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Inhibition of EIF2α Dephosphorylation Decreases Cell Viability and Synergizes with Standard-of-Care Chemotherapeutics in Head and Neck Squamous Cell Carcinoma.

Drug resistance is a common cause of therapy failure in head and neck squamous cell carcinoma (HNSCC). One approach to tackling it is by targeting fundamental cellular processes, such as translation. The eukaryotic translation initiation factor 2α (EIF2α) is a key player in canonical translation initiation and integrates diverse stress signals; when phosphorylated, it curbs global protein synthesis. This study evaluates EIF2α expression and phosphorylation in HNSCC. A small-molecule inhibitor of EIF2α dephosphorylation, salubrinal, was tested in vitro, followed by viability assays, flow cytome

Животные модели периферической нейропатии, вызванной химиотерапией, для гематологических заболеваний: обзор.

Химиотерапия это one основные виды лечения гематологовых магнестов. Однако периферическая нейропатия, вызванная химиотерапией (CIPN) one Наиболее часто встречающиеся долгосрочные токсичные реакции в химиотерапии, а также случаи CIPN влияют на качество жизни пациентов и могут приводить к прерыванию химиотерапии в тяжелых случаях, снижая тем самым эффективность химиотерапии. В настоящее время мы резюмируем существующие зверские модели CIPN, включая характеристики нескольких общих животных моделей, таких, как периферическая нейропатия, вызванная бортезомибами, периферическая нейропатия, вызванная

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… Vincristine impairs microtubules and causes neurotoxicity in cerebral organoids. Neuroscience. 2019;404:530‐540. 10.1016/j.neuroscience.2018.12.047 77. Nama N, Barker MK, Kwan C, et al. Vincristine‐induced peripheral neurotoxicity: a prospective cohort. …

Targeting erythroid progenitor cell metabolism to enhance cancer immunotherapy.

While cancer immunotherapy has transformed clinical management for cancer patients, its low response rates remain a critical challenge to be addressed. Tumor immune evasion now extends beyond the tumor microenvironment (TME), as advanced tumors induce extramedullary hematopoiesis (EMH) in the spleen, leading to a substantial expansion of erythroid progenitor cells (EPCs) with potent immunosuppressive capacity. EPCs are typically transient populations in erythroid maturation and differentiation; however, under tumor burden, they undergo profound metabolic reprogramming that exacerbates their im

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… While organ-on-a-chip systems, including tumor organoids, offer improved in vitro modeling, they often fail to fully recapitulate systemic physiological changes and multi-organ interactions. …

The double-edged sword of tumor-targeted treatment: the influence of targeted therapy on the heart.

As an important means of modern cancer treatment, targeted therapy has significant efficacy, but cardiac toxicity cannot be ignored. From subclinical myocardial injury to severe heart failure (HF), it poses significant challenges to the long-term survival and quality of life of patients. This article summarizes the impact of targeted therapy drugs on cardiac function and their mechanisms, including cardiomyocyte damage, myocardial hypertrophy, and HF, and conducts in-depth research into potential molecular mechanisms. These include direct cardiomyocyte damage through targeted pathway inhibitio

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… Modeling Effects of Immunosuppressive Drugs on Human Hearts Using Induced Pluripotent Stem Cell-Derived Cardiac Organoids and Single-Cell RNA Sequencing. Circulation 2022;145:1367-9. 10.1161/CIRCULATIONAHA.121.054317 49. Karvelas G, Roumpi A, Komporozos C, et al. …

Infiltrative and inflammatory systemic disorders involving the pituitary gland.

The hypothalamic-pituitary region can be affected by a wide and heterogeneous group of infiltrative and inflammatory disorders, including granulomatous, histiocytic, storage, infectious, non-pituitary neoplastic, and autoimmune or inflammatory conditions collectively grouped as hypophysitis. Although individually rare, these disorders are increasingly recognized due to growing awareness, wider use of pituitary imaging, and the emergence of immune checkpoint inhibitor-induced hypophysitis. They typically present with hypopituitarism (often including arginine vasopressin deficiency, which, parti

Translation of PET radiotracers for cancer imaging: recommendations from the National Cancer Imaging Translational Accelerator (NCITA) consensus meeting.

BackgroundThe clinical translation of positron emission tomography (PET) radiotracers for cancer management presents complex challenges. We have developed consensus-based recommendations for preclinical and clinical assessment of novel and established radiotracers, applied to image different cancer types, to improve the standardisation of translational methodologies and accelerate clinical implementation.MethodsA consensus process was developed using the RAND/UCLA Appropriateness Method (RAM) to gather insights from a multidisciplinary panel of 38 key stakeholders on the appropriateness of pre

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… However, it was noted that the equivalent tissue histology (e.g. immunohistochemical staining) in in vitro models (mouse tissues or even human organoids) can be used to confirm radiotracer specificity in cases where tumour histology is not feasible. …

К лечению множественных склерозов

Множественный склероз (MS) является воспалительным и демиелинизирующим заболеванием центральной нервной системы (CNS). У большинства пациентов болезнь начинается с острого наступления, за которым следует этап ремиссии, последующие рецидивы и позднее переход к устойчивой хронической прогрессии. В меньшинстве пациентов эта постепенная фаза развивается с самого начала. Для рецидивов MS характерно в основном деновое образование побочного повреждения CNS и инфильтрация иммунных клеток, в то время как патологические особенности MS прогрессирования включают медленно расширяющиеся повреждения, глобаль

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… Human CNS barrier-forming organoids with cerebrospinal fluid production Science 2020 369 eaaz5626 10.1126/science.aaz5626 32527923 PMC7116154 94. Chen Y. Podojil J.R. Kunjamma R.B. Jones J. Weiner M. Lin W. Miller S.D. Popko B. …

Nanoparticle-based strategy in CAR-T cell immunotherapy: challenges, implications, and perspectives.

Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable progress in treating hematologic malignancies, yet its broader application faces challenges such as manufacturing complexity, solid tumor microenvironment barriers, and immune toxicity. Nanoparticles (NPs), leveraging their precise delivery, immunomodulation, and multifunctional integration capabilities, offer innovative strategies to optimize CAR-T cell therapy. This review provides a comprehensive elucidation of the fundamental framework of CAR-T cell therapy and the challenges in oncological applications. Subsequently, w

Электрохимические датчики на основе полимера для диагностики нейродегенеративных заболеваний.

Острые и хронические нейродегенеративные заболевания (ND), включая множественный склероз (MS), болезнь Альцгеймера (AD) и болезнь Паркинсона (PD), характеризуются нейродегенерацией, которая представляет собой постепенный сбой и повреждение нейронов и аксонов в центральной нервной системе. Благодаря обнаружению соответствующих биомаркеров нейродегенеративных заболеваний (ND) стало возможным совершенствование клинических диагностических исследований, а также разработка и отслеживание успешных методов лечения заболеваний. Важные биомаркеры, такие, как белки тау, амилоид-β и α-синуклеины, имеют ва

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… An analysis of cell culture medium from midbrain organoids unique to Parkinsonian patients, generated from induced pluripotent stem cells, was conducted to demonstrate the possible use of the MIP electrochemical sensor. … The organoids derived from these patients showed considerably lower levels of α-Syn when compared with those of age-matched controls. Recovery is between 95 and 115%, and the relative standard deviation is less than 5% (Lee et al. 2021 ). …

ISEV2019 Abstract Book

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… In vitro : Foetal rat lung organoids were generated with epithelial cells from normal and hypoplastic lungs. Organoids were cultured for 10 days in either medium alone or medium supplemented with AFSC-EVs. Lung organoids from untreated normal pups served as control. … Results : Administration of AFSC-EVs increased terminal bud density and surface area of lung explants back to control levels and promoted lung epithelial cell differentiation in lung organoids (increased SPC and CC10 expression). …

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

Exosome-Enriched Hub Gene Networks Identify Diagnostic Biomarkers and Repurposable Therapeutic Targets in Endometriosis.

Endometriosis is a heterogeneous chronic inflammatory disorder associated with substantial diagnostic delay and limited therapeutic options, highlighting the need of robust non-invasive biomarkers and actionable molecular targets to complement existing low-sensitivity tests. To identify conserved pathogenic mechanisms with translational potential, here, we uniformly reprocessed three independent the Gene Expression Omnibus (GEO) microarray cohorts (GSE7305, GSE25628, and GSE11691) and applied a strict, directionally consistent intersection strategy to identify conserved transcriptional signals

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… Cell Biology and Translational Medicine, Volume 23: Stem Cell in Organoids, Signaling, Regeneration and Cancer. Springer; Cham, Switzerland: 2024. Melanoma Cell Adhesion Molecule (CD 146) in Endometrial Physiology and Disorder; pp. 131–148. 56. …

Targeted and epigenetic therapies for acute myeloid leukemia treatment.

This article provides a comprehensive overview of targeted and epigenetic therapies for acute myeloid leukemia (AML), highlighting their role in advancing treatment strategies. Recognizing that AML arises from complex genetic and epigenetic alterations, a deeper understanding of its pathogenesis has paved the way for precision medicine. The article reviews key targeted therapies, including IDH inhibitors (e.g., ivosidenib, enasidenib) for IDH mutations, FLT3 inhibitors (e.g., midostaurin, gilteritinib) for FLT3 alterations, BCL2 inhibitors (e.g., venetoclax) impacting apoptosis, and emerging M

Biopsy Techniques for Musculoskeletal Tumors: Basic Principles and Specialized Techniques.

Biopsy is a pivotal component in the diagnostic process of bone and soft tissue tumors. The objective is to obtain adequate tissue without compromising local tumor dissemination and the patient's survival. This review explores contemporary principles and practices in musculoskeletal biopsies, emphasizing the critical role of diagnostic accuracy while also delving into the evolving landscape of liquid biopsies as a promising alternative in the field. A thorough literature search was done in PubMed and Google Scholar as well as in physical books in libraries to summarize the available biopsy tec

Mesenchymal-Stem-Cell-Based Therapy against Gliomas.

Glioblastoma is the most aggressive, malignant, and lethal brain tumor of the central nervous system. Its poor prognosis lies in its inefficient response to currently available treatments that consist of surgical resection, radiotherapy, and chemotherapy. Recently, the use of mesenchymal stem cells (MSCs) as a possible kind of cell therapy against glioblastoma is gaining great interest due to their immunomodulatory properties, tumor tropism, and differentiation into other cell types. However, MSCs seem to present both antitumor and pro-tumor properties depending on the tissue from which they c

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… Furthermore, the study demonstrated that Zika virus (a) primarily infects human SOX2+ GSCs and inhibits proliferation in vitro, (b) causes loss of self-renewal and proliferation in glioblastoma organoids, (c) targets GSCs and, with less effects, DGCs and normal neuronal cells in human tissue samples, …

Challenges and opportunities in cancer immunotherapy: a Society for Immunotherapy of Cancer (SITC) strategic vision.

Cancer immunotherapy has flourished over the last 10-15 years, transforming the practice of oncology and providing long-term clinical benefit to some patients. During this time, three distinct classes of immune checkpoint inhibitors, chimeric antigen receptor-T cell therapies specific for two targets, and two distinct classes of bispecific T cell engagers, a vaccine, and an oncolytic virus have joined cytokines as a standard of cancer care. At the same time, scientific progress has delivered vast amounts of new knowledge. For example, advances in technologies such as single-cell sequencing and

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… Longitudinal biospecimens Biospecimen-based models, such as organoids or ex vivo human tumor slice cultures, may alleviate the expense of in vivo models and accelerate the identification of relevant human therapeutic targets for clinical translation. 30 However, they are limited by their ex vivo nature …

Research Hotspots and Trends in Global Cancer immunometabolism:A Bibliometric Analysis from 2000 to 2023.

BackgroundCancer poses a major global health challenge, and immunotherapy, known as the third revolution in cancer treatment, has brought new hope to patients. The emerging field of immunometabolism has further enhanced the safety and efficacy of immunotherapy. Over the past two decades, this field has rapidly evolved in oncology, leading to numerous significant findings. This review systematically examines the literature on immunometabolism in cancer, visualizing research trends and identifying future directions.MethodsA comprehensive literature search was conducted in the Web of Science, Pub

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… Organoids transplantation attenuates intestinal ischemia/reperfusion injury in mice through L-Malic acid-mediated M2 macrophage polarization . Nat Commun . 2023 ; 14 ( 1 ): 6779 . doi: 10.1038/s41467-023-42502-0 37880227 PMC10600233 93. Sun G , Wang B , Wu X , et al. …

Cell-Selective Altered Cargo Properties of Extracellular Vesicles Following In Vitro Exposures to Intermittent Hypoxia.

Intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), is associated with cardiovascular and metabolic dysfunction. However, the mechanisms underlying these morbidities remain poorly delineated. Extracellular vesicles (EVs) mediate intercellular communications, play pivotal roles in a multitude of physiological and pathological processes, and could mediate IH-induced cellular effects. Here, the effects of IH on human primary cells and the release of EVs were examined. Microvascular endothelial cells (HMVEC-d), THP1 monocytes, THP1 macrophages M0, THP1 macrophages M1, THP1 macr

The Host Cell ViroCheckpoint: Identification and Pharmacologic Targeting of Novel Mechanistic Determinants of Coronavirus-Mediated Hijacked Cell States

Most antiviral agents are designed to target virus-specific proteins and mechanisms rather than the host cell proteins that are critically dysregulated following virus-mediated reprogramming of the host cell transcriptional state. To overcome these limitations, we propose that elucidation and pharmacologic targeting of host cell Master Regulator proteins—whose aberrant activities govern the reprogramed state of infected-coronavirus cells—presents unique opportunities to develop novel mechanism-based therapeutic approaches to antiviral therapy, either as monotherapy or as a complement to establ

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… approaches that apply functional genomics to the “infected system as a whole.”( 24 ) The output of these predictions can be used to direct drug repurposing efforts( 21 – 23 ) and to design more focused in vitro screens, with models that better recapitulate disease pathophysiology, such as primary cells, organoids …

Mucosal-Associated Invariant T Cells in Health and Disease.

Mucosal-associated invariant T (MAIT) cells are a population of evolutionarily conserved, unconventional innate-like T lymphocytes that are restricted by major histocompatibility complex Class I-related (MR1) molecules. They can be activated either in a T-cell receptor-MR1- or cytokine-dependent manner. Activated MAIT cells play crucial roles in maintaining homeostasis and the fine regulation of the immune system. This review presents a systematic exploration of the development, biological characteristics, and multiple effects of MAIT cells in health and various diseases. In healthy individual