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Распространение эпсилонного токсина Clostridium Perfringens изолируется среди пациентов с множественным склерозом и расстройством спектра нейромиелита в Иране.

Клостридий перфрингенс эпсилон токсин (ETX) является мощным нейротоксином, который пересекает мозговой барьер (BBB) и который, как было предложено, связан с демиелинизирующими расстройствами CNS. Здесь мы изучили распространенность C. перфрингенов и антиETX иммуноглобулина G (IgG) и иммуноглобулина M (IgM) в стуле и сере пациентов с множественным склерозом (MS) и спектральным расстройством нейромиелита (NMOSD) по сравнению со здоровым контролем. МЕТОДЫ: В период с сентября 2019 года по июнь 2020 года было собрано 43 образца стула и 43 образца серы из MS (n = 33) и NMOSD (n = 10) пациентов, а т

Митохондриальная пригодность как функциональная контрольная точка в раке: метаболическая пластичность, эволюция опухолей и иммунотерапия.

Митохондрия все чаще признается в качестве динамичных регуляторов адаптации к раковым клеткам, иммунной функции и терапевтической реакции. Помимо их канонической роли в производстве энергии, митохондриальный метаболизм, динамика, контроль качества и сигнализация стресса влияют на выживание клеток опухоли и способность клеток иммунного эффекта поддерживать антитумберную активность в микроопухоли. В этом обзоре мы рассматриваем митохондриальную пригодность как многоаспектное функциональное достояние, включающее биоэнергетику, метаболическую гибкость, повторное гомеостаз, контроль качества митохо

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… Under conditions of mitochondrial damage, altered mitochondrial DNA packaging or membrane integrity can enable mitochondrial DNA to reach the cytosol. …

Ход работы 34th Симпозиум ESVN-ECVN 23rd-24th сентябрь 2022.

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Recent advances in biomimetic nanodelivery systems for cancer Immunotherapy.

Tumor immunotherapy is a developing and promising therapeutic method. However, the mechanism of tumor immune microenvironment and individual differences of patients make the clinical application of immunotherapy still very limited. The resulting targeting of the tumor environment and immune system is a suitable strategy for tumor therapy. Biomimetic nanodelivery systems (BNDS) coated with nanoparticles has brought new hope for tumor immunotherapy. Due to its high targeting, maximum drug delivery efficiency and immune escape, BNDS has become one of the options for tumor immunotherapy in the fut

Inhibition of Heat Shock-Induced H3K9ac Reduction Sensitizes Cancer Cells to Hyperthermia.

Heat stress, clinically known as hyperthermia, is a promising adjunctive modality in cancer treatment. However, the efficacy of hyperthermia as a monotherapy is limited and the underlying mechanism remains poorly understood. Targeting histone modifications is an emerging strategy for cancer therapy, but little is known regarding the role of heat stress in altering these modifications. Here, we report that heat shock inhibits H3K9 acetylation (H3K9ac) via histone deacetylase 6 (HDAC6) regulation. Heat shock inhibits the interaction between HDAC6 and heat shock protein 90 (HSP90), enhances nucle

ICAR 2011. Italian Conference on AIDS and Retroviruses, Florence, Italy, 27-29 March 2011. Abstracts.

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Mitochondrial Genetic and Epigenetic Regulations in Cancer: Therapeutic Potential.

Mitochondria are dynamic organelles managing crucial processes of cellular metabolism and bioenergetics. Enabling rapid cellular adaptation to altered endogenous and exogenous environments, mitochondria play an important role in many pathophysiological states, including cancer. Being under the control of mitochondrial and nuclear DNA (mtDNA and nDNA), mitochondria adjust their activity and biogenesis to cell demands. In cancer, numerous mutations in mtDNA have been detected, which do not inactivate mitochondrial functions but rather alter energy metabolism to support cancer cell growth. Increa

HDACs and Their Inhibitors on Post-Translational Modifications: The Regulation of Cardiovascular Disease.

Cardiovascular diseases (CVD), such as myocardial hypertrophy, heart failure, atherosclerosis, and myocardial ischemia/reperfusion (I/R) injury, are among the major threats to human health worldwide. Post-translational modifications alter the function of proteins through dynamic chemical modification after synthesis. This mechanism not only plays an important role in maintaining homeostasis and plays a crucial role in maintaining normal cardiovascular function, but is also closely related to the pathological state of various diseases. Histone deacetylases (HDACs) play an important role in the

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… Histone Deacetylases (HDACs) As the structural units of chromatin, nucleosomes are composed of DNA and histones, which are important for DNA packaging in eukaryotic cells [ 19 ]. …

MicroRNA-21-5p profile in the alveolar bone following tooth extraction in medication-related osteonecrosis of the jaw rat model.

OBJECTIVE: This study aimed to compare microRNA-21-5p expressions at the extraction wound in the maxillary bones of rats with medication-related osteonecrosis of the jaw (MRONJ) and normal rats at different time points. MATERIALS AND METHODS: In total, 18 female, 8-week-old Sprague-Dawley rats were randomly assigned to the experimental group (n = 9) and the control group (n = 9). To establish MRONJ in the right maxillary first molar area in the experimental group, zoledronate (66 µg/kg) and dexamethasone (5 mg/kg) were administered intraperitoneally every other day for 2 weeks before tooth ex

Higher single dose of bortezomib plus thalidomide and dexamethasone is a promising therapy for newly diagnosed multiple myeloma.

BackgroundBortezomib in combination with thalidomide and dexamethasone (VTD) has been widely used for newly diagnosed multiple myeloma (MM). The aim of this study was to evaluate the efficacy and safety of a new high-dose bortezomib plus thalidomide and dexamethasone as an induction and consolidation therapy regimen for MM.MethodsA total of 93 patients with previously untreated symptomatic MM were enrolled in this single-center study. In group-1, 40 patients received bortezomib 1.6 mg/m2 and dexamethasone 40 mg on days 1, 6 and 11, plus thalidomide 100 mg on days 1-21 (VTD-1). In group-2, 53 p

XPO1 inhibitor selinexor enhances the apoptotic effect of azacitidine in T-cell lymphoma with TET2/RHOA mutations via JAK3/STAT3 axis.

BACKGROUND: Peripheral T-cell lymphoma (PTCL) is a highly heterogeneous group of lymphoid malignancies with diverse pathological and molecular features. Patients harboring TET2 and RHOA double mutations exhibit poor response to anthracycline-based chemotherapy and unfavorable prognosis. Azacitidine, a hypomethylating agent, is frequently used in combination with anthracycline-based regimens in PTCL. However, resistance remains a significant challenge. This study aims to explore novel targeted therapies to overcome therapeutic resistance in TET2/RHOA-mutated PTCL patients. METHODS: A systemati

Oncolytic Viruses as Reliable Adjuvants in CAR-T Cell Therapy for Solid Tumors.

Although impactful scientific advancements have recently been made in cancer therapy, there remains an opportunity for future improvements. Immunotherapy is perhaps one of the most cutting-edge categories of therapies demonstrating potential in the clinical setting. Genetically engineered T cells express chimeric antigen receptors (CARs), which can detect signals expressed by the molecules present on the surface of cancer cells, also called tumor-associated antigens (TAAs). Their effectiveness has been extensively demonstrated in hematological cancers; therefore, these results can establish th

Cytokine receptor IL27RA is an NF-κB-responsive gene involved in CD38 upregulation in multiple myeloma.

Multiple myeloma (MM) shows constitutive activation of canonical and noncanonical nuclear factor κB (NF-κB) signaling via genetic mutations or tumor microenvironment (TME) stimulations. A subset of MM cell lines showed dependency for cell growth and survival on the canonical NF-κB transcription factor RELA alone, suggesting a critical role for a RELA-mediated biological program in MM pathogenesis. Here, we determined the RELA-dependent transcriptional program in MM cell lines and found the expression of the cell surface molecules interleukin-27 receptor-α (IL-27Rα) and the adhesion molecule JA

The Role of Complement Activating Collectins and Associated Serine Proteases in Patients With Hematological Malignancies, Receiving High-Dose Chemotherapy, and Autologous Hematopoietic Stem Cell Transplantations (Auto-HSCT).

We conducted a prospective study of 312 patients (194 with multiple myeloma, 118 with lymphomas) receiving high-dose conditioning chemotherapy and autologous hematopoietic stem cell transplantation (auto-HSCT). Polymorphisms of MBL2 and MASP2 genes were investigated and serial measurements of serum concentrations of mannose-binding lectin (MBL), CL-LK collectin and MASP-2 as well as activities of MBL-MASP-1 and MBL-MASP-2 complex were made. Serum samples were taken before conditioning chemotherapy, before HSCT and once weekly after (totally 4-5 samples); in minority of subjects also 1 and/or 3

Proteomic alterations in ovarian cancer-Predicting residual disease status using artificial intelligence and SHAP-based biomarker interpretation.

IntroductionHigh-grade serous ovarian cancer (HGSOC) is the most aggressive and prevalent subtype of ovarian Treatment outcomes are significantly influenced by residual disease status following neoadjuvant chemotherapy (NACT). Predicting residual disease before surgery can improve patient stratification and personalized treatment strategies.MethodsThis study analyzed pre-NACT proteomic data from 20 HGSOC patients treated with NACT. Patients were categorized into two groups based on surgical outcomes: no residual disease (R0, n = 14) and suboptimal residual disease (R1, n = 6). From an initial

Indoleamine 2,3-dioxygenase 1 (IDO1) activity in leukemia blasts correlates with poor outcome in childhood acute myeloid leukemia.

Microenvironmental factors contribute to the immune dysfunction characterizing acute myeloid leukemia (AML). Indoleamine 2,3-dioxygenase 1 (IDO1) is an interferon (IFN)-γ-inducible enzyme that degrades tryptophan into kynurenine, which, in turn, inhibits effector T cells and promotes regulatory T-cell (Treg) differentiation. It is presently unknown whether childhood AML cells express IDO1 and whether IDO1 activity correlates with patient outcome. We investigated IDO1 expression and function in 37 children with newly diagnosed AML other than acute promyelocytic leukemia. Blast cells were cultur

Proceedings to the 2020 Online Conference of the Particle Therapy Cooperative Group (PTCOG2020Online): 13-14 September 2020Organized by the Particle Therapy Cooperative Group (PTCOG), this special online meeting featured abstracts and programs that enabled the communication and cross fertilization for which PTCOG meetings are known.

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Cell and Gene Therapy: Transforming Treatment Paradigms for Patient-Centric Care.

Cell and gene therapies (CGTs) are transforming medicine by offering potential cures for diseases previously considered untreatable. Despite rapid advancements, challenges remain in optimizing efficacy and safety and ensuring patient accessibility and preference due to high costs and clinical uncertainties, particularly for rare diseases and one-time administration. The American Society of Clinical Pharmacology & Therapeutics (ASCPT) held a CGT satellite conference in 2025, titled "Cell and Gene Therapy: Transforming Treatment Paradigms for Patient-Centric Care." This manuscript summarizes the

Convergent targeting of FUNDC1-dependent mitophagy sensitises and overcomes resistance to EGFR inhibition.

Combination therapies are critical for enhancing and prolonging the efficacy of EGFR inhibitors. Here, we uncover FUNDC1-dependent mitophagy as a key protective mechanism in EGFR-mutant non-small cell lung cancer (NSCLC). We discover that nitidine, a bioactive component of the traditional Xihuang Pill formulation, synergises with the EGFR inhibitor osimertinib. Mechanistically, nitidine and osimertinib synergistically disrupt FUNDC1-mediated mitophagy, leading to mitochondrial dysfunction and accumulation of reactive oxygen species in EGFR-mutant NSCLC. We further show that both osimertinib an

The Three Musketeers in Cancer Therapy: Pharmacokinetics, Pharmacodynamics and Personalised Approach.

Cancer therapy is rapidly evolving from a one-size-fits-all paradigm toward highly personalized approaches. Traditional chemotherapies and radiotherapies, while broadly applied, often yield suboptimal outcomes due to tumor heterogeneity and are limited by significant toxicities. In contrast, precision oncology tailors prevention, diagnosis, and treatment to the individual patient's genetic and molecular profile. Key advancements underscore this shift: molecularly targeted drugs (e.g., trastuzumab for HER2-positive breast cancer, EGFR and ALK inhibitors for lung cancer) have improved efficacy a