Bortezomib suppresses acute myelogenous leukaemia stem-like KG-1a cells via NF- κB inhibition and the induction of oxidative stress
J Cell Mol Med. 2024 Apr;28(8):e18333. doi: 10.1111/jcmm.18333.ABSTRACTAcute myelogenous leukaemia (AML) originates and is maintained by leukaemic stem cells (LSCs) that are inherently resistant to antiproliferative therapies, indicating that a critical strategy for overcoming chemoresistance in AML therapy is to eradicate LSCs. In this work, we investigated the anti-AML activity of bortezomib (BTZ), emphasizing its anti-LSC potential, using KG-1a cells, an AML cell line with stem-like properties. BTZ presented potent cytotoxicity to both solid and haematological malignancy cells and reduced the stem-like features of KG-1a...
Source: J Cell Mol Med - April 23, 2024 Category: Molecular Biology Authors: Rafaela G A Costa Maiara de S Oliveira Ana Carolina B da C Rodrigues Suellen L R Silva Ingrid R S B Dias Milena B P Soares Ludmila de Faro Valverde Clarissa Araujo Gurgel Rocha Rosane Borges Dias Daniel P Bezerra Source Type: research

The β3-AR agonist BRL37344 ameliorates the main symptoms of X-linked nephrogenic diabetes insipidus in the mouse model of the disease
J Cell Mol Med. 2024 Apr;28(8):e18301. doi: 10.1111/jcmm.18301.ABSTRACTX-linked nephrogenic diabetes insipidus (X-NDI) is a rare congenital disease caused by inactivating mutations of the vasopressin type-2 receptor (AVPR2), characterized by impaired renal concentrating ability, dramatic polyuria, polydipsia and risk of dehydration. The disease, which still lacks a cure, could benefit from the pharmacologic stimulation of other GPCRs, activating the cAMP-intracellular pathway in the kidney cells expressing the AVPR2. On the basis of our previous studies, we here hypothesized that the β3-adrenergic receptor could be such a...
Source: J Cell Mol Med - April 23, 2024 Category: Molecular Biology Authors: Serena Milano Ilenia Saponara Andrea Gerbino Monica Carmosino Maria Svelto Giuseppe Procino Source Type: research

Dihydroartemisinin induces ferroptosis of hepatocellular carcinoma via inhibiting ATF4-xCT pathway
J Cell Mol Med. 2024 Apr;28(8):e18335. doi: 10.1111/jcmm.18335.ABSTRACTManagement of hepatocellular carcinoma (HCC) remains challenging due to population growth, frequent recurrence and drug resistance. Targeting of genes involved with the ferroptosis is a promising alternative treatment strategy for HCC. The present study aimed to investigate the effect of dihydroartemisinin (DHA) against HCC and explore the underlying mechanisms. The effects of DHA on induction of ferroptosis were investigated with the measurement of malondialdehyde concentrations, oxidised C11 BODIPY 581/591 staining, as well as subcutaneous xenograft e...
Source: J Cell Mol Med - April 23, 2024 Category: Molecular Biology Authors: Jie Ji Ziqi Cheng Jie Zhang Jianye Wu Xuanfu Xu Chuanyong Guo Jiao Feng Source Type: research

MELK aggravates lung adenocarcinoma by regulating EZH2 ubiquitination and H3K27me3 histone methylation of LATS2
This study demonstrated that MELK aggravated LUAD by upregulating EZH2 and downregulating LATS2.PMID:38652219 | PMC:PMC11037405 | DOI:10.1111/jcmm.18216 (Source: J Cell Mol Med)
Source: J Cell Mol Med - April 23, 2024 Category: Molecular Biology Authors: Hui Yu Xianrong Xu Lirong Zhu Shengjie Chen Jincheng He Source Type: research

Single-cell analysis revealed a potential role of T-cell exhaustion in colorectal cancer with liver metastasis
J Cell Mol Med. 2024 Apr;28(8):e18341. doi: 10.1111/jcmm.18341.ABSTRACTLiver metastasis (LM) is an important factor leading to colorectal cancer (CRC) mortality. However, the effect of T-cell exhaustion on LM in CRC is unclear. Single-cell sequencing data derived from the Gene Expression Omnibus database. Data were normalized using the Seurat package and subsequently clustered and annotated into different cell clusters. The differentiation trajectories of epithelial cells and T cells were characterized based on pseudo-time analysis. Single-sample gene set enrichment analysis (ssGSEA) was used to calculate enrichment scores...
Source: J Cell Mol Med - April 22, 2024 Category: Molecular Biology Authors: Tianlong Ling Cheng Zhang Ye Liu Chunhui Jiang Lei Gu Source Type: research

Development of m6A/m5C/m1A regulated lncRNA signature for prognostic prediction, personalized immune intervention and drug selection in LUAD
J Cell Mol Med. 2024 Apr;28(8):e18282. doi: 10.1111/jcmm.18282.ABSTRACTResearch indicates that there are links between m6A, m5C and m1A modifications and the development of different types of tumours. However, it is not yet clear if these modifications are involved in the prognosis of LUAD. The TCGA-LUAD dataset was used as for signature training, while the validation cohort was created by amalgamating publicly accessible GEO datasets including GSE29013, GSE30219, GSE31210, GSE37745 and GSE50081. The study focused on 33 genes that are regulated by m6A, m5C or m1A (mRG), which were used to form mRGs clusters and clusters of...
Source: J Cell Mol Med - April 22, 2024 Category: Molecular Biology Authors: Chao Ma Zhuoyu Gu Yang Yang Source Type: research

From phenotype to mechanism: Prenatal spectrum of NKAP mutation-related disorder and its pathogenesis inducing congenital heart disease
J Cell Mol Med. 2024 Apr;28(8):e18305. doi: 10.1111/jcmm.18305.ABSTRACTNKAP mutations are associated with Hackmann-Di Donato-type X-linked syndromic intellectual developmental disorder (MRXSHD, MIM: #301039). Here, we elucidate the potential prenatal manifestation of NKAP mutation-associated disorder for the first time, alongside revealing the relationship between NKAP mutations and congenital heart defect (CHD) in the Chinese population. An NKAP mutation (NM_024528.4: c.988C>T, p.Arg330Cys) was identified in two foetuses presenting with CHD. Subsequent mechanistic exploration revealed a marked downregulation of NKAP tr...
Source: J Cell Mol Med - April 22, 2024 Category: Molecular Biology Authors: Xiayuan Xu Chengcheng Gao Fenglei Ye Aohui Peng Jianbo Xu Keqin Jin Jun Zhang Yun Ye Yanfen Yang Xuan Zhang Shuangshuang Shen Fan Jin Source Type: research

A robust computational quest: Discovering potential hits to improve the treatment of pyrazinamide-resistant Mycobacterium tuberculosis
This study utilizes a novel integration of computational techniques, including multiscale biomolecular and molecular dynamics simulations, physicochemical and medicinal chemistry predictions, quantum computations and virtual screening from the ZINC and Chembridge databases, to elucidate the resistance mechanism and identify lead compounds that have the potential to improve treatment outcomes for PZA-resistant MTB, namely ZINC15913786, ZINC20735155, Chem10269711, Chem10279789 and Chem10295790. These computational methods offer a cost-effective, rapid alternative to traditional drug trials by bypassing the need for organic s...
Source: J Cell Mol Med - April 18, 2024 Category: Molecular Biology Authors: Muhammad Shahab Gabriel Christian de Farias Morais Shopnil Akash Umberto Laino Fulco Jonas Ivan Nobre Oliveira Guojun Zheng Shahina Akter Source Type: research

Impacts of pro-inflammatory cytokines variant on cardiometabolic profile and premature coronary artery disease: A systematic review and meta-analysis
J Cell Mol Med. 2024 Apr;28(8):e18311. doi: 10.1111/jcmm.18311.ABSTRACTInterleukin-6 (IL-6), a pivotal pro-inflammatory cytokine, is closely linked to vascular wall thickening and atherosclerotic lesion. Since serum IL-6 levels are largely determined by the genetic variant in IL-6, this study was conducted to investigate whether the IL-6 variant impacts cardiometabolic profile and the risk of premature coronary artery disease (PCAD). PubMed, Cochrane Library, Central, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and were searched from May 13, 2022 to June 28, 2023. In total, 40 stud...
Source: J Cell Mol Med - April 18, 2024 Category: Molecular Biology Authors: Yang Liu Yuan Chen Yi Lin Baozhu Wei Zhi Luo Source Type: research

Identification and characterization of novel genetic variants in the first Chinese family of mucopolysaccharidosis IIIC (Sanfilippo C syndrome)
In this study, we utilized whole-exome sequencing (WES) to identify novel compound heterozygous variants in the HGSNAT gene from a Chinese patient with typical MPS IIIC symptoms: c.743G>A; p.Gly248Glu and c.1030C>T; p.Arg344Cys. We performed in silico analysis and experimental validation, which confirmed the deleterious pathogenic nature of both variants, as evidenced by the loss of HGSNAT activity and failure of lysosomal localization. To the best of our knowledge, the MPS IIIC is first confirmed by clinical, biochemical and molecular genetic findings in China. Our study thus expands the spectrum of MPS IIIC pathoge...
Source: J Cell Mol Med - April 13, 2024 Category: Molecular Biology Authors: Hongjun Zhao Lijing Wang Mengfei Zhang Huakun Wang Sizhe Zhang Junjiao Wu Yu Tang Source Type: research

Comprehensive analysis of the interaction of antigen presentation during anti-tumour immunity and establishment of AIDPS systems in ovarian cancer
J Cell Mol Med. 2024 Apr;28(8):e18309. doi: 10.1111/jcmm.18309.ABSTRACTThere are hundreds of prognostic models for ovarian cancer. These genes are based on different gene classes, and there are many ways to construct the models. Therefore, this paper aims to build the most stable prognostic evaluation system known to date through 101 machine learning strategies. We combined 101 algorithm combinations with 10 machine learning algorithms to create antigen presentation-associated genetic markers (AIDPS) with outstanding precision and steady performance. The inclusive set of algorithms comprises the elastic network (Enet), Rid...
Source: J Cell Mol Med - April 13, 2024 Category: Molecular Biology Authors: Wenhuizi Sun Ping Xu Kefei Gao Wenqin Lian Xiang Sun Source Type: research

Integrated analysis highlights the significance role of ITGAL in lung adenocarcinoma
In this study, we utilized the TCGA dataset to analyse ITGAL mRNA expression in LUAD and examined its correlation with clinical prognosis. Three-dimensional (3D) Matrigel culture, 5-bromodeoxyuridine (BrdU) ELISA, wound-healing migration and cell adherence assays were used to demonstrate the potential role of ITGAL in LUAD progression. Additionally, we analysed single-cell sequencing data of LUAD to determine the expression and biological function of ITGAL. Our research revealed that the expression of ITGAL in LUAD samples is an independent predictor of prognosis. Patients with high expression of ITGAL had significantly be...
Source: J Cell Mol Med - April 13, 2024 Category: Molecular Biology Authors: Zengtuan Xiao Zhe Nian Mengzhe Zhang Zuo Liu Zhe Liu Zhenfa Zhang Source Type: research

Pathway-based stratification of gliomas uncovers four subtypes with different TME characteristics and prognosis
This study aimed to develop a reliable molecular stratification based on these key components of TME. The TCGA data set (training cohort) and two independent cohorts from CGGA database (validation cohort) were enrolled in this study. First, the enrichment score of 277 TME-related signalling pathways was calculated by gene set variation analysis (GSVA). Then, consensus clustering identified four stable and reproducible subtypes (AFM, CSS, HIS and GLU) based on TME-related signalling pathways, which were characterized by differences in hypoxia and immune responses, metabolism status, somatic alterations and clinical outcomes...
Source: J Cell Mol Med - April 13, 2024 Category: Molecular Biology Authors: Ruoyu Huang Bo Han Ying Zhang Jingchen Yang Kuanyu Wang Xing Liu Zhiliang Wang Source Type: research

The Hippo signalling pathway and its impact on eye diseases
This article provides the first systematic review of studies on the regulatory and functional roles of mammalian Hippo signalling systems in eye diseases. More comprehensive studies on this pathway are required for a better understanding of the pathophysiology of eye diseases and the development of effective therapies.PMID:38613348 | PMC:PMC11015399 | DOI:10.1111/jcmm.18300 (Source: J Cell Mol Med)
Source: J Cell Mol Med - April 13, 2024 Category: Molecular Biology Authors: Yuxiang Du Source Type: research

The role of autophagy in odontogenesis, dental implant surgery, periapical and periodontal diseases
This study reviews autophagy's dento-alveolar effects, focusing on its role in odontogenesis, periapical diseases, periodontal diseases and dental implant surgery, providing valuable insights for dentists on tooth development and dental applications. A thorough examination of autophagy has the potential to discover novel and efficacious treatment targets within the field of dentistry.PMID:38613351 | PMC:PMC11015398 | DOI:10.1111/jcmm.18297 (Source: J Cell Mol Med)
Source: J Cell Mol Med - April 13, 2024 Category: Molecular Biology Authors: Sevin ç İnan Emre Bar ış Source Type: research