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Унификация одиссеи: искусственный интеллект для диагностирования и лечения редких заболеваний.

Подытожить текущие проблемы в диагностике и лечении редких заболеваний (РД), осветить последние достижения в области искусственного интеллекта (АИ) для РД и предложить модель будущего состояния лечения пациентов РД. Многодисциплинарный экспертный обзор с кратким изложением современных практических задач и мер по ограничению ставок в области РД-клиентов с учетом ключевых клинических и исследовательских соображений в отношении нормативных и экономических ограничений. 10,000 известные РД оказывают коллективное воздействие 1 В 10 Американцы, в целом 30 million Люди. Ежегодно на РД приходится свыше

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… The emerging fields of epigenomics, transcriptomics, proteomics, metabolomics, and metagenomics can provide complementary information regarding gene expression, transcription, translation, stability, and interactions. …

Molecular-Guided Precision Oncology in Cancer of Unknown Primary: A State-of-the-Art Perspective.

Cancer of unknown primary (CUP) is evolving from a diagnosis of exclusion treated with empirical chemotherapy to a molecularly defined entity amenable to precision-based interventions. This heterogeneous entity, comprising 2-3% of all metastatic malignancies, encompasses diverse cancers with clinically occult primary sites at diagnosis after a thorough workup. Recent landmark trials including CUPISCO and Fudan CUP-001 have demonstrated significant survival improvements with molecularly guided therapies compared to empirical chemotherapy, fundamentally enhancing and complementing traditional or

Prognostic value of patient-reported outcome thresholds on survival and adverse events in CLL/SLL: A pooled analysis of ibrutinib trials.

BACKGROUND: EORTC thresholds for clinical importance on the QLQ-C30 have been proposed to improve the interpretability of patient-reported outcomes (PROs), but their clinical relevance remains underexplored in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). OBJECTIVES: This study aimed to evaluate the frequency of clinically important baseline PRO domains and their associations with survival and adverse events in patients with CLL/SLL. DESIGN: This was a pooled retrospective analysis of individual patient data from three randomized clinical trials of ibrutinib-based

Понимание и решение проблемы сопротивления иммуномодуляционным соединениям IMID в множестве миеломы.

Лекарственные средства иммуномодулирования (ИМИД), включая линалидомид и помалидомид в сочетании с протеаозными ингибиторами, дексаметазоном и антиCD38 моноклональными антителами, играют центральную роль в лечении множественной миеломы (ММ) на новых диагностированных и рецидивированных этапах. Эти методы лечения значительно улучшили результаты лечения пациентов во всем мире, в результате чего IMID стали одной из опор MM-терапии. В настоящее время разрабатывается новое поколение более мощных соединений, называемых лигами-модуляторами цереблиона Е3 (CELMODs), которые могут заменить старые IMID.

Fatty acid synthase in chemoresistance: mechanisms and therapeutic opportunities.

Chemoresistance has been a major obstacle to the efficient treatment of cancer. Recently, targeting lipid metabolism has gained significant attention because of its roles not only in promoting cancer progression but also in inducing chemotherapy resistance. Fatty acid synthase (FAS) is the sole enzyme that is in charge of catalyzing the synthesis of palmitate, a long-chain lipid that is essential for membrane construction and post-translational modification in cell biology. Both FAS and its product, palmitate, have been validated as critical players in mediating or causing chemoresistance in c

Личная профилактика нейродегенеративных заболеваний: обзор аналитического исследования и карта пробелов в данных.

Нейродегенеративные заболевания представляют собой серьезную проблему в области общественного здравоохранения в связи с их высокой распространенностью и низким прогнозом. Определение биомаркеров для стратификации людей в силу их риска развития этих заболеваний может помочь в определении новых индивидуализированных профилактических мер. Цель этого исследования заключалась в проведении аналитического обзора биомаркеров для первичной и вторичной индивидуализированной профилактики нейродегенеративных заболеваний. Поиск был нацелен на биомаркеры среди взрослых или групп повышенного риска в клиничес

Нацеливание на природные полифенолы антиоксидантов в целях защиты от нейроинфламмации и нейродегенеративных заболеваний: всеобъемлющий обзор.

Полифенолы, природные фитонутриенты, встречающиеся в растительных продуктах питания, привлекли значительное внимание к их потенциальному терапевтическому воздействию в неврологических заболеваниях и нейроинфламмации. Эти соединения обладают различными возможностями нейрозащиты, включая антиоксидантные, антивоспалительные и антиамильоидные свойства, которые способствуют смягчению развития таких нейродегенеративных заболеваний, как болезнь Альцгеймера (AD), болезнь Паркинсона (PD), деменция, множественный склероз (MS), Строк и болезнь Хантингтона (HD). Полифенолы были тщательно изучены на предме

miRNAs as predictive biomarkers of response to treatment in pediatric patients with acute lymphoblastic leukemia.

MicroRNAs (miRNAs/miRs) are promising prognostic biomarkers in pediatric acute lymphoblastic leukemia (ALL). The present study aimed to identify miRNAs that could serve as prognostic biomarkers or as novel therapeutic targets in ALL. The expression levels of 84 miRNAs were assessed in the bone marrow aspirates of 10 pediatric patients with newly diagnosed ALL at diagnosis and on day 33 of induction of the ALL Intercontinental Berlin-Frankfurt-Münster 2009 protocol, and associations with established prognostic factors were evaluated. The levels at diagnosis of 25 miRNAs were associated with ≥2

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… Epigenomics. 2019;12:69–80. doi: 10.2217/epi-2019-0154. 11. Szczepanek J. Role of microRNA dysregulation in childhood acute leukemias: Diagnostics, monitoring and therapeutics: A comprehensive review. World J Clin Oncol. 2020;11:348–369. doi: 10.5306/wjco.v11.i6.348. 12. …

Advances in Understanding Mitochondrial MicroRNAs (mitomiRs) on the Pathogenesis of Triple-Negative Breast Cancer (TNBC).

Triple-negative breast cancer (TNBC) is characterized by poor outcome and the most challenging breast cancer type to treat worldwide. TNBC manifests distinct profile of mitochondrial functions, which dictates reprogrammed metabolism, fosters tumor progression, and notably serves as therapeutic targets. Mitochondrial microRNAs (mitomiRs) are a group of microRNAs that critically modulate mitochondrial homeostasis. By a pathway-centric manner, mitomiRs tightly orchestrate metabolic reprogramming, redox status, cell apoptosis, mitochondrial dynamics, mitophagy, mitochondrial DNA (mtDNA) maintenanc

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… Analysis of miRNA-mRNA network reveals miR-140-5p as a suppressor of breast cancer glycolysis via targeting GLUT1 Epigenomics 2019 11 9 1021 1036 10.2217/epi-2019-0072 2-s2.0-85068662067 31184216 31 Yao A. Xiang Y. Si Y. R. …

DNA Methylation Is Correlated with Oxidative Stress in Myelodysplastic Syndrome-Relevance as Complementary Prognostic Biomarkers.

Oxidative stress and abnormal DNA methylation have been implicated in cancer, including myelodysplastic syndromes (MDSs). This fact leads us to investigate whether oxidative stress is correlated with localized and global DNA methylations in the peripheral blood of MDS patients. Sixty-six MDS patients and 26 healthy individuals were analyzed. Several oxidative stress and macromolecule damage parameters were analyzed. Localized (gene promotor) and global DNA methylations (5-mC and 5-hmC levels; LINE-1 methylation) were assessed. MDS patients had lower levels of reduced glutathione and total anti

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… Hypomethylation of repeated DNA sequences in cancer Epigenomics 2010 2 245 269 10.2217/epi.10.2 22121873 65. Walker B.A. Wardell C.P. Chiecchio L. Smith E.M. Boyd K.D. Neri A. Davies F.E. Ross F.M. Morgan G.J. …

Insulin-Like Growth Factor 2 mRNA-Binding Protein 3 Modulates Aggressiveness of Ewing Sarcoma by Regulating the CD164-CXCR4 Axis.

Ewing sarcoma (EWS) is the second most common bone and soft tissue-associated malignancy in children and young adults. It is driven by the fusion oncogene EWS/FLI1 and characterized by rapid growth and early metastasis. We have previously discovered that the mRNA binding protein IGF2BP3 constitutes an important biomarker for EWS as high expression of IGF2BP3 in primary tumors predicts poor prognosis of EWS patients. We additionally demonstrated that IGF2BP3 enhances anchorage-independent growth and migration of EWS cells suggesting that IGF2BP3 might work as molecular driver and predictor of E

Cancer stem cells in personalized therapy: mechanisms, microenvironment crosstalk, and therapeutic vulnerabilities.

Cancer stem cells (CSCs) drive tumor progression, therapy resistance, and metastasis through unique membrane biology, glycosylation patterns, and metabolic adaptations. CSCs exhibit a distinct glycocalyx profile enriched in hyaluronan, heparan sulfate, and sialylated glycans, facilitating immune evasion, adhesion, and survival. Key signaling pathways-Wnt/β-catenin, Hedgehog, Notch, JAK/STAT, TGF/SMAD, and PI3K/AKT/mTOR-regulate CSC stemness and therapeutic resistance. Emerging biomarkers (CD44, CD133, ALDH1, EpCAM) and targeted therapies (CAR-T cells, miRNA modulation, lipid metabolism inhibit

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… The integration of artificial intelligence (AI) into CSC research has revolutionized the understanding, diagnosis, and treatment of cancer, which enhanced CSC identification by analyzing multi-omics data (genomics, transcriptomics, proteomics, and epigenomics). …

Ketogenic Diet in Cancer Prevention and Therapy: Molecular Targets and Therapeutic Opportunities.

Although cancer is still one of the most significant global challenges facing public health, the world still lacks complementary approaches that would significantly enhance the efficacy of standard anticancer therapies. One of the essential strategies during cancer treatment is following a healthy diet program. The ketogenic diet (KD) has recently emerged as a metabolic therapy in cancer treatment, targeting cancer cell metabolism rather than a conventional dietary approach. The ketogenic diet (KD), a high-fat and very-low-carbohydrate with adequate amounts of protein, has shown antitumor effe

Influence of Hypoxia on Tumor Heterogeneity, DNA Repair, and Cancer Therapy: From Molecular Insights to Therapeutic Strategies.

Hypoxia, characterized by a reduction in tissue oxygen levels, is a hallmark of many solid tumors and affects a range of cellular processes, including DNA repair. In low-oxygen conditions, cancer cells often suppress key DNA repair pathways such as homologous recombination (HR), leading to the accumulation of DNA damage and increased genomic instability. These changes not only drive tumor progression but also contribute to resistance against conventional therapies. Hypoxia significantly reduces the effectiveness of oxygen-dependent treatments, including radiotherapy and many chemotherapeutic a

Multiple myeloma: signaling pathways and targeted therapy.

Multiple myeloma (MM) is the second most common hematological malignancy of plasma cells, characterized by osteolytic bone lesions, anemia, hypercalcemia, renal failure, and the accumulation of malignant plasma cells. The pathogenesis of MM involves the interaction between MM cells and the bone marrow microenvironment through soluble cytokines and cell adhesion molecules, which activate various signaling pathways such as PI3K/AKT/mTOR, RAS/MAPK, JAK/STAT, Wnt/β-catenin, and NF-κB pathways. Aberrant activation of these pathways contributes to the proliferation, survival, migration, and drug res

Возраст и стадия созревания связаны с последствиями фибриногена для человека Олигодендроголии.

Фибриноген — это протеин, полученный из крови и содержащийся в коагуляции, и он может проникнуть в центральную нервную систему (КНС) после разрушения мозгового барьера. Эта молекула была связана с множественным склерозом (MS), заболеванием, отмеченным воспалением и обезвоживанием в CNS. Однако воздействие этой молекулы не изучалось на миелионирующих клетках человека. В этом исследовании рассматривается вопрос о том, как фибриноген влияет на родственные клетки человека олигодендроцита (OL) на различных этапах развития. Используя индуцированные плюрипотентные стволовые клетки (iPSC) прекурсоры O

Personalized Lifestyle Interventions for Prevention and Treatment of Obesity-Related Cancers: A Call to Action.

The increasing global burden of cancer necessitates innovative approaches to prevention and treatment. Lifestyle factors such as diet, physical activity, and smoking significantly contribute to cancer. At the same time, current guidelines are based on a one-size-fits-all approach, which limits their effectiveness across diverse populations. Obesity is a well-documented risk factor for cancer, directly affecting 13 types of cancer. The complex interplay of genetic, metabolic, hormonal, and environmental factors in obesity's etiology highlights the need for more tailored approaches to obesity-re

Refining risk prediction in pediatric acute lymphoblastic leukemia through DNA methylation profiling.

Acute lymphoblastic leukemia (ALL) is the most prevalent cancer in children, and despite considerable progress in treatment outcomes, relapses still pose significant risks of mortality and long-term complications. To address this challenge, we employed a supervised machine learning technique, specifically random survival forests, to predict the risk of relapse and mortality using array-based DNA methylation data from a cohort of 763 pediatric ALL patients treated in Nordic countries. The relapse risk predictor (RRP) was constructed based on 16 CpG sites, demonstrating c-indexes of 0.667 and 0.

Exosomal AFAP1-AS1 binds to microRNA-15a-5p to promote the proliferation, migration, and invasion of ectopic endometrial stromal cells in endometriosis.

BackgroundEndometriosis (EMS) remains a major challenge to reproductive health due to multifactorial etiology, disease heterogeneity, and the lack of appropriate diagnostic markers and treatment. Eexosome (Exo) has become a major factor in progression of a variety of diseases. However, the mechanisms directing their role in the pathophysiology of EMS are ill-defined. Here, we aimed to investigate the clinical implications of actin filament associated protein 1-Antisense RNA 1 (AFAP1-AS1) in EMS.MethodsBioinformatics analysis was used to predict the expression and interaction of AFAP1-AS1, miR-

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… Wu J Huang H Huang W Wang L Xia X Fang X Analysis of exosomal lncRNA, miRNA and mRNA expression profiles and ceRNA network construction in endometriosis Epigenomics. 2020 12 14 1193 1213 10.2217/epi-2020-0084 32462942 16. …

The DNA damage response network in the treatment of head and neck squamous cell carcinoma.

BACKGROUND: We sought to determine whether DNA damage response (DDR)-related aberrations predict therapeutic benefit in cisplatin-treated head and neck squamous cell carcinoma (HNSCC) patients and how DDR pathways are modulated after treatment with olaparib alone or in combination with cisplatin or durvalumab. PATIENTS AND METHODS: Oxidative stress, abasic sites and DDR-related parameters, including endogenous DNA damage, DNA repair mechanisms and apoptosis rates, were evaluated in HNSCC cell lines and peripheral blood mononuclear cells from 46 healthy controls (HC) and 70 HNSCC patients at b