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Euchromatic Histone Lysine Methyltransferase 2 Inhibition Enhances Carfilzomib Sensitivity and Overcomes Drug Resistance in Multiple Myeloma Cell Lines.

Proteasome inhibitors (PIs) are extensively used for the therapy of multiple myeloma. However, patients continuously relapse or are intrinsically resistant to this class of drugs. In addition, adverse toxic effects such as peripheral neuropathy and cardiotoxicity could arise. Here, to identify compounds that can increase the efficacy of PIs, we performed a functional screening using a library of small-molecule inhibitors covering key signaling pathways. Among the best synthetic lethal interactions, the euchromatic histone-lysine N-methyltransferase 2 (EHMT2) inhibitor UNC0642 displayed a coope

Histone deacetylase upregulation of neuropilin-1 in osteosarcoma is essential for pulmonary metastasis.

The lungs represent the most common site of metastasis for osteosarcoma (OS). Despite our advances in developing targeted therapies for treating solid malignancies, broad acting chemotherapies remain the first line treatment for OS. In assaying the efficacy of approved therapeutics for non-OS malignancies, we previously identified the histone deacetylase 1 and 2 (HDAC1 and 2) inhibitor, romidepsin, as effective for the treatment of established lung metastatic OS. Yet, romidepsin has noted toxicities in humans and so here we aimed to define the primary mechanisms through which HDAC1/2 mediate O

Exploring cellular diversity in lung adenocarcinoma epithelium: Advancing prognostic methods and immunotherapeutic strategies.

Immunotherapy has brought significant advancements in the treatment of lung adenocarcinoma (LUAD), but identifying suitable candidates remains challenging. In this study, we investigated tumour cell heterogeneity using extensive single-cell data and explored the impact of different tumour cell cluster abundances on immunotherapy in the POPLAR and OAK immunotherapy cohorts. Notably, we found a significant correlation between CKS1B+ tumour cell abundance and treatment response, as well as stemness potential. Leveraging marker genes from the CKS1B+ tumour cell cluster, we employed machine learnin

Экстракорпоральное обнаружение биомаркеров и патогенов в слюне: всеобъемлющий, панорамный обзор.

Человеческая слюна представляет собой разнородную жидкость с сложным составом, которая содержит антитела, белки и вирусы, что делает ее применимой в клинической диагностике. Анализ проб слюны имеет несколько преимуществ по сравнению с другими биофильтрами, включая неинвазивную и простую процедуру сбора для эксторального обнаружения. Диагностика биомаркеров или патогенов в слюне может осуществляться различными методами: масс-спектрометрией, ПЦР, ЭЛИСА, электрохимическими и оптическими методами, такими, как флуоресцентная, SPR и SERS. Раннее обнаружение раковых и других биомаркеров заболеваний,

Mechanism-based prediction of drug synergy via network controllability analysis of therapeutic pathways in intractable diseases.

Identifying effective drug combinations for multidrug therapies in intractable diseases remains challenging, and drug synergy depends on regulatory mechanisms. Herein, we introduce a mechanistic framework that redefines drug combination strategies into two distinct synergy paradigms-"boost" and "complement"-and present a network-based method called SYNERGIE to predict associated combinations across diseases. For diseases lacking known therapeutic targets, we introduced network controllability analysis to estimate therapeutic pathways and target molecules. SYNERGIE integrates drug-disease and d

Enhancing the Safety of Nanoparticles in Medicine: Highlights of Progress and Critical Objectives.

Nanoparticles have transformed drug delivery, imaging, vaccination, and precision therapeutics, but their clinical translation remains constrained by safety profiles that are inseparable from material design, biological identity, host factors, and manufacturing. This review critically evaluates recent progress, persistent limitations, and priority objectives for safer nanomedicine. Unlike reviews organized primarily by material class or isolated toxicology endpoints, we integrate physicochemical determinants, protein corona formation, immune recognition, organ disposition, preclinical models,

Мак-1 регулирует иммуноусилительное подавление конкретной стадии болезни через нитриковый путь в аутоиммунном заболевании.

Интегрин Мак-1 играет важнейшую роль в развитии множественного склероза (MS); однако лежащий в его основе механизм не в полной мере изучен. Здесь мы разработали мышь с миелоидной мышью Мак-1-дефицит. Используя экспериментальную аутоиммунную энцефаломиэлит (EAE) модель мыши MS, мы сообщаем, что Мак-1 на миелиоидных клетках является ключом к развитию болезней. Наши данные показывают, что миелиоидный Мак-1 значительно повышает интенсивность EAE и затрудняет регрессию заболеваний. Потеря Mac-1 увеличивает количество клеток Gr-1+ в периферийных тканях и CNS и предпочтительно ускоряет переход моноци

KIF11 promotes rheumatoid arthritis pathogenesis by activating M1 macrophage polarization and promoting inflammatory cytokine secretion.

BACKGROUND AND OBJECTIVE: KIF11, a mitotic kinesin, has been implicated in oncogenesis, but its specific role and mechanism in RA pathogenesis remain largely unexplored. We aim to explore functional role and molecular mechanism of KIF11 to promote RA progression. METHODS: Bioinformatics analysis was first performed on public RA datasets (GSE55457, GSE55235, GSE2053, GSE12021, and GSE1919) to identify KIF11-associated DEGs and their enriched pathways using GO/KEGG and GSEA analysis. Lentivirus-mediated shRNA was employed to knock down KIF11 expression in MH7A cells and M1-polarized macrophages

Antibody drug conjugate: the "biological missile" for targeted cancer therapy.

Antibody-drug conjugate (ADC) is typically composed of a monoclonal antibody (mAbs) covalently attached to a cytotoxic drug via a chemical linker. It combines both the advantages of highly specific targeting ability and highly potent killing effect to achieve accurate and efficient elimination of cancer cells, which has become one of the hotspots for the research and development of anticancer drugs. Since the first ADC, Mylotarg® (gemtuzumab ozogamicin), was approved in 2000 by the US Food and Drug Administration (FDA), there have been 14 ADCs received market approval so far worldwide. Moreove

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… Instead of stochastic coupling, disulfide re-bridging involves the reaction with cysteine-selective cross-linking reagents, such as bissulfone reagents, 102 next-generation maleimides (NGMs), 103 and pyridazinediones (PDs). 104 The bis-reactive reagents enable the reconnection of the polypeptide chains …

Global inequalities in tracheal, bronchus, and lung cancer care quality from 1990 to 2021.

Tracheal, bronchus, and lung cancer remains a major global cancer burden, but cross-national comparisons using composite proxy indicators are limited. Using Global Burden of Disease 1990-2021 estimates, we constructed a quality-of-care index (QCI) from incidence, mortality, prevalence, and disability outcomes; assessed temporal and geographic patterns; modeled associations with linear mixed models; and compared older adults with the overall population. Age-standardized incidence and death rates declined globally, but QCI remained highly unequal across 204 countries. QCI was higher in high-deve

Identification of the Distinct Immune Microenvironment Features Associated with Progression Following High-Dose Melphalan and Autologous Stem Cell Transplant in Multiple Myeloma.

A key treatment for patients with multiple myeloma is high-dose melphalan followed by autologous stem cell transplant (ASCT). It can provide a deep response with long-term remission. However, some patients progress quickly, and it is not clear why. In this study, we performed single-cell RNA and T-cell receptor sequencing of the immune microenvironment of 40 patients before and after ASCT to determine if differences in the immune composition could define those who would progress. Clear differences in cell populations were identified in progressors, including increased T-cell infiltration, decr

Noncanonical SQSTM1/p62-Nrf2 pathway activation mediates proteasome inhibitor resistance in multiple myeloma cells via redox, metabolic and translational reprogramming.

Multiple Myeloma (MM) is a B-cell malignancy characterized by the accumulation of clonal plasma cells in the bone marrow, with drug resistance being a major cause of therapeutic failure. We established a carfilzomib-resistant derivative of the LP-1 MM cell line (LP-1/Cfz) and found that the transcription factor NF-E2 p45-related factor 2 (Nrf2; gene symbol NFE2L2) contributes to carfilzomib resistance. The mechanism of Nrf2 activation involved enhanced translation of Nrf2 as well as its positive regulator, the autophagy receptor sequestosome 1 (SQSTM1)/p62. The eukaryotic translation initiatio

Levels of active tyrosine kinase receptor determine the tumor response to Zalypsis.

BackgroundZalypsis(®) is a marine compound in phase II clinical trials for multiple myeloma, cervical and endometrial cancer, and Ewing's sarcoma. However, the determinants of the response to Zalypsis are not well known. The identification of biomarkers for Zalypsis activity would also contribute to broaden the spectrum of tumors by selecting those patients more likely to respond to this therapy.MethodsUsing in vitro drug sensitivity data coupled with a set of molecular data from a panel of sarcoma cell lines, we developed molecular signatures that predict sensitivity to Zalypsis. We verified

Превышение зависимости от предыдущих ожиданий при пересылке множественных склерозов.

Когнитивное расстройство является общей и недействующей особенностью множественного склероза (МС). Байезийские модели восприятия и действий обеспечивают мощную основу для понимания того, как познавательные процессы изменяются в НР. В этом исследовании по контролю мы использовали модель временнóго воспроизведения в байесовской системе для выявления когнитивной дисфункции у пациентов с релапсирующим MS, используя модифицированную байезскую модель наблюдателя, которая разделяет время на сенсорные измерения, оценки и моторные ступени. Как НР, так и контрольные группы переоценивали короткие промежу

Quality indicators and patient outcome measures for palliative care in cancer patients: a systematic review.

IntroductionWith the exponential rise in global cancer incidence, the surge in demand for palliative care has outstripped capacity, limiting patients' access to quality and holistic palliative care, especially in low- and middle-income countries. Despite an upturn in research activity, evidence in palliative care remains limited, given its complexity as well as the shortage of standardised quality indicators (QIs) and patient outcome measures (POMs). The objective of this systematic review is to assess the QIs and POMs used to evaluate palliative care service on aggregated and individual level

Abstracts from the 11th International Conference for Healthcare and Medical Students (ICHAMS) : Virtual. 10-12 February 2022.

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Health Risks from Microplastics in Intravenous Infusions: Evidence from Italy, Spain, and Ecuador.

The rising incidence of microplastics (MPs) is a possible health risk to humans. The present study aims to analyze the presence of MPs in intravenous (IV) infusions and compare MP concentrations from multiple brands. The IV solutions of 29 medical devices (IV-MDs) from seven brands commercialized in Ecuador, Spain, and Italy have been selected under specific consideration to carry out the study. The detection of MPs has been quite obvious in almost all of the samples from brands in the mentioned countries. MP concentrations ranged from 9 to 20 MPs/L in glass containers to 166-299 MPs/L in plas

Panobinostat reduces hypoxia-induced cisplatin resistance of non-small cell lung carcinoma cells via HIF-1α destabilization.

BackgroundLung cancer is one of the most frequent cancer types and the leading cause of cancer death worldwide. Cisplatin is a widely used chemotherapeutic for non-small cell lung carcinoma (NSCLC), however, its positive effects are diminished under hypoxia. We wanted to determine if co-treatment with cisplatin and histone deacetalyse (HDAC) inhibitor panobinostat can reduce hypoxia-induced cisplatin resistance in NSCLC cells, and to elucidate mechanism involved.MethodsExpression status of different HDACS was determined in two cell lines and in tumor tissue from 20 patients. Cells were treated

Exosomes derived from BMSCs ameliorate cyclophosphamide-induced testosterone deficiency by enhancing the autophagy of Leydig cells via the AMPK-mTOR signaling pathway.

Cyclophosphamide-induced testosterone deficiency (CPTD) during the treatment of cancers and autoimmune disorders severely influences the quality of life of patients. Currently, several guidelines recommend patients suffering from CPTD receive testosterone replacement therapy (TRT). However, TRT has many disadvantages underscoring the requirement for alternative, nontoxic treatment strategies. We previously reported bone marrow mesenchymal stem cells-derived exosomes (BMSCs-exos) could alleviate cyclophosphamide (CP)-induced spermatogenesis dysfunction, highlighting their role in the treatment

Human antigen R-regulated CCL20 contributes to osteolytic breast cancer bone metastasis.

Breast cancer mainly spreads to bone, causing decreased survival of patient. Human antigen R (HuR) and chemokines are important molecules associated with mRNA stability and cell-cell interaction in cancer biology. Here, HuR knockdown inhibited bone metastasis and osteolysis of metastatic breast cancer cells in mice and HuR expression promoted the metastatic ability of cancer cells via CCL20 and GM-CSF. In contrast with the findings for GM-CSF, ELAVL1 and CCL20 expressions were markedly increased in breast tumor tissues and ELAVL1 expression showed a strong positive correlation with CCL20 expre