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The use of anti-inflammatory peptides (AIPs) as an alternative therapeutic approach for inflammatory diseases holds great research significance. Due to the high cost and difficulty in identifying AIPs with experimental methods, the discovery and design of peptides by computational methods before the experimental stage have become promising technology. In this study, we present BertAIP, a bidirectional encoder representation from transformers (BERT)-based method for predicting AIPs directly from their amino acid sequence without using any other information. BertAIP implements a BERT model to extract features of a protein, and uses a fully connected feed-forward network for AIP classification. It was constructed and evaluated using the AIP datasets that were reconstructed from the latest Immune Epitope Database. The experimental results showed that BertAIP achieved an accuracy of 0.751 and a Matthews correlation coefficient of 0.451, which were higher than other commonly used methods. The results of the independent test suggested that BertAIP outperformed the existing AIP predictors. In addition, to enhance the interpretability of BertAIP, we explored and visualized the amino acids that the model considered important for AIP prediction. We believe that the BertAIP proposed herein will be a useful tool for large-scale screening and identifying novel AIPs for drug development and therapeutic research related to inflammatory diseases.
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This study represents the first analysis of the bacterial community in chickens affected by swollen head syndrome, utilizing 16S rRNA gene sequencing. Samples were obtained from clinical laying chickens and were examined for the presence of Avibacterium paragallinarum (APG) and Ornithobacterium rhinotracheale (ORT) using conventional polymerase chain reaction (PCR). From the samples, five APG-positive (APG) and APG-negative (N-APG) samples were chosen, along with five specific pathogen-free chickens, for 16S rRNA gene sequencing. Results showed that APG and ORT were widely detected in the chicken samples with swollen head syndrome (SHS, 9/10), while APG was detected in all five specific pathogen-free (SPF) samples. In contrast, conventional PCR sensitivity was found to be inadequate for diagnosis, with only 35.7% (5/14) and 11.1% (1/9) sensitivity for APG and ORT, respectively, based on 16S rRNA gene sequencing data. Furthermore, 16S rRNA gene sequencing was able to quantify the bacteria in the samples, revealing that the relative abundance of APG in the APG group ranged from 2.7 to 81.3%, while the relative abundance of APG in the N-APG group ranged from 0.1 to 21.0%. Notably, a low level of APG was also detected in all 5 SPF samples. The study also identified a significant number of animal and human common bacterial pathogens, including but not limited to Gallibacterium anatis, Riemerella columbina, Enterococcus cecorum, Mycoplasma synoviae, Helicobacter hepaticus, and Staphylococcus lentus. In conclusion, 16S rRNA gene sequencing is a valuable tool for bacterial pathogen diagnosis and the discovery of novel bacterial pathogens, while conventional PCR is not reliable for diagnosis.
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Poulets , Réaction de polymérisation en chaîne , Maladies de la volaille , ARN ribosomique 16S , ARN ribosomique 16S/génétique , Animaux , Poulets/microbiologie , Réaction de polymérisation en chaîne/méthodes , Maladies de la volaille/microbiologie , Maladies de la volaille/diagnostic , Bactéries/génétique , Bactéries/classification , Bactéries/isolement et purification , ADN bactérien/génétique , Analyse de séquence d'ADN , PhylogenèseRÉSUMÉ
Histone lysine crotonylation, an evolutionarily conserved modification differing from acetylation, exerts pivotal control over diverse biological processes. Among these are gene transcriptional regulation, spermatogenesis, and cell cycle processes. However, the dynamic changes and functions of histone crotonylation in preimplantation embryonic development in mammals remain unclear. Here, we show that the transcription coactivator P300 functions as a writer of histone crotonylation during embryonic development. Depletion of P300 results in significant developmental defects and dysregulation of the transcriptome of embryos. Importantly, we demonstrate that P300 catalyzes the crotonylation of histone, directly stimulating transcription and regulating gene expression, thereby ensuring successful progression of embryo development up to the blastocyst stage. Moreover, the modification of histone H3 lysine 18 crotonylation (H3K18cr) is primarily localized to active promoter regions. This modification serves as a distinctive epigenetic indicator of crucial transcriptional regulators, facilitating the activation of gene transcription. Together, our results propose a model wherein P300-mediated histone crotonylation plays a crucial role in regulating the fate of embryonic development.
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Blastocyste , Protéine p300-E1A , Développement embryonnaire , Régulation de l'expression des gènes au cours du développement , Histone , Lysine , Histone/métabolisme , Animaux , Développement embryonnaire/génétique , Femelle , Souris , Protéine p300-E1A/métabolisme , Protéine p300-E1A/génétique , Blastocyste/métabolisme , Lysine/métabolisme , Humains , Maturation post-traductionnelle des protéines , Régions promotrices (génétique) , Épigenèse génétique , MâleRÉSUMÉ
BACKGROUND: Solitary fibrous tumor (SFT) is a rare fibroblastic mesenchymal tumor that mostly involves the pleura and infrequently involves extra-pleural sites. De novo SFT of the kidney is uncommon, and malignant SFT is extremely rare. CASE PRESENTATION: We report a case of a 51-year-old man with a large malignant SFT in the left kidney. Pathological examination confirmed the diagnosis of SFT based on typical morphology, nuclear STAT6 expression, and NAB2-STAT6 gene fusion. The malignant subtype was determined by a large tumor size (≥ 15 cm) and high mitotic counts (8/10 high-power fields). KRAS mutation was identified by DNA sequencing. Insulin-like growth factor 2 (IGF2) was diffusely and strongly expressed in tumor cells, however, hypoglycemia was not observed. Hyperglycemia and high adrenocorticotropic hormone (ACTH) concentration were observed one month after surgery. Hormone measurements revealed normal blood cortisol and aldosterone levels, and increased urinary free cortisol level. A pituitary microadenoma was identified using brain magnetic resonance imaging, which may be responsible for the promotion of hyperglycemia. CONCLUSIONS: We report a case of renal malignant SFT with a KRAS mutation, which was previously unreported in SFT and may be associated with its malignant behavior. Additionally, we emphasize that malignant SFT commonly causes severe hypoglycemia due to the production of IGF2. However, this effect may be masked by the presence of other lesions that promote hyperglycemia. Therefore, when encountering a malignant SFT with diffuse and strong IGF2 expression and without hypoglycemia, other lesions promoting hyperglycemia need to be ruled out.
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Hypoglycémie , Facteur de croissance IGF-II , Tumeurs du rein , Protéines proto-oncogènes p21(ras) , Tumeurs fibreuses solitaires , Humains , Facteur de croissance IGF-II/métabolisme , Facteur de croissance IGF-II/génétique , Mâle , Tumeurs fibreuses solitaires/anatomopathologie , Tumeurs fibreuses solitaires/chirurgie , Tumeurs fibreuses solitaires/métabolisme , Tumeurs fibreuses solitaires/génétique , Tumeurs fibreuses solitaires/diagnostic , Adulte d'âge moyen , Tumeurs du rein/anatomopathologie , Tumeurs du rein/chirurgie , Tumeurs du rein/métabolisme , Tumeurs du rein/génétique , Tumeurs du rein/diagnostic , Hypoglycémie/métabolisme , Hypoglycémie/étiologie , Hypoglycémie/anatomopathologie , Hypoglycémie/diagnostic , Protéines proto-oncogènes p21(ras)/génétique , Pronostic , MutationRÉSUMÉ
BACKGROUND: In December 2022, a large-scale epidemic occurred in China due to Omicron variant of SARS-CoV-2. This study explored risk factors for Omicron infection in transplant recipients at our institution and investigated the factors influencing the severity of SARS-CoV-2 Omicron infection among recipients of allo-HSCT. METHODS: This single-center study investigated totally 63 allogeneic hematopoietic stem cell transplant patients infected with Omicron variant at the Beijing GoBroad Boren Hospital Transplant Center during December 2022 and analyzed their risk factors. RESULTS: The study included 63 allogeneic hematopoietic stem cell transplant patients who developed Omicron infection. There were 34 mild and 29 moderate to severe cases. Their median age was 22 years (range, 1-65 years), with the male-to-female ratio being 1:1.1. Acute myeloid leukemia (53.97%), acute lymphoblastic leukemia (42.86%), and non-Hodgkin lymphoma (3.17%) were underlying diseases. The median time between HCT and Omicron infection was 8.45 months. Significant predictive factors for moderate to severe Omicron infection included older age (p < .0001), cGVHD (p = .0195), concurrent bacterial infection (p < .0001), low absolute lymphocyte count (p = .026), low CD4/CD8 ratio (p = .0091), high CRP (p < .0001), high serum ferritin (p = .0023), high D-dimer (p < .0001), low CD4 absolute count (p = .0057), and low B-cell absolute count (p = .0154). A moderate to high HCT-CI score tended to be associated with moderate to severe infection (p = .0596). CONCLUSION: This study indicates that risk factors for severe Omicron infection include certain clinical characteristics, such as age, cGVHD, and inflammatory response.
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COVID-19 , Tumeurs hématologiques , Transplantation de cellules souches hématopoïétiques , SARS-CoV-2 , Humains , COVID-19/épidémiologie , COVID-19/complications , Mâle , Transplantation de cellules souches hématopoïétiques/effets indésirables , Femelle , Adulte , Adulte d'âge moyen , Adolescent , Facteurs de risque , Tumeurs hématologiques/thérapie , Tumeurs hématologiques/épidémiologie , SARS-CoV-2/isolement et purification , Jeune adulte , Enfant , Sujet âgé , Enfant d'âge préscolaire , Nourrisson , Chine/épidémiologie , Transplantation homologue/effets indésirables , Indice de gravité de la maladie , Études rétrospectivesRÉSUMÉ
Background and aims: Patients with relapsed/refractory aggressive B-cell lymphoma(r/r aBCL)who progressed after CD19-specific chimeric antigen receptor T-cell therapy (CD19CART) had a poor prognosis. Application of CAR T-cells targeting a second different antigen (CD20) expressed on the surface of B-cell lymphoma as subsequent anti-cancer salvage therapy (CD20-SD-CART) is also an option. This study aimed to evaluate the survival outcome of CD20-SD-CART as a salvage therapy for CD19 CART treatment failure. Methods: This retrospective cohort study enrolled patients with aBCL after the failure of CD19 CART treatment at Beijing Gobroad Boren Hospital from December 2019 to May 2022. Patients were subsequently treated with CD20CART therapy or non-CART therapy (polatuzumab or non-polatuzumab). Results: A total of 93 patients were included in the study, with 54 patients receiving CD20-SD-CART therapy. After a median follow-up of 18.54 months, the CD20-SD-CART group demonstrated significantly longer median progression-free survival (4.04 months vs. 2.27 months, p=0.0032) and median overall survival (8.15 months vs. 3.02 months, p<0.0001) compared to the non-CART group. The complete response rate in the CD20-SD-CART group (15/54, 27.8%) was also significantly higher than the non-CART group (3/38, 7.9%, p=0.03). Multivariate analysis further confirmed that CD20CART treatment was independently associated with improved overall survival (HR, 0.28; 95% CI, 0.16-0.51; p<0.0001) and progression-free survival (HR, 0.46; 95% CI, 0.27-0.8; p=0.005). Conclusion: CD20-SD-CART could serve as an effective therapeutic option for patients with relapsed or refractory aggressive B-cell lymphoma after CD19CART treatment failure.
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Targeted protein degradation (TPD) modulates protein function beyond inhibition of enzyme activity or protein-protein interactions. Most degraders function by proximity induction, and directly bridge an E3 ligase with the target to be degraded. However, many proteins might not be addressable via proximity-based degraders, and other challenges, such as resistance acquisition, exist. Here, we identified pseudo-natural products derived from (-)-myrtanol, termed iDegs, that inhibit and induce degradation of the immunomodulatory enzyme indoleamine-2,3-dioxygenase 1 (IDO1) by a distinct mechanism. iDegs induce a unique conformational change and, thereby, boost IDO1 ubiquitination and degradation by the cullin-RING E3 ligase CRL2KLHDC3, which we identified to also mediate native IDO1 degradation. Therefore, iDegs supercharge the native proteolytic pathway of IDO1, rendering this mechanism of action distinct from traditional degrader approaches involving proteolysis-targeting chimeras (PROTACs) or molecular-glue degraders (MGDs). In contrast to clinically explored IDO1 inhibitors, iDegs reduce formation of kynurenine by both inhibition and induced degradation of the enzyme and should also modulate non-enzymatic functions of IDO1. This unique mechanism of action may open up new therapeutic opportunities for the treatment of cancer beyond classical inhibition of IDO1.
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Background: Cardiovascular diseases (CVDs) are the leading age-related disorders worldwide, with their prevalence increasing annually. Cathepsins are protein-degrading enzymes essential for processes such as intracellular protein breakdown, apoptosis, and immune responses. Recent studies suggest a potential link between cathepsins and CVDs, yet the exact causal relationship remains to be elucidated. To address this, we propose using Mendelian randomization (MR) to explore the causal relationships between cathepsins and CVDs. Methods: We obtained single nucleotide polymorphism (SNP) data for cathepsins from the INTERVAL study, a publicly accessible genome-wide association study (GWAS) dataset. Outcome SNP data were sourced from seven distinct GWAS datasets, ensuring a comprehensive analysis across multiple cardiovascular outcomes. For MR analysis, we primarily employed the inverse variance weighted (IVW) method, known for its efficiency when all SNPs are valid instruments. This was supplemented by the weighted median and MR-Egger methods to provide robustness against potential violations of MR assumptions, such as pleiotropy. The IVW method offers precision and efficiency, the weighted median method adds robustness against invalid instruments, and the MR-Egger method helps identify and correct for pleiotropic biases. Cochran's Q test was utilized to assess heterogeneity, and sensitivity analyses were conducted using MR-PRESSO and the leave-one-out approach. Results: The strength of the associations between exposure and outcome was measured using odds ratios (ORs), and results were presented with 95% confidence intervals (CIs). The cathepsin E increases the risk of myocardial infarction (MI) (OR = 1.053%, 95% CI: 1.007-1.101, p = 0.024) and ischemic stroke (IS) (OR = 1.06%, 95% CI: 1.019-1.103, p = 0.004). Conversely, cathepsin L2 decreases the risk of chronic heart failure (CHF) (OR = 0.922%, 95% CI: 0.859-0.99, p = 0.025) and atrial fibrillation (AF) (OR = 0.956%, 95% CI: 0.918-0.996, p = 0.033). Cathepsin O was associated with an increased risk of IS (OR = 1.054%, 95% CI: 1.008-1.102, p = 0.021) and AF (OR = 1.058%, 95% CI: 1.02-1.098, p = 0.002). Conclusion: Our MR analysis reveals that cathepsin E is a risk factor for MI and IS, cathepsin L2 offers protective effects against CHF and AF, and cathepsin O increases the risk for IS and AF.
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Magnons, bosonic quasiparticles carrying angular momentum, can flow through insulators for information transmission with minimal power dissipation. However, it remains challenging to develop a magnon-based logic due to the lack of efficient electrical manipulation of magnon transport. Here we show the electric excitation and control of multiferroic magnon modes in a spin-source/multiferroic/ferromagnet structure. We demonstrate that the ferroelectric polarization can electrically modulate the magnon-mediated spin-orbit torque by controlling the non-collinear antiferromagnetic structure in multiferroic bismuth ferrite thin films with coupled antiferromagnetic and ferroelectric orders. In this multiferroic magnon torque device, magnon information is encoded to ferromagnetic bits by the magnon-mediated spin torque. By manipulating the two coupled non-volatile state variables-ferroelectric polarization and magnetization-we further present reconfigurable logic operations in a single device. Our findings highlight the potential of multiferroics for controlling magnon information transport and offer a pathway towards room-temperature voltage-controlled, low-power, scalable magnonics for in-memory computing.
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This study aimed to investigate the impact of different strains of Lactiplantibacillus plantarum on malolactic fermentation (MLF), antioxidant activity, and aroma of ciders. A commercial strain of Saccharomyces cerevisiae and six indigenous L. plantarum strains were co-inoculated into apple juice to induce simultaneous alcoholic fermentation (AF) and MLF. The findings indicated that despite belonging to the same species, the different L. plantarum strains significantly differed (p < 0.05) in terms of antioxidant activity and aroma compounds in the ciders. MLF induced by L. plantarum resulted in the substantial consumption of malic acid and increased levels of lactic acid in the ciders, with strain-specific effects observed, particularly with L. plantarum SCFF284. In addition, ciders produced from mixed fermentations exhibited higher levels of antioxidant activity than those from pure S. cerevisiae fermentation (p < 0.05), especially for LAM284. Furthermore, ciders produced from mixed fermentations exhibited higher levels of aroma compounds, such as ethyl acetate and isoamyl alcohol, and also received higher sensory scores compared to ciders produced through pure S. cerevisiae fermentation (p < 0.05). These results highlight the effectiveness of MLF induced by L. plantarum in enhancing the antioxidant activity and aroma profile of ciders.
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BACKGROUND: Colorectal cancer, which originates from the human colon or rectum, is one of the leading causes of death worldwide. Timely diagnosis and interventional therapy can significantly improve the prognostic survival of colorectal cancer patients, making regular screening and early detection essential. AIM: To investigate the regulatory function of lncRNA CTBP1-DT (CTBP1-DT) on colorectal cancer cells and to assess its diagnostic significance. METHODS: A total of 102 patients with colorectal cancer and 92 healthy individuals were selected. The levels of CTBP1-DT and microRNA-30a-5p (miR-30a-5p) in serum and cell samples of the above subjects were compared by RT-qPCR. The effects of CTBP1-DT and miR-30a-5p dysregulation on the biological functions of colorectal cancer cells were analyzed via CCK-8, flow cytometry and Transwell assays. In addition, the ability of CTBP1-DT and miR-30a-5p to early identify colorectal cancer patients was determined through ROC curve. RESULTS: Serum CTBP1-DT was elevated in patients with colorectal cancer, which was obviously higher than in healthy controls. The expression of serum miR-30a-5p was downregulated in colorectal cancer. Both CTBP1-DT and miR-30a-5p have the value of distinguishing colorectal cancer, and the combined diagnostic ability is higher. Knockdown of CTBP1-DT directly targeted miR-30a-5p to repress cell activity and metastatic ability, whereas deregulation of miR-30a-5p eliminated the above inhibitory effects. CONCLUSION: Overexpression of CTBP1-DT has a certain application potential in the diagnosis of colorectal cancer and may be a therapeutic target for colorectal cancer.
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The liver plays a crucial role in maintaining systemic iron homeostasis by secreting hepcidin, which is essential for coordinating iron levels in the body. Imbalances in iron homeostasis are associated with various clinical disorders related to iron deficiency or iron overload. Despite the clinical significance, the mechanisms underlying how hepatocytes sense extracellular iron levels to regulate hepcidin synthesis and iron storage are not fully understood. In this study, we identified Foxo1, a well-known regulator of macronutrient metabolism, that translocates to the nucleus of hepatocytes in response to high-iron feeding, holo-transferrin, and BMP6 treatment. Furthermore, Foxo1 plays a crucial role in mediating hepcidin induction in response to both iron and BMP signals by directly interacting with evolutionally conserved Foxo binding sites within the hepcidin promoter region. These binding sites were found to colocalize with Smad-binding sites. To investigate the physiological relevance of Foxo1 in iron metabolism, we generated mice with hepatocyte-specific deletion of Foxo1. These mice exhibited reduced hepatic hepcidin expression and serum hepcidin levels, accompanied by elevated serum iron and liver non-heme iron concentrations. Moreover, high-iron diet further exacerbated these abnormalities in iron metabolism in mice lacking hepatic Foxo1. Conversely, hepatocyte-specific Foxo1 overexpression increased hepatic hepcidin expression and serum hepcidin levels, thereby ameliorating iron overload in a murine model of hereditary hemochromatosis (Hfe-/- mice). In summary, our study identifies Foxo1 is a critical regulator of hepcidin and systemic iron homeostasis. Targeting Foxo1 may offer therapeutic opportunities for managing conditions associated with aberrant iron metabolism.
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BACKGROUND: Uncertainties still existed about the effect of high-quality protein supplementation on cardiovascular disease (CVD) risk factors, although high-quality proteins such as soy and milk proteins have proposed to be beneficial for cardiometabolic health. METHODS: A systematic search in PubMed, Web of Science, Cochrane Library, Scopus, and Embase was conducted to quantify the impact of high-quality protein on CVD risk factors. RESULTS: 63 RCTs on 4 types of high-quality protein including soy protein, milk protein, whey, and casein were evaluated. Soy protein supplementation decreased systolic blood pressure (SBP, -1.42 [-2.68, -0.17] mmHg), total cholesterol (TC, -0.18 [-0.30, -0.07] mmol/L), and low-density lipoprotein cholesterol (LDL-C, -0.16 [-0.27, -0.05] mmol/L). Milk protein supplementation decreased SBP (-2.30 [-3.45, -1.15] mmHg) and total cholesterol (-0.27 [-0.51, -0.03] mmol/L). Whey supplementation decreased SBP (-2.20 [-3.89, -0.51] mmHg), diastolic blood pressure (DBP, -1.07 [-1.98, -0.16] mmHg), triglycerides (-0.10 [-0.17, -0.03] mmol/L), TC (-0.18 [-0.35, -0.01] mmol/L), LDL-C (-0.09 [-0.16, -0.01] mmol/L) and fasting blood insulin (FBI, -2.02 [-3.75, -0.29] pmol/L). Casein supplementation decreased SBP (-4.10 [-8.05, -0.14] mmHg). In the pooled analysis of four high-quality proteins, differential effects were seen in individuals with different health status. In hypertensive individuals, high-quality proteins decreased both SBP (-2.69 [-3.50, -1.87] mmHg) and DBP (-1.34 [-2.09, -0.60] mmHg). In overweight/obese individuals, high-quality proteins improved SBP (-1.40 [-2.22, -0.59] mmHg), DBP (-2.59 [-3.20, -1.98] mmHg), triglycerides (-0.09 [-0.15, -0.02] mmol/L), TC (-0.14 [-0.22, -0.05] mmol/L), LDL-C (-0.12 [-0.16, -0.07] mmol/L), and HDL-C levels (0.02 [0.01, 0.04] mmol/L). According to the benefits on CVD risks factors, whey ranked top for improving cardiometabolic health in hypertensive or overweight/obese individuals. CONCLUSION: Our study supports a beneficial role of high-quality protein supplementation to reduce CVD risk factors. Further studies are still warranted to investigate the effects of different high-quality proteins on CVD risks in individuals with cardiometabolic disorders.
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Maladies cardiovasculaires , Compléments alimentaires , Facteurs de risque de maladie cardiaque , Maladies métaboliques , Essais contrôlés randomisés comme sujet , Humains , Maladies cardiovasculaires/prévention et contrôle , Maladies métaboliques/prévention et contrôle , Protéines alimentaires/administration et posologie , Protéines de soja/administration et posologie , Protéines de lait/administration et posologie , Pression sanguine/effets des médicaments et des substances chimiques , Protéines de lactosérum/administration et posologie , Facteurs de risqueRÉSUMÉ
PURPOSE: Head and neck cancer is the sixth most common type of cancer worldwide, wherein the immune responses are closely associated with disease occurrence, development, and prognosis. Investigation of the role of immunogenic cell death-related genes (ICDGs) in adaptive immune response activation may provide cues into the mechanism underlying the outcome of HNSCC immunotherapy. METHODS: ICDGs expression patterns in HNSCC were analyzed, after which consensus clustering in HNSCC cohort conducted. A 4-gene prognostic model was constructed through LASSO and Cox regression analyses to analyze the prognostic index using the TCGA dataset, followed by validation with two GEO datasets. The distribution of immune cells and the response to immunotherapy were compared between different risk subtypes through multiple algorithms. Moreover, immunohistochemical (IHC) analyses were conducted to validate the prognostic value of HSP90AA1 as a predictor of HNSCC patient prognosis. In vitro assays were performed to further detect the effect of HSP90AA1 in the development of HNSCC. RESULTS: A novel prognostic index based on four ICDGs was constructed and proved to be useful as an independent factor of HNSCC prognosis. The risk score derived from this model grouped patients into high- and low-risk subtypes, wherein the high-risk subtype had worse survival outcomes and poorer immunotherapy response. IHC analysis validated the applicability of HSP90AA1 as a predictor of prognosis of HNSCC patients. HSP90AA1 expression in tumor cells promotes the progression of HNSCC. CONCLUSIONS: Together, these results highlight a novel four-gene prognostic signature as a valuable tool to assess survival status and prognosis of HNSCC patients.
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Protéines du choc thermique HSP90 , Tumeurs de la tête et du cou , Carcinome épidermoïde de la tête et du cou , Humains , Carcinome épidermoïde de la tête et du cou/immunologie , Carcinome épidermoïde de la tête et du cou/génétique , Carcinome épidermoïde de la tête et du cou/anatomopathologie , Carcinome épidermoïde de la tête et du cou/métabolisme , Pronostic , Protéines du choc thermique HSP90/génétique , Protéines du choc thermique HSP90/métabolisme , Tumeurs de la tête et du cou/immunologie , Tumeurs de la tête et du cou/anatomopathologie , Tumeurs de la tête et du cou/génétique , Tumeurs de la tête et du cou/métabolisme , Femelle , Mâle , Mort cellulaire immunogène , Marqueurs biologiques tumoraux/génétique , Marqueurs biologiques tumoraux/métabolisme , Adulte d'âge moyen , Immunothérapie/méthodes , Régulation de l'expression des gènes tumorauxRÉSUMÉ
The prognosis of patients diagnosed with relapsed or refractory (R/R) T-lymphoblastic leukemia/lymphoma (T-ALL/LBL) has consistently been unsatisfactory, with limited treatment options. As reports, the CAG regimen can serve as a salvage treatment for R/R T-ALL/LBL, but there remains a subset of patients who do not benefit from it. Recent studies have indicated that daratumumab (Dara) and venetoclax (Ven) may offer promising therapeutic benefits for T-ALL/LBL. In light of these findings, we conducted a safety and efficacy evaluation of the enhanced treatment regimen, combining Dara and Ven with aclarubicin, cytarabine, granulocyte colony-stimulating factor, and etoposide (CAGE), in patients suffering from R/R T-ALL/LBL. The participants in this phase I trial were patients with R/R T-ALL/LBL who fail to standard treatment regimens. During each 28-day cycle, the patients were treated by Dara, Ven, cytarabine, aclarubicin, granulocyte colony-stimulating factor, etoposide. The primary endpoint of this study was the rate of remission. This report presents the prospective outcomes of 21 patients who received the salvage therapy of Dara and Ven combined with the CAGE regimen (Dara + Ven + CAGE). The objective remission rate (ORR) was determined to be 57.1%, while the complete remission (CR) rate was 47.6%. Notably, patients with the early T-cell precursor (ETP) subtype exhibited a significantly higher remission rate in the bone marrow compared to non-ETP patients (100% vs. 44.4%, p = 0.044). The Dara + Ven + CAGE regimen demonstrated a favorable remission rate in patients with R/R T-ALL/LBL. Moreover, the treatment was well-tolerated.
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Anticorps monoclonaux , Protocoles de polychimiothérapie antinéoplasique , Composés hétérocycliques bicycliques , Cytarabine , Étoposide , Sulfonamides , Humains , Sulfonamides/administration et posologie , Sulfonamides/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/usage thérapeutique , Protocoles de polychimiothérapie antinéoplasique/effets indésirables , Protocoles de polychimiothérapie antinéoplasique/administration et posologie , Mâle , Femelle , Adulte d'âge moyen , Adulte , Étoposide/administration et posologie , Étoposide/effets indésirables , Étoposide/usage thérapeutique , Cytarabine/administration et posologie , Cytarabine/usage thérapeutique , Composés hétérocycliques bicycliques/usage thérapeutique , Composés hétérocycliques bicycliques/administration et posologie , Anticorps monoclonaux/usage thérapeutique , Anticorps monoclonaux/administration et posologie , Anticorps monoclonaux/effets indésirables , Facteur de stimulation des colonies de granulocytes/usage thérapeutique , Facteur de stimulation des colonies de granulocytes/administration et posologie , Leucémie-lymphome lymphoblastique à précurseurs T/traitement médicamenteux , Aclarubicine/administration et posologie , Aclarubicine/usage thérapeutique , Jeune adulte , Thérapie de rattrapage , Sujet âgé , AdolescentRÉSUMÉ
BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as key players in tumorigenesis and tumour progression. However, the biological functions and potential mechanisms of lncRNAs in colorectal cancer (CRC) are unclear. METHODS: The novel lncRNA POU6F2-AS1 was identified through bioinformatics analysis, and its expression in CRC patients was verified via qRT-PCR and FISH. In vitro and in vivo experiments, such as BODIPY staining, Oil Red O staining, triglyceride (TAG) assays, and liquid chromatography mass spectrometry (LC-MS) were subsequently performed with CRC specimens and cells to determine the clinical significance, and functional roles of POU6F2-AS1. Biotinylated RNA pull-down, RIP, Me-RIP, ChIP, and patient-derived organoid (PDO) culture assays were performed to confirm the underlying mechanism of POU6F2-AS1. RESULTS: The lncRNA POU6F2-AS1 is markedly upregulated in CRC and associated with adverse clinicopathological features and poor overall survival in CRC patients. Functionally, POU6F2-AS1 promotes the growth and lipogenesis of CRC cells both in vitro and in vivo. Mechanistically, METTL3-induced m6A modification is involved in the upregulation of POU6F2-AS1. Furthermore, upregulated POU6F2-AS1 could tether YBX1 to the FASN promoter to induce transcriptional activation, thus facilitating the growth and lipogenesis of CRC cells. CONCLUSIONS: Our data revealed that the upregulation of POU6F2-AS1 plays a critical role in CRC fatty acid metabolism and might provide a novel promising biomarker and therapeutic target for CRC.
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Tumeurs colorectales , microARN , ARN long non codant , Humains , ARN long non codant/génétique , ARN long non codant/métabolisme , Régulation positive , Lignée cellulaire tumorale , Prolifération cellulaire/génétique , microARN/génétique , Tumeurs colorectales/anatomopathologie , Acides gras , Régulation de l'expression des gènes tumoraux , Mouvement cellulaire/génétique , Facteurs de transcription à domaine POU/génétique , Facteurs de transcription à domaine POU/métabolisme , Methyltransferases/métabolisme , Fatty acid synthase type I/génétique , Fatty acid synthase type I/métabolismeRÉSUMÉ
Inconsistent findings exist regarding the relationship between heme iron intake and type 2 diabetes (T2D) among Western and Eastern populations. Easterners tend to consume a plant-based diet which is abundant in antioxidant minerals. To examine the hypothesis that antioxidant mineral may modify the relationship between iron and T2D, we performed a case-control study by measuring the serum mineral levels in 2198 Chinese subjects. A total of 2113 T2D patients and 2458 controls were invited; 502 T2D patients and 1696 controls were finally analyzed. In the total population, high serum iron showed a positive association with T2D odds (odds ratio [OR] = 1.27 [1.04, 1.55]); high magnesium (OR = 0.18 [0.14, 0.22]), copper (OR = 0.27 [0.21, 0.33]), zinc (OR = 0.37 [0.30, 0.46]), chromium (OR = 0.61 [0.50, 0.74]), or selenium concentrations (OR = 0.39 [0.31, 0.48]) were inversely associated with T2D odds. In contrast, in individuals with higher magnesium (>2673.2 µg/dL), zinc (>136.7 µg/dL), copper (>132.1 µg/dL), chromium (>14.0 µg/dL), or selenium concentrations (>16.8 µg/dL), serum iron displayed no association with T2D (p > 0.05). Serum copper and magnesium were significant modifiers of the association between iron and T2D in individuals with different physiological status (p < 0.05). Our findings support the idea that consuming a diet rich in antioxidant minerals is an effective approach for preventing T2D.
Sujet(s)
Diabète de type 2 , Sélénium , Humains , Fer , Antioxydants , Magnésium , Cuivre , Diabète de type 2/épidémiologie , Études cas-témoins , Minéraux , Zinc , Chrome , ChineRÉSUMÉ
Magnetic skyrmions have great potential for developing novel spintronic devices. The electrical manipulation of skyrmions has mainly relied on current-induced spin-orbit torques. Recently, it was suggested that the skyrmions could be more efficiently manipulated by surface acoustic waves (SAWs), an elastic wave that can couple with magnetic moment via the magnetoelastic effect. Here, by designing on-chip piezoelectric transducers that produce propagating SAW pulses, we experimentally demonstrate the directional motion of Néel-type skyrmions in Ta/CoFeB/MgO/Ta multilayers. We find that the shear horizontal wave effectively drives the motion of skyrmions, whereas the elastic wave with longitudinal and shear vertical displacements (Rayleigh wave) cannot produce the motion of skyrmions. A longitudinal motion along the SAW propagation direction and a transverse motion due to topological charge are simultaneously observed and further confirmed by our micromagnetic simulations. This work demonstrates that acoustic waves could be another promising approach for manipulating skyrmions, which could offer new opportunities for ultra-low power skyrmionics.
RÉSUMÉ
Background: The effect of pain genes (NAV1, EHMT2, SP1, SLC6A4, COMT, OPRM1, OPRD1, CYP2D6, and CYP3A4) have not been reported previously in kidney renal clear cell carcinoma (KIRC) patients and thus we made a comprehensive analysis of pain genes in the prognosis of KIRC and tumor immunotherapy. Methods: In this study, TCGA, Kaplan-Meier plotter, Metascape, STRING, Human Protein Atlas, Single Cell Expression Atlas database, LinkedOmics, cBioPortal, MethSurv, CancerSEA, COSMIC database and R package (ggplot2, version 3.3.3) were used for comprehensive analysis of pain genes in KIRC. Pearson and Spearman correlation coefficients were for co-expression analysis. Immunotherapy and TISIDB database were used for tumor Immunotherapy. Results: Representative pain genes (SP1, SLC6A4, COMT, OPRD1, CYP2D6, and CYP3A4) were statistically significant (p < 0.0001) in the prognosis of KIRC. Immunotherapy (anti-PD-1 therapy, anti-PD-L1 therapy, and anti-CTLA4 therapy) and immunomodulator (immunoinhibitor, immunostimulator, and MHC molecule) in KIRC were significant associated with pain genes (SP1, SLC6A4, COMT, OPRD1, CYP2D6, and CYP3A4), which were the important addition to clinical decision making for patients. Conclusions: Our study uncovered a mechanism for the effect of pain genes on KIRC outcome via the modulation of associated co-expression gene networks, gene variation, and tumor Immunotherapy.
RÉSUMÉ
Noncolinear spin textures, including chiral stripes and skyrmions, have shown great potential in spintronics. Basic configurations of spin textures are either Bloch or Néel types, and the intermediate hybrid type has rarely been reported. A major challenge in identifying hybrid spin textures is to quantitatively determine the hybrid angle, especially in ferrimagnets with weak net magnetization. Here, we develop an approach to quantify magnetic parameters, including chirality, saturation magnetization, domain wall width, and hybrid angle with sub-5 nm spatial resolution, based on Lorentz four-dimensional scanning transmission electron microscopy (Lorentz 4D-STEM). We find strong nanometer-scale variations in the hybrid angle and domain wall width within structurally and chemically homogeneous FeGd ferrimagnetic films. These variations fluctuate during different magnetization circles, revealing intrinsic local magnetization inhomogeneities. Furthermore, hybrid skyrmions can also be nucleated in FeGd films. These analyses demonstrate that the Lorentz 4D-STEM is a quantitative tool for exploring complex spin textures.