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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

Mechanistic insights into bone destruction in multiple myeloma: Cellular and molecular perspectives.

Multiple myeloma (MM) is a hematological malignancy that leads to significant bone destruction, resulting in debilitating pain and skeletal-related events. The pathophysiology of osteolytic bone destruction in MM involves complex interactions between malignant plasma cells (PCs) and the bone marrow (BM) microenvironment. This review aims to provide a comprehensive synthesis of the cellular and molecular pathways underlying MM-associated bone disease. We discuss the role of osteoclast (OC), osteoblast (OB), osteocytes, along with the complex interactions between immune cells and the BM microenv

The Role of Progranulin (PGRN) in the Pathogenesis of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) represents the most common and aggressive malignant form of brain tumour in adults and is characterized by an extremely poor prognosis with dismal survival rates. Currently, expanding concepts concerning the pathophysiology of GBM are inextricably linked with neuroinflammatory phenomena. On account of this fact, the identification of novel pathomechanisms targeting neuroinflammation seems to be crucial in terms of yielding successful individual therapeutic strategies. In recent years, the pleiotropic growth factor progranulin (PGRN) has attracted significant atten

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… In this case, after binding PGRN to SORT1, the whole ligand–receptor complex undergoes endocytosis from the extracellular space, which is associated with the further delivery of PGRN to the lysosomes. …

Galectin-9 - ligand axis: an emerging therapeutic target for multiple myeloma.

Galectin-9 (Gal-9) is a tandem-repeat galectin with diverse roles in immune homeostasis, inflammation, malignancy, and autoimmune diseases. In cancer, Gal-9 displays variable expression patterns across different tumor types. Its interactions with multiple binding partners, both intracellularly and extracellularly, influence key cellular processes, including immune cell modulation and tumor microenvironment dynamics. Notably, Gal-9 binding to cell-specific glycoconjugate ligands has been implicated in both promoting and suppressing tumor progression. Here, we provide insights into Gal-9 and its

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… Gal-9 secretion into the extracellular space does not follow the classical secretory pathway due to the absence of the signal secretion peptide essential for its transport into the endoplasmic reticulum ( 33 , 34 ). …

Engineering Next-Generation CAR-T Cells for Better Toxicity Management.

Immunoadoptive therapy with genetically modified T lymphocytes expressing chimeric antigen receptors (CARs) has revolutionized the treatment of patients with hematologic cancers. Although clinical outcomes in B-cell malignancies are impressive, researchers are seeking to enhance the activity, persistence, and also safety of CAR-T cell therapy-notably with a view to mitigating potentially serious or even life-threatening adverse events like on-target/off-tumor toxicity and (in particular) cytokine release syndrome. A variety of safety strategies have been developed by replacing or adding variou

Study on Effects of Cyclophosphamide Combined with Vinorelbine in Advanced Small Cell Lung Cancer and Anteroposterior Changes in MRI.

ObjectiveTo explore the effects of cyclophosphamide combined with vinorelbine in advanced small cell lung cancer (SCLC) and anteroposterior changes in MRI.MethodsThe clinical data of 90 patients with advanced SCLC admitted to our hospital from April 2020 to April 2021 were retrospectively analyzed. They were divided into the control group and the study group according to the order of admission, with 45 cases in each group. The control group received the routine treatment, while the study group was treated with cyclophosphamide and vinorelbine to compare the indexes of imaging data and clinical

Anticancer Activities of Novel Nicotinamide Phosphoribosyltransferase Inhibitors in Hematological Malignancies.

Targeting cancer cells that are highly dependent on the nicotinamide adenine dinucleotide (NAD+) metabolite is a promising therapeutic strategy. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme catalyzing NAD+ production. Despite the high efficacy of several developed NAMPT inhibitors (i.e., FK866 (APO866)) in preclinical studies, their clinical activity was proven to be limited. Here, we report the synthesis of new NAMPT Inhibitors, JJ08, FEI191 and FEI199, which exhibit a broad anticancer activity in vitro. Results show that these compounds are potent NAMPT inhibito

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… Another possible type of cell death is necrosis, which correlates with the release of the cytosolic enzymes, especially lactate dehydrogenase (LDH), into the extracellular space. Therefore, the detection of LDH in the medium is used as a marker of necrotic cell death [ 32 ]. …

Role of Osteocytes in Myeloma Bone Disease: Anti-sclerostin Antibody as New Therapeutic Strategy.

Osteocytes are terminally differentiated cells of the osteoblast lineage. They are involved in the regulation of bone remodeling by increasing osteoclast formation or decreasing bone formation by the secretion of the osteoblast inhibitor sclerostin. Monoclonal antibody anti-sclerostin, Romosozumab, has been developed and tested in clinical trials in patients with osteoporosis. In the last years, the role of osteocytes in the development of osteolytic bone lesions that occurs in multiple myeloma, have been underlined. Myeloma cells increase osteocyte death through the up-regulation of both apop

От ожирения до митохондриальной дисфункции в периферальных тканях и в центральной нервной системе.

Ожирение - это состояние хронического низкосортного воспаления, затрагивающего периферийные органы тела, а также центральную нервную систему. Дефункция жировой ткани, возникающая в условиях ожирения, является ключевым фактором возникновения и развития различных заболеваний, включая нейродегенеративные расстройства. Митохондрия, ключевые органеллы в производстве клеточной энергии, играет важную роль в этой дисфункции тканей. В многочисленных исследованиях подчеркивается тесная связь между ожирением и дисфункцией митохондриалов адипоцита, что приводит к чрезмерному производству ROS и воспалению

IL-20RB mediates tumoral response to osteoclastic niches and promotes bone metastasis of lung cancer.

Bone is a common site of metastasis in lung cancer, but the regulatory mechanism remains incompletely understood. Osteoclasts are known to play crucial roles in osteolytic bone metastasis by digesting bone matrix and indirectly enhancing tumor colonization. In this study, we found that IL receptor 20 subunit β (IL-20RB) mediated a direct tumoral response to osteoclasts. Tumoral expression of IL-20RB was associated with bone metastasis of lung cancer, and functionally, IL-20RB promoted metastatic growth of lung cancer cells in bone. Mechanistically, tumor cells induced osteoclasts to secrete th

Emerging markers of cachexia predict survival in cancer patients.

BACKGROUND: Cachexia may occur in 40% of cancer patients, representing the major cause of death in more than 20% of them. The aim of this study was to investigate the role of leptin, ghrelin and obestatin as diagnostic and predictive markers of cachexia in oncologic patients. Their impact on patient survival was also evaluated. METHODS: 140 adults with different cancer diagnoses were recruited. Thirty healthy volunteers served as control. Serum ghrelin, obestatin and leptin were tested at baseline and after a follow-up period of 18 months. RESULTS: Ghrelin levels were significantly higher in

A Novel Paradigm for Targeting Challenging Targets: Advancing Technologies and Future Directions of Molecular Glue Degraders.

Molecular glue degraders (MGDs) constitute a class of innovative therapeutic agents within the field of targeted protein degradation (TPD). In contrast to proteolysis-targeting chimeras (PROTACs), MGDs induce protein degradation by stabilizing the interaction between an E3 ubiquitin ligase and a target protein. They typically exhibit favorable drug-like characteristics, including lower molecular weight and enhanced bioavailability. Although their discovery was historically serendipitous, recent advances in high-throughput screening, bioinformatics, and artificial intelligence are enabling more

Многомасштабная разработка и оптимизация производства антител с помощью гибких сетей.

Антитела представляют собой терапевтические белки, имеющие множество видов применения в медицине, таких, как лечение вирусных инфекций, различных видов рака и распространенных заболеваний, таких, как псориаз и множественный склероз. Китайские клетки хомячков (CHO) являются наиболее широко используемыми клетками для производства антител из-за их длительного использования и благоприятных особенностей. Однако нынешняя конструкция систем производства антител часто опирается на подход "испытания и ошибки" для манипулирования клетками ЦХО. Такой подход требует больших затрат времени и затрат и может

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… It also has an artificial biomass composition reaction, precise reaction stoichiometry for mass and energy balance, and accounts for the following cellular compartments: cytosol, mitochondria, endoplasmic reticulum, and extracellular space. …

Development, efficacy and side effects of antibody‑drug conjugates for cancer therapy (Review).

Antibody-drug conjugates (ADCs) are anticancer drugs that combine cytotoxic small-molecule drugs (payloads) with monoclonal antibodies through a chemical linker and that transfer toxic payloads to tumor cells expressing target antigens. All ADCs are based on human IgG. In 2009, the Food and Drug Administration (FDA) approved gemtuzumab ozogamicin as the initial first-generation ADC. Since then, at least 100 ADC-related projects have been initiated, and 14 ADCs are currently being tested in clinical trials. The limited success of gemtuzumab ozogamicin has led to the development of optimization

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… Low bioavailability prevents the antibody from penetrating the capillary inner cortex and the extracellular space. However, if the molecular weight of the antibody is too low, its half-life in the body is reduced, which may lead to easy removal ( 10 ). …

Comprehensive Updates in the Role of Imaging for Multiple Myeloma Management Based on Recent International Guidelines.

The diagnostic and treatment methods of multiple myeloma (MM) have been rapidly evolving owing to advances in imaging techniques and new therapeutic agents. Imaging has begun to play an important role in the management of MM, and international guidelines are frequently updated. Since the publication of 2015 International Myeloma Working Group (IMWG) criteria for the diagnosis of MM, whole-body magnetic resonance imaging (MRI) or low-dose whole-body computed tomography (CT) and 18F-fluorodeoxyglucose positron emission tomography/CT have entered the mainstream as diagnostic and treatment respons

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… Due to its small molecular size (500–1000 Da), gadolinium can reach the extracellular space by passing the vascular endothelium via passive diffusion, except in the brain and spinal cord. …

Эгоистические нейрофармацевтики: открытие кровеносного барьера для лечения следующего поколения.

Блокирование мозга крови (ББД) представляет собой огромную проблему в нейрофармакологии, ограничивая доставку терапевтических агентов в мозг. Экзосомы, нанокарьеры природы, стали многообещающим решением из-за их биосовместимости, низкой иммуногенности и врожденной способности пересекать ББД. Тщательное изучение анатомии и физиологии ББД свидетельствует о сложности доставки неврологических наркотиков и подчеркивает ограниченность традиционных методов. В настоящем обзоре изучается потенциал нейрофармацевтики с экзосомной силой, при этом особое внимание уделяется их структурным и функциональным с

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… When MVBs fuse with the plasma membrane, the ILVs are released as exosomes into the extracellular space [ 19 ]. …

Терапевтический потенциал зубных мезенхимальных стволовых клеток в сравнении с мезенхимальными стволовыми клетками из других источников: систематический обзор исследований животных.

ЦЕНТРАЛЬНАЯ терапия на основе стволовых клеток, являющаяся одной из важнейших областей регенеративной медицины, направлена на совершенствование механизмов ремонта тела (d) путем стимулирования, модуляции и регулирования внутренних стволовых клеток или пополнения пулов клеток, способствуя тем самым развитию гомеостаза и регенерации тканей и предлагая перспективное лечение многочисленных системных заболеваний. В настоящем систематическом обзоре содержится всеобъемлющее резюме исследований животных, в ходе которых изучается эффективность зубоврачебных мезенхимальных стволовых клеток (НКЦ) в лечен

Advances in materials used for minimally invasive treatment of vertebral compression fractures.

Vertebral compression fractures are becoming increasingly common with aging of the population; minimally invasive materials play an essential role in treating these fractures. However, the unacceptable processing-performance relationships of materials and their poor osteoinductive performance have limited their clinical application. In this review, we describe the advances in materials used for minimally invasive treatment of vertebral compression fractures and enumerate the types of bone cement commonly used in current practice. We also discuss the limitations of the materials themselves, and

Tumour Cell Size Control and Its Impact on Tumour Cell Function.

Cell size is an important component of cell morphological characteristics. It reflects the characteristics of the cell type, nutritional status, growth stage and physiological function. The cell size of cells of the same type tends to be homogeneous and stable. However, in tumour cells, mutations in cell cycle genes and cytoskeletal genes and overexpression of the corresponding signalling pathways often lead to large variations in tumour cell size. Tumour cells regulate cell size and growth and proliferation through multiple signalling pathways, such as PI3K/Akt/mTOR, Myc and Hippo pathways, w

Ancient genes establish stress-induced mutation as a hallmark of cancer.

Cancer is sometimes depicted as a reversion to single cell behavior in cells adapted to live in a multicellular assembly. If this is the case, one would expect that mutation in cancer disrupts functional mechanisms that suppress cell-level traits detrimental to multicellularity. Such mechanisms should have evolved with or after the emergence of multicellularity. This leads to two related, but distinct hypotheses: 1) Somatic mutations in cancer will occur in genes that are younger than the emergence of multicellularity (1000 million years [MY]); and 2) genes that are frequently mutated in cance