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1.
Clin Ophthalmol ; 18: 2397-2406, 2024.
Article de Anglais | MEDLINE | ID: mdl-39221077

RÉSUMÉ

Purpose: To compare the interocular symmetry and investigate the intermachine reproducibility of optic disc and macular data measured by spectral-domain high-definition optical coherence tomography (HD-OCT) Cirrus HD-OCT 4000 and HD-OCT 5000 from healthy subjects. Patients and Methods: Forty-three volunteers were examined with both HD-OCT 4000 and HD-OCT 5000 at the same visit. Optic nerve head (ONH) and macular data were acquired using ONH Cube 200×200 scans and macular volume cube 512×128 scans, respectively. Results: The average age of the participants was 33 ± 8.6 years. Interocular OCT parameters of ONH and macula showed a high correlation between the right and left eyes regardless of HD-OCT models, displaying a low coefficient of variation (CV). However, the average retinal nerve fiber layer (RNFL) was thicker (96.67±11.19µm vs 95.3±10.89µm, p<0.01), and the average central subfield thickness (261.51±17.45µm vs 262.51±17.39 µm, p<0.01) and cube average thickness (283.91± 13.59µm vs 286.55±13.09µm, p<0.05) were thinner when measured by Cirrus 4000 compared to 5000. Intermachine reproducibility and reliability of RNFL and macular parameters exhibited a high intraclass correlation coefficient (ICC) (0.985) and low CV (2.4%). Ganglion cell-inner plexiform layer (GCIPL) measured by two OCT models showed similar values with an average thickness of 85 µm and had high intermachine reproducibility with high ICC (0.993) and low CV (1.2%). Conclusion: High interocular symmetry was observed across both HD-OCT models. Intermachine reproducibility for RNFL and all macular parameters was also high. GCIPL showed minimal intermachine differences with high reproducibility and reliability. Thus, the results imply that GCIPL values measured by two Cirrus OCT models may be used interchangeably.

2.
Environ Sci Technol ; 2024 Aug 15.
Article de Anglais | MEDLINE | ID: mdl-39146316

RÉSUMÉ

Perfluorohexanesulfonic acid (PFHxS), an emerging short-chain per- and polyfluoroalkyl substance, has been frequently detected in aquatic environments. Adverse outcome pathway studies have shown that perfluorinated compounds impair lipid homeostasis through peroxisome proliferator activated receptors (PPARs). However, many of these studies were performed at high concentrations and may thus be a result of overt toxicity. To better characterize the molecular and key events of PFHxS to biota, early life-stage zebrafish (Danio rerio) were exposed to concentrations detected in the environment (0.01, 0.1, 1, and 10 µg/L). Lipidomic and transcriptomic evaluations were integrated to predict potential molecular targets. PFHxS significantly impaired lipid homeostasis by the dysregulation of glycerophospholipids, fatty acyls, glycerolipids, sphingolipids, prenol lipids, and sterol lipids. Informatic analyses of the lipidome and transcriptome indicated alterations of the PPAR signaling pathway, with downstream changes to retinol, linoleic acid, and glycerophospholipid metabolism. To assess the role of PPARs, potential binding of PFHxS to PPARs was predicted and animals were coexposed to a PPAR antagonist (GW6471). Molecular simulation indicated PFHxS had a 27.1% better binding affinity than oleic acid, an endogenous agonist of PPARα. Antagonist coexposures rescued impaired glycerophosphocholine concentrations altered by PFHxS. These data indicate PPARα activation may be an important molecular initiating event for PFHxS.

3.
Angew Chem Int Ed Engl ; : e202412643, 2024 Aug 05.
Article de Anglais | MEDLINE | ID: mdl-39101718

RÉSUMÉ

While metal nanoparticles (NPs) have demonstrated their great potential in catalysis, introducing chiral microenvironment around metal NPs to achieve efficient conversion and high enantioselectivity remains a long-standing challenge. In this work, tiny Rh NPs, modified by chiral diene ligands (Lx) bearing diverse functional groups, are incorporated into a covalent organic framework (COF) for the asymmetric 1,4-addition reactions between arylboronic acids and nitroalkenes. Though Rh NPs hosted in the COF are inactive, decorating Rh NPs with Lx creates the active Rh-Lx interface and induces high activity. Moreover, chiral microenvironment modulation around Rh NPs by altering the groups on chiral diene ligands greatly optimizes the enantioselectivity (up to 95.6% ee). Mechanistic investigations indicate that the formation of hydrogen-bonding interaction between Lx and nitroalkenes plays critical roles in the resulting enantioselectivity. This work highlights the significance of chiral microenvironment modulation around metal NPs by chiral ligand decoration for heterogeneous asymmetric catalysis.

4.
J Virol ; : e0133524, 2024 Aug 30.
Article de Anglais | MEDLINE | ID: mdl-39212385

RÉSUMÉ

Ubiquitin modification of viral proteins to degrade or regulate their function is one of the strategies of the host to resist viral infection. Here, we report that ubiquitin protein ligase E3C (UBE3C), an E3 ubiquitin ligase, displayed inhibitory effects on EV-A71 replication. UBE3C knockdown resulted in increased viral protein levels and virus titers, whereas overexpression of UBE3C reduced EV-A71 replication. To explore the mechanism by which UBE3C affected EV-A71 infection, we found that the C-terminal of UBE3C bound to 2C protein and facilitated K33/K48-linked ubiquitination degradation of 2C K268. Moreover, UBE3C lost its ability to degrade 2C K268R and had a diminished inhibitory impact against the replication of recombinant EV-A71-FY-2C K268R. In addition, UBE3C also promoted ubiquitination degradation of the 2C protein of CVB3 and CVA16 and inhibited viral replication. Thus, our findings reveal a novel mechanism that UBE3C acts as an enterovirus host restriction factor, including EV-A71, by targeting the 2C protein. IMPORTANCE: The highly conserved 2C protein of EV-A71 is a multifunctional protein and plays a key role in the replication cycle. In this study, we demonstrated for the first time that UBE3C promoted the degradation of 2C K268 via K33/K48-linked ubiquitination, thereby inhibiting viral proliferation. Our findings advance the knowledge related to the roles of 2C in EV-A71 virulence and the ubiquitination pathway in the host restriction of EV-A71 infection.

5.
Ecotoxicol Environ Saf ; 284: 116914, 2024 Aug 24.
Article de Anglais | MEDLINE | ID: mdl-39182281

RÉSUMÉ

Selenium nanoparticles (SeNPs) have been used as a potential alternative to other forms of selenium in nutritional supplements for the treatment and prevention of inflammatory and oxidative stress-related diseases. Zearalenone (ZEA) is a foodborne mycotoxin present in grains that poses a health threat. Here, we investigated the adverse impacts of ZEA on intestinal homeostasis and explored the protective effects of probiotic-synthesized SeNPs against its damage. Results showed that ZEA reduced mucin and tight junction proteins expression in jejunum, induced inflammatory process and oxidative stress which in turn increased intestinal permeability in mice. ZEA-induced intestinal toxicity was further verified in vitro. Intracellular redox imbalance triggered endoplasmic reticulum (ER) stress in intestinal epithelial cells, which caused structural damage to the ER. Remarkably, SeNPs exhibited a counteractive effect by inducing a decrease in intracellular levels of Inositol 1,4,5-trisphosphate (IP3) and Ca2+, along with a reduction in the expression level of IP3 receptor. SeNPs effectively mitigated ZEA-induced ER stress was related to the increased activity of selenium-dependent antioxidant enzymes and the expression of ER-resident selenoproteins. Furthermore, SeNPs significantly inhibited the activation of PERK/eIF2α/ATF4/CHOP pathway in vitro and in vivo. In addition, SeNPs effectively reversed ZEA-induced gut microbiota dysbiosis and increased the abundance of short-chain fatty acid-producing beneficial bacteria (Alloprevotella and Muribaculaceae). The Spearman correlation analysis suggested that the structure of gut microbiota was closely related to the SeNPs attenuation of ZEA-induced intestinal toxicity. This study provides new insights into ZEA-induced intestinal toxicity and identifies a novel potential nutrient SeNPs to overcome adverse effects.

6.
BMC Bioinformatics ; 25(1): 269, 2024 Aug 20.
Article de Anglais | MEDLINE | ID: mdl-39164632

RÉSUMÉ

BACKGROUND: Fluorescence microscopy (FM) is an important and widely adopted biological imaging technique. Segmentation is often the first step in quantitative analysis of FM images. Deep neural networks (DNNs) have become the state-of-the-art tools for image segmentation. However, their performance on natural images may collapse under certain image corruptions or adversarial attacks. This poses real risks to their deployment in real-world applications. Although the robustness of DNN models in segmenting natural images has been studied extensively, their robustness in segmenting FM images remains poorly understood RESULTS: To address this deficiency, we have developed an assay that benchmarks robustness of DNN segmentation models using datasets of realistic synthetic 2D FM images with precisely controlled corruptions or adversarial attacks. Using this assay, we have benchmarked robustness of ten representative models such as DeepLab and Vision Transformer. We find that models with good robustness on natural images may perform poorly on FM images. We also find new robustness properties of DNN models and new connections between their corruption robustness and adversarial robustness. To further assess the robustness of the selected models, we have also benchmarked them on real microscopy images of different modalities without using simulated degradation. The results are consistent with those obtained on the realistic synthetic images, confirming the fidelity and reliability of our image synthesis method as well as the effectiveness of our assay. CONCLUSIONS: Based on comprehensive benchmarking experiments, we have found distinct robustness properties of deep neural networks in semantic segmentation of FM images. Based on the findings, we have made specific recommendations on selection and design of robust models for FM image segmentation.


Sujet(s)
Référenciation , Traitement d'image par ordinateur , Microscopie de fluorescence , , Microscopie de fluorescence/méthodes , Référenciation/méthodes , Traitement d'image par ordinateur/méthodes , Sémantique , Apprentissage profond , Algorithmes , Humains
7.
J Ophthalmol ; 2024: 6685092, 2024.
Article de Anglais | MEDLINE | ID: mdl-39041005

RÉSUMÉ

This study aimed to evaluate the efficacy and safety of intravitreal dexamethasone implants in the treatment of ocular toxocariasis (OT). A retrospective analysis was performed on 6 cases in which laboratory tests diagnosed OT. All patients were administered with intravitreal dexamethasone implants with or without vitrectomy. The average follow-up time was 19.7 months. All operated eyes achieved anatomic success, and all patients' visual acuity was improved. Five of these six had a visual acuity of 20/100, and three had final acuity of 20/40 or even better. Intravitreal dexamethasone implants can be used to treat different types of OT, which not only effectively control inflammation and improve the patient's vision but also reduce the use of systemic glucocorticoids.

8.
World J Clin Cases ; 12(19): 3676-3683, 2024 Jul 06.
Article de Anglais | MEDLINE | ID: mdl-38994301

RÉSUMÉ

Otogenic vertigo is a common disorder that affects the vestibular system, which often results in considerable discomfort and impaired daily functioning. Traditional Chinese medicine (TCM), including acupuncture and moxibustion, has been historically utilized to manage the symptoms of vertigo. However, the effectiveness and methodology of these treatments have rarely been investigated in the medical literature. This study reviews the existing literature on the point selection, method, and therapeutic effect of acupuncture and moxibustion to provide a reference for the TCM treatment of otogenic vertigo. A literature search was performed using the PubMed search engine. The terms used included otogenic vertigo, acupuncture treatment, and acupuncture point selection. A total of 34 relevant articles were retrieved from PubMed. These suggest that the clinical treatment of otogenic vertigo should consider the functions of zang-fu organs and meridians and select different acupuncture treatment methods according to syndrome differentiation based on the difference between deficiency and excess. Acupuncture and moxibustion therapy should be based on acupoint selection, considering the syndrome differentiation, supplemented with experience. The treatment of otogenic vertigo with acupuncture and moxibustion refers to the selection of appropriate acupuncture methods under the guidance of TCM theory and following the principles of syndrome, disease, and meridian differentiation. Common acupuncture methods include body acupuncture, auricular acupuncture, scalp acupuncture, acupoint injection, electroacupuncture, and moxibustion. There are many acupuncture and moxibustion acupoints selected for the treatment of otogenic vertigo. Individualized treatment according to the patient's specific condition is effective and safe, which can help to improve the patient's vertigo symptoms and cerebral blood perfusion.

9.
Environ Sci Technol ; 2024 Jul 08.
Article de Anglais | MEDLINE | ID: mdl-38976350

RÉSUMÉ

Perfluorooctane sulfonamide (PFOSA) is an immediate perfluorooctanesulfonate (PFOS) precursor (PreFOS). Previous studies have shown PFOSA to induce stronger toxic responses compared to other perfluorinated compounds (PFCs). However, the specific nature of PFOSA-induced toxicity, whether autonomous or mediated by its metabolite PFOS, has not been fully elucidated. This study systematically investigates the immunomodulatory effects of PFOSA and PFOS in zebrafish (Danio rerio). Exposure to PFOSA compromised the zebrafish's ability to defend against pathogenic infections, as evidenced by increased bacterial adhesion to their skin and reduced levels of the biocidal protein lysozyme (LYSO). Moreover, PFOSA exposure was associated with disruptions in inflammatory markers and immune indicators, along with a decrease in immune cell counts. The findings from this study suggest that the immunotoxicity effects of PFOSA are primarily due to its own toxicity rather than its metabolite PFOS. This conclusion was supported by dose-dependent responses, the severity of observed effects, and multivariate analysis. In addition, our experiments using NF-κB-morpholino knock-down techniques further confirmed the role of the Nuclear factor-κappa B pathway in mediating PFOSA-induced immunotoxicity. In conclusion, this study reveals that PFOSA impairs the immune system in zebrafish through an autotoxic mechanism, providing valuable insights for assessing the ecological risks of PFOSA.

11.
J Appl Microbiol ; 135(7)2024 Jul 02.
Article de Anglais | MEDLINE | ID: mdl-39066493

RÉSUMÉ

AIMS: Microbial transformation to modify saponins and enhance their biological activities has received increasing attention in recent years. This study aimed to screen the strain that can biotransform notoginsenoside R1, identify the product and study its biological activity. METHODS AND RESULTS: A lactic acid bacteria strain S165 with glycosidase-producing activity was isolated from traditional Chinese fermented foods, which was identified and grouped according to API 50 CHL kit and 16S rDNA sequence analysis. Subsequently, notoginsenoside R1 underwent a 30-day fermentation period by the strain S165, and the resulting products were analyzed using High-performance liquid chromatography (HPLC), Ultra-performance liquid chromatography (UPLC)-mass spectrometry (MS)/MS, and 13C-Nuclear magnetic resonance (NMR) techniques. Employing a model of Lipopolysaccharide (LPS)-induced damage to Caco-2 cells, the damage of Caco-2 cells was detected by Hoechst 33 258 staining, and the activity of notoginsenoside R1 biotransformation product was investigated by CCK-8 and western blotting assay. The strain S165 was identified as Lactiplantibacillus plantarum and was used to biotransform notoginsenoside R1. Through a 30-day biotransformation, L. plantarum S165 predominantly converts notoginsenoside R1 into 3ß,12ß-dihydroxydammar-(E)-20(22),24-diene-6-O-ß-D-xylopyranosyl-(1→2)-ß-D-glucopyranoside, temporarily named notoginsenoside T6 (NGT6) according to HPLC, UPLC-MS/MS, and 13C-NMR analysis. Results from CCK-8 and Hoechst 33258 staining indicated that the ability notoginsenoside T6 to alleviate the intestinal injury induced by LPS in the Caco-2 cell was stronger than that of notoginsenoside R1. In addition, Western blotting result showed that notoginsenoside T6 could prevent intestinal injury by protecting tight junction proteins (Claudin-1, Occludin, and ZO-1). CONCLUSION: Notoginsenoside R1 was biotransformed into the notoginsenoside T6 by L. plantarum S165, and the biotransformed product showed an enhanced intestinal protective effect in vitro.


Sujet(s)
Ginsénosides , Lipopolysaccharides , Ginsénosides/métabolisme , Ginsénosides/pharmacologie , Humains , Cellules Caco-2 , Lipopolysaccharides/métabolisme , Fermentation , Biotransformation , Chromatographie en phase liquide à haute performance , Lactobacillus plantarum/métabolisme , Aliments fermentés/microbiologie
12.
Drug Des Devel Ther ; 18: 1821-1832, 2024.
Article de Anglais | MEDLINE | ID: mdl-38845851

RÉSUMÉ

Aim: Natural medicines possess significant research and application value in the field of atherosclerosis (AS) treatment. The study was performed to investigate the impacts of a natural drug component, notoginsenoside R1, on the development of atherosclerosis (AS) and the potential mechanisms. Methods: Rats induced with AS by a high-fat-diet and vitamin D3 were treated with notoginsenoside R1 for six weeks. The ameliorative effect of NR1 on AS rats was assessed by detecting pathological changes in the abdominal aorta, biochemical indices in serum and protein expression in the abdominal aorta, as well as by analysing the gut microbiota. Results: The NR1 group exhibited a noticeable reduction in plaque pathology. Notoginsenoside R1 can significantly improve serum lipid profiles, encompassing TG, TC, LDL, ox-LDL, and HDL. Simultaneously, IL-6, IL-33, TNF-α, and IL-1ß levels are decreased by notoginsenoside R1 in lowering inflammatory elements. Notoginsenoside R1 can suppress the secretion of VCAM-1 and ICAM-1, as well as enhance the levels of plasma NO and eNOS. Furthermore, notoginsenoside R1 inhibits the NLRP3/Cleaved Caspase-1/IL-1ß inflammatory pathway and reduces the expression of the JNK2/P38 MAPK/VEGF endothelial damage pathway. Fecal analysis showed that notoginsenoside R1 remodeled the gut microbiota of AS rats by decreasing the count of pathogenic bacteria (such as Firmicutes and Proteobacteria) and increasing the quantity of probiotic bacteria (such as Bacteroidetes). Conclusion: Notoginsenoside R1, due to its unique anti-inflammatory properties, may potentially prevent the progression of atherosclerosis. This mechanism helps protect the vascular endothelium from damage, while also regulating the imbalance of intestinal microbiota, thereby maintaining the overall health of the body.


Sujet(s)
Athérosclérose , Cholécalciférol , Alimentation riche en graisse , Microbiome gastro-intestinal , Ginsénosides , Inflammation , Rat Sprague-Dawley , Animaux , Microbiome gastro-intestinal/effets des médicaments et des substances chimiques , Ginsénosides/pharmacologie , Ginsénosides/administration et posologie , Rats , Athérosclérose/traitement médicamenteux , Athérosclérose/prévention et contrôle , Athérosclérose/anatomopathologie , Alimentation riche en graisse/effets indésirables , Mâle , Cholécalciférol/pharmacologie , Cholécalciférol/administration et posologie , Inflammation/traitement médicamenteux , Endothélium vasculaire/effets des médicaments et des substances chimiques , Endothélium vasculaire/métabolisme
13.
Asian J Psychiatr ; 98: 104106, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38865883

RÉSUMÉ

BACKGROUND: In patients with schizophrenia, there is abnormal regional functional synchrony. However, whether it also in patients with adolescent-onset schizophrenia (AOS) remains unclear. The goal of this study was to analyze the regional homogeneity (ReHo) of resting functional magnetic resonance imaging to explore the functional abnormalities of the brain in patients with AOS. METHODS: The study included 107 drug-naive first-episode AOS patients and 67 healthy, age, sex, and education-matched controls using resting-state functional magnetic resonance imaging scans. The ReHo method was used to analyze the imaging dataset. RESULTS: Compared with the control group, the ReHo values of the right inferior frontal gyrus orbital part, right middle frontal gyrus (MFG.R), left inferior parietal, but supramarginal and angular gyri, and left precentral gyrus (PreCG.L) were significantly increased and the ReHo value of the left posterior cingulate cortex/anterior cuneiform lobe was significantly decreased in schizophrenia patients. ROC analysis showed that the ReHo values of the MFG.R and PreCG.L might be regarded as potential markers in helping to identify patients. Furthermore, the PANSS scores in the patient group and the ReHo values showed a positive correlation between MFG.R ReHo values and general scores. CONCLUSIONS: Our results suggested that AOS patients had ReHo abnormalities. The ReHo values of these abnormal regions may serve as potential imaging biomarkers for the identification of AOS patients.


Sujet(s)
Imagerie par résonance magnétique , Schizophrénie , Humains , Schizophrénie/imagerie diagnostique , Schizophrénie/physiopathologie , Mâle , Femelle , Adolescent , Jeune adulte , Cortex cérébral/imagerie diagnostique , Cortex cérébral/physiopathologie , Âge de début
14.
BMC Anesthesiol ; 24(1): 210, 2024 Jun 21.
Article de Anglais | MEDLINE | ID: mdl-38907338

RÉSUMÉ

BACKGROUND: Dexmedetomidine and midazolam are commonly used sedatives in children. We conducted a systematic review and meta-analysis to compare the safety and effectiveness of sedation provided by dexmedetomidine combined with midazolam versus other sedatives including chloral hydrate, midazolam and other sedatives in pediatric sedation. METHODS: The Embase, Web of Science, Cochrane Library, and PubMed databases, and Clinicaltrials.gov register of controlled trials were searched from inception to June 2022. All randomized controlled trials used dexmedetomidine-midazolam in pediatric sedation were enrolled. The articles search, data extraction, and quality assessment of included studies were performed independently by two researchers. The success rate of sedation was considered as the primary outcome. The secondary outcomes included onset time of sedation, recovery time of sedation and occurrence of adverse events. RESULTS: A total of 522 studies were screened and 6 RCTs were identified; 859 patients were analyzed. The administration of dexmedetomidine combined with midazolam was associated with a higher sedation success rate and a lower incidence of nausea and vomiting in computed tomography, magnetic resonance imaging, Auditory Brainstem Response test or fiberoptic bronchoscopy examinations than the other sedatives did (OR = 2.92; 95% CI: 1.39-6.13, P = 0.005, I2 = 51%; OR = 0.23, 95% CI: 0.07-0.68, P = 0.008, I2 = 0%, respectively). Two groups did not differ significantly in recovery time and the occurrence of adverse reactions (WMD = - 0.27, 95% CI: - 0.93 to - 0.39, P = 0.42; OR 0.70; 95% CI: 0.48-1.02, P = 0.06, I2 = 45%. respectively). However, the results of the subgroup analysis of ASA I-II children showed a quicker onset time in dexmedetomidine-midazolam group than the other sedatives (WMD=-3.08; 95% CI: -4.66 to - 1.49, P = 0.0001, I2 = 30%). CONCLUSIONS: This meta-analysis showed that compared with the control group, dexmedetomidine combined with midazolam group provided higher sedation success rates and caused a lower incidence of nausea and vomiting in completing examinations, indicating a prospective outpatient clinical application for procedural sedation.


Sujet(s)
Dexmédétomidine , Hypnotiques et sédatifs , Midazolam , Dexmédétomidine/administration et posologie , Humains , Hypnotiques et sédatifs/administration et posologie , Midazolam/administration et posologie , Enfant , Association de médicaments , Essais contrôlés randomisés comme sujet/méthodes
15.
N Biotechnol ; 83: 26-35, 2024 Nov 25.
Article de Anglais | MEDLINE | ID: mdl-38936658

RÉSUMÉ

D-1,2,4-butanetriol (BT) is a widely used fine chemical that can be manufactured by engineered Escherichia coli expressing heterologous pathways and using xylose as a substrate. The current study developed a glucose-xylose dual metabolic channel system in an engineered E. coli and Combinatorially optimized it using multiple strategies to promote BT production. The carbon catabolite repression effects were alleviated by deleting the gene ptsG that encodes the major glucose transporter IICBGlc and mutating the gene crp that encodes the catabolite repressor protein, thereby allowing C-fluxes of both glucose and xylose into their respective metabolic channels separately and simultaneously, which increased BT production by 33% compared with that of the original MJ133K-1 strain. Then, the branch metabolic pathways of intermediates in the BT channel were investigated, the transaminase HisC, the ketoreductases DlD, OLD, and IlvC, and the aldolase MhpE and YfaU were identified as the enzymes for the branched metabolism of 2-keto-3-deoxy-xylonate, deletion of the gene hisC increased BT titer by 21.7%. Furthermore, the relationship between BT synthesis and the intracellular NADPH level was examined, and deletion of the gene pntAB that encodes a transhydrogenase resulted in an 18.1% increase in BT production. The combination of the above approaches to optimize the metabolic network increased BT production by 47.5%, resulting in 2.67 g/L BT in 24 deep-well plates. This study provides insights into the BT biosynthesis pathway and demonstrates effective strategies to increase BT production, which will promote the industrialization of the biosynthesis of BT.


Sujet(s)
Escherichia coli , Glucose , Génie métabolique , Xylose , Escherichia coli/métabolisme , Escherichia coli/génétique , Xylose/métabolisme , Glucose/métabolisme , Butanols/métabolisme , Protéines Escherichia coli/métabolisme , Protéines Escherichia coli/génétique
16.
Tissue Eng Regen Med ; 21(6): 897-914, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38842768

RÉSUMÉ

BACKGROUND: The therapeutic potential of exosomes from human umbilical cord mesenchymal stem cells (HUMSCs-Exo) for delivering specific circular RNAs (circRNAs) in treating premature ovarian failure (POF) is not well understood. This study aimed to explore the efficacy of HUMSCs-Exo in delivering hsa_circ_0002021 for POF treatment, focusing on its effects on granulosa cell (GC) senescence and ovarian function. METHODS: Bioinformatic analysis was conducted on circRNA profiles using the GSE97193 dataset from GEO, targeting granulosa cells from varied age groups. To simulate granulosa cell senescence, KGN cells were treated with cyclophosphamide (CTX). HUMSCs were transfected with pcDNA 3.1 vectors to overexpress hsa_circ_0002021, and the HUMSCs-Exo secreted were isolated. These exosomes were characterized by transmission electron microscopy (TEM) and Western blotting to confirm exosomal markers CD9 and CD63. Co-culture of these exosomes with CTX-treated KGN cells was performed to assess ß-galactosidase activity, oxidative stress markers, ROS levels, and apoptosis via flow cytometry. Interaction between hsa_circ_0002021, microRNA-125a-5p (miR-125a-5p), and cyclin-dependent kinase 6 (CDK6) was investigated using dual-luciferase assays and RNA immunoprecipitation (RIP). A POF mouse model was induced with CTX, treated with HUMSCs-Exo, and analyzed histologically and via immunofluorescence staining. Gene expression was quantified using RT-qPCR and Western blot. RESULTS: hsa_circ_0002021 was under expressed in both in vivo and in vitro POF models and was effectively delivered by HUMSCs-Exo to KGN cells, showing a capability to reduce GC senescence. Overexpression of hsa_circ_0002021 in HUMSCs-Exo significantly enhanced these anti-senescence effects. This circRNA acts as a competitive adsorbent of miR-125a-5p, regulating CDK6 expression, which is crucial in modulating cell cycle and apoptosis. Enhanced expression of hsa_circ_0002021 in HUMSCs-Exo ameliorated GC senescence in vitro and improved ovarian function in POF models by modulating oxidative stress and cellular senescence markers. CONCLUSION: This study confirms that hsa_circ_0002021, when delivered through HUMSCs-Exo, can significantly mitigate GC senescence and restore ovarian function in POF models. These findings provide new insights into the molecular mechanisms of POF and highlight the therapeutic potential of circRNA-enriched exosomes in treating ovarian aging and dysfunction.


Sujet(s)
Exosomes , Cellules de la granulosa , Cellules souches mésenchymateuses , Insuffisance ovarienne primitive , ARN circulaire , Cordon ombilical , Insuffisance ovarienne primitive/thérapie , Insuffisance ovarienne primitive/métabolisme , Insuffisance ovarienne primitive/génétique , Femelle , Exosomes/métabolisme , Cellules souches mésenchymateuses/métabolisme , Humains , Cellules de la granulosa/métabolisme , ARN circulaire/génétique , ARN circulaire/métabolisme , Animaux , Cordon ombilical/cytologie , Cordon ombilical/métabolisme , Souris , Vieillissement de la cellule , Apoptose , microARN/génétique , microARN/métabolisme
17.
Schizophr Res ; 270: 281-288, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38944974

RÉSUMÉ

BACKGROUND: The striatum is thought to play a critical role in the pathophysiology and antipsychotic treatment of schizophrenia. Previous studies have revealed abnormal functional connectivity (FC) of the striatum in early-onset schizophrenia (EOS) patients. However, no prior studies have examined post-treatment changes of striatal FC in EOS patients. METHODS: We recruited 49 first-episode drug-naïve EOS patients to have resting-state functional magnetic resonance imaging scans at baseline and after 8 weeks of treatment with antipsychotics, along with baseline scanning of 34 healthy controls (HCs) for comparison purposes. We examined the FC values between each seed in striatal subregion and the rest of the brain. The Positive and Negative Syndrome Scale (PANSS) was applied to measure psychiatric symptoms in patients. RESULTS: Compared with HCs at baseline, EOS patients exhibited weaker FC of striatal subregions with several brain regions of the salience network and default mode network. Meanwhile, FC between the dorsal caudal putamen (DCP) and left supplementary motor area, as well as between the DCP and right postcentral gyrus, was negatively correlated with PANSS negative scores. Furthermore, after 8 weeks of treatment, EOS patients showed decreased FC between subregions of the putamen and the triangular part of inferior frontal gyrus, middle frontal gyrus, supramarginal gyrus and inferior parietal lobule. CONCLUSIONS: Decreased striatal FC is evident, even in the early stages of schizophrenia, and enhance our understanding of the neurodevelopmental abnormalities in schizophrenia. The findings also demonstrate that reduced striatal FC occurs after antipsychotic therapy, indicating that antipsychotic effects need to be accounted for when considering striatal FC abnormalities in schizophrenia.


Sujet(s)
Neuroleptiques , Connectome , Corps strié , Imagerie par résonance magnétique , Schizophrénie , Humains , Schizophrénie/traitement médicamenteux , Schizophrénie/physiopathologie , Schizophrénie/imagerie diagnostique , Mâle , Femelle , Neuroleptiques/pharmacologie , Neuroleptiques/administration et posologie , Corps strié/imagerie diagnostique , Corps strié/effets des médicaments et des substances chimiques , Corps strié/physiopathologie , Adolescent , Adulte , Jeune adulte , Réseau du mode par défaut/imagerie diagnostique , Réseau du mode par défaut/physiopathologie , Réseau du mode par défaut/effets des médicaments et des substances chimiques , Réseau nerveux/imagerie diagnostique , Réseau nerveux/effets des médicaments et des substances chimiques , Réseau nerveux/physiopathologie , Âge de début
18.
Orphanet J Rare Dis ; 19(1): 208, 2024 May 21.
Article de Anglais | MEDLINE | ID: mdl-38773525

RÉSUMÉ

BACKGROUND: When using traditional extensible intramedullary rods to treat congenital pseudarthrosis of the tibia (CPT), there were cases of re-fracture and internal fixation fracture. Therefore, the authors propose a research hypothesis that a thicker distal extensible intramedullary rod can better protect the tibia and reduce the incidence of refracture PURPOSE: To investigate the clinical efficacy of new and traditional extensible intramedullary rods in the treatment of CPT in children METHODS: From January 2017 to December 2021, the clinical data of 49 children with CPT who were treated with traditional extensible intramedullary rod combined surgery (group A) and new extensible intramedullary rod combined surgery (group B) in our hospital were collected. Inclusive criteria: ① Crawford type IV CPT children; ② The operation was performed by the same team. EXCLUSION CRITERIA: patients with multiple tibial angulation. During follow-up, the initial healing, proximal tibial valgus, tibial length, ankle valgus, refracture and intramedullary rod displacement of CPT children in the two groups were evaluated RESULTS: It was a retrospective investigation. In group A, 26 cases met the inclusion criteria, 24 cases achieved primary healing, with an primary healing rate of 92%, including 1 case of nonunion due to osteomyelitis complications after surgery, and 1 case of delayed healing, with an average healing time of 4.7 ± 0.8 months. 17 cases (68%) had unequal tibia length, with an average difference of 1.6 ± 0.8 cm. Ankle valgus occurred in 10 cases (40%) with an average of 14.4°±4.8°; Proximal tibial valgus occurred in 6 cases (24%) with an average of 7 °± 1.8 °. 20 cases (80%) had tip of the rod migration.10 cases (40%) had re-fracture; The average follow-up time was 2.4 ± 0.4 years. In group B, 22 patients achieved primary healing, and the primary healing rate was 95%, including 1 case with delayed healing. The average healing time was 4.7 ± 1.7months. 14 cases (61%) had unequal tibia length, with an average difference of 1 ± 0.5 cm. Ankle valgus occurred in 4 cases (17%) with an average of 12.3 °±4.9°; The proximal tibia valgus occurred in 9 cases (39%), with an average of 7.7 °±2.5 °. 14 cases (61%) had new type of intramedullary rod displacement. 3 cases (13%) had re-fracture; The average follow-up time was 2.3 ± 0.6years CONCLUSION: Compared with the traditional extended intramedullary rod combined operation, the new type of extended intramedullary rod combined operation has a lower incidence of re-fracture after CPT, but it still needs to be verified by large sample and multi-center research.


Sujet(s)
Pseudarthrose , Tibia , Humains , Pseudarthrose/chirurgie , Pseudarthrose/congénital , Femelle , Mâle , Études rétrospectives , Tibia/chirurgie , Enfant d'âge préscolaire , Ostéosynthese intramedullaire/méthodes , Enfant , Fractures du tibia/chirurgie , Résultat thérapeutique
19.
Games Health J ; 2024 May 29.
Article de Anglais | MEDLINE | ID: mdl-38808471

RÉSUMÉ

Objective: College students experience intense anxiety, for which biofeedback mindfulness techniques show effectiveness in relief. However, typical biofeedback products often lead to user fatigue and boredom because of a single or fixed feedback and lack of focus on mindfulness enhancement. Materials and Methods: In this research, we developed Mindjourney, a VR-based respiratory feedback mindfulness system, designed to enhance mindfulness and alleviate anxiety through continuous/noncontinuous feedback and nonjudgmental reward/punishment for self-perception and attention management. A randomized controlled trial involved 72 college students, split equally into short-term (n = 34, age: 23.11 ± 1.729) and 4-week long-term (n = 38, age: 24.12 ± 1.408) groups, with equal randomization for intervention and control groups. Pre/postintervention tests were measured by using Trait Anxiety Inventory (TAI) and Five Facet Mindfulness Questionnaire (FFMQ) for long-term groups and Galvanic Skin Response and State Anxiety Inventory (SAI) for short-term groups. Results: Results showed that the long-term intervention group showed a significant increase in mindfulness (P = 0.001 for FFMQ total score). Furthermore, observe and act with awareness subscales showed significant increase after intervention (P = 0.034 for observe, P < 0.001 for act with awareness) compared with the control group. Both intervention groups demonstrated a significant decrease in anxiety levels compared with the control groups (P = 0.049 for SAI, P = 0.01 for TAI). Moreover, participants expressed high interest in this biofeedback mindfulness system and willingness for long-term usage. Conclusion: The proposed biofeedback mindfulness practice system could potentially facilitate mindfulness practice and serve as a convenient tool for anxiety relief in campus college students.

20.
Front Cell Infect Microbiol ; 14: 1382029, 2024.
Article de Anglais | MEDLINE | ID: mdl-38817443

RÉSUMÉ

Infections of hepatotropic viruses cause a wide array of liver diseases including acute hepatitis, chronic hepatitis and the consequently developed cirrhosis and hepatocellular carcinoma (HCC). Among the five classical hepatotropic viruses, hepatitis B virus (HBV) and hepatitis C virus (HCV) usually infect human persistently and cause chronic hepatitis, leading to major troubles to humanity. Previous studies have revealed that several types of inflammasomes are involved in the infections of HBV and HCV. Here, we summarize the current knowledge about their roles in hepatitis B and C. NLRP3 inflammasome can be activated and regulated by HBV and HCV. It is found to exert antiviral function or mediates inflammatory response in viral infections depending on different experimental models. Besides NLRP3 inflammasome, IFI16 and AIM2 inflammasomes participate in the pathological process of hepatitis B, and NALP3 inflammasome may sense HCV infection in hepatocytes. The inflammasomes affect the pathological process of viral hepatitis through its downstream secretion of inflammatory cytokines interleukin-1ß (IL-1ß) and IL-18 or induction of pyroptosis resulting from cleaved gasdermin D (GSDMD). However, the roles of inflammasomes in different stages of viral infection remains mainly unclear. More proper experimental models of viral hepatitis should be developed for specific studies in future, so that we can understand more about the complexity of inflammasome regulation and multifunction of inflammasomes and their downstream effectors during HBV and HCV infections.


Sujet(s)
Hepacivirus , Virus de l'hépatite B , Hépatite B chronique , Hépatite C chronique , Inflammasomes , Protéine-3 de la famille des NLR contenant un domaine pyrine , Humains , Inflammasomes/métabolisme , Inflammasomes/immunologie , Hépatite C chronique/immunologie , Protéine-3 de la famille des NLR contenant un domaine pyrine/métabolisme , Hepacivirus/immunologie , Hépatite B chronique/immunologie , Hépatite B chronique/métabolisme , Virus de l'hépatite B/immunologie , Protéines de liaison à l'ADN/métabolisme , Interleukine-1 bêta/métabolisme , Pyroptose , Animaux , Phosphoprotéines/métabolisme , Protéines nucléaires/métabolisme , Hépatocytes/virologie , Hépatocytes/immunologie , Interleukine-18/métabolisme , Protéines de liaison aux phosphates/métabolisme , Gasdermines
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