Результаты поиска

Биоразлагаемый электроспун PLGA Nanofibers-Encapsolated Trichinella Sphiralis Antigens защищает от повторного использования экспериментального аутоиммунного энцефаломилита и связанного с ним микробиота дисбиоз.

ЦЕЛЬ: " Тричинелла спиралис " создала сложные механизмы иммуномодуляции при посредничестве экскременто-секретарских продуктов (ESL1), которые позволяют ей выжить в принимающей стране. Следовательно, антигены ESL1 обладают прекрасным потенциалом для лечения аутоиммунных заболеваний, таких, как множественный склероз (MS). Однако вопрос о том, могут ли своевременные контролируемые поставки антигенов ESL1 в vivo, как и в случае естественных инфекций, повысить его терапевтический потенциал в отношении MS, до сих пор неизвестен.Для этого мы ввели антигены ESL1 в полихлорированные (лактидно

Терапевтический потенциал моделей Purmorphamine через болезни.

Purmorphamine (PUR) — тройная субституция пурина, которая выборочно активирует сгущенный рецептор, тем самым инициируя Sonic Hedgehog (Shhh) сигнализирующий путь, имеющий решающее значение для эмбриональной модели, нейронной спецификации и регенерации тканей в различных системах различных органов. Регулирование сигнала " Шш " причастно к дегенеративным заболеваниям, однако терапевтические меры, направленные на этот путь, по-прежнему ограничены. PUR демонстрирует широкую терапевтическую эффективность различных моделей предклинических заболеваний путем активации как транскрипции с помо

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

Совпадение в полном тексте источника
… These cells are characterized by the presence of tight junctions (TJs), which are composed of proteins such as claudins, occludin, and zonula occludens-1 (ZO-1) (Fig.  3 B). These proteins work together to restrict paracellular permeability, ensuring the selective transport of substances. … Among these mechanisms, paracellular transport, which occurs between adjacent endothelial cells, is tightly regulated by proteins such as claudins, occludins, and junctional adhesion molecules (JAMs). …

Микроэкология и тренировка: целевое воздействие на ось микробиота-Гут-Брэйна для лечения заболеваний центральной нервной системы.

Кишечная микробиота (ГМ) может играть решающую роль в развитии и развитии заболеваний центральной нервной системы (ЦНС). Микроэкология и упражнение могут влиять на состав и функции ГМ, оказывая тем самым позитивное воздействие на НКЦ. Ожидается, что комбинированные физические упражнения и микроэкология позволят более комплексно и эффективно решать проблемы, связанные с заболеваниями CNS, через ось микробиота-гут-мозгов (MMBA), потенциально превысив результаты отдельных мероприятий. Однако в настоящее время по этой теме не проводится соответствующих обзоров. В этом обзоре мы изучаем взаимосвязь

Тип перегонки 1 диабет через ось эндоканнабиноидома-микробиота: системная биологическая перспектива.

Тип 1 диабет (T1D) давно признан аутоиммунным заболеванием на основе Т. Вместе с тем все больше фактов свидетельствует об участии в его развитии факторов, связанных с метаболизмом, подстрекательством и кишечной микробиотой. Эндоканнабиноидная система (ЭКС), являющаяся одним из ключевых регуляторов иммунного и метаболического гомеостаза, все чаще привлекается к аутоиммунной патофизиологии, в частности благодаря ее взаимодействию с кишечными метаболитами. В этой гипотетической статье подчеркивается необходимость пересмотра патофизиологии Т1D путем интеграции дисфункции ЭКС, кишечного дисбиоза и

Совпадение в полном тексте источника
… Tight junction proteins (claudins & occludins) are significantly reduced, indicating increased intestinal permeability (“leaky gut”), while zonulin levels are elevated, further supporting the presence of compromised gut barrier function. … Tight junction proteins (claudins & occludins) are significantly reduced, indicating increased intestinal permeability (“leaky gut”), while zonulin levels are elevated, further supporting the presence of compromised gut barrier function. …

Brain endothelial dysfunction in cerebral adrenoleukodystrophy.

See Aubourg (doi:10.1093/awv271) for a scientific commentary on this article.X-linked adrenoleukodystrophy is caused by mutations in the ABCD1 gene leading to accumulation of very long chain fatty acids. Its most severe neurological manifestation is cerebral adrenoleukodystrophy. Here we demonstrate that progressive inflammatory demyelination in cerebral adrenoleukodystrophy coincides with blood-brain barrier dysfunction, increased MMP9 expression, and changes in endothelial tight junction proteins as well as adhesion molecules. ABCD1, but not its closest homologue ABCD2, is highly expressed i

Bispecific Antibody-Based Immune-Cell Engagers and Their Emerging Therapeutic Targets in Cancer Immunotherapy.

Cancer is the second leading cause of death worldwide after cardiovascular diseases. Harnessing the power of immune cells is a promising strategy to improve the antitumor effect of cancer immunotherapy. Recent progress in recombinant DNA technology and antibody engineering has ushered in a new era of bispecific antibody (bsAb)-based immune-cell engagers (ICEs), including T- and natural-killer-cell engagers. Since the first approval of blinatumomab by the United States Food and Drug Administration (US FDA), various bsAb-based ICEs have been developed for the effective treatment of patients with

A Drug Screening Reveals Minocycline Hydrochloride as a Therapeutic Option to Prevent Breast Cancer Cells Extravasation across the Blood-Brain Barrier.

Among breast cancer (BC) patients, 15-25% develop BC brain metastases (BCBM), a severe condition due to the limited therapeutic options, which points to the need for preventive strategies. We aimed to find a drug able to boost blood-brain barrier (BBB) properties and prevent BC cells (BCCs) extravasation, among PI3K, HSP90, and EGFR inhibitors and approved drugs. We used BCCs (4T1) and BBB endothelial cells (b.End5) to identify molecules with toxicity to 4T1 cells and safe for b.End5 cells. Moreover, we used those cells in mixed cultures to perform a high-throughput microscopy screening of dru

Next-generation immunotherapeutic approaches for blood cancers: Exploring the efficacy of CAR-T and cancer vaccines.

Recent advancements in immunotherapy, particularly Chimeric antigen receptor (CAR)-T cell therapy and cancer vaccines, have significantly transformed the treatment landscape for leukemia. CAR-T cell therapy, initially promising in hematologic cancers, faces notable obstacles in solid tumors due to the complex and immunosuppressive tumor microenvironment. Challenges include the heterogeneous immune profiles of tumors, variability in antigen expression, difficulties in therapeutic delivery, T cell exhaustion, and reduced cytotoxic activity at the tumor site. Additionally, the physical barriers w

Uncovering potential targets for antibody-drug conjugates in the treatment of gynecologic malignancies.

BackgroundAntibody-drug conjugates (ADCs) play an important role in the targeted therapy of gynecological malignancies. The purpose of this study was to investigate the expression of targets in gynecologic malignancies in order to predict the selection of targets for the development of antibody-drug conjugates.MethodsIn this article, we identified existing ADCs and their targets through clinical trial databases and public genomic datasets, performed differential analysis of tumor antigen targets (TATs) expression between tumor and normal tissues, and evaluated the necessity of the targets for

Chronic stress and myeloid immunosuppression in cancer: A neuroimmune link to behavioral dysfunction.

Cancer progression is profoundly influenced by the complex interplay between the tumor microenvironment (TME), the immune system, and the patient's psychological state. This review delineates a critical pathway linking chronic stress to worsened cancer outcomes through inflammatory factors, anti-tumor immune suppression, and the induction of behavioral comorbidities. We postulate that sustained stress hormone signaling via the sympathetic nervous system and hypothalamic-pituitary-adrenal axis activation orchestrates a systemic immunosuppressive cascade. A central mechanism is the stress-induce

Adoptive cell therapies in solid tumors: current clinical landscape, challenges, and future directions.

Adoptive cell therapy (ACT) has emerged as a transformative strategy in cancer immunotherapy, offering durable clinical benefit in hematologic malignancies and expanding therapeutic potential in solid tumors. However, the translation of ACT to solid malignancies remains constrained by biological, immunological, and logistical challenges. This narrative review provides an evidence based overview of the current clinical landscape of ACT in solid tumors, with a focus on chimeric antigen receptor T cell (CAR-T), tumor-infiltrating lymphocyte (TIL), and T cell receptor-engineered T cell (TCR-T) the

Antibody-Drug Conjugates: Pharmacotherapeutic Properties and Future Perspectives.

Background: The clinical landscape for antibody-drug conjugates (ADCs) is currently experiencing an unprecedented expansion, with more than 20 agents approved to date and hundreds presently under clinical evaluation, underscoring their growing impact in precision oncology. By combining the cytotoxic potency of chemotherapy with the selectivity of monoclonal antibodies, ADCs have redefined targeted cancer therapy. Nevertheless, challenges related to toxicity, resistance, and suboptimal drug delivery continue to limit their full clinical potential. Objectives: This review provides a comprehensiv

Prominent Role of Histone Modifications in the Regulation of Tumor Metastasis.

Tumor aggressiveness and progression is highly dependent on the process of metastasis, regulated by the coordinated interplay of genetic and epigenetic mechanisms. Metastasis involves several steps of epithelial to mesenchymal transition (EMT), anoikis resistance, intra- and extravasation, and new tissue colonization. EMT is considered as the most critical process allowing cancer cells to switch their epithelial characteristics and acquire mesenchymal properties. Emerging evidence demonstrates that epigenetics mechanisms, DNA methylation, histone modifications, and non-coding RNAs participate

Совпадение в полном тексте источника
… Additional transcription factors such as the Forkhead Box C2 (FOXC2) and Transcription Factor 4 (TCF4) are involved in EMT without binding to CDH1 but by suppressing the expression of claudins and desmosomes present in cell junctions, or through interaction with other transcription factors. … Permissive PTMs may induce the upregulation of mesenchymal genes, such as N -cadherin ( CDH2 ), VE-cadherin ( CDH5 ), fibronectin ( FN1 ), and vimentin, whereas repressive histone modifications mainly participate in the suppression of epithelial genes, such as CDH1 , claudin 1 ( CLDN1 ), claudin 10 ( …

Antibody-Antineoplastic Conjugates in Gynecological Malignancies: Current Status and Future Perspectives.

In the last decade, antibody-drug conjugates (ADCs), normally formed by a humanized antibody and a small drug via a chemical cleavable or non-cleavable linker, have emerged as a potential treatment strategy in cancer disease. They allow to get a selective delivery of the chemotherapeutic agents at the tumor level, and, consequently, to improve the antitumor efficacy and, especially to decrease chemotherapy-related toxicity. Currently, nine antibody-drug conjugate-based formulations have been already approved and more than 80 are under clinical trials for the treatment of several tumors, especi

Совпадение в полном тексте источника
… SC-004 SC-004 is another pyrrolobenzodiazepine-based antibody drug conjugate that consists of a monoclonal antibody targeted to claudins 6 and 9 (CLDN6/9), tight junctional proteins, that are overexpressed in ovarian tumors [ 117 ], bound to a pyrrolobenzodiazepine dimer. … A partial response in the patients that overexpress claudins, was just detected in one patient. The low efficacy-toxicity balance indicates that the clinical investigation with this ADC should be discontinued ( NCT03138408 ) [ 118 ]. 3.5. …

Bortezomib-induced gastrointestinal dysfunction, peripheral neuropathy and neuroimmune signalling are influenced by the gut microbiota in mice.

BACKGROUND: Peripheral neuropathy and gastrointestinal dysfunction are frequent, debilitating side effects of the neurotoxic myeloma drug bortezomib that reduce quality of life and adherence to optimal therapy. Therapeutic strategies to manage these complications are limited. Here, we have developed a mouse model of bortezomib side effects to investigate the role of the gut microbiota in their development. METHODS: C57BL/6 specific pathogen-free (SPF), germ-free (GF) and ex-GF mice (colonised with healthy gut microbiota via faecal microbiota transplantation [FMT]) were treated with bortezomib

Протеиновый ингибитор смягчает белку в мышах Lmx1b с дисфункциональной доменой LIM.

Мутации в коэффициенте транскрипции LMX1B были определены в качестве причины синдрома автосомали-доминантного заболевания гвозди-пареллы. Он проявляется в небольших или отсутствующих пателле и диспластике или в отсутствии пальцев и ногтей, но прогноз пациентов определяется появлением почечных симптомов из-за дисфункциональных подоцитов. Патогенетические механизмы, ведущие к повреждению подоцита, и их связь с конкретными мутациями в гене LMX1B не понимаются, что препятствует разработке конкретных терапевтических стратегий. Здесь мы идентифицируем патогенетический механизм, затрагивающий многих

Sox8: многогранный фактор транскрипции развития и болезней.

Sox8 — коэффициент транскрипции, который относится к семейству Sox в домене высокомобильной группы, содержащем белки, и тесно связан с Sox9 и Sox10. Во время дородового развития Sox8 выражается в нескольких эктодермовых, эндодермовых и мезодермовых тканях и причастно к процессам органогенеза и дифференциации. Выражение Sox8 встречается в ряде важных клеток, таких как клетки Sertoli в мужском гонаде, глиальные клетки, спутниковые клетки и хондроциты. Однако Sox8 не имеет существенного значения для надлежащей разработки любой из соответствующих систем, поскольку он работает излишне с Sox9 или So

The Mechanisms of Altered Blood-Brain Barrier Permeability in CD19 CAR T-Cell Recipients.

Cluster of differentiation 19 (CD19) chimeric antigen receptor (CAR) T cells are a highly effective immunotherapy for relapsed and refractory B-cell malignancies, but their utility can be limited by the development of immune effector cell-associated neurotoxicity syndrome (ICANS). The recent discovery of CD19 expression on the pericytes in the blood-brain barrier (BBB) suggests an important off-target mechanism for ICANS development. In addition, the release of systemic cytokines stimulated by the engagement of CD19 with the CAR T cells can cause endothelial activation and decreased expression

Совпадение в полном тексте источника
… The tight junction strands consist of three major types of proteins: claudins, MARVEL/D3, and immunoglobulin-like junctional adhesion molecules. … Although claudins and MARVEL/D3 proteins play a complementary role in maintaining the transportation of solutes across the cell membrane, the junctional adhesion molecules play a key role in immune cell trafficking across the BBB [ 11 ]. …

Integrated Engineering of CAR-T Cells for Solid Tumours.

Chimeric antigen receptor (CAR) T-cell therapy has achieved durable efficacy in hematologic malignancies but encounters persistent obstacles in solid tumours, including antigen heterogeneity, a suppressive tumour microenvironment (TME), and intrinsic T-cell dysfunction. This review examines the transition from single-axis engineering to an integrated framework that addresses these hurdles in sequence. We delineate how next-generation CAR-T cells are designed for precise spatiotemporal activation through logic-gated and pharmacologically regulatable receptors, while being reinforced by metaboli