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Clostridium butyricum alleviates multiple myeloma by remodeling the bone marrow microenvironment and inhibiting PI3K/AKT pathway through the gut‒bone axis.

Emerging evidence reveals a strong connection between the gut microbiota and cancer. However, the exact role of gut microbiota dysbiosis in multiple myeloma (MM) is poorly understood, and the therapeutic potential of microbiota-targeted interventions represents a promising strategy that demands urgent mechanistic and translational investigation. First, we conducted a comprehensive microbiome-metabolite analysis between MM patients and healthy individuals. The result revealed a marked compositional difference characterized by reduced abundances of butyrate-producing bacteria and diminished buty

Biomimetic materials for medical applications.

AbstractRecent advances in biomedical research have facilitated the exploration of biomimetic materials and their potential for diagnosing and treating diseases. This review synthesizes reports of recent research into biomimetic materials and provides a focused analysis of their therapeutic and diagnostic efficacy across multiple physiological systems, including the locomotor, digestive, respiratory, urinary, endocrine, nervous, integumentary, hematopoietic, and circulatory systems. These findings highlight the transformative potential of these materials in the management of systemic diseases.

No patient left behind: The promise of immune priming with epigenetic agents.

Checkpoint inhibitors, monoclonal antibodies that inhibit PD-1 or CTLA-4, have revolutionized the treatment of multiple cancers. Despite the enthusiasm for the clinical successes of checkpoint inhibitors, and immunotherapy, in general, only a minority of patients with specific tumor types actually benefit from treatment. Emerging evidence implicates epigenetic alterations as a mechanism of clinical resistance to immunotherapy. This review presents evidence for that association, summarizes the epi-based mechanisms by which tumors evade immunogenic cell death, discusses epigenetic modulation as

Hematopoietic Niche Hijacking in Bone Metastases: Roles of Megakaryocytes, Erythroid Lineage Cells, and Perivascular Stromal Subsets.

Bone metastases mark a critical and often terminal phase in cancer progression, where disseminated tumor cells (DTCs) manage to infiltrate and exploit the complex microenvironments of the bone marrow. While most current therapies focus on the well-known late-stage "vicious cycle" of osteolysis, they often overlook the earlier stages, namely, tumor cell colonization and dormancy. During these early phases, cancer cells co-opt hematopoietic stem cell (HSC) niches, using them as sanctuaries for long-term survival. In this review, we bring together emerging insights that highlight a trio of undera

Discovery and validation of surface N-glycoproteins in MM cell lines and patient samples uncovers immunotherapy targets.

BackgroundMultiple myeloma (MM) is characterized by clonal expansion of malignant plasma cells in the bone marrow. While recent advances in treatment for MM have improved patient outcomes, the 5-year survival rate remains ~50%. A better understanding of the MM cell surface proteome could facilitate development of new directed therapies and assist in stratification and monitoring of patient outcomes.MethodsIn this study, we first used a mass spectrometry (MS)-based discovery-driven cell surface capture (CSC) approach to map the cell surface N-glycoproteome of MM cell lines. Next, we developed t

The role of hypoxic microenvironment in autoimmune diseases.

The hypoxic microenvironment, characterized by significantly reduced oxygen levels within tissues, has emerged as a critical factor in the pathogenesis and progression of various autoimmune diseases (AIDs). Central to this process is the hypoxia-inducible factor-1 (HIF-1), which orchestrates a wide array of cellular responses under low oxygen conditions. This review delves into the multifaceted roles of the hypoxic microenvironment in modulating immune cell function, particularly highlighting its impact on immune activation, metabolic reprogramming, and angiogenesis. Specific focus is given to

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… Their overactivation results in accumulation in inflammatory areas, where they generate ROS, activate proteases of soluble proteins, induce innate and adaptive immune responses, release neutrophil extracellular traps (NETs), mediate gene expression and cell signaling, cellular metabolism, ultimately …

Comprehensive analysis of plasma cell heterogeneity and immune interactions in multiple myeloma.

This study focused on the role of plasma cells in multiple myeloma (MM) and the associated potential mechanisms. Transcriptomic data of MM and various gene sets from several public databases were downloaded for subsequent analyses. Through single-cell sequencing, 10 major cell types were identified and annotated. The differential gene expression and pathway enrichment between different plasma cell subtypes as well as cell communication analysis, transcriptional regulation analysis, and enrichment analysis in conjunction with the malignant subpopulation were performed. Next, the samples were cl

Role of CCR1/5/7 in hepatocellular carcinoma: a study on prognostic evaluation, molecular subtyping, and association with immune infiltration.

This study aims to assess the prognostic value of the C-C motif chemokine receptor (CCR) gene family in hepatocellular carcinoma (HCC) and its relationship with immune infiltration and molecular subtypes of HCC. The evaluation of the GSE14520 dataset and TCGA database confirmed the prognostic significance of CCR. Building upon the correlation between CCR1, CCR5, and CCR7 and favorable prognosis, we further validated the prognostic importance of CCR1, CCR5, and CCR7 in ICGC database and an independent cohort from Guangxi autonomous region. Then, we constructed a risk prognosis model. Additional

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… A recent study reported that chemokine receptor agonists could induce neutrophil extracellular traps that interfere with immune cytotoxicity [ 20 ]. Lesch et al. showed that CXCR6 + T cell adoptive therapy was effective in treating pancreatic cancer in mice [ 21 ]. … CXCR1 and CXCR2 Chemokine Receptor Agonists Produced by Tumors Induce Neutrophil Extracellular Traps that Interfere with Immune Cytotoxicity. …

A comprehensive review of Sjögren's syndrome: Classification criteria, risk factors, and signaling pathways.

Sjögren's syndrome (SS) is a chronic autoimmune disease that affects the exocrine glands and may lead to a range of systemic symptoms that impact various organs. Both innate and adaptive immune pathways might trigger the disease. Studying the signaling pathways underlying SS is crucial for enhancing diagnostic and therapeutic effectiveness. SS poses an ongoing challenge for medical professionals owing to the limited therapeutic options available. This review offers a comprehensive understanding of the intricate nature of SS, encompassing disease classification criteria, risk factors, and signa

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… Additionally, in patients with SS, activation of IFN-I in neutrophils causes damage to mitochondria and results in the production of reactive oxygen species, which leads to the creation of neutrophil extracellular traps. … The substances released by neutrophil extracellular traps may act as auto-antigens, triggering immune responses and releasing inflammatory substances [ 156 ]. IFN-γ has been reported to promote autoimmune germinal centers (GCs) via interaction with the B cell IFN-γ receptor [ 161 , 162 ]. …

Vasculopathy as a mechanical barrier to cancer spread: Clinical evidence and a rheology-based model in lung cancer and other solid tumors.

Metastatic dissemination in lung cancer (LC) and other solid tumors is influenced not only by tumor-intrinsic biology and immune-inflammatory responses, but also by the physical properties of the vascular system through which circulating tumor cells (CTCs) migrate. Peripheral arterial disease (PAD), particularly when associated with aneurysmal dilation, is frequent among long-term smokers and is characterized by chronic vascular inflammation and altered hemodynamics. We hypothesized that PAD-related vascular remodeling and rheological alterations may influence tumor metastatic capacity. Throug

Лечение связанного с лекарствами остеонекроза челюсти с помощью клеточной терапии.

Введение: Остеонекроз челюсти (MRONJ), связанный с лекарственными препаратами, представляет собой серьезную проблему с учетом отсутствия «золотого стандартного» лечения. Клеточная терапия и тканевая инженерия предлагают перспективные терапевтические альтернативы. Цель этого исследования заключалась в использовании регенеративных свойств стромальной сосудистой фракции (AT-SVF) и лейкоцитного фибрина с высоким содержанием лейкоцита (L-PRF) для обработки MRONJ. AT-SVF содержит мезенхимальные стромальные клетки (MSC) и эндотелиальные клетки потомства (EPC), которые способствуют образованию костей,

Nanoparticles and bone microenvironment: a comprehensive review for malignant bone tumor diagnosis and treatment.

Malignant bone tumors, which are difficult to treat with current clinical strategies, originate from bone tissues and can be classified into primary and secondary types. Due to the specificity of the bone microenvironment, the results of traditional means of treating bone tumors are often unsatisfactory, so there is an urgent need to develop new treatments for malignant bone tumors. Recently, nanoparticle-based approaches have shown great potential in diagnosis and treatment. Nanoparticles (NPs) have gained significant attention due to their versatility, making them highly suitable for applica

Organelle-oriented nanomedicines in tumor therapy: Targeting, escaping, or collaborating?

Precise tumor therapy is essential for improving treatment specificity, enhancing efficacy, and minimizing side effects. Targeting organelles is a key strategy for achieving this goal and is a frontier research area attracting a considerable amount of attention. The concept of organelle targeting has a significant effect on the structural design of the nanodrugs employed. Most notably, the intricate interactions among different organelles in a tumor cell essentially create a unified system. Unfortunately, this aspect might have been somewhat overlooked when existing organelle-targeting nanodru

Contribution of Macrophages and T Cells in Skeletal Metastasis.

Bone is a common site for metastases with a local microenvironment that is highly conducive for tumor establishment and growth. The bone marrow is replete with myeloid and lymphoid linage cells that provide a fertile niche for metastatic cancer cells promoting their survival and growth. Here, we discuss the role of macrophages and T cells in pro- and anti-tumoral mechanisms, their interaction to support cancer cell growth, and their contribution to the development of skeletal metastases. Importantly, immunotherapeutic strategies targeting macrophages and T cells in cancer are also discussed in

Hyaluronan, fluid pressure, and stromal resistance in pancreas cancer.

Pancreatic ductal adenocarcinomas (PDAs) are notoriously aggressive and resistant to treatment. They distinguish themselves further by their robust fibroinflammatory, or desmoplastic, stromal reaction and degree of hypovascularity. Recent findings have revealed multiple mechanisms of stromal complicity in disease pathogenesis and resistance. In this review, we focus on altered physicomechanics as one mechanism of what we term as 'stromal resistance' in PDA. Extremely high interstitial fluid pressures and a dense extracellular matrix combine to limit the delivery and distribution of therapeutic

Cystatin M/E Ameliorates Multiple Myeloma-Induced Hyper Osteolytic Bone Resorption.

Multiple myeloma (MM) is a malignancy of terminally differentiated B-cells that is localized primarily in the bone marrow (BM) but also can be present in peripheral blood and tissue/organs [...].

Chemotherapy-Associated Thrombotic Microangiopathy.

Thrombotic microangiopathy (TMA) is a syndrome of microangiopathic hemolytic anemia and thrombocytopenia with end-organ dysfunction. Although the advent of plasma exchange, immunosuppression, and complement inhibition has improved morbidity and mortality for primary TMAs, the management of secondary TMAs, particularly drug-induced TMA, remains less clear. TMA related to cancer drugs disrupts the antineoplastic treatment course, increasing the risk of cancer progression. Chemotherapeutic agents such as mitomycin-C, gemcitabine, and platinum-based drugs as well as targeted therapies such as anti

Comprehensive analysis of mRNA-microRNA-lncRNA expression profiles in post-traumatic elbow heterotopic ossification using RNA sequencing and experimental validation.

BackgroundThis study aimed to profile the molecular signatures of post-traumatic elbow heterotopic ossification (HO) to identify key regulators and potential therapeutic targets.MethodsTotal RNA from post-traumatic elbow HO tissues (n=4) and normal bone tissues (n=6) was subjected to high-throughput sequencing to identify differentially expressed mRNAs (DEGs), microRNAs (DEMs), and lncRNAs (DELs). Bioinformatics analyses included Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction network construction, and transcription factor (TF)

Extracellular Vesicles in Tumors: A Potential Mediator of Bone Metastasis.

As one of the most common metastatic sites, bone has a unique microenvironment for the growth and prosperity of metastatic tumor cells. Bone metastasis is a common complication for tumor patients and accounts for 15-20% of systemic metastasis, which is only secondary to lung and liver metastasis. Cancers prone to bone metastasis include lung, breast, and prostate cancer. Extracellular vesicles (EVs) are lipid membrane vesicles released from different cell types. It is clear that EVs are associated with multiple biological phenomena and are crucial for intracellular communication by transportin

Update on the role of bone turnover markers in the diagnosis and management of osteoporosis: a consensus paper from The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO), International Osteoporosis Foundation (IOF), and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC).

PurposeThe International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) have proposed procollagen type I N propeptide (PINP) and β isomerized C-terminal telopeptide of type I collagen (β-CTX-I) as reference bone turnover markers (BTMs) for osteoporosis. This report examines the published literature since the 2011 IOF-IFCC position paper in order to determine the clinical potential of the reference BTMs and newer markers for the prediction of fracture risk and monitoring the treatment of osteoporosis.MethodsEvidence for the re