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1.
World J Psychiatry ; 14(6): 913-919, 2024 Jun 19.
Article de Anglais | MEDLINE | ID: mdl-38984336

RÉSUMÉ

BACKGROUND: Severe acute pancreatitis (SAP) is a familiar critical disease in the intensive care unit (ICU) patients. Nursing staff are important spiritual pillars during the treatment of patients, and in addition to routine nursing, more attention needs be paid to the patient's psychological changes. AIM: To investigate the effects of psychological intervention in ICU patients with SAP. METHODS: One hundred ICU patients with SAP were hospitalized in the authors' hospital between 2020 and 2023 were selected, and divided into observation and control groups per the hospitalization order. The control and observation groups received routine nursing and psychological interventions, respectively. Two groups are being compared, using the Self-rating Anxiety Scale (SAS), Self-Determination Scale (SDS), Acute Physiology and Chronic Health Evaluation (APACHE) II, and 36-item Short Form Health Survey (SF-36) scores; nursing satisfaction of patients; ICU care duration; length of stay; hospitalization expenses; and the incidence of complications. RESULTS: After nursing, the SDS, SAS, and APACHE II scores in the experimental group were significantly lower than in the control group (P < 0.05). The SF-36 scores in the observation group were significantly higher than those in the control group (P < 0.05). The nursing satisfaction of patients in the experimental group was 94.5%, considerably higher than that of 75.6% in the control group (P < 0.05). The ICU care duration, length of stay, and hospitalization expenses in the observation group were significantly lower than those in the control group, and the incidence of complications was lower (P < 0.05). CONCLUSION: For patients with SAP, the implementation of standardized psychological intervention measures can effectively alleviate adverse psychological conditions.

2.
Acta Histochem ; 126(5-7): 152174, 2024 Jul 07.
Article de Anglais | MEDLINE | ID: mdl-38976933

RÉSUMÉ

Choroidal melanoma (CM), a highly metastatic eye tumor, exhibits vasculogenic mimicry (VM) facilitated by hypoxia-induced angiogenesis. This study explored the inhibitory impact of the anti-malarial drug Artesunate (ART) on CM VM through modulation of the HIF-1α/VEGF/PDGF pathway. Immunohistochemistry (IHC) confirmed VM in CM with elevated VEGF and PDGF expression. Hypoxia promoted CM proliferation, upregulating HIF-1α, VEGF and PDGF. VEGF and PDGF enhanced CM migration, invasion and VM, with HIF-1α playing a crucial role. ART mitigated VM formation by suppressing the HIF-1α/VEGF/PDGF pathway, highlighting its potential as an anti-tumor agent in CM.

3.
Ann Hematol ; 2024 Jul 16.
Article de Anglais | MEDLINE | ID: mdl-39012516

RÉSUMÉ

Acute myeloid leukemia (AML) is a notably lethal disease, characterized by malignant clonal proliferation of hematopoietic stem cells in the bone marrow. This study seeks to unveil potential therapeutic targets for AML, using a combined approach of microarray analysis and Mendelian randomization (MR). We collected data samples from the Gene Expression Omnibus (GEO) database and extracted pQTL data from genome-wide association studies (GWAS) to identify overlapping genes between the DEGs and GWAS data. Gene enrichment and pathway annotation analyses were performed on these genes. Furthermore, we validated gene expression levels and assessed their clinical relevance. By taking the intersection of these gene sets, we obtained a list of co-expressed genes, including four upregulated genes (REC8, TPM2, ZMIZ1, CD82) and two downregulated genes (IFNAR1, TMCO3). MR analysis demonstrated that genetically predicted protein levels of CD82, REC8, ZMIZ1, and TPM2 were significantly associated with increased odds of AML, while IFNAR1 and TMCO3 showed a protective effect. Gene ontology and KEGG pathway analyses revealed significant enrichment in functions related to female gamete generation, meiosis, p53 signaling pathway, and cardiac muscle contraction. Differences in immune cell profiles were observed between AML survivors and those with poor prognosis, including lower levels of neutrophils and higher levels of follicular helper T cells in the latter group. This study identifies a causal relationship between gene expression and AML and highlights the potential role of REC8 in leukemogenesis, possibly through its impact on gametocyte meiotic abnormalities. The findings provide new insights into the prevention and treatment of leukemia.

4.
World J Gastrointest Oncol ; 16(6): 2520-2530, 2024 Jun 15.
Article de Anglais | MEDLINE | ID: mdl-38994151

RÉSUMÉ

BACKGROUND: Colorectal cancer is currently the third most common malignant tumor and the second leading cause of cancer-related death worldwide. Neoadjuvant chemoradiotherapy (nCRT) is standard for locally advanced rectal cancer (LARC). Except for pathological examination after resection, it is not known exactly whether LARC patients have achieved pathological complete response (pCR) before surgery. To date, there are no clear clinical indicators that can predict the efficacy of nCRT and patient outcomes. AIM: To investigate the indicators that can predict pCR and long-term outcomes following nCRT in patients with LARC. METHODS: Clinical data of 128 LARC patients admitted to our hospital between September 2013 and November 2022 were retrospectively analyzed. Patients were categorized into pCR and non-pCR groups. Univariate analysis (using the χ 2 test or Fisher's exact test) and logistic multivariate regression analysis were used to study clinical predictors affecting pCR. The 5-year disease-free survival (DFS) and overall survival (OS) rates were calculated using Kaplan-Meier analysis, and differences in survival curves were assessed with the log-rank test. RESULTS: Univariate analysis showed that pretreatment carcinoembryonic antigen (CEA) level, lymphocyte-monocyte ratio (LMR), time interval between neoadjuvant therapy completion and total mesorectal excision, and tumor size were correlated with pCR. Multivariate results showed that CEA ≤ 5 ng/mL (P = 0.039), LMR > 2.73 (P = 0.023), and time interval > 10 wk (P = 0.039) were independent predictors for pCR. Survival analysis demonstrated that patients in the pCR group had significantly higher 5-year DFS rates (94.7% vs 59.7%, P = 0.002) and 5-year OS rates (95.8% vs 80.1%, P = 0.019) compared to the non-pCR group. Tumor deposits (TDs) were significantly correlated with shorter DFS (P = 0.002) and OS (P < 0.001). CONCLUSION: Pretreatment CEA, LMR, and time interval contribute to predicting nCRT efficacy in LARC patients. Achieving pCR demonstrates longer DFS and OS. TDs correlate with poor prognosis.

5.
Parasit Vectors ; 17(1): 299, 2024 Jul 10.
Article de Anglais | MEDLINE | ID: mdl-38987795

RÉSUMÉ

BACKGROUND: Toxoplasma gondii infection causes adverse pregnancy outcomes by affecting the expression of immunotolerant molecules in decidual immune cells. Galectin-9 (Gal-9) is widely expressed in decidual macrophages (dMφ) and is crucial for maintaining normal pregnancy by interacting with the immunomodulatory protein T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3). However, the effects of T. gondii infection on Gal-9 expression in dMφ, and the impact of altered Gal-9 expression levels on the maternal-fetal tolerance function of decidual natural killer (dNK) cells, are still unknown. METHODS: Pregnancy outcomes of T. gondii-infected C57BL/6 and Lgals9-/- pregnant mice models were recorded. Expression of Gal-9, c-Jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK), and Forkhead box protein O1 (FOXO1) was detected by western blotting, flow cytometry or immunofluorescence. The binding of FOXO1 to the promoter of Lgals9 was determined by chromatin immunoprecipitation-polymerase chain reaction (ChIP-PCR). The expression of extracellular signal-regulated kinase (ERK), phosphorylated ERK (p-ERK), cAMP-response element binding protein (CREB), phosphorylated CREB (p-CREB), T-box expressed in T cells (T-bet), interleukin 10 (IL-10), and interferon gamma (IFN-γ) in dNK cells was assayed by western blotting. RESULTS: Toxoplasma gondii infection increased the expression of p-JNK and FOXO1 in dMφ, resulting in a reduction in Gal-9 due to the elevated binding of FOXO1 with Lgals9 promoter. Downregulation of Gal-9 enhanced the phosphorylation of ERK, inhibited the expression of p-CREB and IL-10, and promoted the expression of T-bet and IFN-γ in dNK cells. In the mice model, knockout of Lgals9 aggravated adverse pregnancy outcomes caused by T. gondii infection during pregnancy. CONCLUSIONS: Toxoplasma gondii infection suppressed Gal-9 expression in dMφ by activating the JNK/FOXO1 signaling pathway, and reduction of Gal-9 contributed to dysfunction of dNK via Gal-9/Tim-3 interaction. This study provides new insights for the molecular mechanisms of the adverse pregnancy outcomes caused by T. gondii.


Sujet(s)
Galectines , Cellules tueuses naturelles , Macrophages , Souris de lignée C57BL , Toxoplasma , Toxoplasmose , Animaux , Femelle , Grossesse , Galectines/génétique , Galectines/métabolisme , Souris , Cellules tueuses naturelles/immunologie , Macrophages/immunologie , Toxoplasma/immunologie , Toxoplasmose/immunologie , Caduques/immunologie , Souris knockout , Récepteur cellulaire-2 du virus de l'hépatite A/génétique , Récepteur cellulaire-2 du virus de l'hépatite A/métabolisme , Issue de la grossesse , Protéine O1 à motif en tête de fourche/génétique , Protéine O1 à motif en tête de fourche/métabolisme
6.
BMC Musculoskelet Disord ; 25(1): 552, 2024 Jul 17.
Article de Anglais | MEDLINE | ID: mdl-39014409

RÉSUMÉ

BACKGROUND: To evaluate the effectiveness of a sequential internal fixation strategy and intramedullary nailing with plate augmentation (IMN/PA) for bone reconstruction in the management of infected femoral shaft defects using the Masquelet technique. METHODS: We performed a retrospective descriptive cohort study of 21 patients (mean age, 36.4 years) with infected bone defects of the femoral shaft treated by the Masquelet technique with a minimum follow-up of 18 months after second stage. After aggressive debridement, temporary stabilisation (T1) was achieved by an antibiotic-loaded bone cement spacer and internal fixation with a bone cement-coated locking plate. At second stage (T2), the spacer and the locking plate were removed following re-debridement, and IMN/PA was used as definitive fixation together with bone grafting. We evaluated the following clinical outcomes: infection recurrence, bone union time, complications, and the affected limb's knee joint function. RESULTS: The median and quartiles of bone defect length was 7 (4.75-9.5) cm. Four patients required iterative debridement for infection recurrence after T1. The median of interval between T1 and T2 was 10 (9-19) weeks. At a median follow-up of 22 (20-27.5) months, none of the patients experienced recurrence of infection. Bone union was achieved at 7 (6-8.5) months in all patients, with one patient experiencing delayed union at the distal end of bone defect due to screws loosening. At the last follow-up, the median of flexion ROM of the knee joint was 120 (105-120.0)°. CONCLUSIONS: For infected femoral shaft bone defects treated by the Masquelet technique, sequential internal fixation and IMN/PA for the reconstruction can provide excellent mechanical stability, which is beneficial for early functional exercise and bone union, and does not increase the rate of infection recurrence.


Sujet(s)
Clous orthopédiques , Plaques orthopédiques , Débridement , Fractures du fémur , Ostéosynthese intramedullaire , Humains , Mâle , Études rétrospectives , Femelle , Adulte , Fractures du fémur/chirurgie , Adulte d'âge moyen , Débridement/méthodes , Ostéosynthese intramedullaire/méthodes , Ostéosynthese intramedullaire/instrumentation , Jeune adulte , Résultat thérapeutique , Transplantation osseuse/méthodes , Ostéosynthèse interne/méthodes , Ostéosynthèse interne/instrumentation , Études de suivi , Ciments osseux/usage thérapeutique , Antibactériens/usage thérapeutique , Antibactériens/administration et posologie , Fémur/chirurgie , Adolescent
7.
Article de Anglais | MEDLINE | ID: mdl-38830044

RÉSUMÉ

OBJECTIVES: This study aimed to investigate the value of a deep learning (DL) model based on greyscale ultrasound (US) images for precise assessment and accurate diagnosis of primary Sjögren's syndrome (pSS). METHODS: This was a multicentre prospective analysis. All pSS patients were diagnosed according to 2016 ACR/EULAR criteria. 72 pSS patients and 72 sex- and age-matched healthy controls recruited between January 2022 and April 2023, together with 41 patients and 41 healthy controls recruited from June 2023 to February 2024 were used for DL model development and validation, respectively. DL model was constructed based on the ResNet 50, input with preprocessed all participants' bilateral submandibular glands (SMGs), parotid glands (PGs), and lacrimal glands (LGs) greyscale US images. Diagnostic performance of the model was compared with two radiologists. The accuracy of prediction and identification performance of DL model were evaluated by calibration curve. RESULTS: 864 and 164 greyscale US images of SMGs, PGs, and LGs were collected for development and validation of the model. The AUCs of DL model in the SMG, PG, and LG were 0.92, 0.93, 0.91 in the model cohort, and were 0.90, 0.88, 0.87 in the validation cohort respectively, outperforming both radiologists. Calibration curves showed the prediction probability of DL model were consistent with the actual probability in both model cohort and validation cohort. CONCLUSION: DL model based on greyscale US images showed diagnostic potential in the precise assessment of pSS patients in the SMG, PG, and LG, outperforming conventional radiologist evaluation.

8.
Article de Anglais | MEDLINE | ID: mdl-38836738

RÉSUMÉ

Objective: The autonomy theory holds that the autonomy of individuals in the rehabilitation process is crucial to the success of rehabilitation. To explore the use of autonomous rehabilitation programs in patients with bronchiectasis, This study was conducted through the construction of a stable family rehabilitation program for bronchiectasis patients and the application of patients self-determination theory. To further explore the value of autonomy theory in rehabilitation therapy. Method: The experimental group used self-determination theory as the guide for intervention on the basis of the control groups. The two groups of observation indexes included St. George's Respiratory Questionnaire, FEV1 and FEV1 values, lung capacity, V25, V50, maximal ventilation, compliance questionnaire, anxiety self-assessment scale, and depression self-assessment scale. Results: (1) The lung capacity of the experimental group patients (3.01 ± 0.82) L was higher than that of the control group (2.86 ± 0.36) L, and the V25 value (2.63 ± 0.31) L/s, V50 value (4.31 ± 1.01) L/s, and maximum ventilation volume (71.63 ± 18.35) L/min were all higher than those of the control group, with P < .05; (2) After intervention, the SGRO score of patients in the experimental group (38.66 ± 8.67)score was lower than that of the control group (56.48 ± 9.86)score. The FEV1 score of patients in the experimental group (9.35 ± 2.36)L was higher than that of the control group (1.04 ± 0.29)L. After intervention, the FEV1 score of patients in the experimental group was% (56.83 ± 9.21)% higher than that of the control group (46.37 ± 7.67)%, with P < .05; (3) Comparison of compliance scores between two groups of patients before and after intervention: the experimental group had scores for timed medication (4.89 ± 0.64)score, moderate exercise (4.61 ± 1.04)score, and dietary regulation (4.72 ± 0.87)score after intervention, all of which were higher than those of the control group (P < .05); (4) The comparison of anxiety and depression between two groups of patients showed that the anxiety score (10.16 ± 3.03)score of the experimental group after intervention was lower than that of the control group (13.03 ± 3.67)score, and the depression score (9.35 ± 2.36)score of the experimental group after intervention was lower than that of the control group (12.34 ± 3.01)score, with P < .05. Conclusion: Using the theory of autonomy to construct and apply the rehabilitation program in the home stabilization stage of bronchiectasis patients can improve respiratory and lung function. At the same time, it has a certain degree of promoting effect on improving patients' treatment compliance, and can improve patients' emotional state and reduce the occurrence of anxiety and depression. The results of this study will provide a certain theoretical basis for the construction of the treatment and rehabilitation program of clinically related diseases. In the future clinical treatment, personalized treatment intervention can be carried out according to the autonomy of patients to improve the clinical prognosis.

10.
Heliyon ; 10(9): e29948, 2024 May 15.
Article de Anglais | MEDLINE | ID: mdl-38694081

RÉSUMÉ

The prevalence of COVID-19 has drawn increasing attention to olfactory dysfunction among researchers. Olfactory dysfunction manifests in various clinical types, influenced by numerous pathogenic factors. Despite this diversity, the underlying pathogenesis remains largely elusive, contributing to a lack of standardized treatment approaches. However, the potential regeneration of olfactory neurons within the nasal cavity presents a promising avenue for addressing olfactory dysfunction effectively. Our review aims to delve into the current research landscape and treatment modalities concerning olfactory dysfunction, emphasizing etiology, pathogenesis, clinical interventions, and the role of stem cells in regenerating olfactory nerves. Through this comprehensive examination, we aim to provide valuable insights into understanding the onset, progression, and treatment of olfactory dysfunction diseases.

11.
Front Endocrinol (Lausanne) ; 15: 1372518, 2024.
Article de Anglais | MEDLINE | ID: mdl-38800486

RÉSUMÉ

Background: Aging has always been considered as a risk factor for neurodegenerative diseases, but there are individual differences and its mechanism is not yet clear. Epigenetics may unveil the relationship between aging and neurodegenerative diseases. Methods: Our study employed a bidirectional two-sample Mendelian randomization (MR) design to assess the potential causal association between epigenetic aging and neurodegenerative diseases. We utilized publicly available summary datasets from several genome-wide association studies (GWAS). Our investigation focused on multiple measures of epigenetic age as potential exposures and outcomes, while the occurrence of neurodegenerative diseases served as potential exposures and outcomes. Sensitivity analyses confirmed the accuracy of the results. Results: The results show a significant decrease in risk of Parkinson's disease with GrimAge (OR = 0.8862, 95% CI 0.7914-0.9924, p = 0.03638). Additionally, we identified that HannumAge was linked to an increased risk of Multiple Sclerosis (OR = 1.0707, 95% CI 1.0056-1.1401, p = 0.03295). Furthermore, we also found that estimated plasminogen activator inhibitor-1(PAI-1) levels demonstrated an increased risk for Alzheimer's disease (OR = 1.0001, 95% CI 1.0000-1.0002, p = 0.04425). Beyond that, we did not observe any causal associations between epigenetic age and neurodegenerative diseases risk. Conclusion: The findings firstly provide evidence for causal association of epigenetic aging and neurodegenerative diseases. Exploring neurodegenerative diseases from an epigenetic perspective may contribute to diagnosis, prognosis, and treatment of neurodegenerative diseases.


Sujet(s)
Vieillissement , Épigenèse génétique , Étude d'association pangénomique , Analyse de randomisation mendélienne , Maladies neurodégénératives , Humains , Vieillissement/génétique , Maladies neurodégénératives/génétique , Maladies neurodégénératives/épidémiologie , Prédisposition génétique à une maladie , Maladie d'Alzheimer/génétique , Maladie d'Alzheimer/épidémiologie , Inhibiteur-1 d'activateur du plasminogène/génétique , Facteurs de risque , Maladie de Parkinson/génétique , Maladie de Parkinson/épidémiologie
12.
Biotechnol Biofuels Bioprod ; 17(1): 59, 2024 May 03.
Article de Anglais | MEDLINE | ID: mdl-38702823

RÉSUMÉ

BACKGROUND: Taurine, a semi-essential micronutrient, could be utilized as a sulfur source for some bacteria; however, little is known about its effect on the accumulation of fermentation products. Here, it investigated the effect of taurine on co-production of bioethanol and Monascus azaphilone pigments (MonAzPs) for a fungus. RESULTS: A newly isolated fungus of 98.92% identity with Monascus purpureus co-produced 23.43 g/L bioethanol and 66.12, 78.01 and 62.37 U/mL red, yellow and orange MonAzPs for 3 d in synthetic medium (SM). Taurine enhanced bioethanol titer, ethanol productivity and ethanol yield at the maximum by 1.56, 1.58 and 1.60 times than those of the control in corn stover hydrolysates (CSH), and red, yellow and orange MonAzPs were raised by 1.24, 1.26 and 1.29 times, respectively. Taurine was consumed extremely small quantities for M. purpureus and its promotional effect was not universal for the other two biorefinery fermenting strains. Taurine intensified the gene transcription of glycolysis (glucokinase, phosphoglycerate mutase, enolase and alcohol dehydrogenase) and MonAzPs biosynthesis (serine hydrolases, C-11-ketoreductase, FAD-dependent monooxygenase, 4-O-acyltransferase, deacetylase, NAD(P)H-dependent oxidoredutase, FAD-dependent oxidoredutase, enoyl reductase and fatty acid synthase) through de novo RNA-Seq assays. Furthermore, taurine improved cell membrane permeability through changing cell membrane structure by microscopic imaging assays. CONCLUSIONS: Taurine reinforced co-production of bioethanol and MonAzPs by increasing gene transcription level and cell membrane permeability for M. purpureus. This work would offer an innovative, efficient and taurine-based co-production system for mass accumulation of the value-added biofuels and biochemicals from lignocellulosic biomass.

13.
BMC Pediatr ; 24(1): 309, 2024 May 06.
Article de Anglais | MEDLINE | ID: mdl-38711130

RÉSUMÉ

Schinzel-Giedion syndrome (SGS) is a severe multisystem disorder characterized by distinctive facial features, profound intellectual disability, refractory epilepsy, cortical visual impairment, hearing loss, and various congenital anomalies. SGS is attributed to gain-of-function (GoF) variants in the SETBP1 gene, with reported variants causing canonical SGS located within a 12 bp hotspot region encoding SETBP1 residues aa868-871 (degron). Here, we describe a case of typical SGS caused by a novel heterozygous missense variant, D874V, adjacent to the degron. The female patient was diagnosed in the neonatal period and presented with characteristic facial phenotype (midface retraction, prominent forehead, and low-set ears), bilateral symmetrical talipes equinovarus, overlapping toes, and severe bilateral hydronephrosis accompanied by congenital heart disease, consistent with canonical SGS. This is the first report of a typical SGS caused by a, SETBP1 non-degron missense variant. This case expands the genetic spectrum of SGS and provides new insights into genotype-phenotype correlations.


Sujet(s)
Malformations multiples , Protéines de transport , Anomalies morphologiques congénitales de la main , Mutation faux-sens , Ongles malformés , Humains , Femelle , Malformations multiples/génétique , Protéines de transport/génétique , Nouveau-né , Protéines nucléaires/génétique , Déficience intellectuelle/génétique , Malformations crâniofaciales/génétique , Malformations crâniofaciales/complications , Pied bot varus équin congénital/génétique , Phénotype , Cardiopathies congénitales/génétique , Cardiopathies congénitales/complications ,
14.
BMC Med Genomics ; 17(1): 137, 2024 May 22.
Article de Anglais | MEDLINE | ID: mdl-38778403

RÉSUMÉ

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a prevalent cancer with a poor survival rate due to anatomical limitations of the head and a lack of reliable biomarkers. Cuproptosis represents a novel cellular regulated death pathway, and N6-methyladenosine (m6A) is the most common internal RNA modification in mRNA. They are intricately connected to tumor formation, progression, and prognosis. This study aimed to construct a risk model for HNSCC using a set of mRNAs associated with m6A regulators and cuproptosis genes (mcrmRNA). METHODS: RNA-seq and clinical data of HNSCC patients from The Cancer Genome Atlas (TCGA) database were analyzed to develop a risk model through the least absolute shrinkage and selection operator (LASSO) analysis. Survival analysis and receiver operating characteristic (ROC) analysis were performed for the high- and low-risk groups. Additionally, the model was validated using the GSE41613 dataset from the Gene Expression Omnibus (GEO) database. GSEA and CIBERSORT were applied to investigate the immune microenvironment of HNSCC. RESULTS: A risk model consisting of 32 mcrmRNA was developed using the LASSO analysis. The risk score of patients was confirmed to be an independent prognostic indicator by multivariate Cox analysis. The high-risk group exhibited a higher tumor mutation burden. Additionally, CIBERSORT analysis indicated varying levels of immune cell infiltration between the two groups. Significant disparities in drug sensitivity to common medications were also observed. Enrichment analysis further unveiled significant differences in metabolic pathways and RNA processing between the two groups. CONCLUSIONS: Our risk model can predict outcomes for HNSCC patients and offers valuable insights for personalized therapeutic approaches.


Sujet(s)
Adénosine , Tumeurs de la tête et du cou , Carcinome épidermoïde de la tête et du cou , Humains , Carcinome épidermoïde de la tête et du cou/génétique , Carcinome épidermoïde de la tête et du cou/anatomopathologie , Tumeurs de la tête et du cou/génétique , Tumeurs de la tête et du cou/anatomopathologie , Adénosine/analogues et dérivés , Adénosine/métabolisme , Mâle , ARN messager/génétique , ARN messager/métabolisme , Pronostic , Femelle , Marqueurs biologiques tumoraux/génétique , Appréciation des risques , Régulation de l'expression des gènes tumoraux , Adulte d'âge moyen , Microenvironnement tumoral
15.
Nat Commun ; 15(1): 4237, 2024 May 18.
Article de Anglais | MEDLINE | ID: mdl-38762492

RÉSUMÉ

Immune checkpoint inhibition targeting the PD-1/PD-L1 pathway has become a powerful clinical strategy for treating cancer, but its efficacy is complicated by various resistance mechanisms. One of the reasons for the resistance is the internalization and recycling of PD-L1 itself upon antibody binding. The inhibition of lysosome-mediated degradation of PD-L1 is critical for preserving the amount of PD-L1 recycling back to the cell membrane. In this study, we find that Hsc70 promotes PD-L1 degradation through the endosome-lysosome pathway and reduces PD-L1 recycling to the cell membrane. This effect is dependent on Hsc70-PD-L1 binding which inhibits the CMTM6-PD-L1 interaction. We further identify an Hsp90α/ß inhibitor, AUY-922, which induces Hsc70 expression and PD-L1 lysosomal degradation. Either Hsc70 overexpression or AUY-922 treatment can reduce PD-L1 expression, inhibit tumor growth and promote anti-tumor immunity in female mice; AUY-922 can further enhance the anti-tumor efficacy of anti-PD-L1 and anti-CTLA4 treatment. Our study elucidates a molecular mechanism of Hsc70-mediated PD-L1 lysosomal degradation and provides a target and therapeutic strategies for tumor immunotherapy.


Sujet(s)
Antigène CD274 , Protéines du choc thermique HSC70 , Lysosomes , Protéines du choc thermique HSC70/métabolisme , Antigène CD274/métabolisme , Antigène CD274/génétique , Lysosomes/métabolisme , Animaux , Souris , Humains , Femelle , Lignée cellulaire tumorale , Protéolyse , Endosomes/métabolisme , Tumeurs/immunologie , Tumeurs/métabolisme , Protéines du choc thermique HSP90/métabolisme , Protéines du choc thermique HSP90/antagonistes et inhibiteurs , Souris de lignée C57BL , Inhibiteurs de points de contrôle immunitaires/pharmacologie , Inhibiteurs de points de contrôle immunitaires/usage thérapeutique , Antigène CTLA-4/métabolisme , Antigène CTLA-4/antagonistes et inhibiteurs , Antigène CTLA-4/immunologie , Membrane cellulaire/métabolisme , Protéines de la myéline , Protéines à domaine MARVEL
16.
Plant J ; 2024 May 31.
Article de Anglais | MEDLINE | ID: mdl-38818975

RÉSUMÉ

Chemical compositions of crops are of great agronomical importance, as crops serve as resources for nutrition, energy, and medicines for human and livestock. For crop metabolomics research, the lack of crop reference metabolome and high-quality reference compound mass spectra, as well as utilities for metabolic profiling, has hindered the discovery and functional study of phytochemicals in crops. To meet these challenging needs, we have developed the Crop Metabolome database (abbreviated as CropMetabolome) that is dedicated to the construction of crop reference metabolome, repository, and dissemination of crop metabolomic data, and profiling and analytic tools for metabolomics research. CropMetabolome contains a metabolomics database for more than 50 crops (belonging to eight categories) that integrated self-generated raw mass spectral data and public-source datasets. The reference metabolome for 59 crop species was constructed, which have functions that parallel those of reference genome in genomic studies. CropMetabolome also contains 'Standard compound mass spectral library', 'Flavonoids library', 'Pesticide library', and a set of related analytical tools that enable metabolic profiling based on a reference metabolome (CropRefMetaBlast), annotation and identification of new metabolites (CompoundLibBlast), deducing the structure of novel flavonoid derivatives (FlavoDiscover), and detecting possible residual pesticides in crop samples (PesticiDiscover). In addition, CropMetabolome is a repository to share and disseminate metabolomics data and a platform to promote collaborations to develop reference metabolome for more crop species. CropMetabolome is a comprehensive platform that offers important functions in crop metabolomics research and contributes to improve crop breeding, nutrition, and safety. CropMetabolome is freely available at https://www.cropmetabolome.com/.

17.
Bioresour Technol ; 402: 130777, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38701978

RÉSUMÉ

This research systematically assessed the changes in carbon, nitrogen and microbial profiling during pig and chicken manure transformation by black soldier fly larvae (BSFL) and subsequent composting process. BSFL had higher conversion efficiency for chicken manure. The pH, phosphorus and potassium contents in fresh BSFL frass increased than raw manure, but conductivity, total-/nitrate-/ammonium-nitrogen decreased. After BSFL conversion, pig manure had a larger nitrogen loss (25 %) while chicken manure had a larger carbon loss (32 %). During subsequent composting, the indicator changes (e.g. humus, ammonium nitrogen) in frass composts basically remained stable after 20-30 days. Compared to natural composts, frass composts had higher humification degree, cellulase activities, and more cellulose-degrading bacteria. Subsequent composting further reduced potential pathogens (reduced by 98.9 %-99.7 % than raw manure), and elevated the aromaticity and humification of frass. The findings gave an insight into the maturation management of manure-sourced insect frass.


Sujet(s)
Poulets , Compostage , Larve , Fumier , Azote , Animaux , Compostage/méthodes , Carbone , Suidae , Diptera , Concentration en ions d'hydrogène , Phosphore , Sol/composition chimique , Dépollution biologique de l'environnement
18.
bioRxiv ; 2024 Apr 01.
Article de Anglais | MEDLINE | ID: mdl-38712203

RÉSUMÉ

The ocular surface is a mucosal barrier tissue colonized by commensal microbes, which tune local immunity by eliciting IL-17 from conjunctival γδ T cells to prevent pathogenic infection. The commensal Corynebacterium mastitidis (C. mast) elicits protective IL-17 responses from conjunctival Vγ4 T cells through a combination of γδ TCR ligation and IL-1 signaling. Here, we identify Vγ6 T cells as a major C. mast-responsive subset in the conjunctiva and uncover its unique activation requirements. We demonstrate that Vγ6 cells require not only extrinsic (via dendritic cells) but also intrinsic TLR2 stimulation for optimal IL-17A response. Mechanistically, intrinsic TLR2 signaling was associated with epigenetic changes and enhanced expression of genes responsible for metabolic shift to fatty acid oxidation to support Il17a transcription. We identify one key transcription factor, IκBζ, which is upregulated by TLR2 stimulation and is essential for this program. Our study highlights the importance of intrinsic TLR2 signaling in driving metabolic reprogramming and production of IL-17A in microbiome-specific mucosal γδ T cells.

20.
Chemosphere ; 360: 142428, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38797211

RÉSUMÉ

In recent years, the concentrations of cadmium (Cd) and diclofenac (DCF) in water have frequently exceeded the standard; however, the toxic effects of these two pollutants on grass carp under single and combined exposure are unknown. In this study, the concentrations of pollutants in different tissues were detected, and the toxicities of the two pollutants to grass carp under different exposure conditions were compared based on growth traits, biochemical responses, gut microbiome, and transcriptomes. Based on these findings, the brain showed the lowest levels of Cd and DCF accumulation. Oxidative stress and pathological damage were observed in the brain and intestines. Changes in the structure and abundance of the gut microflora affect the synthesis of neurotransmitters, such as GABA and steroids. Differentially expressed genes in the brain were enriched in circadian rhythm functions. The expression of PER, CLOCK,1L-1ß, 1L-17, and other genes are related to the abundance of Akkermansia, which indicates that the disorder of gut microflora will affect the normal circadian rhythm of the brain. All indices in the recovery group showed an increasing trend. Overall, the toxicity of Cd and DCF showed antagonism, and a single exposure had a stronger effect on gut microorganisms and circadian rhythm, which provided a scientific basis for exploring the comprehensive effects of different pollutants.


Sujet(s)
Cadmium , Carpes (poisson) , Diclofenac , Microbiome gastro-intestinal , Transcriptome , Polluants chimiques de l'eau , Animaux , Microbiome gastro-intestinal/effets des médicaments et des substances chimiques , Cadmium/toxicité , Polluants chimiques de l'eau/toxicité , Diclofenac/toxicité , Transcriptome/effets des médicaments et des substances chimiques , Stress oxydatif/effets des médicaments et des substances chimiques , Encéphale/effets des médicaments et des substances chimiques , Encéphale/métabolisme
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