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Comprehensive machine learning analysis of PANoptosis signatures in multiple myeloma identifies prognostic and immunotherapy biomarkers.

PANoptosis is closely associated with tumorigenesis and therapeutic response, yet its role in multiple myeloma (MM) remains unclear. This study analyzed bulk transcriptomic and clinical data from the TCGA and GEO databases to identify seven PANoptosis-related genes (PRGs) using machine learning (LASSO regression and random forest models) and univariate Cox analysis, and constructed a prognostic risk model. The model demonstrated robust predictive performance across three external validation cohorts. High-risk patients exhibited higher tumor purity, increased tumor mutational burden, and distin

Review: progression and heterogeneity of multiple sources of mesenchymal stromal cells for the treatment of rheumatoid arthritis.

Rheumatoid arthritis is often a neglected autoimmune disease characterized by inflammation and destruction of the joints leading to pain, swelling and restricted movement, particularly affecting specific population groups and severely reducing the quality of life of patients. Certain risk factors (smoking, diet, infections) contribute to the increased prevalence of the disease in patients, with targeted interventions to alleviate symptoms. Due to the complexity of current medications and the lack of a systematic approach to decision-making, Mesenchymal stromal cells therapy has become increasi

The effects of twenty-four nutrients and phytonutrients on immune system function and inflammation: A narrative review.

BACKGROUND AND AIM: Recently, optimal immune function has become a primary focus of worldwide attention not only in the prevention of chronic disease but also as one strategy to reduce the severity of acute illness. Inflammation, a process largely controlled by the immune system, has long been studied and recognized for its role in chronic disease. Optimizing immune function or managing inflammation using individual nutrients and phytonutrients is not well understood by the average person. Thus, this narrative literature review summarizes many of the more recent findings about how certain nutr

Algae-Derived Bioactive Compounds as Platforms for Translational Biotechnology and Health Applications.

Marine macroalgae, microalgae, and associated microorganisms are increasingly recognised as valuable sources of bioactive compounds with applications across biotechnology and health. The environmental and ecological conditions they inhabit shape their metabolite diversity, leading to the production of high-value compounds such as sulphated polysaccharides, lipids, pigments, phenolics, and peptides. These compounds exhibit conserved biological activities that underpin potent antioxidant, anti-inflammatory, cytotoxic, and pro-regenerative effects with strong potential for translation. Although e

Autophagy in tumor immune escape and immunotherapy.

The immunotherapy targeting tumor immune escape mechanisms has become a critical strategy in anticancer treatment; however, the challenge of immune resistance remains significant. Autophagy, a cellular response to various stressors, involves the degradation of damaged proteins and organelles via lysosomal pathways, maintaining cellular homeostasis. This process not only supports tumor cell survival but also profoundly impacts the efficacy of cancer immunotherapies. The modulation of autophagy in tumor cells or immune cells exerts dual effects on tumor immune escape and immunotherapy. However,

Клинические эффекты пробиотических добавок на метаболический синдром: систематический обзор и мета-анализ.

Пробиотики привлекли к себе большое внимание в силу их способности модифицировать метаболизм питательных веществ или иммуноводство. Цель этого исследования заключается в оценке эффективности биотического дополнения при лечении метаболического синдрома. МЕТОДЫ: В период с момента создания базы данных по июль проводились систематические обыски в библиотеке < < Пубмед > > , < < Web of Science > > , < < Эмбаза > > и < < Кохрейн > > . 2024. СТАТА/СЕ 14.0 Программное обеспечение использовалось для статистического анализа. РЕЗУЛЬТАТЫ: Всего 12 клиническ

Non-canonical NFκB mutations reinforce pro-survival TNF response in multiple myeloma through an autoregulatory RelB:p50 NFκB pathway.

Environmental drug resistance constitutes a serious impediment for therapeutic intervention in multiple myeloma. Tumor-promoting cytokines, such as tumor necrosis factor (TNF), induce nuclear factor-κB (NFκB)- driven expression of pro-survival factors, which confer resistance in myeloma cells to apoptotic insults from TNF-related apoptosis-inducing ligand (TRAIL) and other chemotherapeutic drugs. It is thought that RelA:p50 dimer, activated from IκBα-inhibited complex in response to TNF-induced canonical NFκB signal, mediates the pro-survival NFκB function in cancerous cells. Myeloma cells add

Совпадение в полном тексте источника
… The NF-kappaB factor RelB and histone H3 lysine methyltransferase G9a directly interact to generate epigenetic silencing in endotoxin tolerance . J Biol Chem 2009 ; 284 : 27857 –27865. 19690169 10.1074/jbc.M109.000950 PMC2788836 Siggers T, Chang AB, Teixeira A, Wong D, Williams KJ, Ahmed B et al. …

The sirtuin family in health and disease.

Sirtuins (SIRTs) are nicotine adenine dinucleotide(+)-dependent histone deacetylases regulating critical signaling pathways in prokaryotes and eukaryotes, and are involved in numerous biological processes. Currently, seven mammalian homologs of yeast Sir2 named SIRT1 to SIRT7 have been identified. Increasing evidence has suggested the vital roles of seven members of the SIRT family in health and disease conditions. Notably, this protein family plays a variety of important roles in cellular biology such as inflammation, metabolism, oxidative stress, and apoptosis, etc., thus, it is considered a

Safety and Efficacy of the Intravenous Infusion of Umbilical Cord Mesenchymal Stem Cells in Patients With Heart Failure: A Phase 1/2 Randomized Controlled Trial (RIMECARD Trial [Randomized Clinical Trial of Intravenous Infusion Umbilical Cord Mesenchymal Stem Cells on Cardiopathy]).

RationaleUmbilical cord-derived mesenchymal stem cells (UC-MSC) are easily accessible and expanded in vitro, possess distinct properties, and improve myocardial remodeling and function in experimental models of cardiovascular disease. Although bone marrow-derived mesenchymal stem cells have been previously assessed for their therapeutic potential in individuals with heart failure and reduced ejection fraction, no clinical trial has evaluated intravenous infusion of UC-MSCs in these patients.ObjectiveEvaluate the safety and efficacy of the intravenous infusion of UC-MSC in patients with chronic

Targeting the P-selectin/PSGL-1 pathway: discovery of disease-modifying therapeutics for disorders of thromboinflammation.

P-selectin is a membrane glycoprotein and a member of the selectin family of cell adhesion molecules. It is prestored in α-granules of platelets and Weibel-Palade bodies of endothelial cells and is rapidly expressed on their surfaces upon activation during the course of an inflammatory response. Although a critical component of the innate immune system, the interaction of P-selectin with its cognate ligand, P-selectin glycoprotein ligand 1 (PSGL-1) may mediate maladaptive events central to the pathophysiology of venous thromboembolism, cardiovascular disease, stroke, metabolic syndrome, and si

Acute Pneumonia

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Emerging insights into the gut microbiota as a key regulator of immunity and response to immunotherapy in hepatocellular carcinoma.

The gut microbiota, a complex microbial ecosystem closely connected to the liver via the portal vein, has emerged as a critical regulator of liver health and disease. Numerous studies have underscored its role in the onset and progression of liver disorders, including alcoholic liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). This review provides a comprehensive overview of current insights into the influence of the gut microbiota on HCC progre

Pulmonary Hypertension in an Oncologic Intensive Care Unit

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Dose-escalation studies of mesenchymal stromal cell therapy for decompensated liver cirrhosis: phase Ia/Ib results and immune modulation insights.

Decompensated liver cirrhosis (DLC) is characterized by severe liver dysfunction and immune dysregulation, posing significant treatment challenges. Mesenchymal stromal cell (MSC) therapy has shown promise in DLC treatment, but the optimal dosing strategies and dose-dependent therapeutic mechanisms in humans remain unclear, limiting its clinical application. We conducted sequential Phase Ia/Ib trials using a single-arm, dose-escalation design to evaluate the safety and tolerability of MSC therapy in DLC patients while also exploring its immunomodulatory effects and gathering preliminary therape

In vitro расширила человека CD4+CD25+ регуляционные T клетки, подавляющие распространение Т клеток.

Регулирующие Т клетки (Tregs) оказались критически важными в балансе между автоиммунизацией и терпимостью и были связаны с несколькими аутоиммунными заболеваниями человека. Однако небольшое число трегов в периферии крови ограничивает их терапевтический потенциал. Поэтому мы разработали протокол, который позволит расширить "Трегз" при сохранении их подавляющей активности. Мы изолировали клетки CD4+CD25 hi от человеческой периферической крови и расширили их in vitro в присутствии anti-CD3 и anti-CD28 Магнитные кситы и высокие концентрации внешнего интерлейкина (IL) -2. Траги были эффективно расш

Exercise-modulated IL-6 in cancer cachexia: molecular mechanisms and therapeutic potential.

BACKGROUND: Cancer cachexia is a multifactorial metabolic syndrome marked by progressive skeletal muscle wasting, systemic inflammation, reduced quality of life, and poor clinical outcomes. Interleukin-6 (IL-6) is a central mediator in cachexia pathophysiology, driving inflammatory signaling, catabolic metabolism, and muscle atrophy. However, IL-6 also rises transiently during exercise, where it exerts beneficial metabolic and anti-inflammatory effects, highlighting the context-dependent nature of IL-6 signaling. MAIN BODY: This review summarizes current knowledge on the regulation and functio

Postbiotics as Emerging Strategy Targeting Obesity- and Aging-Related Breast Cancer-Prospects in Prophylaxis and Therapy.

Aging and obesity accompanied with hormonal disequilibrium represent critical, inter-related risk factors for breast cancer, significantly influencing disease incidence, progression, and therapeutic outcomes. This review aims to elucidate the multifaceted biological mechanisms linking obesity and aging to breast carcinogenesis, with a particular focus on the emerging therapeutic and preventive potential of postbiotics as molecules targeting cellular events important for cancer growth and responsiveness. Despite continuous advancement, breast cancer therapy still poses several challenges, such

Barriers to Treg therapy in Europe: From production to regulation.

There has been an increased interest in cell based therapies for a range of medical conditions in the last decade. This explosion in novel therapeutics research has led to the development of legislation specifically focused on cell and gene based therapies. In Europe, the European medicines agency (EMA) designates any medicines for human use which are based on genes, tissues, or cells as advanced therapy medicinal products or advanced therapy medicinal products (ATMPs). In this article we discuss the hurdles to widespread adoption of ATMPs in Europe, with a focus on regulatory T cells (Tregs).

Enhancing the Bioavailability of Resveratrol: Combine It, Derivatize It, or Encapsulate It?

Overcoming the limited bioavailability and extensive metabolism of effective in vitro drugs remains a challenge that limits the translation of promising drugs into clinical trials. Resveratrol, despite its well-reported therapeutic benefits, is not metabolically stable and thus has not been utilized as an effective clinical drug. This is because it needs to be consumed in large amounts to overcome the burdens of bioavailability and conversion into less effective metabolites. Herein, we summarize the more relevant approaches to modify resveratrol, aiming to increase its biological and therapeut

Passive Monoclonal and Polyclonal Antibody Therapies

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