FTO inhibition represses B-cell acute lymphoblastic leukemia progression by inducing nucleolar stress and mitochondrial dysfunction.

B-cell acute lymphoblastic leukemia (B-ALL) is a hematological malignancy characterized by the aberrant accumulation of malignant and immature B cells in the bone marrow. Recent reports including ours have demonstrated that RNA modifications play pivotal roles in B-ALL progression and drug resistance. In the current study, we show that fat mass and obesity-associated protein (FTO), a demethylase of N-methyladenosine (mA) RNA modifications, is highly expressed in relapsed or refractory (R/R) B-ALL patients and B-ALL cell lines.

RPS15a knockdown impedes the progression of B-ALL by inducing p53-mediated nucleolar stress.

Ribosome biogenesis is intricately linked to the pathogenesis of B-cell acute lymphoblastic leukemia (B-ALL), but the precise regulatory mechanisms remain to be elucidated. First of all, our study identify that RPS15a, the ribosomal small subunit structural protein, is significantly higher expressed in B-ALL patients, indicating a potential crucial role of RPS15a in modulating B-ALL progression. Next in importance, our findings found that RPS15a knockdown (KD) results in the impede of cell proliferation and cell cycle progression, while concurrently inducing apoptosis of B-ALL cells.

Ribosomal protein L9 is a potential therapeutic target for B-ALL through the activation of the p53 signaling pathway.

B-cell acute lymphocytic leukemia (B-ALL) is a malignant hematological disorder marked by the aberrant proliferation of abnormal B lymphocytes. Although recent advancements have highlighted the pivotal role of ribosomes in the progression of B-ALL, the specific function of ribosomal protein L9 (RPL9), a key component of ribosomal structural protein, still unclear. In this study, we observed a significant upregulation of RPL9 in human B-ALL cells compared to normal B cells, suggesting RPL9's potential key role in B-ALL progression.

Health Technology Assessment: Evaluation of 8 CGRP-Targeted Therapy Drugs for the Treatment of Migraine.

Purpose: In order to scientifically evaluate the clinical value of the comprehensive attributes of Calcitonin gene-related peptide (CGRP) inhibitor drugs, a comprehensive literature-based clinical evaluation of CGRP-targeted therapy drugs was conducted using the drug evaluation method modified by expert discussion in the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions (Second Edition).

Methods: Based on evidence-based data and the relevant elements and weighting in the "Selection Guidelines" quantification record form for drug evaluation and selection in medical institutions, adjustments were made according to the characteristics of CGRP-targeted therapy drugs. We systematically evaluated erenumab, galcanezumab, fremanezumab, eptinezumab, rimegepant, ubrogepant, atogepant, zavegepant for safety, efficacy, economy, and pharmacological properties.

Comprehensive Assessment of PCSK9 Inhibitors for Lipid Management: Scientific Guidance Based on Drug Selection Recommendations for Chinese Medical Institutions.

Objective: This study aims to support the selection of PCSK9 inhibitors for patients requiring lipid management within medical institutions. By quantitatively evaluating four PCSK9 inhibitors, we provide evidence-based guidance for optimal selection in this patient population.

Methods: According to the Rapid Guide for Drug Evaluation and Selection in Chinese Medical Institutions (Second Edition) released in 2023, relevant databases such as PubMed, Cochrane, Embase, drug labels, and clinical guidelines were searched for drug information.

Molecular Design of Phthalocyanine-Based Drug Coassembly with Tailored Function.

Coassemblies with tailored functions, such as drug loading, tissue targeting and releasing, therapeutic and/or imaging purposes, and so on, have been widely studied and applied in biomedicine. design of these coassemblies hinges on an integrated approach involving synergy between various design strategies, ranging from structure screening of combinations of "phthalocyanine-chemotherapeutic drug" molecules for molecular scaffolds, exploration of related fabrication principles to verification of intended activity of specific designs. Here, we propose an integrated approach combining computation and experiments to design from scratch coassembled nanoparticles.

YTHDC1 is a therapeutic target for B-cell acute lymphoblastic leukemia by attenuating DNA damage response through the KMT2C-H3K4me1/me3 epigenetic axis.

B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive malignancy characterized by the aberrant accumulation of immature and dysfunctional B cells in bone marrow (BM). Although chemotherapy and other therapies have been widely applied, some patients such as relapsed or drug-refractory (R/R) B-ALL patients exhibit limited response. YT521-B homologous domain-containing protein 1 (YTHDC1) is a nuclear reader of N-methyladenosine (mA) RNA modification, which has been implicated in different malignancies including leukemia.

SMAD4 enhances the cytotoxic efficacy of human NK cells against colorectal cancer cells via the mA reader YTHDF2.

Background: Colorectal cancer (CRC) ranks as the third most prevalent malignant neoplasm in terms of both morbidity and mortality. Within the tumor microenvironment (TME) of CRC, the diminished presence and diminished cytotoxic function of natural killer (NK) cells serve as important factors driving the advancement of CRC; however, the precise regulatory mechanisms governing this phenomenon remain incompletely understood. Consequently, the identification of novel, potential anti-CRC targets associated with NK cells emerges as a pressing and paramount concern warranting immediate attention.

A Health Technology Assessment Based on Chinese Guideline: Active Vitamin D and Its Analogs in the Treatment of Osteoporosis.

Objective: To quantitatively assess all dosage forms of three active vitamin D and its analogs, namely, calcitriol, alfacalcidol, and eldecalcitol, to provide a basis for the selection of active vitamin D and its analogs in hospitals.

Methods: In this study, three active vitamin D and its analogs were evaluated by quantitative scoring in five dimensions, including pharmaceutical properties (28 points), efficacy (27 points), safety (25 points), economy (10 points), and other attributes (10 points).

Results: The final scores of quantitative assessment for the selection of alfacalcidol soft capsules, calcitriol soft capsules I, calcitriol soft capsules II, alfacalcidol tablets, alfacalcidol capsules, alfacalcidol oral drops, calcitriol injection, and eldecalcitol soft capsules were 73.

Sulfonium-Stapled Peptides-Based Neoantigen Delivery System for Personalized Tumor Immunotherapy and Prevention.

Neoantigen peptides hold great potential as vaccine candidates for tumor immunotherapy. However, due to the limitation of antigen cellular uptake and cross-presentation, the progress with neoantigen peptide-based vaccines has obviously lagged in clinical trials. Here, a stapling peptide-based nano-vaccine is developed, comprising a self-assembly nanoparticle driven by the nucleic acid adjuvant-antigen conjugate.

Clinical characteristics, diagnosis and management of nivolumab-induced myocarditis.

Nivolumab can cause fatal myocarditis. We aimed to analyze the clinical characteristics of nivolumab-induced myocarditis and provide evidence for clinical diagnosis, treatment, and prevention. Studies involving nivolumab-induced myocarditis were identified in electronic databases from 2000 to 2023 for retrospective analysis.

Direct structure determination of vemurafenib polymorphism from compact spherulites using 3D electron diffraction.

The spherulitic morphology is considered to be the most common morphology of crystalline materials and is particularly apparent in melt-crystallized products. Yet, historically, the polycrystalline nature of spherulites has hindered successful crystal structure determination. Here, we report the direct structure determination of a clinical drug, vemurafenib (VMN), in compact spherulite form using 3D electron diffraction (3D ED).

miR-582 Suppresses the Proliferation of B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) Cells and Protects Them From Natural Killer Cell-Mediated Cytotoxicity.

B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a malignancy characterized by the aberrant accumulation of immature B-cell precursors in bone marrow and other lymphoid organs. Although several intrinsic regulatory signals participating in BCP-ALL have been clarified, detailed intrinsic and extrinsic mechanisms that regulate BCP-ALL progression have not been fully understood. In the current study, we report that miR-582 is downregulated in BCP-ALL cells compared with normal B cells.

Variant analyses of candidate genes in orofacial clefts in multi-ethnic populations.

Objectives: Cleft lip with/without cleft palate and cleft palate only is congenital birth defects where the upper lip and/or palate fail to fuse properly during embryonic facial development. Affecting ~1.2/1000 live births worldwide, these orofacial clefts impose significant social and financial burdens on affected individuals and their families.

[Prokaryotic Expression and Purification of the Notch Ligand and Its Effect on Hematopoiesis after Carbon Tetrachloride Damage].

Objective: To express and purify the mouse endothelial cell-targeted recombinant Notch ligand protein mD1R, and to investigate its effect on hematopoiesis after carbon tetrachloride damage.

Methods: PCR was performed to clone and construct the expression vector pET22b(+)-mD1R. The mD1R successfully transformed into E.

[Correlation between Plasma microRNA Expression and Acute Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation].

Objective: To investigate the microRNA (miRNA) expression in plasma of patients with aGVHD and without aGVHD after allo-hematopoietic stem cell transplantation (allo-HSCT).

Methods: The miRNAs (miR-423, mirR199a-3p, miR93*, miR377) expression levels in peripheral blood plasma of 25 patients before and after allo-HSCT were detected by real-time PCR.

Results: miR-423, miR199a-3p and miR-93* in aGVHD group were significantly upregulated (P<0.

Disruption of Notch signaling aggravates irradiation-induced bone marrow injury, which is ameliorated by a soluble Dll1 ligand through Csf2rb2 upregulation.

Physical and chemical insult-induced bone marrow (BM) damage often leads to lethality resulting from the depletion of hematopoietic stem and progenitor cells (HSPCs) and/or a deteriorated BM stroma. Notch signaling plays an important role in hematopoiesis, but whether it is involved in BM damage remains unclear. In this study, we found that conditional disruption of RBP-J, the transcription factor of canonical Notch signaling, increased irradiation sensitivity in mice.

[Construction and expression of fusion protein TRX-hJagged1 in E.coli BL21].

This study was purposed to construct prokaryotic expression vector and to investigate the expression of Notch ligand Jagged1 in E.coli. An expression vector pET-hJagged1 was constructed, which can be inserted in Jagged1 with different lengths, but the DSL domain of human Jagged1 should be contained.

FHL1C induces apoptosis in Notch1-dependent T-ALL cells through an interaction with RBP-J.

Background: Aberrantly activated Notch signaling has been found in more than 50% of patients with T-cell acute lymphoblastic leukemia (T-ALL). Current strategies that employ γ-secretase inhibitors (GSIs) to target Notch activation have not been successful. Many limitations, such as non-Notch specificity, dose-limiting gastrointestinal toxicity and GSI resistance, have prompted an urgent need for more effective Notch signaling inhibitors for T-ALL treatment.

Obsessive-compulsive disorder in general hospital outpatients: prevalence, correlates, and comorbidity in Lanzhou, China.

Introduction: The prevalence of obsessive-compulsive disorder (OCD), risk factors, and comorbidity rates of Chinese outpatients in Lanzhou general hospitals are unknown.

Method: The prevalence rate of OCD was estimated in a representative sample of outpatients in three classes of general hospitals in Lanzhou, China. The rate of OCD within the sample, which was composed of 1,576 individuals aged 16 years or older, was assessed using the World Health Organization Composite International Diagnostic Interview Version 3.

Myc induced miR-144/451 contributes to the acquired imatinib resistance in chronic myelogenous leukemia cell K562.

Imatinib resistance remains the big hurdle for CML therapy. Previous study reveals that c-myc is important for bcr-abl CML cell proliferation, while its role in imatinib resistance is largely unknown. In this study, we first found that c-myc expression is upregulated in imatinib resistant K562R cells, which in turn enhances the expression of miR-144/451.

[Clinical analysis of peripheral blood stem cell mobilization regimens in autologous transplantation for treating non-Hodgkin's lymphoma].

The purpose of this study was to compare the efficacy of CEP plus G-CSF and CVP plus G-CSF regimens in the mobilization and collection of peripheral blood hematopoietic stem cells (PBHSC), and in the hematopoietic recovery. 57 patients with non-Hodgkin's lymphoma (NHL) underwent autologous PBHSC transplantation were analyzed retrospectively. The PBHSC were mobilized and collected by using CEP plus G-CSF and CVP plus G-CSF respectively, and were retransfused into these NHL patients after preconditioning, then the mobilization efficacy, adverse reactions and hematopoietic recovery were analyzed.

miR-153 sensitized the K562 cells to As2O3-induced apoptosis.

Relapse remains the biggest hurdle of leukemia therapy, while elucidating the molecular mechanism holds promise for the solution. Recently, microRNAs are emerging as an important regulator of cell function. In this study, we for the first time found that miR-153 was downregulated in As2O3-induced drug-resistant K562 cells.

Knockdown of SOD1 sensitizes the CD34+ CML cells to imatinib therapy.

Leukemia stem cell is thought to be one of the leading causes of imatinib resistance and the resultant relapse of chronic myelogenous leukemia (CML). Eradicating the leukemia stem cells holds the promise of CML treatment. In this study, we found that the CD34+ subpopulation in the CML cell line K562 had a higher expression of SOD1 than that in the CD34 negative cells.