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Взгляды пациентов и группы по уходу за почками на лечащую нагрузку и способность пожилых людей с хроническими заболеваниями почек: качественное исследование.

ЦЕЛЬ: Хроническая болезнь почек (КХД) часто является множественным заболеванием, а прогрессирование к более серьезным заболеваниям, как правило, связано с увеличением потребностей в управлении, включая изменение образа жизни, увеличение количества медикаментов и расширение участия клинических работников. В ходе этого исследования были изучены взгляды группы по уходу за пациентами и почками на характер и масштабы этой рабочей нагрузки (нагрузка на лечение), а также факторы, способствующие укреплению способности (способности управлять здоровьем) пожилых людей, имеющих ККД. DESIGN: Качественное п

Chidamide increases the sensitivity of Non-small Cell Lung Cancer to Crizotinib by decreasing c-MET mRNA methylation.

Introduction: Crizotinib is a kinase inhibitor targeting c-MET/ALK/ROS1 used as the first-line chemical for the treatment of non-small cell lung cancer (NSCLC) with ALK mutations. Although c-MET is frequently overexpressed in 35-72% of NSCLC, most NSCLCs are primarily resistant to crizotinib treatment. Method: A set of NSCLC cell lines were used to test the effect of chidamide on the primary crizotinib resistance in vitro and in vivo. Relationships between the synergistic effect of chidamide and c-MET expression and RNA methylation were systemically studied with a battery of molecular biologic

Concise Review: Regulation of Self-Renewal in Normal and Malignant Hematopoietic Stem Cells by Krüppel-Like Factor 4.

Pluripotent and tissue-specific stem cells, such as blood-forming stem cells, are maintained through a balance of quiescence, self-renewal, and differentiation. Self-renewal is a specialized cell division that generates daughter cells with the same features as the parental stem cell. Although many factors are involved in the regulation of self-renewal, perhaps the most well-known factors are members of the Krüppel-like factor (KLF) family, especially KLF4, because of the landmark discovery that this protein is required to reprogram somatic cells into induced pluripotent stem cells. Because KLF

A Decade of FGF Receptor Research in Bladder Cancer: Past, Present, and Future Challenges.

Fibroblast growth factors (FGFs) orchestrate a variety of cellular functions by binding to their transmembrane tyrosine-kinase receptors (FGFRs) and activating downstream signalling pathways, including RAS/MAPK, PLCγ1, PI3K, and STATs. In the last ten years, it has become clear that FGF signalling is altered in a high proportion of bladder tumours. Activating mutations and/or overexpression of FGFR3 are common in urothelial tumours with low malignant potential and low-stage and -grade urothelial carcinomas (UCs) and are associated with a lower risk of progression and better survival in some su

EHA evaluation of the ESMO-Magnitude of Clinical Benefit Scale version 1.1 (ESMO-MCBS v1.1) for haematological malignancies.

ObjectiveValue frameworks in oncology have not been validated for the assessment of treatments in haematological malignancies, but to avoid overlaps and duplications it appears reasonable to build up experience on existing value frameworks, such as the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale (ESMO-MCBS).MethodsHere we present the results of the first feasibility testing of the ESMO-MCBS v1.1 for haematological malignancies based on the grading of 80 contemporary studies for acute leukaemia, chronic leukaemia, lymphoma, myeloma and myelodysplastic syndromes. Th

Острый инфекционный мононуклеоз порождает стойкие, функциональные антитела EBNA-1 с высокой поперечной реактивностью до альфа-кристаллической бета.

Мы исследуем масштаб, специфичность и функциональные свойства ядерного антигена 1 (EBNA-1) вируса Эпштейн-Барр (EBV) у молодых людей в ходе первичной инфекции. Обнаружены специфические связующие антитела EBNA-1, а также антитела, способные к осаждению клеточного фагоцитоза (ADCP) и дополняющего антитела (ADCD). Эти антитела в первую очередь направлены против региона EBNA-1, который, как известно, вызывает перекрестные антитела для нескольких самопептидов. У лиц, имеющих по крайней мере один аллеле HLA-DRB1*15:01, отмечаются высшие связующие и ADCD антитела EBNA-1. Альфакристалллин бета (КРИАБ)

Bi- and Tri-specific antibodies in non-Hodgkin lymphoma: current data and perspectives.

Bispecific antibodies (BsAbs) are a new group of targeted therapies that are revolutionizing the treatment landscape of B-cell non-Hodgkin's lymphoma (B-NHL). In the relapsed/refractory setting, salvage chemotherapy and autologous stem cell transplantation are capable of curing 50% of patients, whereas the other half will have a dismal outcome with a median overall survival of less than 12 months. This unmet need reinforced the importance of innovative therapies like the BsAbs and CAR-T cell therapies. In this review, we delve into BsAbs in B-NHL from the preclinical development to clinical da

Клемастин фумарат ускоряет аккумуляцию инвалидности в прогрессивном множественном склерозе, усиливая пироптоз.

Множественный склероз (MS) — иммунопосредованное демиелинизирующее заболевание CNS. Клемастин фумарат, внезапный антигистамин и мускариновый блокатор рецепторов, обладает ремиелионирующим потенциалом в MS. Климастичная рука была добавлена в текущее клиническое исследование платформы, нацеленное на остаточную активность на основе точности, биомаркированной комбинированной терапии множественных склерозов (TRAP-MS) (Clinical Procures.gov). NCT03109288), для выявления сигнатуры ремиелинирования цереброспиновой жидкости (CSF) и для сбора данных о безопасности клемастина у пациентов независимо от ре

FDA-Approved Drugs Containing Amide Functionality in the Last Five Years (2021-2025): Pharmaceutical Use, Trends and Synthetic Approaches.

The amide functional group remains a cornerstone of medicinal chemistry, serving as an indispensable scaffold in the design of modern therapeutics. This review presents an analysis of FDA-approved drugs (small molecules and peptides with MW ®), amides form the structural backbone of peptidomimetics, enabling high-affinity binding to a viral protease. In precision oncology, as seen with adagrasib (Krazati®), the amide acts as a critical, metabolically stable linker that positions a covalent warhead for selective inhibition of a mutant kinase. This analysis underscores that amide's unique combin

Immunosenescence and the Geriatric Giants: Molecular Insights into Aging and Healthspan.

Aging is associated with complex immune dysfunction that contributes to the onset and progression of the "geriatric giants", including frailty, sarcopenia, cognitive decline, falls, and incontinence. Central to these conditions is immunosenescence, marked by thymic involution, the loss of naïve T cells, T-cell exhaustion, impaired B-cell class switch recombination, and increased autoreactivity. Concurrently, innate immunity deteriorates due to macrophage, neutrophil, and NK cell dysfunction, while chronic low-grade inflammation-or "inflammaging"-amplifies systemic decline. Key molecular pathwa

Rituximab resistance in ITP and beyond.

The pathophysiology of immune thrombocytopenia (ITP) is complex and encompasses innate and adaptive immune responses, as well as megakaryocyte dysfunction. Rituximab is administered in relapsed cases and has the added benefit of inducing treatment-free remission in over 50% of patients. Nevertheless, the responses to this therapy are not long-lasting, and resistance development is frequent. B cells, T cells, and plasma cells play a role in developing resistance. To overcome this resistance, targeting these pathways through splenectomy and novel therapies that target FcγR pathway, FcRn, complem

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… Sirolimus complexes with family of intracellular binding proteins termed FKBPs (FK binding proteins) targeting mTOR and inhibiting the mTOR-mediated signal-transduction pathways, which results in cell cycle arrest in G1 phase ( 80 ). …

Micronutrient Status and Breast Cancer: A Narrative Review.

Breast cancer is one of the most common cancers worldwide, at the same time being one of the most prevalent causes of women's death. Many factors such as alcohol, weight fluctuations, or hormonal replacement therapy can potentially contribute to breast cancer development and progression. Another important factor in breast cancer onset includes micronutrient status. In this narrative review, we analyzed 23 micronutrients and their possible influence on breast cancer onset and progression. Further, the aim of this study was to investigate the impact of micronutrient status on the prevention of b

Neurobiology of Cancer: Introduction of New Drugs in the Treatment and Prevention of Cancer.

Research on the neurobiology of cancer, which lies at the border of neuroscience and oncology, has elucidated the mechanisms and pathways that enable the nervous system to modulate processes associated with cancer initiation and progression. This research has also shown that several drugs which modulate interactions between the nervous system and the tumor micro- and macroenvironments significantly reduced the progression of cancer in animal models. Encouraging results were also provided by prospective clinical trials investigating the effect of drugs that reduce adrenergic signaling on the co

Targeting of multiple myeloma-related angiogenesis by miR-199a-5p mimics: in vitro and in vivo anti-tumor activity.

Multiple myeloma (MM) cells induce relevant angiogenic effects within the human bone marrow milieu (huBMM) by the aberrant expression of angiogenic factors. Hypoxia triggers angiogenic events within the huBMM and the transcription factor hypoxia-inducible factor-1α (HIF-1α) is over-expressed by MM cells. Since synthetic miR-199a-5p mimics negatively regulates HIF-1α, we here investigated a miRNA-based therapeutic strategy against hypoxic MM cells. We indeed found that enforced expression of miR-199a-5p led to down-modulated expression of HIF-1α as well as of other pro-angiogenic factors such a

Loss of EGFR activity in skeletal stem/progenitor cells is associated with impaired fracture healing in aged mice.

The cellular and molecular events responsible for fracture healing becoming delayed with aging remain unclear. Epidermal growth factor receptor (EGFR) signaling has been reported to play a critical role in bone regeneration. However, knowledge of its specific function in skeletal stem cells during aging-induced fracture delayed union remains scant. In the present study, we first demonstrated that EGFR activity in skeletal stem/progenitor cells decreased as mice aged and thus resulted in delayed fracture healing. To further investigate whether the EGFR signaling can be targeted as a potential t

Effects of Obesity and Calorie Restriction on Cancer Development.

The risk of malignant tumor development is increasing in the world. Obesity is an established risk factor for various malignancies. There are many metabolic alterations associated with obesity which promote cancerogenesis. Excessive body weight leads to increased levels of estrogens, chronic inflammation and hypoxia, which can play an important role in the development of malignancies. It is proved that calorie restriction can improve the state of patients with various diseases. Decreased calorie uptake influences lipid, carbohydrate and protein metabolism, hormone levels and cell processes. Ma

Резюме книги: Тема: 13th Международный симпозиум на тему " Ходжкин лимфома " ; октябрь 2024

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Targeting Amyloid Fibrils by Passive Immunotherapy in Systemic Amyloidosis.

Systemic amyloidoses are characterized by the unrelenting deposition of autologous proteins as highly ordered fibrils in target organs. The ensuing, potentially fatal organ dysfunction is the result of the combined damage caused by the proteotoxic effect of prefibrillar species and by the cytotoxicity and the structural alterations produced by the amyloid fibrils. Current therapy is focused on eliminating the amyloid protein, thus extinguishing the amyloid cascade at its origin. While this approach may end the cell damage caused by prefibrillar aggregates and prevent further amyloid accumulati

Safety and Tolerability of Letetresgene Autoleucel (GSK3377794): Pilot Studies in Patients with Advanced Non-Small Cell Lung Cancer.

PurposeThe study aims to evaluate the safety, tolerability, and antitumor response of letetresgene autoleucel (lete-cel), genetically modified autologous T cells expressing a T-cell receptor specific for New York esophageal squamous cell carcinoma 1 (NY-ESO-1)/LAGE-1a shared epitope, alone or in combination with pembrolizumab, in HLA-A*02-positive (HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06) patients with NY-ESO-1- and/or LAGE-1a-positive non-small cell lung cancer.Patients and methodsStudy 208749 was a single-arm study of lete-cel alone. Study 208471 was a multiarm study of lete-cel alone o

Успехи в сочетании CAR-T-терапии с небольшими молекуловыми реагентами для гематологовых магнатов.

Терапия против антигенного рецептора Т-клеток (CAR-T) стала краеугольным камнем лечения гематологовых магнестов. Однако, будучи монотерапией, она по-прежнему сталкивается с серьезными проблемами, такими, как сопротивление терапии, рецидив заболеваний и минимальное остаточное заболевание (МСД) после возвращения. Небольшие молекулные соединения, такие, как ингибиторы тирозиновой киназы Брютона (БТК), гипометилирующие вещества и иммуномодуляторные препараты, могут повысить эффективность антипухоза клеток CAR-T с помощью различных механизмов, повышая их стойкость и способность к разжижению. Комбин