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Targeting aberrant DNA methylation in mesenchymal stromal cells as a treatment for myeloma bone disease.

Multiple myeloma (MM) progression and myeloma-associated bone disease (MBD) are highly dependent on bone marrow mesenchymal stromal cells (MSCs). MM-MSCs exhibit abnormal transcriptomes, suggesting the involvement of epigenetic mechanisms governing their tumor-promoting functions and prolonged osteoblast suppression. Here, we identify widespread DNA methylation alterations of bone marrow-isolated MSCs from distinct MM stages, particularly in Homeobox genes involved in osteogenic differentiation that associate with their aberrant expression. Moreover, these DNA methylation changes are recapitul

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… Chromatin immunoprecipitation (ChIP)-quantitative PCR MSCs (15 × 10 3 cells per IP) were cross-linked with 1% formaldehyde for 15 min and subjected to chromatin immunoprecipitation after sonication. …

Current Perspectives of the Applications of Polyphenols and Flavonoids in Cancer Therapy.

The development of anticancer therapies that involve natural drugs has undergone exponential growth in recent years. Among the natural compounds that produce beneficial effects on human health, polyphenols have shown potential therapeutic applications in cancer due to their protective functions in plants, their use as food additives, and their excellent antioxidant properties. The possibility of combining conventional drugs-which are usually more aggressive than natural compounds-with polyphenols offers very valuable advantages such as the building of more efficient anticancer therapies with l

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… Sonication tailored enhance cytotoxicity of naringenin nanoparticle in pancreatic cancer: Design, optimization, and in vitro studies. Drug Dev. Ind. Pharm. 2020;46:659–672. doi: 10.1080/03639045.2020.1747485. 106. …

S100A4 in Cancer Metastasis: Wnt Signaling-Driven Interventions for Metastasis Restriction.

The aberrant activity of Wnt signaling is an early step in the transformation of normal intestinal cells to malignant tissue, leading to more aggressive tumors, and eventually metastases. In colorectal cancer (CRC), metastasis accounts for about 90% of patient deaths, representing the most lethal event during the course of the disease and is directly linked to patient survival, critically limiting successful therapy. This review focuses on our studies of the metastasis-inducing gene S100A4, which we identified as transcriptional target of β-catenin. S100A4 increased migration and invasion in v

Демиелинция производит сдвиг в населении кортикальных нейронов, которые синапсируют с каллосальными олигодендроцитными клетками.

Клетки потомства олигодендроцитов (ОРК) получают синаптическое воздействие от различных нейронов в мозгу развивающихся и взрослых. Понимание того, меняются ли нейронные популяции, которые синапируют с OPC в здоровом мозге в результате обезвоживания и/или ремиэлирования, может способствовать совершенствованию стратегий нейрозащиты или миелинового ремонта, разрабатываемых для демиелинизирующих заболеваний, таких, как множественный склероз. Чтобы изучить эту возможность, мы использовали трансгенную технологию крелокса, чтобы облегчить инфекцию ОПС модифицированным вирусом бешенства, что позволяет

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… Tamoxifen administration Tamoxifen (Sigma; 10540-29-1) was dissolved to 40 mg/ml in corn oil (Sigma; 8001-30-7) by sonication at 21°C for ∼2 h and administered to adult mice by oral gavage as four consecutive daily doses (300 mg/kg). …

Novel insight and perspectives of nanoparticle-mediated gene delivery and immune-modulating therapies for pancreatic cancer.

Current standard-of-care therapies have failed to improve the survival of patients with metastatic pancreatic cancer (PCA). Therefore, exploring novel therapeutic approaches for cancer targeting is of utmost need. During the past few years, many efforts have been made to develop conventional treatment strategies to reduce chemotherapy resistance. However, critical challenges have impeded current cancer management outcomes, and limited clinical responses have been achieved due to unfavorable off-target effects. Advances in nanotechnology-based gene and immune-modulator delivery systems have exc

Emerging Roles of Mesenchymal Stem/Stromal-Cell-Derived Extracellular Vesicles in Cancer Therapy.

Despite the tremendous efforts of many researchers and clinicians, cancer remains the second leading cause of mortality worldwide. Mesenchymal stem/stromal cells (MSCs) are multipotent cells residing in numerous human tissues and presenting unique biological properties, such as low immunogenicity, powerful immunomodulatory and immunosuppressive capabilities, and, in particular, homing abilities. Therapeutic functions of MSCs are mediated mostly by the paracrine effect of released functional molecules and other variable components, and among them the MSC-derived extracellular vesicles (MSC-EVs)

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… The most common approaches to temporarily physically permeabilize the EV membrane are electroporation, sonication, freeze–thaw cycles, and extrusion. These methods were shown to be successful for small molecules as well as macromolecules [ 109 , 110 , 111 ]. …

Blood Vessels and Peripheral Nerves as Key Players in Cancer Progression and Therapy Resistance.

Cancer cells continuously interact with the tumor microenvironment (TME), a heterogeneous milieu that surrounds the tumor mass and impinges on its phenotype. Among the components of the TME, blood vessels and peripheral nerves have been extensively studied in recent years for their prominent role in tumor development from tumor initiation. Cancer cells were shown to actively promote their own vascularization and innervation through the processes of angiogenesis and axonogenesis. Indeed, sprouting vessels and axons deliver several factors needed by cancer cells to survive and proliferate, inclu

Googling the Guggul (Commiphora and Boswellia) for Prevention of Chronic Diseases.

Extensive research during last 2 decades has revealed that most drugs discovered today, although costs billions of dollars for discovery, and yet they are highly ineffective in their clinical response. For instance, the European Medicines Agency has approved 68 anti-cancer drugs, and out of which 39 has reached the market level with no indication of increased survival nor betterment of quality of life. Even when drugs did improve survival rate compared to available treatment strategies, most of these were found to be clinically insignificant. This is a fundamental problem with modern drug disc

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The cross talk of ubiquitination and chemotherapy tolerance in colorectal cancer.

Ubiquitination, a highly adaptable post-translational modification, plays a pivotal role in maintaining cellular protein homeostasis, encompassing cancer chemoresistance-associated proteins. Recent findings have indicated a potential correlation between perturbations in the ubiquitination process and the emergence of drug resistance in CRC cancer. Consequently, numerous studies have spurred the advancement of compounds specifically designed to target ubiquitinates, offering promising prospects for cancer therapy. In this review, we highlight the role of ubiquitination enzymes associated with c

Cancer-Associated Fibroblasts: Heterogeneity, Cancer Pathogenesis, and Therapeutic Targets.

Cancer-associated fibroblasts (CAFs) are functionally diverse stromal regulators that orchestrate tumor progression, metastasis, and therapy resistance through dynamic crosstalk within the tumor microenvironment (TME). Recent advances in single-cell multiomics and spatial transcriptomics have identified conserved CAF subtypes with distinct molecular signatures, spatial distributions, and context-dependent roles, highlighting their dual capacity to promote immunosuppression or restrain tumor growth. However, therapeutic strategies struggle to reconcile this functional duality, hindering clinica

Targeting the HPGDS-PGD2 axis to treat Th17 cell-mediated autoimmunity in multiple sclerosis.

Th17 cells are central drivers of autoimmune pathology, including multiple sclerosis (MS), yet the endogenous metabolic signals that shape their pathogenic differentiation remain incompletely defined. Prostaglandin D₂ (PGD2) is traditionally viewed as an extracellular mediator in allergic diseases. Here, we identify PGD2 as a cell-intrinsic antagonist of the nuclear receptor PPARγ, thereby promoting Th17 cell differentiation and exacerbating EAE pathology. PGD2 is selectively elevated in patients with MS compared with healthy individuals. Within the MS cohort, PGD2 correlates with Th17 cell fr

Natural killer cells, macrophages and dendritic cells as innate immune therapies for blood cancers.

Innate immune cells are emerging as powerful allies in the fight against blood cancers. Natural Killer (NK) cells, macrophages, and dendritic cells (DCs)—once viewed mainly as supporting players—are now at the forefront of next-generation immunotherapies, owing to their rapid, antigen-independent tumor recognition and potent effector functions. This review highlights their distinct anti-tumor roles: NK cells’ cytotoxicity and “missing-self” recognition, the dual and adaptable nature of macrophages in the tumor microenvironment (TME), and the antigen-presenting capabilities of DCs that bridge i

Адипоцитный β-гидроксибутират обеспечивает метаболическую стойкость в множестве миеломы.

Множественная миелома (ММ) остается неизлечимым раком крови. Ожирение является известным фактором риска, но то, как адипоциты способствуют прогрессу MM, не в полной мере понятно. Здесь мы обнаруживаем метаболический перекресток между адипоцитами и клетками MM, который способствует выживанию клеток MM под глюкозой. Мы показываем, что ограничение глюкозы активирует АМПК, срывает связь HSP90-IRF4 и делает IRF4 восприимчивым к протеасомной деградации при помощи TRIM21. Парадоксально, но такой же стресс стимулирует адипоциты к производству β-гидроксибутирата (β-OHB). Клетки MM используют β-OHB при

Strategies to Improve Sensitivity to Radiotherapy in Pediatric Solid Tumors.

The primary goal in the treatment of pediatric malignancies is to maintain effective cancer control while minimizing toxicities and late effects. Radiotherapy is a component of standard therapy against many pediatric cancers, but tumor cell DNA damage repair mechanisms and the hypoxic tumor microenvironment may limit the effectiveness of this modality. Additionally, irradiated cancer cells often acquire resistance to radiotherapy that permits cancer cell survival or stimulates tumor regrowth after treatment, further limiting the efficacy of radiotherapy. Various preclinical studies have invest

Искусственный интеллект в педиатрической нейрорадиологии: текущий ландшафт, проблемы и будущие направления.

В настоящем обзоре содержится информация о нынешнем ландшафте искусственного интеллекта (АИ) в области педиатрической и эмбриональной нейрорадиологии, критическая оценка текущей практики, барьеров на пути к клиническому усыновлению и будущего потенциала. Мы искали рецензированные исследования за последнее десятилетие, сфокусировавшись на сегментации изображений, обнаружении повреждений, классификации, прогнозировании и поддержке клинического решения при педиатрической съемке мозга. Особое внимание было уделено уникальным педиатрическим факторам, таким, как развитие мозга и нехватка данных. Мет

LncRNA NEAT1 restrains the malignant biological characteristics of acute myeloid leukemia via regulating CTCF/CXCR2 axis.

Acute myeloid leukemia (AML) is notorious in the field of hematology for its poor efficacy, frustrating prognosis, and it is prone to refractory or relapsed conditions. Previous studies in our team have shown that some Long noncoding RNAs (lncRNAs) and chemokine receptors play key regulatory roles in AML. The findings of this study demonstrated that the expression of NEAT1 was atypically low in both clinical AML specimens and AML cell lines. Overexpression of NEAT1 was capable of attenuating the malignant biological characteristics of AML cells, including inhibiting the malignant proliferation

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… Next, they were resuspended in lysis buffer for sonication. The chromatin lysates (containing 25 mg chromatin) were immunoprecipitated with 5 mg anti-CTCF (Abcam, USA) or anti-IgG antibody (Abcam, USA) and 20 mL of Protein-A/G-Sepharose beads (Beyotime, China). …

Emerging Frontiers in Colorectal Cancer Therapy: From Targeted Molecules to Immunomodulatory Breakthroughs and Cell-Based Approaches.

Colorectal cancer (CRC) is ranked as the second leading cause of cancer-related deaths globally, necessitating urgent advancements in therapeutic approaches. The emergence of groundbreaking therapies, including chimeric antigen receptor-T (CAR-T) cell therapies, oncolytic viruses, and immune checkpoint inhibitors, marks a transformative era in oncology. These innovative modalities, tailored to individual genetic and molecular profiles, hold the promise of significantly enhancing patient outcomes. This comprehensive review explores the latest clinical trials and advancements, encompassing targe

Экспериментальный аутоиммунный энцефаломиэлит патогенез меняется в зависимости от возраста животных: воздействие выражения S100B.

Множественный склероз (MS) является основной провокационной и нетравматической причиной инвалидности среди молодых людей, при этом у пациентов среднего возраста часто появляются поздние МБ, что приводит к более слабому лечению и худшим прогнозам. Протеина S100B, связывающего кальций, выше у пациентов с сеток, и ее целевая направленность показала, что в экспериментальных моделях аутоиммунного энцефаломиелита (EAE) она может снизить остроту заболеваний. Однако в большинстве исследований по патологии MS основное внимание уделяется моделям молодого животного, что оставляет пробел в понимании возде

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… Protein pellets were resuspended in an 8 M urea (in 1 M Tris HCl, pH 8) and 1% SDS (1:1) followed by sonication and centrifugation at 3200 g for 10 min. Total protein concentration was measured using Nanodrop® ND-100 Spectrophotometer (NanoDrop Technologies) and stored at −80ºC. …

Молекулярные модели, связанные с ущербом от митохондриала: нейроиммуномодуляторы в патофизиологии центральной нервной системы.

Нейроинфламмация способствует широкому спектру нейродегенеративных заболеваний, включая болезнь Альцгеймера, болезнь Паркинсона, болезнь Хантингтона и множественный склероз. Его движут неевропейские глиальные клетки, главным образом микроглии и астроциты. Микроглии являются постоянными иммунными клетками центральной нервной системы, в то время как астроциты являются основными элементами поддержки нейронных функций, но могут также участвовать в нейроиммунной реакции. Оба этих типа глиальных клеток могут стать реактивными при обнаружении определенных внутриклеточных молекул, которые появляются в