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The role of CD38 in HIV infection.

The widely-expressed molecule CD38 is a single-stranded type II transmembrane glycoprotein that is mainly involved in regulating the differentiation and activation state of the cell. CD38 has broad and complex functions, including enzymatic activity, intercellular signal transduction, cell activation, cytokine production, receptor function and adhesion activity, and it plays an important role in the physiological and pathological processes of many diseases. Many studies have shown that CD38 is related to the occurrence and development of HIV infection, and CD38 may regulate its progression thr

Metabolic crosstalk between stromal and malignant cells in the bone marrow niche.

Bone marrow is the primary site of blood cell production in adults and serves as the source of osteoblasts and osteoclasts that maintain bone homeostasis. The medullary microenvironment is also involved in malignancy, providing a fertile soil for the growth of blood cancers or solid tumors metastasizing to bone. The cellular composition of the bone marrow is highly complex, consisting of hematopoietic stem and progenitor cells, maturing blood cells, skeletal stem cells, osteoblasts, mesenchymal stromal cells, adipocytes, endothelial cells, lymphatic endothelial cells, perivascular cells, and n

Novel Insights into the Links between N6-Methyladenosine and Regulated Cell Death in Musculoskeletal Diseases.

Musculoskeletal diseases (MSDs), including osteoarthritis (OA), osteosarcoma (OS), multiple myeloma (MM), intervertebral disc degeneration (IDD), osteoporosis (OP), and rheumatoid arthritis (RA), present noteworthy obstacles associated with pain, disability, and impaired quality of life on a global scale. In recent years, it has become increasingly apparent that N6-methyladenosine (m6A) is a key regulator in the expression of genes in a multitude of biological processes. m6A is composed of 0.1-0.4% adenylate residues, especially at the beginning of 3'-UTR near the translation stop codon. The m

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… METTL3-mediated m 6 A modification of ATG7 regulates autophagy-GATA4 axis to promote cellular senescence and osteoarthritis progression Ann. Rheum. Dis. 2022 81 87 99 10.1136/annrheumdis-2021-221091 34706873 128. Cheng S. Xu X. Wang R. Chen W. Qin K. Yan J. …

Targeting the ubiquitin-proteasome system: a novel therapeutic strategy for neuroblastoma.

Neuroblastoma (NB) stands as a common and formidable malignant tumor among children, characterized by marked tumor heterogeneity and resistance to conventional treatments. Central to the regulation of protein stability, localization, and function is the process of ubiquitination-a critical protein modification. The therapeutic potential of drugs that target deubiquitination, demonstrated in the treatment of refractory multiple myeloma, warrants investigation in the context of NB. This review endeavors to demystify the intricate biological implications of ubiquitination within NB pathology, syn

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… Optimal combination of MYCN differential gene and cellular senescence gene predicts adverse outcomes in patients with neuroblastoma . Front Immunol . ( 2023 ) 14 : 1309138 . doi: 10.3389/fimmu.2023.1309138 38035110 PMC10687280 3 Hu X Zhou Y Hill C Chen K Cheng C Liu X . …

Chromatin structure, transcriptional activity and DNA repair efficiency affect the outcome of chemotherapy in multiple myeloma.

BackgroundMelphalan is one of the most active chemotherapeutic agents in the treatment of multiple myeloma (MM). However, the mechanism underlying differential patient responses to melphalan therapy is unknown.MethodsChromatin structure, transcriptional activity and DNA damage response signals were examined following ex vivo treatment with melphalan of both malignant bone marrow plasma cells (BMPCs) and peripheral blood mononuclear cells (PBMCs) of MM patients, responders (n=57) or non-responders (n=28) to melphalan therapy. PBMCs from healthy controls (n=25) were also included in the study.Re

Потенциальная роль TNFRSF12A в установлении связи между глиобластомой и болезнью Альцгеймера через общие пути подавления опухолей.

Гены, подавляющие опухоль, являются критическими регуляторами клеточного гомеостаза и широко изучаются в области онкологической биологии. Однако их роль в нейродегенеративных заболеваниях, особенно в болезни Альцгеймера, остается слабой. Недавние данные об обратной связи между раком и АД указывают на существование общих молекулярных механизмов. Мы провели комплексный анализ для выявления ТГС, которые могут участвовать как в AD, так и в глиобластоме (GBM), с использованием менделийской случайности, транскриптомного профилирования (булка и одноклеточная RNA-seq), вывода в отношении связи между к

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… Targeting cellular senescence in cancer and aging: Roles of p53 and its isoforms. Carcinogenesis 41 (8), 1017–1029. 10.1093/carcin/bgaa071 (2020). 11. Jia, Y. et al. Chemical toolkit for PARK7: Potent, selective, and high-throughput. J. Med. …

JAK inhibition in PD-1 immunotherapy and tumor microenvironment.

Targeting the programmed cell death 1 (PD-1)/PD-L1 axis has revolutionized cancer therapy; however, the durability of clinical responses is frequently compromised by chronic inflammation and an immunosuppressive tumor microenvironment (TME). The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway serves as a central intracellular node integrating cytokine signals that drive these resistance mechanisms. While physiological JAK/STAT signaling is essential for antitumor immunity, its persistent aberrant activation promotes malignant progression, upregulates

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… Rb-mediated heterochromatin formation and silencing of E2F target genes during cellular senescence . Cell . ( 2003 ) 113 : 703–16 . doi: 10.1016/s0092-8674(03)00401-x , PMID: 12809602 28 Christova R Jones T Wu P-J Bolzer A Costa-Pereira AP Watling D . …

Extracellular RNA in melanoma: Advances, challenges, and opportunities.

Melanoma, a malignant mass lesion that originates in melanocytes and has a high rate of malignancy, metastasis, and mortality, is defined by these characteristics. Malignant melanoma is a kind of highly malignant tumor that produces melanin and has a high mortality rate. Its incidence accounts for 1%-3% of all malignant tumors and shows an obvious upward trend. The discovery of biomolecules for the diagnosis and treatment of malignant melanoma has important application value. So far, the exact molecular mechanism of melanoma development relevant signal pathway still remains unclear. According

Role of bone marrow adipocytes in bone metastasis development and progression: a systematic review.

PurposeBone marrow adipocytes (BMAs) are the most plentiful cells in the bone marrow and function as an endocrine organ by producing fatty acids, cytokines, and adipokines. Consequently, BMAs can interact with tumor cells, influencing both tumor growth and the onset and progression of bone metastasis. This review aims to systematically evaluate the role of BMAs in the development and progression of bone metastasis.MethodsA comprehensive search was conducted on PubMed, Web of Science, and Scopus electronic databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analys

Роль агентов CELMOD в Мультимиломе.

Несмотря на то, что в последние десятилетия наблюдалось дальнейшее улучшение положения в области выживания пациентов с множественными миеломами, это заболевание в значительной степени остается неизлечимым, и большинство пациентов переживают рецидивы и/или становятся невосприимчивыми к лечению. Таким образом, по-прежнему остро ощущается потребность в новых методах лечения, особенно для тех пациентов с рецидивистской или рефрактной множественной миеломой. Новейшие методы лечения, такие, как целевая деградация белка, вызывают особый интерес, поскольку они позволяют расширить диапазон поддающихся

Recent clinical trials with stem cells to slow or reverse normal aging processes.

Aging is associated with a decline in the regenerative potential of stem cells. In recent years, several clinical trials have been launched in order to evaluate the efficacy of mesenchymal stem cell interventions to slow or reverse normal aging processes (aging conditions). Information concerning those clinical trials was extracted from national and international databases (United States, EU, China, Japan, and World Health Organization). Mesenchymal stem cell preparations were in development for two main aging conditions: physical frailty and facial skin aging. With regard to physical frailty,

The underexplored links between cancer and the internal body climate: Implications for cancer prevention and treatment.

In order to effectively manage and cure cancer we should move beyond the general view of cancer as a random process of genetic alterations leading to uncontrolled cell proliferation or simply a predictable evolutionary process involving selection for traits that increase cell fitness. In our view, cancer is a systemic disease that involves multiple interactions not only among cells within tumors or between tumors and surrounding tissues but also with the entire organism and its internal "milieu". We define the internal body climate as an emergent property resulting from spatial and temporal in

Understanding the Mechanisms of Resistance to CAR T-Cell Therapy in Malignancies.

Taking advantage of the immune system to exert an antitumor effect is currently a novel approach in cancer therapy. Adoptive transfer of T cells engineered to express chimeric antigen receptors (CARs) targeting a desired antigen has shown extraordinary antitumor activity, especially in refractory and relapsed B-cell malignancies. The most representative in this respect, as well as the most successful example, is CD19 CAR T-cell therapy in B-cell acute lymphoblastic leukemia (B-ALL). However, with the widespread use of CAR T-cell therapy, problems of resistance and relapse are starting to be co

Age-Related Disease Burden in China, 1997-2017: Findings From the Global Burden of Disease Study.

Background: The population is aging much faster in China than other low- and middle-income countries. With the accelerated aging of the population, incidence and disease burden of age-related diseases have also continued to increase. Exploring the burden of age-related diseases is crucial for early disease prevention, assessing the extent of population aging, and achieving the goal of healthy aging. Methods: We used the dataset from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), and selected data on incidence, prevalence, and disease burden in China, in 1997, 2007, and

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… Cellular senescence as a therapeutic target for age-related diseases: a review . Adv Ther. ( 2020 ) 37 : 1407 – 24 . 10.1007/s12325-020-01287-0 32185730 PMC7140757 26. Searle SD Mitnitski A Gahbauer EA Gill TM Rockwood K . A standard procedure for creating a frailty index . … Cellular senescence in ageing, age-related disease and longevity . Curr Vasc Pharmacol. ( 2014 ) 12 : 698 – 706 . 10.2174/1570161111666131219094045 24350932 36. Shlisky J Bloom DE Beaudreault AR Tucker KL Keller HH Freund-Levi Y . …

Mitophagy related gene signature for prognosis and therapeutic evaluation in KIRC.

This study conducted a comprehensive investigation of the prognostic significance and immunological features associated with mitophagy-related gene signatures in clear cell renal cell carcinoma (KIRC). Our primary aim was to establish an optimized predictive model for precise prognosis stratification and treatment response prediction in KIRC patients. Through LASSO Cox regression analysis, we systematically identified mitophagy-related genes (MRGs) and implemented them to develop a prognostic risk stratification model. The model's reliability was rigorously validated using both internal cohort

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… Wu H Blockade of the lncRNA-PART1-PHB2 axis confers resistance to PARP inhibitor and promotes cellular senescence in ovarian cancer Cancer Lett. 2024 602 217192 10.1016/j.canlet.2024.217192 39181433 Wu, H. et al. … Blockade of the lncRNA-PART1-PHB2 axis confers resistance to PARP inhibitor and promotes cellular senescence in ovarian cancer. Cancer Lett. 602 , 217192. 10.1016/j.canlet.2024.217192 (2024). 39181433 10.1016/j.canlet.2024.217192 30. …

The Role of Nucleotide Excision Repair in Cisplatin-Induced Peripheral Neuropathy: Mechanism, Prevention, and Treatment.

Platinum-based chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common dose-limiting effects of cancer treatment and results in dose reduction and discontinuation of life-saving chemotherapy. Its debilitating effects are often permanent and lead to lifelong impairment of quality of life in cancer patients. While the mechanisms underlying the toxicity are not yet fully defined, dorsal root ganglia sensory neurons play an integral role in symptom development. DNA-platinum adducts accumulate in these cells and inhibit normal cellular function. Nucleotide excision repair (NER)

Reprogramming of nitrogen metabolism in tumors: mechanisms and therapeutic implications.

Nitrogen metabolism plays a key role in maintaining normal physiological functions of the organism and cell proliferation and differentiation. Nitrogen metabolism in normal human body maintains a dynamic balance to meet the body's demand for synthesis of biological macromolecules such as proteins and nucleic acids. However, in the process of tumor development, the nitrogen metabolism of tumor cells is reprogrammed to meet the demand of rapid proliferation, showing significantly different metabolic characteristics from normal cells. Key enzymes in the tumor microenvironment affect nitrogen meta

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… Deletion of SLC4A11 induces hepatocellular carcinoma cellular senescence and reduces β-cyclin-driven tumor growth in vivo through the blockade of ammonia excretion(Wang et al. 2024b ). …

The JAK/STAT signaling pathway: from bench to clinic.

The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway was discovered more than a quarter-century ago. As a fulcrum of many vital cellular processes, the JAK/STAT pathway constitutes a rapid membrane-to-nucleus signaling module and induces the expression of various critical mediators of cancer and inflammation. Growing evidence suggests that dysregulation of the JAK/STAT pathway is associated with various cancers and autoimmune diseases. In this review, we discuss the current knowledge about the composition, activation, and regulation of the JAK/STAT pat

Epigenetic Regulation of Autophagy in Bone Metabolism.

The skeletal system is crucial for supporting bodily functions, protecting vital organs, facilitating hematopoiesis, and storing essential minerals. Skeletal homeostasis, which includes aspects such as bone density, structural integrity, and regenerative processes, is essential for normal skeletal function. Autophagy, an intricate intracellular mechanism for degrading and recycling cellular components, plays a multifaceted role in bone metabolism. It involves sequestering cellular waste, damaged proteins, and organelles within autophagosomes, which are then degraded and recycled. Autophagy's i

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… Knockdown of SUV39H1 leads to a reduction in H3K9me3 levels, enhancing DNA repair capabilities and delaying cellular senescence in progeroid cells. 75 Table 2. … Epigenetic regulation of cellular senescence and aging . Front Genet . 2017 ; 8 : 138 . 29018479 10.3389/fgene.2017.00138 PMC5622920 76. Basta MD , Petruk S , Mazo A , Walker JL . Fibrosis-the tale of H3K27 histone methyltransferases and demethylases . …

MSC-EV therapy for bone/cartilage diseases.

Mesenchymal stromal cells (MSCs) have been utilized in cell therapy for various diseases. Recent studies have demonstrated that extracellular vesicles (EVs) released by MSCs play an important role in their therapeutic activities. EVs contain a variety of bioactive molecules such as proteins, messenger RNAs (mRNAs), and micro RNAs (miRNAs) and modify the function of the recipient cells by transferring these molecules. Despite the promising potential of EV therapy as a substitute for MSC therapy, there are challenges that need to be addressed for the clinical success of EV therapy. EV quality ha