Результаты поиска

Learn from antibody-drug conjugates: consideration in the future construction of peptide-drug conjugates for cancer therapy.

Cancer is one of the leading causes of death worldwide due to high heterogeneity. Although chemotherapy remains the mainstay of cancer therapy, non-selective toxicity and drug resistance of mono-chemotherapy incur broad criticisms. Subsequently, various combination strategies have been developed to improve clinical efficacy, also known as cocktail therapy. However, conventional "cocktail administration" is just passable, due to the potential toxicities to normal tissues and unsatisfactory synergistic effects, especially for the combined drugs with different pharmacokinetic properties. The drug

Совпадение в полном тексте источника
… The free payload can either passively enter the extracellular space or be released due to loss of membrane integrity, namely passive diffusion, transporter-mediated uptake, or other non-specific endocytosis mechanisms to cause cytotoxicity [ 19 ]. …

Advances in Understanding Mitochondrial MicroRNAs (mitomiRs) on the Pathogenesis of Triple-Negative Breast Cancer (TNBC).

Triple-negative breast cancer (TNBC) is characterized by poor outcome and the most challenging breast cancer type to treat worldwide. TNBC manifests distinct profile of mitochondrial functions, which dictates reprogrammed metabolism, fosters tumor progression, and notably serves as therapeutic targets. Mitochondrial microRNAs (mitomiRs) are a group of microRNAs that critically modulate mitochondrial homeostasis. By a pathway-centric manner, mitomiRs tightly orchestrate metabolic reprogramming, redox status, cell apoptosis, mitochondrial dynamics, mitophagy, mitochondrial DNA (mtDNA) maintenanc

The emerging role of exosomes in innate immunity, diagnosis and therapy.

Exosomes, which are nano-sized transport bio-vehicles, play a pivotal role in maintaining homeostasis by exchanging genetic or metabolic information between different cells. Exosomes can also play a vital role in transferring virulent factors between the host and parasite, thereby regulating host gene expression and the immune interphase. The association of inflammation with disease development and the potential of exosomes to enhance or mitigate inflammatory pathways support the notion that exosomes have the potential to alter the course of a disease. Clinical trials exploring the role of exo

Совпадение в полном тексте источника
… The fusion of multivesicular bodies with the plasma membrane results in the release of intraluminal vesicles into the extracellular space, giving rise to “exosomes” ( 2 , 8 , 9 ). This is primarily an endosomal sorting complex required for transport (ESCRT)-dependent processes. …

Precision-Engineered CD3 T-Cell Engagers for Solid Tumours: Conditional Activation, Microenvironment Modulation, and Clinical Translation.

BackgroundT-cell-engaging bispecific antibodies (TCEs) have transformed haematological malignancy treatment (blinatumomab > 40% complete remission), yet solid tumour efficacy remains limited (MethodsReview of 55 phase I-III trials of CD3-based TCEs in solid tumours, including tarlatamab (DLL3-targeted, small-cell lung cancer) and xaluritamig (STEAP1-targeted, prostate cancer). Analysis of next-generation engineering strategies and resistance mechanisms via genomic and immunohistochemical data.ResultResponse rates now approach ~40% in selected settings, marking an inflection point. In extensive

Абстрактный сборник ISEV2022.

Аннотация не предоставлена источником. Откройте карточку для перехода к публикации.

Совпадение в полном тексте источника
… While large EVs are directly secreted from the plasma membrane, sEVs bud into the lumen of late endosomal compartments and are released into the extracellular space upon fusion of the endosomes with the cell membrane. …

Endothelial dysfunction and hemostatic imbalance in CAR T-cell-associated toxicities: pathophysiological insights and the role of circulating biomarkers.

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of relapsed or refractory hematologic malignancies. While its clinical efficacy is well established, CAR T-cell therapy is frequently associated with severe immune-mediated toxicities, including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), coagulopathy, and hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS). Increasing evidence suggests that endothelial dysfunction, hemostatic imbalance, and complement activation are key contributors to the pathogenesis of

Совпадение в полном тексте источника
… Primary hemostasis markers The relationship between endothelial damage and activation of primary hemostasis is particularly evident following the enhanced release of VWF into the plasma and extracellular space. …

Bench-to-bedside review: Angiopoietin signalling in critical illness - a future target?

Multiple organ dysfunction syndrome (MODS) occurs in response to major insults such as sepsis, severe haemorrhage, trauma, major surgery and pancreatitis. The mortality rate is high despite intensive supportive care. The pathophysiological mechanism underlying MODS are not entirely clear, although several have been proposed. Overwhelming inflammation, immunoparesis, occult oxygen debt and other mechanisms have been investigated, and - despite many unanswered questions - therapies targeting these mechanisms have been developed. Unfortunately, only a few interventions, usually those targeting mu

Burden, Outcome, and Comorbidities of Extrahepatic Manifestations in Hepatitis B Virus Infections.

Hepatitis B virus (HBV) infections affect approximately 296 million people around the world, and the prevalence of any past or present HBV infection during the years 2015-2018 was as high as 4.3%. Acute HBV infection often presents with nonspecific symptoms and is usually self-limited, but 5% of patients can have persistent infections leading to chronic HBV infection and the risk of turning into chronic HBV infection is significantly higher in babies with vertical transmission (95%). Patients with chronic HBV infection are usually asymptomatic, but 15 to 40% of chronic HBV carriers develop cir

The Bone Extracellular Matrix as an Ideal Milieu for Cancer Cell Metastases.

Bone is a preferential site for cancer metastases, including multiple myeloma, prostate, and breast cancers.The composition of bone, especially the extracellular matrix (ECM), make it an attractive site for cancer cell colonization and survival. The bone ECM is composed of living cells embedded within a matrix composed of both organic and inorganic components. Among the organic components, type I collagen provides the tensile strength of bone. Inorganic components, including hydroxyapatite crystals, are an integral component of bone and provide bone with its rigidity. Under normal circumstance

Translational horizons in the tumor microenvironment: harnessing breakthroughs and targeting cures.

Chemotherapy and targeted therapy have opened new avenues in clinical oncology. However, there is a lack of response in a substantial percentage of cancer patients and diseases frequently relapse in those who even initially respond. Resistance is, at present, the major barrier to conquering cancer, the most lethal age-related pathology. Identification of mechanisms underlying resistance and development of effective strategies to circumvent treatment pitfalls thereby improving clinical outcomes remain overarching tasks for scientists and clinicians. Growing bodies of data indicate that stromal

Innovative Approaches in Bone Tissue Engineering: Strategies for Cancer Treatment and Recovery.

Cancer has rapidly emerged as a leading global cause of premature mortality, with significant economic implications projected to reach USD 25.2 trillion from 2020 to 2050. Among the various types of cancer, primary bone cancers, though uncommon, are projected to see nearly 4000 new cases diagnosed in the United States in 2024. The complexity of treating bone cancer arises from its rarity, diversity, and the challenges associated with surgical interventions, metastatic spread, and post-operative complications. Advancements in bone tissue engineering (BTE) have introduced innovative therapeutic

Искусственный интеллект основывается на достижениях в области наномедицины для лечения мозговых расстройств: обновленный обзор повествования.

Наномедицина - это наномасштабные, биосопоставимые материалы, которые предлагают перспективные альтернативы традиционным методам лечения расстройств мозга. Технологические достижения в области искусственного интеллекта (АИ), в частности машинного обучения (МЛ) и глубокого обучения (ДЛ), трансформируют область наномедицины путем совершенствования диагностики заболеваний, биомаркировки, прогнозирования и мониторинга заболеваний, целевых поставок наркотиков и терапевтического вмешательства, а также содействия расчетным и методологическим разработкам. Эти успехи могут быть достигнуты за счет анали

Activation of Kir4.1 Channels by 2-D08 Promotes Myelin Repair in Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory disease that leads to myelin loss and neurological dysfunction. Clinical studies show increased anti-Kir4.1 antibody levels in MS patients' serum, indicating its diagnostic potential. However, the specific mechanism has remained elusive. In a mouse model of experimental autoimmune encephalomyelitis (EAE), it is found that impaired Kir4.1 channels in oligodendrocyte precursor cells (OPCs) hindered myelin repair in the spinal cord. Using a thermal shift assay (TSA), the small molecule 2-D08 is identified, which effectively activated Kir4.1 channe

Совпадение в полном тексте источника
… Since the deficits of Kir4.1 could lead to an elevated K + level in extracellular space due to the decline in buffering potassium ion capacity, we next performed in vivo potassium ion measurements by K + nanosensor. [ 18 , 34 ] The fluorescence intensity of the K + probe revealed a significant …

Stage-specific biomarkers in triple-negative breast cancer: Preliminary findings from bioinformatics approaches.

BackgroundIntegrated bioinformatics approaches were used to identify stage-specific candidate genes and potential drug targets in triple-negative breast cancer (TNBC).MethodsMicroarray (164 early-stage, 33 advanced-stage, and 53 normal samples) and RNA-seq (113 normal, 163 early-stage, and 30 advanced-stage TNBC samples) datasets were analyzed. Differentially expressed genes (DEGs) were identified, followed by co-expression analysis using Weighted Gene Co-expression Network Analysis (WGCNA) and protein-protein interaction analysis using the STRING database. miRNA co-regulation was evaluated us

Etiological Treatment of Cardiac Amyloidosis: Standard of Care and Future Directions.

Purpose of reviewCardiac amyloidosis (CA) is a condition caused by interstitial infiltration of misfolded proteins structured into amyloid fibrils. Transthyretin (ATTR) and immunoglobulin light chain (AL) amyloidosis represent the most common forms of CA. CA was traditionally perceived as a rare and incurable disease, but diagnostic and therapeutic advances have undermined the conventional paradigm.Recent findingsThe standard of care for ATTR-CA include agents capable of selectively stabilizing the precursor protein (e.g., tafamidis), whereas the plasma cell clone is the main target of chemoth

Совпадение в полном тексте источника
… Introduction Amyloidosis includes a heterogeneous category of diseases in which autologous proteins undergo misfolding and aggregation into amyloid fibrillary structures, which deposit in the extracellular space of various tissues [ 1 ]. …

Менделийская случайность выявляет белки, связанные с нейродегенеративными заболеваниями.

Протеины участвуют в многочисленных биологических функциях. Технологии высокой производительности позволили измерять тысячи белков в биобанках населения. В этом исследовании мы стремились выявить белки, связанные с болезнью Альцгеймера, болезнью Паркинсона, множественным склерозом и амиотропическим боковым склерозом, используя крупномасштабные генетические и протеомические данные. Мы провели двухвыборное исследование цисов менделий случайности, выбрав инструментальные переменные для изобилия >2700 белков, измеряемых либо Olink, либо SomaScan платформами в плазме из UK Biobank и DeCODE Health S

Совпадение в полном тексте источника
… WARS, a protein newly associated with MS, is an aminoacyl-tRNA synthetase with a role as an innate immune activator in the extracellular space, acting as a primary defence system against infections, especially antiviral immunity. 117 , 118 Moreover, a newly identified MS protein, PARP1, is involved …

Потенциальные цели микроглии в лечении нейродегенеративных заболеваний: механизм и терапевтические последствия.

В случае различных нейродегенеративных расстройств активируются микроглиальные клетки. Кроме того, дисфункциональная и гиперактивированная микроглия инициирует митохондриальную автофагию, окислительный стресс и патологическое накопление белка, заканчивающееся нейроинфламмацией, которая усугубляет повреждения допаминергических нейронов и вносит значительный вклад в патологию нейродегенеративного расстройства. Микроглиальная чрезмерная активация тесно связана с секрецией провоспалительных цитокинов, фагоцитозом травмированных нейронов и модуляцией нейротоксичной среды. В этом обзоре резюмируется

Совпадение в полном тексте источника
… To maintain homeostasis, excess copper ions are exported to the extracellular space by copper pumps (ATP7A/B). …

The Role of TAM Receptors in Bone.

The TAM (TYRO3, MERTK, and AXL) family of receptor tyrosine kinases are pleiotropic regulators of adult tissue homeostasis maintaining organ integrity and self-renewal. Disruption of their homeostatic balance fosters pathological conditions like autoinflammatory or degenerative diseases including rheumatoid arthritis, lupus erythematodes, or liver fibrosis. Moreover, TAM receptors exhibit prominent cell-transforming properties, promoting tumor progression, metastasis, and therapy resistance in various cancer entities. Emerging evidence shows that TAM receptors are involved in bone homeostasis

Amyloid Proteins and Peripheral Neuropathy.

Painful peripheral neuropathy affects millions of people worldwide. Peripheral neuropathy develops in patients with various diseases, including rare familial or acquired amyloid polyneuropathies, as well as some common diseases, including type 2 diabetes mellitus and several chronic inflammatory diseases. Intriguingly, these diseases share a histopathological feature-deposits of amyloid-forming proteins in tissues. Amyloid-forming proteins may cause tissue dysregulation and damage, including damage to nerves, and may be a common cause of neuropathy in these, and potentially other, diseases. He

Совпадение в полном тексте источника
… In hTTRv FAP patients, amyloid fibrils are present in extracellular spaces of the endoneurium, whereas amorphous deposits are present around micro vessels and in the subperineural space [ 313 ]. …

Acute kidney injury: pathogenesis and therapeutic interventions.

Acute kidney injury (AKI) is a prevalent clinical condition that is associated with unacceptably high morbidity and mortality, as well as the development of chronic kidney disease (CKD). The pathogenesis of AKI is highly complex and heterogeneous, primarily attributed to metabolic disturbances arising from the disease itself and the administration of medications related to treatment. In recent years, AKI in cancer patients is highly concerned. The emergence of AKI caused injuries and dysfunction of remote organs but also enhanced the health-care costs. It's essential for early recognition of A