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Current reconstruction chemistry studies are mainly operated at the laboratory scale, where the operating parameters are different from those used in industrial water electrolyzers. This gap leads to unclear reconstruction behaviors under industrial conditions and constrains the application of catalysts. Here, this work presents a new reconstruction mechanism and anomalous detachment phenomena observed in leaching-type oxygen-evolving precatalysts under industrial conditions, different from the reported results obtained under laboratory conditions. The identified detachment issues are closely linked to the production of a potassium salt separate phase, which proves sensitive to the local environment, and its instability easily leads to catalyst stripping from the substrate. By establishing detachment critical point and operating parameter-detachment correlation, a targeted reconstruction strategy is proposed to achieve smooth ligand leaching and effectively solve the detachment issue. Theoretical analyses validate the dual-site regulation in directionally reconstructed catalysts with optimized intermediate adsorption. Under industrial conditions, the coupled electrolyzer delivers an industrial-level current density at low cell voltage with prolonged durability, 1 A cm-2 at 2 V for over 340 h. This work bridges the gap of leaching-type precatalysts between laboratory test conditions and industrial operating conditions.
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BACKGROUND: An mRNA-based RSV vaccine, mRNA-1345, is under clinical investigation to address RSV disease burden in older adults. METHODS: This phase 1, randomized, observer-blind, placebo-controlled, dose-ranging study evaluated safety, reactogenicity, and immunogenicity of mRNA-1345 in adults 65-79 years (NCT04528719). Participants were randomized to receive 1-dose of mRNA-1345 (12.5, 25, 50, 100, or 200-µg) or placebo and matched mRNA-1345 booster or placebo at 12-months. RESULTS: Overall, 298 participants received the first injection; 247 received the 12-month booster injection. mRNA-1345 was generally well-tolerated after both injections, with the most frequently reported solicited adverse reactions being injection-site pain, fatigue, headache, arthralgia, and myalgia. Reactogenicity was higher after the booster injection than the first injection but similar severity, time-to-onset, and duration. A single mRNA-1345 injection boosted RSV-A and RSV-B neutralizing antibody titers (nAb) and prefusion-F-binding antibody (preF-bAb) concentrations at 1-month (geometric mean-fold rises: RSV-A, 10.2-16.5; RSV-B, 5.3-12.5; preF-bAb, 7.2-12.1). RSV antibody levels remained above baseline through 12-months, indicating immune persistence. A 12-month booster injection also increased RSV-A and RSV-B nAb titers and preF-bAb concentrations; titers post-booster injection were numerically lower compared to titers after the first-dose, with overlapping 95% CIs. CONCLUSIONS: mRNA-1345 was well-tolerated and immunogenic following a single injection and a 12-month booster. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04528719.
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BACKGROUND: Chimeric antigen receptor (CAR) T cells for refractory or relapsed (r/r) B cell no-Hodgkin lymphoma (NHL) patients have shown promising clinical effectiveness. However, the factors impacting the clinical response of CAR-T therapy have not been fully elucidated. We here investigate the independent influencing factors of the efficacy of CD19 CAR-T cell infusion in the treatment of r/r B-NHL and to establish an early prediction model. METHODS: A total of 43 r/r B-NHL patients were enrolled in this retrospective study. The patients' general data were recorded, and the primary endpoint is the patients' treatment response. The independent factors of complete remission (CR) and partial remission (PR) were investigated by univariate and binary logistic regression analysis, and the prediction model of the probability of CR was constructed according to the determined independent factors. Receiver operating characteristic (ROC) and calibration plot were used to assess the discrimination and calibration of the established model. Furthermore, we collected 15 participators to validate the model. RESULTS: Univariate analysis and binary logistic regression analysis of 43 patients showed that the ratio of central memory T cell (Tcm) and naïve T cell (Tn) in cytotoxic T cells (Tc) was an independent risk factor for response to CD19 CAR-T cell therapy in r/r B-NHL. On this basis, the area under the curve (AUC) of Tcm in the Tc and Tn in the Tc nomogram model was 0.914 (95%CI 0.832-0.996), the sensitivity was 83%, and the specificity was 74.2%, which had excellent predictive value. We did not found the difference of the progression-free survival (PFS). CONCLUSIONS: The ratio of Tcm and Tn in Tc was found to be able to predict the treatment response of CD19 CAR-T cells in r/r B-NHL. We have established a nomogram model for the assessment of the CD19 CAR-T therapy response presented high specificity and sensitivity.
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Receptores Quiméricos de Antígenos , Humanos , Nomogramas , Estudios Retrospectivos , Inmunoterapia Adoptiva , Subgrupos de Linfocitos T , Antígenos CD19RESUMEN
Chimeric antigen receptor T (CAR-T) cell therapy targeting CLL1 has been considered a potent weapon for patients with acute myeloid leukemia (AML). This study aims to evaluate the efficacy and toxicity of CLL1 CAR-T cell therapy in a larger cohort, with particular attention to cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Among the 32 patients assessed for efficacy, complete remission occurred in 71.88% (23/32) of cases and undetectable minimal residual disease in 14 patients. The CRS developed in all patients, with 8 individuals experiencing ICANS. Severe CRS and ICANS were observed in 11 and 2 patients, respectively. Furthermore, the Endothelial Activation and Stress Index (EASIX) and its derivatives measured before and after CLL1 CAR-T cell infusion were employed for predicting the severe complications. Significant differences were observed in EASIX scores on the day before lymphodepletion (Day BL, P = 0.023), -1 (P < 0.001), +1 (P < 0.001), and +3(P = 0.014); sEASIX scores on Day BL (P = 0.007), -1 (P < 0.001), +1 (P < 0.001), and +3 (P < 0.001); and mEASIX score on Day -1 (P = 0.004) between patients with mild and severe CRS/ICANS. Additionally, there was a significant difference in mEASIX scores between responders and non-responders on Day BL (P = 0.004) and Day -1 (P = 0.044). Our findings indicate that pre- and post-infusion assessments of EASIX/mEASIX/sEASIX scores serve as reliable prognostic indicators for severe CRS/ICANS and treatment response following CLL1 CAR-T cell therapy, which can assist physicians in implementing preemptive treatment strategies for potential severe complications and screening patients who are suitable candidates for CLL1 CAR-T cell therapy. EASIX/mEASIX/sEASIX scores serve as reliable prognostic indicators for severe CRS/ICANS following CLL1 CAR-T cell therapy. The preinfusion mEASIX scores of CLL1 CAR-T cells can effectively predict treatment response.
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Leucemia Mieloide Aguda , Síndromes de Neurotoxicidad , Receptores Quiméricos de Antígenos , Humanos , Síndrome de Liberación de Citoquinas , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Tratamiento Basado en Trasplante de Células y TejidosRESUMEN
BACKGROUND: The Interferon-induced protein with tetratricopeptide repeat (IFIT) family, IFIT1/2/3/5, play an important role in different tumors progression. However, the prognosis significance and biological role of IFIT family members in acute myeloid leukemia (AML) remains unclear. METHODS: We obtained the gene expression data and clinical information of 173 AML patients from The Cancer Genome Atlas (TCGA) database. Several databases were used in our study, including GEPIA, MethSurv, STRING, GSCA and GeneMANIA database. RESULTS: The mRNA expression of IFIT1/2/3/5 was elevated in AML patients and had a high ability to distinguish AML from controls based on the receiver operating characteristic (ROC) curve (AUC > 0.9). Kaplan-Meier survival analysis showed that higher levels of IFIT2/3/5 expression predict poor prognosis in AML patients. Besides, the DNA methylation analysis suggested that 7 CpG sites of IFIT2, 4 CpG sites of IFIT3 and 10 CpG sites of IFIT5 were significantly associated with the prognosis of AML patients. In addition, IFIT2/3/5 expression was significantly positively associated with the immune cell infiltration and immune checkpoint expression, such as CTLA4, PDCD1, LAG3, and TIGIT. Finally, drug sensitivity analysis revealed that AML patients with high expression of IFIT2/3/5 were resistant to multiple drugs, but sensitive to dasatinib. CONCLUSION: IFIT family genes might serve as biomarkers for diagnosis, prognosis and drug sensitivity in AML patients. The activation or blocking of IFIT-related signaling pathways may provide novel insights into immunotherapy for patients with AML.
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Leucemia Mieloide Aguda , Humanos , Pronóstico , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Interferones , Transducción de SeñalRESUMEN
OPINION STATEMENT: Acute myeloid leukemia (AML) is a fatal blood malignancy. With the development of immunotherapy, particularly chimeric antigen receptor T cells (CAR-T), the treatment of AML has undergone a significant change. Despite its advantages, CAR-T still faces a number of limitations and challenges while treating AML. Finding novel targets, altering the structure of CAR to increase efficacy while lowering side effects, and using double-target CAR and logic circuits are typical examples of key to answer these problems. With the advancement of gene editing technology, gene editing of tumor cells or normal cells to create therapeutic effects has grown in popularity. Additionally, the combination of multiple drugs is routinely used to address some of the obstacles and difficulties associated with CAR-T therapy. The review's primary goal was to summarize recent strategies and developments of CAR-T therapy for AML.
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Leucemia Mieloide Aguda , Receptores Quiméricos de Antígenos , Humanos , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/uso terapéutico , Linfocitos T , Inmunoterapia Adoptiva/efectos adversos , Leucemia Mieloide Aguda/genética , InmunoterapiaRESUMEN
T-cell acute lymphoblastic leukemia (T-ALL) is a highly heterogeneous and aggressive subtype of hematologic malignancy, with limited therapeutic options due to the complexity of its pathogenesis. Although high-dose chemotherapy and allogeneic hematopoietic stem cell transplantation have improved outcomes for T-ALL patients, there remains an urgent need for novel treatments in cases of refractory or relapsed disease. Recent research has demonstrated the potential of targeted therapies aimed at specific molecular pathways to improve patient outcomes. Chemokine-related signals, both upstream and downstream, modulate the composition of distinct tumor microenvironments, thereby regulating a multitude of intricate cellular processes such as proliferation, migration, invasion and homing. Furthermore, the progress in research has made significant contributions to precision medicine by targeting chemokine-related pathways. This review article summarizes the crucial roles of chemokines and their receptors in T-ALL pathogenesis. Moreover, it explores the advantages and disadvantages of current and potential therapeutic options that target chemokine axes, including small molecule antagonists, monoclonal antibodies, and chimeric antigen receptor T-cells.
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Trasplante de Células Madre Hematopoyéticas , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Quimiocinas , Anticuerpos Monoclonales , Linfocitos T , Inmunoterapia Adoptiva/efectos adversos , Microambiente TumoralRESUMEN
The intestine is critically crucial for nutrient absorption and host defense against exogenous stimuli. Inflammation-related intestinal diseases, including enteritis, inflammatory bowel disease (IBD), and colorectal cancer (CRC), are heavy burdens for human beings due to their high incidence and devastating clinical symptoms. Current studies have confirmed that inflammatory responses, along with oxidative stress and dysbiosis as critical pathogenesis, are involved in most intestinal diseases. Polyphenols are secondary metabolites derived from plants, which possess convincible anti-oxidative and anti-inflammatory properties, as well as regulation of intestinal microbiome, indicating the potential applications in enterocolitis and CRC. Actually, accumulating studies based on the biological functions of polyphenols have been performed to investigate the functional roles and underlying mechanisms over the last few decades. Based on the mounting evidence of literature, the objective of this review is to outline the current research progress regarding the category, biological functions, and metabolism of polyphenols within the intestine, as well as applications for the prevention and treatment of intestinal diseases, which might provide ever-expanding new insights for the utilization of natural polyphenols.
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Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Humanos , Polifenoles/farmacología , Polifenoles/uso terapéutico , Enfermedades Inflamatorias del Intestino/metabolismo , Intestinos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Microbioma Gastrointestinal/fisiologíaRESUMEN
PURPOSE: Acute myeloid leukemia (AML) is a highly heterogeneous neoplastic disease with a poor prognosis that relapses even after its treatment with chimeric antigen receptor (CAR)-T cells targeting a single antigen. CD123 and CLL1 are expressed in most AML blasts and leukemia stem cells, and their low expression in normal hematopoietic stem cells makes them ideal targets for CAR-T. In this study, we tested the hypothesis that a new bicistronic CAR targeting CD123 and CLL1 can enhance antigenic coverage and prevent antigen escape and subsequent recurrence of AML. METHODS: CD123 and CLL1 expressions were evaluated on AML cell lines and blasts. Then, in addition to concentrating on CD123 and CLL1, we introduced the marker/suicide gene RQR8 with a bicistronic CAR. Xenograft models of disseminated AML and in vitro coculture models were used to assess the anti-leukemia efficacy of CAR-T cells. The hematopoietic toxicity of CAR-T cells was evaluated in vitro by colony cell formation assays. It was demonstrated in vitro that the combination of rituximab and NK cells caused RQR8-mediated clearance of 123CL CAR-T cells. RESULTS: We have successfully established bicistronic 123CL CAR-T cells that can target CD123 and CLL1. 123CL CAR-T cells effectively cleared AML cell lines and blasts. They also demonstrated appreciable anti-AML activity in animal transplant models. Moreover, 123CL CAR-T cells can be eliminated in an emergency by a natural safety switch and don't target hematopoietic stem cells. CONCLUSIONS: The bicistronic CAR-T cells targeting CD123 and CLL1 may be a useful and secure method for treating AML.
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The high expression of CD7 targets in T-cell acute lymphoblastic leukemia (T-ALL) and T-lymphoma has attracted considerable attention from researchers. However, because CD7 chimeric antigen receptor (CAR) T-cells undergo fratricide, CD7 CAR T-cells develop an exhaustion phenotype that impairs the effect of CAR T-cells. There have been significant breakthroughs in CD7-targeted CAR T-cell therapy in the past few years. The advent of gene editing, protein blockers, and other approaches has effectively overcome the adverse effects of conventional methods of CD7 CAR T-cells. This review, in conjunction with recent advances in the 64th annual meeting of the American Society of Hematology (ASH), provides a summary of the meaningful achievements in CD7 CAR T-cell generations and clinical trials over the last few years.
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Inmunoterapia Adoptiva , Leucemia Mieloide Aguda , Linfoma , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Humanos , Linfoma/metabolismo , Linfocitos TRESUMEN
EpsteinâBarr virus (EBV) is a human herpes virus that is saliva-transmissible and universally asymptomatic. It has been confirmed that more than 90% of the population is latently infected with EBV for life. EBV can cause a variety of related cancers, such as nasopharyngeal carcinoma, diffuse large B-cell lymphoma, and Burkitt lymphoma. Currently, many clinical studies have demonstrated that EBV-specific cytotoxic T lymphocytes and other cell therapies can be safely and effectively transfused to prevent and treat some diseases caused by EBV. This review will mainly focus on discussing EBV-specific cytotoxic T lymphocytes and will touch on therapeutic EBV vaccines and chimeric antigen receptor T-cell therapy briefly.
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Linfoma de Burkitt , Infecciones por Virus de Epstein-Barr , Humanos , Herpesvirus Humano 4 , Linfoma de Burkitt/terapia , Linfocitos T Citotóxicos , InmunoterapiaRESUMEN
Chimeric antigen receptor T cell therapy (CAR-T) is a novel treatment that has produced unprecedented clinical effects in patients with hematological malignancies. Acute adverse events often occur following adoptive immunotherapy. Therefore, a suicide gene is helpful, which is a genetically encoded mechanism that allows selective destruction of adoptively transferred T cells in the face of unacceptable toxicity. RQR8 is a gene that integrates CD34 and CD20 epitopes. In our study, we incorporated the suicide gene RQR8 into CAR-T cells, so it enabled rituximab to eliminate vector/transgene-expressing T cells via antibody-dependent cell-mediated cytotoxicity and complement dependent cytotoxicity. In this work, we explored the functionality of RQR8 CAR-T cells in vitro and in vivo. We believe that RQR8 as a safety switch will make CAR-T cell therapy safer and less costly.
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Receptores Quiméricos de Antígenos , Linfocitos T , Humanos , Receptores Quiméricos de Antígenos/genética , Inmunoterapia Adoptiva , Rituximab , Apoptosis , Antígenos CD19/genéticaRESUMEN
Introduction: Hematologic toxicity (HT) is a joint adverse event after CAR-T cells infusion. Some patients experience prolonged hematologic toxicity (PHT), which is challenging to treat. Methods: We collected clinical data from patients with relapsed refractory B-ALL treated with CD19 CAR-T cells. Patients with PHT who did not respond to erythropoietin, platelet receptor agonists, transfusion, or G-CSF and eventually received low-dose prednisone therapy were included in the analysis. We retrospectively analyzed the efficacy and safety of low-dose prednisone on PHT. Results: Among 109 patients treated with CD19 CAR-T cells, 78.9% (86/109) of patients were evaluated as PHT. Of these, 15 patients had persistent hematological toxicity after infusion (12 were grade 3/4 cytopenia, 12 were trilineage cytopenia and 3 were bilineage cytopenia), 2 developed cytopenia without apparent cause after D28. The initial prednisone dose was 0.5 mg/kg/day, and the median response time was 21 days (7-40 days). The recovery rate of blood count was 100%, and the complete recovery rate ranged from 60% to 66.67%. Especially exciting was that HT recurred in 6 patients after stopping prednisone. They were relieved again after the administration of prednisone. The median follow-up time was 14.97 months (4.1-31.2 months). Twelve-month duration of PFS and OS rates were 58.8% (±11.9%) and 64.7% (±11.6%). We did not observe any other side effects of prednisone apart from drug-controllable hyperglycemia and hypertension. Discussion: We suggest that low-dose prednisone is a beneficial and tolerable therapy for PHT after CAR-T cells. The trials have been registered at www.chictr.org.cn as ChiCTR-ONN-16009862 (November 14, 2016) and ChiCTR1800015164 (March 11, 2018).
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Receptores Quiméricos de Antígenos , Humanos , Prednisona/efectos adversos , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Antígenos CD19 , Tratamiento Basado en Trasplante de Células y TejidosRESUMEN
Ion insertions always involve electrode-electrolyte interface process, desolvation for instance, which determines the electrochemical kinetics. However, it's still a challenge to achieve fast ion insertion and investigate ion transformation at interface. Herein, the interface deprotonation of NH4 + and the introduced dissociation of H2 O molecules to provide sufficient H3 O+ to insert into materials' structure for fast energy storages are revealed. Lewis acidic ion-NH4 + can, on one hand provide H3 O+ itself via deprotonation, and on the other hand hydrolyze with H2 O molecules to produce H3 O+ . In situ attenuated total reflection-Fourier transform infrared ray method probed the interface accumulation and deprotonation of NH4 + , and density functional theory calculations manifested that NH4 + tend to thermodynamically adsorb on the surface of monoclinic VO2 , and deprotonate to provide H3 O+ . In addition, the inserted NH4 + has a positive effect for stabilizing the VO2 (B) structure. Therefore, high specific capacity (>300â mAh g-1 ) and fast ionic insertion/extraction (<20â s) can be realized in VO2 (B) anode. This interface derivation proposes a new path for designing proton ion insertion/extraction in mild electrolyte.
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OPINION STATEMENT: Although chimeric antigen receptor T cell immunotherapy has been successfully applied in patients with hematological malignancies, several obstacles still need to be overcome, such as high relapse rates and side effects. Overcoming the limitations of CAR-T cell therapy and boosting the efficacy of CAR-T cell therapy are urgent issues that must be addressed. The exploration of small-molecule compounds in combination with CAR-T cell therapies has achieved promising success in pre-clinical and clinical studies in recent years. Protein kinase inhibitors, demethylating drugs, HDAC inhibitors, PI3K inhibitors, immunomodulatory drugs, Akt inhibitors, mTOR inhibitors, and Bcl-2 inhibitors exhibited potential synergy in combination with CAR-T cell therapy. In this review, we will discuss the recent application of these combination therapies for improved outcomes of CAR-T cell therapy.
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Neoplasias Hematológicas , Receptores Quiméricos de Antígenos , Humanos , Fosfatidilinositol 3-Quinasas , Inmunoterapia Adoptiva/efectos adversos , Neoplasias Hematológicas/terapia , Inhibidores de Proteínas Quinasas , Tratamiento Basado en Trasplante de Células y TejidosRESUMEN
lovo-cel (bb1111; LentiGlobin for sickle cell disease [SCD]) gene therapy (GT) comprises autologous transplantation of hematopoietic stem and progenitor cells transduced with the BB305 lentiviral vector encoding a modified ß-globin gene (ßA-T87Q ) to produce anti-sickling hemoglobin (HbAT87Q ). The efficacy and safety of lovo-cel for SCD are being evaluated in the ongoing phase 1/2 HGB-206 study (ClinicalTrials.gov: NCT02140554). The treatment process evolved over time, using learnings from outcomes in the initial patients to optimize lovo-cel's benefit-risk profile. Following modest expression of HbAT87Q in the initial patients (Group A, n = 7), alterations were made to the treatment process for patients subsequently enrolled in Group B (n = 2, patients B1 and B2), including improvements to cell collection and lovo-cel manufacturing. After 6 months, median Group A peripheral blood vector copy number (≥0.08 c/dg) and HbAT87Q levels (≥0.46 g/dL) were inadequate for substantial clinical effect but stable and sustained over 5.5 years; both markedly improved in Group B (patient B1: ≥0.53 c/dg and ≥2.69 g/dL; patient B2: ≥2.14 c/dg and ≥6.40 g/dL, respectively) and generated improved biologic and clinical efficacy in Group B, including higher total hemoglobin and decreased hemolysis. The safety of the lovo-cel for SCD treatment regimen largely reflected the known side effects of HSPC collection, busulfan conditioning regimen, and underlying SCD; acute myeloid leukemia was observed in two patients in Group A and deemed unlikely related to insertional oncogenesis. Changes made during development of the lovo-cel treatment process were associated with improved outcomes and provide lessons for future SCD GT studies.
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Anemia de Células Falciformes , Trasplante de Células Madre Hematopoyéticas , Humanos , Lentivirus/genética , Anemia de Células Falciformes/genética , Anemia de Células Falciformes/terapia , Terapia Genética/efectos adversos , Hemoglobinas/genéticaRESUMEN
Helicobacter pylori (H. pylori) is one of the main causes of gastric cancer. It has been reported that circRNAs play a vital role in the development of multiple types of cancer. However, the role of H. pylori-induced circRNAs in the development of gastric cancer has not been studied. In this study, we found that H. pylori could induce the upregulation of circMAN1A2 in AGS and BGC823 cells independent of CagA. The downregulation of circMAN1A2 could inhibit the proliferation, migration and invasion of gastric cancer cells, and circMAN1A2 could promote the progression of gastric cancer induced by H. pylori by sponging miR-1236-3p to regulate MTA2 expression. Furthermore, circMAN1A2 knockdown inhibited xenograft tumour growth in vivo, and the overexpression of circMAN1A2 was associated with the progression of gastric cancer. Hence, Helicobacter pylori induced circMAN1A2 expression to promote the carcinogenesis of gastric cancer, and circMAN1A2 might be a new potential diagnostic marker and therapeutic target for gastric cancer.
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Infecciones por Helicobacter , Helicobacter pylori , MicroARNs , Neoplasias Gástricas , Infecciones por Helicobacter/complicaciones , Infecciones por Helicobacter/genética , Infecciones por Helicobacter/metabolismo , Helicobacter pylori/metabolismo , Histona Desacetilasas/metabolismo , Humanos , MicroARNs/metabolismo , ARN Circular/genética , Proteínas Represoras/metabolismo , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismoRESUMEN
Uneven distribution of electric fields at the electrolyte-anode interface and associated Zn dendrite growth is one of the most critical barriers that limit the life span of aqueous zinc-ion batteries. Herein, new-type Zn-A-O (A = Si, Ti) interface layers with thin and uniform thickness, porosity, and hydrophilicity properties are developed to realize homogeneous and smooth Zn plating. For ZnSiO3 nanosheet arrays on Zn foil (Zn@ZSO), their formation follows an "etching-nucleation-growth" mechanism that is confirmed by a well-designed Zn-island-based identical-location microscopy method, the geometric area of which is up to 1000 cm2 in one-pot synthesis based on a low-temperature wet-chemical method. Guided by the structural advantages of the ZSO layer, the Zn2+ flux gets equalized. Besides ultralow polarization, the life spans of symmetric cells and full cells coupled with a high-mass-loading K0.27 MnO2 ·0.54H2 O (8 mg cm-2 ) cathode, are increased by 3-7 times with the Zn@ZSO anode. Moreover, the large-scale preparation of Zn@ZSO foil contributes to a 0.5 Ah multilayer pouch cell with high performance, further confirming its prospects for practical application.
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With the gradual improvement of treatment regimens, the survival time of multiple myeloma (MM) patients has been significantly prolonged. Even so, MM is still a nightmare with an inferior prognosis. B-cell maturation antigen (BCMA) is highly expressed on the surface of malignant myeloma cells. For the past few years, significant progress has been made in various BCMA-targeted immunotherapies for treating patients with RRMM, including anti-BCMA mAbs, antibody-drug conjugates, bispecific T-cell engagers, and BCMA-targeted adoptive cell therapy like chimeric antigen receptor (CAR)-T cell. The 63rd annual meeting of the American Society of Hematology updated some information about the application of BCMA in MM. This review summarizes part of the related points presented at this conference.
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Inmunoconjugados , Mieloma Múltiple , Receptores Quiméricos de Antígenos , Antígeno de Maduración de Linfocitos B , Humanos , Inmunoconjugados/uso terapéutico , Inmunoterapia Adoptiva , Mieloma Múltiple/tratamiento farmacológico , Receptores Quiméricos de Antígenos/uso terapéuticoRESUMEN
BACKGROUND: Betibeglogene autotemcel (beti-cel) gene therapy for transfusion-dependent ß-thalassemia contains autologous CD34+ hematopoietic stem cells and progenitor cells transduced with the BB305 lentiviral vector encoding the ß-globin (ßA-T87Q) gene. METHODS: In this open-label, phase 3 study, we evaluated the efficacy and safety of beti-cel in adult and pediatric patients with transfusion-dependent ß-thalassemia and a non-ß0/ß0 genotype. Patients underwent myeloablation with busulfan (with doses adjusted on the basis of pharmacokinetic analysis) and received beti-cel intravenously. The primary end point was transfusion independence (i.e., a weighted average hemoglobin level of ≥9 g per deciliter without red-cell transfusions for ≥12 months). RESULTS: A total of 23 patients were enrolled and received treatment, with a median follow-up of 29.5 months (range, 13.0 to 48.2). Transfusion independence occurred in 20 of 22 patients who could be evaluated (91%), including 6 of 7 patients (86%) who were younger than 12 years of age. The average hemoglobin level during transfusion independence was 11.7 g per deciliter (range, 9.5 to 12.8). Twelve months after beti-cel infusion, the median level of gene therapy-derived adult hemoglobin (HbA) with a T87Q amino acid substitution (HbAT87Q) was 8.7 g per deciliter (range, 5.2 to 10.6) in patients who had transfusion independence. The safety profile of beti-cel was consistent with that of busulfan-based myeloablation. Four patients had at least one adverse event that was considered by the investigators to be related or possibly related to beti-cel; all events were nonserious except for thrombocytopenia (in 1 patient). No cases of cancer were observed. CONCLUSIONS: Treatment with beti-cel resulted in a sustained HbAT87Q level and a total hemoglobin level that was high enough to enable transfusion independence in most patients with a non-ß0/ß0 genotype, including those younger than 12 years of age. (Funded by Bluebird Bio; HGB-207 ClinicalTrials.gov number, NCT02906202.).