentially expressed genes (DEGs) and 77 differentially expressed metabolites (DEMs) were identified in leaves from pruned and unpruned trees (pdLvsupdL), whereas 423 DEGs and 29 DEMs were identified in fruits from the pairwise comparison pdFvsupdF. The content of three auxin analogues was upregulated in the leaves of pruned trees, the content of all flavonoids detected in the leaves decreased, and the expression of almost all genes involved in the flavonoid biosynthesis pathway decreased. The phenolic acid and amino acid metabolites detected in fruits from pruned trees were downregulated, and all terpenoids were upregulated. The correlation analysis revealed that DEGs and DEMs in leaves were enriched in tryptophan metabolism, auxin signal transduction, and flavonoid biosynthesis. DEGs and DEMs in fruits were enriched in flavonoid and phenylpropanoid biosynthesis, as well as L-glutamic acid biosynthesis. CONCLUSIONS: Pruning has different effects on the leaves and fruits of peach trees, affecting mainly the secondary metabolism and hormone signalling pathways in leaves and amino acid biosynthesis in fruits.


Sujet(s)
Fruit , Analyse de profil d'expression de gènes , Métabolomique , Feuilles de plante , Prunus persica , Feuilles de plante/métabolisme , Feuilles de plante/génétique , Prunus persica/génétique , Prunus persica/métabolisme , Prunus persica/croissance et développement , Fruit/métabolisme , Fruit/génétique , Fruit/croissance et développement , Régulation de l'expression des gènes végétaux , Métabolome , Transcriptome , Flavonoïdes/métabolisme , Acides indolacétiques/métabolisme
3.
J Biol Chem ; : 107530, 2024 Jul 04.
Article de Anglais | MEDLINE | ID: mdl-38971310

RÉSUMÉ

Microsomal glutathione transferase 3 (MGST3) regulates eicosanoid and glutathione metabolism. These processes are associated with oxidative stress and apoptosis, suggesting that MGST3 might play a role in the pathophysiology of Alzheimer's disease (AD). Here, we report that knockdown (KD) of MGST3 in cell lines reduced the protein level of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and the resulting amyloidogenesis. Interestingly, MGST3 KD did not alter intracellular ROS level but selectively reduced the expression of apoptosis indicators which could be associated with the receptor of cysteinyl leukotrienes (cysLTs), the downstream metabolites of MGST3 in arachidonic acid pathway. We then showed that the effect of MGST3 on BACE1 was independent of cysLTs but involved a translational mechanism. Further RNA-seq analysis identified that regulator of G-protein signaling 4 (RGS4) was a target gene of MGST3. Silencing of RGS4 inhibited BACE1 translation and prevented MGST3 KD-mediated reduction of BACE1. The potential mechanism was related to AKT activity, as the protein level of phosphorylated AKT (p-AKT) was significantly reduced by silencing of MGST3 and RGS4, and the AKT inhibitor abolished the effect of MGST3/RGS4 on p-AKT and BACE1. Together, MGST3 regulated amyloidogenesis by controlling BACE1 protein expression, which was mediated by RGS4 and downstream AKT signaling pathway.

4.
J Geriatr Cardiol ; 21(6): 642-650, 2024 Jun 28.
Article de Anglais | MEDLINE | ID: mdl-38973828

RÉSUMÉ

OBJECTIVE: To investigate three features of dietary cooking oil intake, namely, the consumption, cooking style, and composition of fatty acids in relation to several cardiometabolic measurements in an elderly Chinese population. METHODS: The elderly (≥ 65 years) participants for this study were recruited from two community health centers in the urban area of Shanghai. A questionnaire was administered to collect information on dietary oil consumption (low, medium and high) and cooking styles (fry or stir-fry vs. others) and the composition of fatty acids (poly-unsaturated vs. mono-unsaturated). The cardiometabolic measurements included anthropometry, blood pressure, fasting plasma glucose and serum lipids. RESULTS: The 1186 study participants had a mean age of 70.9 ± 5.4 years. The mean dietary oil consumption was 35.0 g/d, being low (< 25 g/d), medium (25-49 g/d) and high (≥ 50 g/d) in 485,467 and 234 participants, respectively. The proportion of the fry or stir-fry cooking style and oils rich in mono-unsaturated fatty acids was 30.4% and 27.4%, respectively. Both before and after adjustment for sex, age, current smoking and alcohol intake, dietary oil consumption was significantly (P ≤ 0.02) and positively associated with the prevalence of treated hypertension and fasting plasma glucose concentration. With similar adjustments as above and additional adjustment for dietary oil consumption, the fry or stir-fry cooking style was significantly (P ≤ 0.048) and positively associated with body mass index, but inversely with systolic and diastolic blood pressure and serum low-density lipoprotein cholesterol, and the dietary intake of oils rich in mono-unsaturated fat acids was significantly (P ≤ 0.02) and positively associated with diastolic blood pressure, serum triglycerides, total cholesterol and low-density lipoprotein cholesterol, and the prevalence of hypertriglyceridemia and hypercholesterolemia. CONCLUSIONS: This study showed that both the consumption and composition of fatty acids of the dietary oils mattered with regard to several cardiometabolic measurements in an elderly Chinese population.

5.
Mar Drugs ; 22(6)2024 Jun 06.
Article de Anglais | MEDLINE | ID: mdl-38921573

RÉSUMÉ

Three new cyclic lipopeptides, olenamidonins A-C (1-3), in addition to two previously reported metabolites (4 and 5), were accumulated in the ΔdtxRso deletion mutant of deepsea-derived Streptomyces olivaceus SCSIO 1071. The structures of these cyclic lipopeptides were determined by a combination of spectroscopic methods and circular dichroism (CD) measurement. The antibacterial assay results showed that compounds 1-5 displayed different degrees of growth inhibition against multidrug-resistant (MDR) bacterial strains Enterococcus faecalis CCARM 5172 and Enterococcus faecium CCARM 5203 with minimum inhibitory concentrations (MICs) of 1.56-6.25 µg/mL.


Sujet(s)
Antibactériens , Enterococcus faecalis , Lipopeptides , Tests de sensibilité microbienne , Peptides cycliques , Streptomyces , Streptomyces/génétique , Streptomyces/métabolisme , Lipopeptides/pharmacologie , Lipopeptides/isolement et purification , Antibactériens/pharmacologie , Antibactériens/composition chimique , Antibactériens/isolement et purification , Enterococcus faecalis/effets des médicaments et des substances chimiques , Peptides cycliques/pharmacologie , Peptides cycliques/composition chimique , Peptides cycliques/isolement et purification , Enterococcus faecium/effets des médicaments et des substances chimiques , Multirésistance bactérienne aux médicaments/effets des médicaments et des substances chimiques , Protéines bactériennes/génétique
6.
Environ Sci Technol ; 2024 Jun 25.
Article de Anglais | MEDLINE | ID: mdl-38916160

RÉSUMÉ

The widespread ozone (O3) pollution is extremely hazardous to human health and ecosystems. Catalytic decomposition into O2 is the most promising method to eliminate ambient O3, while the fast deactivation of catalysts under humid conditions remains the primary challenge for their application. Herein, we elaborately developed a splendidly active and stable Mn-based catalyst with double hydrophobic protection of active carbon (AC) and CeO2 (CeMn@AC), which possessed abundant interfacial oxygen vacancies and excellent desorption of peroxide intermediates (O22-). Under extremely humid (RH = 90%) conditions and a high space velocity of 1200 L h-1 g-1, the optimized CeMn@AC achieved nearly 100% O3 conversion (140 h) at 5 ppm, showing unprecedented catalytic activity and moisture resistance toward O3 decomposition. In situ DRIFTS and theory calculations confirmed that the exceptional moisture resistance of CeMn@AC was ascribed to the double protection effect of AC and CeO2, which cooperatively prevented the competitive adsorption of H2O molecules and their accumulation on the active sites of MnO2. AC provided a hydrophobic reaction environment, and CeO2 further alleviated moisture deterioration of the MnO2 particles exposed on the catalyst surface via the moisture-resistant oxygen vacancies of MnO2-CeO2 crystal boundaries. This work offers a simple and efficient strategy for designing moisture-resistant materials and facilitates the practical application of the O3 decomposition catalysts in various environments.

7.
Microbiol Spectr ; : e0354923, 2024 Jun 25.
Article de Anglais | MEDLINE | ID: mdl-38916335

RÉSUMÉ

In recent years, most studies on the gut microbiome have primarily focused on feces samples, leaving the microbial communities in the intestinal mucosa relatively unexplored. To address this gap, our study employed shotgun metagenomics to analyze the microbial compositions in normal rectal mucosa and matched feces from 20 patients with colonic polyps. Our findings revealed a pronounced distinction of the microbial communities between these two sample sets. Compared with feces, the mucosal microbiome contains fewer genera, with Burkholderia being the most discriminating genus between feces and mucosa, highlighting its significant influence on the mucosa. Furthermore, based on the microbial classification and KEGG Orthology (KO) annotation results, we explored the association between rectal mucosal microbiota and factors such as age, gender, BMI, and polyp risk level. Notably, we identified novel biomarkers for these phenotypes, such as Clostridium ramosum and Enterobacter cloacae in age. The mucosal microbiota showed an enrichment of KO pathways related to sugar transport and short chain fatty acid metabolism. Our comprehensive approach not only bridges the knowledge gap regarding the microbial community in the rectal mucosa but also underscores the complexity and specificity of microbial interactions within the human gut, particularly in the Chinese population. IMPORTANCE: This study presents a system-level map of the differences between feces and rectal mucosal microbial communities in samples with colorectal cancer risk. It reveals the unique microecological characteristics of rectal mucosa and its potential influence on health. Additionally, it provides novel insights into the role of the gut microbiome in the pathogenesis of colorectal cancer and paves the way for the development of new prevention and treatment strategies.

8.
Aging Dis ; 2024 May 28.
Article de Anglais | MEDLINE | ID: mdl-38916730

RÉSUMÉ

Tauopathies, a group of neurodegenerative disorders, are characterized by disrupted homeostasis of the microtubule binding protein tau. Nogo-A mainly hinders axonal growth and development in neurons, but the underlying mechanism of tau vulnerability has not been determined. Here, to gain more comprehensive insights into the impact of Nogo-A on tau protein expression, we showed that Nogo-A induces tau hyperphosphorylation, synapse loss and cognitive dysfunction. Consistent with the biological function of tau hyperphosphorylation, Nogo-A-induced tau hyperphosphorylation altered microtubule stability, which causes synaptic dysfunction. Mechanistically, Nogo-A-induced tau hyperphosphorylation was abolished by the Nogo-A antagonist NEP1-40 in primary neurons. Surprisingly, downregulation of Nogo-A in the hippocampus of AD mice (hTau. P301S) inhibited tau hyperphosphorylation at the AT8, Thr181, The231 and Ser404 sites and rescued synaptic loss and cognitive impairment in AD mice. Our findings exhibit a strong degree of consistency with Nogo-A-induced tauopathy vulnerability, reinforcing the coherence and reliability of our research. Furthermore, in mice, Nogo-A increases tauopathy vulnerability to exacerbate AD progression via ROCK/AKT/GSK3ß signaling. Together, our findings provide new insight into the function of Nogo-A in regulating tau hyperphosphorylation and reveal an effective treatment strategy for tauopathies.

9.
J Phys Chem B ; 128(26): 6272-6282, 2024 Jul 04.
Article de Anglais | MEDLINE | ID: mdl-38904939

RÉSUMÉ

Coiled-coil protein origami (CCPO) is a modular strategy for the de novo design of polypeptide nanostructures. It represents a type of modular design based on pairwise-interacting coiled-coil (CC) units with a single-chain protein programmed to fold into a polyhedral cage. However, the mechanisms underlying the self-assembly of the protein tetrahedron are still not fully understood. In the present study, 18 CCPO cages with three different topologies were modeled in silico. Then, molecular dynamics simulations and CC parameters were calculated to characterize the dynamic properties of protein tetrahedral cages at both the local and global levels. Furthermore, a deformed CC unit was redesigned, and the stability of the new cage was significantly improved.


Sujet(s)
Simulation de dynamique moléculaire , Protéines , Protéines/composition chimique , Nanostructures/composition chimique , Conformation des protéines
10.
Redox Biol ; 74: 103236, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38875958

RÉSUMÉ

The pathogenesis of epilepsy remains unclear; however, a prevailing hypothesis suggests that the primary underlying cause is an imbalance between neuronal excitability and inhibition. Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme in the pentose phosphate pathway, which is primarily involved in deoxynucleic acid synthesis and antioxidant defense mechanisms and exhibits increased expression during the chronic phase of epilepsy, predominantly colocalizing with neurons. G6PD overexpression significantly reduces the frequency and duration of spontaneous recurrent seizures. Furthermore, G6PD overexpression enhances signal transducer and activator of transcription 1 (STAT1) expression, thus influencing N-methyl-d-aspartic acid receptors expression, and subsequently affecting seizure activity. Importantly, the regulation of STAT1 by G6PD appears to be mediated primarily through reactive oxygen species signaling pathways. Collectively, our findings highlight the pivotal role of G6PD in modulating epileptogenesis, and suggest its potential as a therapeutic target for epilepsy.


Sujet(s)
Glucose 6-phosphate dehydrogenase , Espèces réactives de l'oxygène , Récepteurs du N-méthyl-D-aspartate , Facteur de transcription STAT-1 , Crises épileptiques , Glucose 6-phosphate dehydrogenase/métabolisme , Glucose 6-phosphate dehydrogenase/antagonistes et inhibiteurs , Glucose 6-phosphate dehydrogenase/génétique , Espèces réactives de l'oxygène/métabolisme , Animaux , Récepteurs du N-méthyl-D-aspartate/métabolisme , Récepteurs du N-méthyl-D-aspartate/génétique , Crises épileptiques/métabolisme , Crises épileptiques/traitement médicamenteux , Facteur de transcription STAT-1/métabolisme , Épilepsie/métabolisme , Épilepsie/traitement médicamenteux , Épilepsie/génétique , Transduction du signal/effets des médicaments et des substances chimiques , Souris , Humains , Neurones/métabolisme , Mâle , Rats , Modèles animaux de maladie humaine
11.
Anesth Analg ; 2024 Jun 13.
Article de Anglais | MEDLINE | ID: mdl-38870069

RÉSUMÉ

BACKGROUND: Increasing the temperature of intrathecal local anesthetics has been shown to increase the speed of onset and block height of spinal anesthesia. However, how this influences dose requirement has not been fully quantified. The aim of this study was to determine and compare the effective dose for anesthesia for cesarean delivery in 50% of patients (ED50) of intrathecal bupivacaine given at temperatures of 37 °C (body temperature) or 24 °C (room temperature). METHODS: Eighty healthy parturients having elective cesarean delivery under combined spinal-epidural anesthesia were randomly assigned to receive intrathecal hyperbaric bupivacaine stored at 37 °C (body temperature group) or 24 °C (room temperature group). The first subject in each group received a bupivacaine dose of 10 mg. The dose for each subsequent subject in each group was varied with an increment or decrement of 1 mg based on the response (effective or noneffective) of the previous subject. Patients for whom the dose was noneffective received epidural supplementation after data collection with lidocaine 2% as required until anesthesia was sufficient for surgery. Values for ED50 were calculated using modified up-down sequential analysis with probit analysis applied as a backup sensitivity analysis. These values were compared and the relative mean potency was calculated. RESULTS: The ED50 (mean [95% confidence interval, CI]) of intrathecal hyperbaric bupivacaine was lower in the body temperature group (6.7 [5.7-7.6] mg) compared with the room temperature group (8.1 [7.7-8.6] mg) (P < .05). The relative potency ratio for intrathecal bupivacaine for the room temperature group versus the body temperature group was 0.84 (95% CI, 0.77-0.93). CONCLUSIONS: Warming hyperbaric bupivacaine to body temperature reduced the dose requirement for spinal anesthesia for cesarean delivery by approximately 16% (95% CI, 7%-23%).

12.
Article de Anglais | MEDLINE | ID: mdl-38842991

RÉSUMÉ

BACKGROUND: Drug-coated balloon (DCB) angioplasty seems a safe and effective option for specific de novo coronary lesions. However, the beneficial effect of intravascular ultrasound (IVUS)-guided DCB angioplasty in de novo lesions remains uncertain. OBJECTIVES: This study aimed to assess the benefits of IVUS guidance over angiography guidance during DCB angioplasty in de novo coronary lesions. METHODS: A total of 260 patients with high bleeding risk who had a de novo coronary lesion (reference vessel diameter 2.0-4.0 mm, and lesion length ≤15 mm) were randomly assigned to either an IVUS-guided or an angioplasty-guided DCB angioplasty group. The primary endpoint was in-segment late lumen loss (LLL) at 7 months after procedure. The secondary endpoint was target vessel failure at 6 months. RESULTS: A total of 2 patients in the angiography-guided group and 7 patients in the IVUS-guided group underwent bailout stent implantation (P = 0.172). The primary endpoint of 7-month LLL was 0.03 ± 0.52 mm with angiography guidance vs -0.10 ± 0.34 mm with IVUS guidance (mean difference 0.14 mm; 95% CI: 0.02-0.26; P = 0.025). IVUS guidance was also associated with a larger 7-month minimal lumen diameter (2.06 ± 0.62 mm vs 1.75 ± 0.63 mm; P < 0.001) and a smaller diameter stenosis (28.15% ± 13.88% vs 35.83% ± 17.69%; P = 0.001) compared with angiography guidance. Five target vessel failures occurred at 6 months, with 4 (3.1%) in the angiography-guided group and 1 (0.8%) in the IVUS-guided group (P = 0.370). CONCLUSIONS: This study demonstrated that IVUS-guided DCB angioplasty is associated with a lower LLL in patients with a de novo coronary lesion compared with angiography guidance. (Intravascular Ultrasound Versus Angiography Guided Drug-Coated Balloon [ULTIMATE-III]; NCT04255043).

13.
Sci Total Environ ; 943: 173748, 2024 Sep 15.
Article de Anglais | MEDLINE | ID: mdl-38857793

RÉSUMÉ

In many coastal cities around the world, continuing water degradation threatens the living environment of humans and aquatic organisms. To assess and control the water pollution situation, this study estimated the Biochemical Oxygen Demand (BOD) concentration of Hong Kong's marine waters using remote sensing and an improved machine learning (ML) method. The scheme was derived from four ML algorithms (RBF, SVR, RF, XGB) and calibrated using a large amount (N > 1000) of in-situ BOD5 data. Based on labeled datasets with different preprocessing, i.e., the original BOD5, the log10(BOD5), and label distribution smoothing (LDS), three types of models were trained and evaluated. The results highlight the superior potential of the LDS-based model to improve BOD5 estimate by dealing with imbalanced training dataset. Additionally, XGB and RF outperformed RBF and SVR when the model was developed using log10(BOD5) or LDS(BOD5). Over two decades, the BOD5 concentration of Hong Kong marine waters in the autumn (Sep. to Nov.) shows a downward trend, with significant decreases in Deep Bay, Western Buffer, Victoria Harbour, Eastern Buffer, Junk Bay, Port Shelter, and the Tolo Harbour and Channel. Principal component analysis revealed that nutrient levels emerged as the predominant factor in Victoria Harbour and the interior of Deep Bay, while chlorophyll-related and physical parameters were dominant in Southern, Mirs Bay, Northwestern, and the outlet of Deep Bay. LDS provides a new perspective to improve ML-based water quality estimation by alleviating the imbalance in the labeled dataset. Overall, the remotely sensed BOD5 can offer insight into the spatial-temporal distribution of organic matter in Hong Kong coastal waters and valuable guidance for the pollution control.


Sujet(s)
Surveillance de l'environnement , Apprentissage machine , Eau de mer , Hong Kong , Surveillance de l'environnement/méthodes , Eau de mer/composition chimique , Technologie de télédétection , Analyse de la demande biologique en oxygène , Pollution de l'eau/statistiques et données numériques , Pollution de l'eau/analyse , Polluants chimiques de l'eau/analyse
14.
Apoptosis ; 2024 Jun 17.
Article de Anglais | MEDLINE | ID: mdl-38886311

RÉSUMÉ

Disulfidptosis is a novel form of cell death that is distinguishable from established programmed cell death pathways such as apoptosis, pyroptosis, autophagy, ferroptosis, and oxeiptosis. This process is characterized by the rapid depletion of nicotinamide adenine dinucleotide phosphate (NADPH) in cells and high expression of solute carrier family 7 member 11 (SLC7A11) during glucose starvation, resulting in abnormal cystine accumulation, which subsequently induces andabnormal disulfide bond formation in actin cytoskeleton proteins, culminating in actin network collapse and disulfidptosis. This review aimed to summarize the underlying mechanisms, influencing factors, comparisons with traditional cell death pathways, associations with related diseases, application prospects, and future research directions related to disulfidptosis.

15.
Nat Sci Sleep ; 16: 751-760, 2024.
Article de Anglais | MEDLINE | ID: mdl-38894978

RÉSUMÉ

Purpose: To investigate sleep problems in children with self-limited epilepsy with central temporal spiking (SeLECTS) and to assess the relationship between sleep problems and attention network dysfunction. Patients and methods: 107 children 6-14 years of age with SeLECTS and 90 age- and sex-matched healthy controls were recruited for this study. The sleep status of these participants was evaluated using the Children's Sleep Habits Questionnaire (CSHQ), while attentional network function was assessed with the attention network function test (ANT). Results: Together, these analyses revealed that children with SeLECTS exhibited higher total CSHQ scores and sleep disorder incidence relative to healthy controls (P< 0.001). Children with SeLECTS had higher scores in delayed sleep onset, sleep duration, night awakenings, parasomnias, daytime sleepiness and sleep anxiety (P<0.01). Total CSHQ scores were negatively correlated with average ANT correct rates (ρ= -0.253, P<0.01), while they were positively correlated with total reaction time (ρ=0.367, P<0.01) and negatively correlated with the efficiency of the alerting and executive control networks (ρ=-0.344 P<0.01; ρ=-0.418 P<0.01). Conclusion: Children with SeLECTS face a higher risk of experiencing sleep disorders relative to age-matched healthy children, while also demonstrating that the magnitude of the impairment of attentional network function in these children is positively correlated with sleep disorder severity. Thus, the prognosis and quality of life of children with SeLECTS can be improved by interventions addressing sleep disorders.

16.
FASEB J ; 38(12): e23723, 2024 Jun 30.
Article de Anglais | MEDLINE | ID: mdl-38865198

RÉSUMÉ

Hypoxia-induced inflammation and apoptosis are important pathophysiological features of heat stroke-induced acute kidney injury (HS-AKI). Hypoxia-inducible factor (HIF) is a key protein that regulates cell adaptation to hypoxia. HIF-prolyl hydroxylase inhibitor (HIF-PHI) stabilizes HIF to increase cell adaptation to hypoxia. Herein, we reported that HIF-PHI pretreatment significantly improved renal function, enhanced thermotolerance, and increased the survival rate of mice in the context of HS. Moreover, HIF-PHI could alleviate HS-induced mitochondrial damage, inflammation, and apoptosis in renal tubular epithelial cells (RTECs) by enhancing mitophagy in vitro and in vivo. By contrast, mitophagy inhibitors Mdivi-1, 3-MA, and Baf-A1 reversed the renoprotective effects of HIF-PHI. Mechanistically, HIF-PHI protects RTECs from inflammation and apoptosis by enhancing Bcl-2 adenovirus E18 19-kDa-interacting protein 3 (BNIP3)-mediated mitophagy, while genetic ablation of BNIP3 attenuated HIF-PHI-induced mitophagy and abolished HIF-PHI-mediated renal protection. Thus, our results indicated that HIF-PHI protects renal function by upregulating BNIP3-mediated mitophagy to improve HS-induced inflammation and apoptosis of RTECs, suggesting HIF-PHI as a promising therapeutic agent to treat HS-AKI.


Sujet(s)
Atteinte rénale aigüe , Coup de chaleur , Protéines membranaires , Mitophagie , Inhibiteurs de prolyle hydroxylases , Animaux , Mâle , Souris , Atteinte rénale aigüe/traitement médicamenteux , Atteinte rénale aigüe/métabolisme , Atteinte rénale aigüe/anatomopathologie , Atteinte rénale aigüe/étiologie , Apoptose/effets des médicaments et des substances chimiques , Coup de chaleur/complications , Coup de chaleur/traitement médicamenteux , Coup de chaleur/métabolisme , Protéines membranaires/métabolisme , Protéines membranaires/génétique , Souris de lignée C57BL , Protéines mitochondriales/métabolisme , Protéines mitochondriales/génétique , Mitophagie/effets des médicaments et des substances chimiques , Inhibiteurs de prolyle hydroxylases/pharmacologie , Inhibiteurs de prolyle hydroxylases/usage thérapeutique
18.
J Clin Ultrasound ; 2024 Jun 06.
Article de Anglais | MEDLINE | ID: mdl-38840562

RÉSUMÉ

Non-Hodgkin lymphoma (NHL) is a highly aggressive malignant tumor arising in lymph nodes or extra-nodal lymphoid tissues, with an incidence of 8.3 per million. It accounts for approximately 7% of childhood and adolescent malignancies, second only to leukemia and brain tumors. Despite the gastrointestinal tract being the most common extra-nodal site involved by lymphoma, primary intestinal lymphoma (PIL) is rare and typically affects middle-aged men without specific clinical symptoms. Here, we present the case of a 2-year-old child indicative of PIL with the informed consent of the parents.

19.
Diabetes Metab Syndr Obes ; 17: 2243-2257, 2024.
Article de Anglais | MEDLINE | ID: mdl-38854443

RÉSUMÉ

Background: Perioperative anesthetic management of patients with diabetic foot undergoing surgical treatment is challenging due to their poor cardiovascular health status. According to previous literature, general anesthesia and peripheral nerve block have their own advantages and disadvantages for such patients. We reported the effect of these two anesthesia techniques on perioperative hemodynamics and prognosis in these patients. Methods: This study employed a prospective randomized controlled design, where patients meeting the inclusion criteria were assigned to two groups: the general anesthesia group (GA group) and the peripheral nerve block group (PNB group). The primary outcomes were the differences in intraoperative hemodynamic stability and the incidence of postoperative complications between the two groups. The second outcomes were postoperative numerical rating scale scores, analgesic drug remedies, postoperative sleep conditions monitored by sleep bracelets and health status assessed by EQ-5D-5 L scores. Results: One hundred and nine subjects were enrolled in this study, including 54 in the GA group and 55 in the PNB group. The baseline parameters of the two groups were comparable. The GA group exhibited a significantly higher incidence of hypotension, and Colloid intake and total fluid intake were significantly higher in the GA group than in the PNB group. Additionally, a larger proportion of patients in the GA group. The scores of postoperative pain during the 48 hours after surgery were significantly higher, and more patients needed tramadol for postoperative analgesia during the 24 h after surgery in the GA group than in the PNB group. Patients in the PNB group slept better, first feeding time, earlier out-of-bed activity and earlier discharge from the hospital, compared to the GA group. However, there was no obvious difference in postoperative complications between the two groups except pharyngeal pain. Conclusion: Peripheral nerve block is a better option in patients with diabetes undergoing elective below-knee surgery than general anesthesia.

20.
BMJ Open ; 14(6): e088312, 2024 Jun 05.
Article de Anglais | MEDLINE | ID: mdl-38839394

RÉSUMÉ

BACKGROUND: Little is known about the impact of an ecological dynamics (ED) intervention (EDI) on primary school children's physical literacy and well-being in the Hong Kong context. The aim of this project is to introduce a physical literacy and well-being framework through an EDI that allows primary school children to develop good physical activity (PA) and daily behavioural habits. METHODS AND ANALYSIS: A four-arm (cluster) randomised controlled trial will be conducted to examine the effect of EDI on physical literacy and well-being in primary schools located in each of the 18 administrative districts of Hong Kong. Four classes in senior primary students (grade 4) at each school will be randomly assigned to the four different conditions. These participating schools will be equipped with sit-stand desks, PA recess facility and equipment, and sleep pillows. The research team will adopt both objective measures (aerobic fitness, fundamental movement skills, daily behaviour-physical activity and cognitive function) and self-reported measures (perceived physical literacy, quality of life, sleep quality) covering the elements and domains of physical literacy and well-being to examine the effects of EDIs at four time points, including baseline assessment, 3 months after intervention, postintervention and 3-month follow-up assessment. One-way analyses of variance (ANOVAs) will be used to test for differences in the baseline characteristics of participants between groups. Repeated measure ANOVAs and MANCOVA, with time (baseline, after intervention and follow-up) as within-subjects factor, and intervention group as between-subjects factors, will be used to evaluate the effects of different interventions on the students' physical literacy and well-being. A Bonferonni correction to the p value will be calculated to adjust for multiple tests. ETHICS AND DISSEMINATION: Ethical approval was sought from the Joint CUHK-NTEC Clinical Research Ethics Committee in Hong Kong (CREC Ref.No.:2024.027). The finding of this study will be disseminated via peer-reviewed journals, international conference presentations and academic lectures. For secondary analysis of the data, please contact the corresponding author for permission. TRIAL REGISTRATION NUMBER: ISRCTN84025914.


Sujet(s)
Exercice physique , Qualité de vie , Établissements scolaires , Humains , Hong Kong , Enfant , Promotion de la santé/méthodes , Femelle , Essais contrôlés randomisés comme sujet , Mâle , Compétence informationnelle en santé , Aptitude physique , Étudiants/psychologie , Services de santé scolaire
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