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Соответствующие патологии и их влияние на болезнь Паркинсона: описывающий обзор текущих доказательств.

Многие медицинские и патологические исследования указывают на наличие множества коморбидов/сопатологий в ходе болезни Паркинсона (PD). Патология тела леви, морфологическая характеристика PD, редко существует в изоляции, но обычно ассоциируется с другими сопутствующими патологиями, в частности с изменениями, связанными с болезнью Альцгеймера (ALDC), цереброваскулярными патологиями (макро- и микроинфаркты, болезнью церебральных малых судов, церебральной амилоидной ангиопатией), патологией TDP-43, а также множественными патологическими комбинациями. К ним относятся сердечно-сосудистые расстройств

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

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… ER stress triggers the activation of the unfolded protein response (UPR), a response which alters the expression of genes involved in ER quality control. The UPR aims to recover ER homeostasis or trigger apoptosis when cells are irreversibly damaged. …

A review of recent clinical trials to evaluate disease-modifying therapies in the treatment of cardiac amyloidosis.

Cardiac amyloidosis (CA) is a serious condition that results in infiltrative cardiomyopathy and heart failure with preserved ejection fraction (HFpEF) that is caused by the extracellular deposition of amyloid fibrils within heart tissue. While many important features of CA have been known for years, its prevalence in elderly patients with HF is increasingly being recognized. Plasma cells produce monoclonal immunoglobulin light chains which results in the formation and aggregation of amyloid fibrils that are responsible for AL amyloidosis. CA is classified as originating from either transthyret

miR-708-5p: a microRNA with emerging roles in cancer.

MicroRNAs (miRNAs) are small non-coding RNAs that negatively regulate gene expression post-transcriptionally. They are crucial for normal development and maintaining homeostasis. Researchers have discovered that dysregulated miRNA expression contributes to many pathological conditions, including cancer. miRNAs can augment or suppress tumorigenesis based on their expression and transcribed targetome in various cell types. In recent years, researchers have begun to identify miRNAs commonly dysregulated in cancer. One recently identified miRNA, miR-708-5p, has been shown to have profound roles in

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… CHOP is an important sensor in the unfolded protein response (UPR), which is initiated after an increase in endoplasmic reticulum (ER) stress due to accumulation or un- or mis-folded proteins. … A review of the mammalian unfolded protein response. Biotechnol Bioeng. 2011;108:2777–93. doi: 10.1002/bit.23282. 46. Szegezdi E, Logue SE, Gorman AM, Samali A. Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep. 2006;7:880–5. doi: 10.1038/sj.embor.7400779. 47. …

Alpha-lipoic acid alters the antitumor effect of bortezomib in melanoma cells in vitro.

Bortezomib (BOZ) is a proteasome inhibitor chemotherapeutic agent utilized to treat multiple myeloma and recently offered to cure melanoma. Bortezomib-induced neuropathy is one of the dose-limiting side-effects, which can be treated with antioxidants (e.g. alpha-lipoic acid-ALA and Vitamin B1-vit B1). We hypothesized that these antioxidants may counteract the antitumor activity by disrupting the BOZ-induced pathways (e.g. proteasome inhibition or reactive oxygen species generation). The objectives were: (i) to verify the anti-proliferative effect of BOZ; (ii) to compare the influence of the an

Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.

Reactive oxygen species (ROS) act as critical secondary messengers in various intracellular signaling pathways that regulate cellular proliferation, differentiation, and survival under normal physiological conditions. However, dysregulation of redox signaling-driven by genetic mutations, epigenetic alterations, and posttranscriptional or posttranslational modifications-plays a central role in malignant transformation and cancer progression. Cancer cells typically exhibit elevated basal ROS levels due to increased metabolic activity, mitochondrial dysfunction, and oncogene activation. This mode

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… Ero1 also promotes the conversion of reduced glutathione (GSH) to glutathione disulfide (GSSG), contributing to ROS accumulation and ER stress. 46 Disruptions in these pathways can lead to protein misfolding and accumulation, triggering ER stress and the unfolded protein response (UPR), thereby inducing …

Структура-ориентированное исследование ДНК-аптамера, целевого PTK7, выявляет сложную 3D-составляющую, направляющую оптимизацию функции.

DNA аптамеры вышли в качестве новых молекулярных инструментов в терапевтической и диагностической медицине благодаря своей высокой аффинности и специфичности к белковым целям, что определяется их способностью сворачиваться в отличительные трехмерные (3D) структуры. Однако при проектировании и моделировании аптамеров часто игнорируются тонкие атомные взаимодействия, формирующие 3D структуры, что приводит к неэффективной оптимизации функциональных свойств. Проблемы сохраняются при определении высокоразрешающих структур комплексов аптамер-белок. Кроме того, экспериментально определенные 3D структ

Cellular Senescence and Aging: Mechanisms, Disease Convergence, and Therapeutic Frontiers.

Cellular senescence, a stress-induced, irreversible cell cycle arrest coupled with a proinflammatory secretory phenotype, has emerged as both a central driver of aging and a tractable therapeutic target. Although acute senescence contributes beneficially to tumor suppression and wound healing, chronic accumulation of senescent cells sustains systemic inflammaging and accelerates organ dysfunction. This review synthesizes current progress in aging biology into a unified mechanistic and translational framework. We first examine how primary aging hallmarks, such as genomic instability and epigene

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… Mitochondrial homeostasis is safeguarded by an integrated quality control network encompassing the mitochondrial unfolded protein response (UPRmt) and mitophagy [ 62 ]. … Ying Z., Xin Y., Liu Z., et al., “The Mitochondrial Unfolded Protein Response Inhibits Pluripotency Acquisition and Mesenchymal‐to‐epithelial Transition in Somatic Cell Reprogramming,” Nature Metabolism 7, no. 5 (2025): 940–951. 66. …

Patient reported outcome measures in a large cohort of patients with type 1 Gaucher disease.

BackgroundIt is now acknowledged that the input of patients in health outcome assessment is vital to understanding the impact of diseases and interventions for those diseases. This study is the first report of patient-reported outcome measures (PROM) in a large cohort of patients with type 1 Gaucher disease (GD1) enabling us to study predictors of the reported outcomes.MethodThe PROM was sent via a mobile phone survey to 405 adult patients with GD1. Demographics, clinical data, and treatment status were extracted from clinic charts. Age, sex, severity score index (SSI) at presentation and trea

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… Maor G Rencus-Lazar S Filocamo M Steller H Segal D Horowitz M Unfolded protein response in Gaucher disease: from human to Drosophila Orphanet J Rare Dis 2013 8 140 10.1186/1750-1172-8-140 24020503 PMC3819655 30. …

NF-κB in biology and targeted therapy: new insights and translational implications.

NF-κB signaling has been discovered for nearly 40 years. Initially, NF-κB signaling was identified as a pivotal pathway in mediating inflammatory responses. However, with extensive and in-depth investigations, researchers have discovered that its role can be expanded to a variety of signaling mechanisms, biological processes, human diseases, and treatment options. In this review, we first scrutinize the research process of NF-κB signaling, and summarize the composition, activation, and regulatory mechanism of NF-κB signaling. We investigate the interaction of NF-κB signaling with other importa

Management of Severe Acute Pancreatitis.

Sepsis‑induced abnormalities in brain function or sepsis‑associated encephalopathy (SAE) can manifest as cognitive dysfunction and other neuropsychiatric symptoms; however, the underlying mechanisms remain unclear. The aim of the present study was to elucidate the possible effects and mechanism of capsaicin, a transient receptor potential vanilloid 1 (TRPV1) agonist, on the pathological features of SAE. A model of SAE in C57BL/6 mice was generated using cecal ligation and puncture (CLP). Capsaicin (1 mg/kg) was injected subcutaneously before surgery. Cognitive function in mice was evaluated us

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… Blocking of transient receptor potential vanilloid 1 (TRPV1) promotes terminal mitophagy in multiple myeloma, disturbing calcium homeostasis and targeting ubiquitin pathway and bortezomib-induced unfolded protein response. J Hematol Oncol. 2020;13:158. doi: 10.1186/s13045-020-00993-0. 32. …

Organelle-oriented nanomedicines in tumor therapy: Targeting, escaping, or collaborating?

Precise tumor therapy is essential for improving treatment specificity, enhancing efficacy, and minimizing side effects. Targeting organelles is a key strategy for achieving this goal and is a frontier research area attracting a considerable amount of attention. The concept of organelle targeting has a significant effect on the structural design of the nanodrugs employed. Most notably, the intricate interactions among different organelles in a tumor cell essentially create a unified system. Unfortunately, this aspect might have been somewhat overlooked when existing organelle-targeting nanodru

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… Cells then initiate the unfolded protein response (UPR) to recycle or remove harmful proteins [ 196 ]. Ca 2+ stored in the ER is crucial for intracellular signaling regulating cell activities. …

Inflammation in Cardiomyopathies: Cellular Mechanisms Across Cardiac Phenotype.

Cardiomyopathies are traditionally classified by structural and genetic phenotypes, but emerging evidence highlights chronic myocardial inflammation as a pivotal driver of disease progression across different etiologies. This review synthesizes the current literature on the cellular and molecular inflammatory mechanisms underlying hypertrophic cardiomyopathy, Anderson-Fabry disease, cardiac amyloidosis, arrhythmogenic cardiomyopathy, and dilated cardiomyopathy. Across these distinct conditions, endogenous triggers such as metabolic substrates, misfolded amyloid fibrils, mechanical stress, or v

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… Seminal in vitro work demonstrates that amyloidogenic light chains activate oxidative stress pathways, mitochondrial depolarization, unfolded protein response signalling, and pro-inflammatory transcriptional reprogramming. …

Bortezomib-Loaded Mesoporous Silica Nanoparticles Selectively Alter Metabolism and Induce Death in Multiple Myeloma Cells.

A mesoporous silica-based nanodevice bearing the antineoplastic drug bortezomib (BTZ), whose release is triggered in acidic environment and grafted with folic acid (FOL) as a targeting function (FOL-MSN-BTZ) was tested on folate receptor overexpressing (FR+) multiple myeloma (MM) cells and on FR negative (FR-) normal cells. FOL-MSN-BTZ efficacy studies were conducted by means of growth experiments, TEM, TUNEL assay and Western Blotting analysis (WB). Metabolic investigations were performed to assess cells metabolic response to MSNs treatments. FOL-MSN-BTZ exclusively killed FR+ MM cells, leadi

Computational Drug Repurposing Across the Multiple Myeloma Spectrum: From MGUS to MM.

Background/objectivesMultiple myeloma (MM) is a challenging, B cell malignancy characterised by the uncontrolled proliferation of plasma cells within the bone marrow. Despite significant advances in treatment options nowadays, MM remains an incurable malignancy, with the majority of patients succumbing to the disease. MM develops from a pre-malignant state known as monoclonal gammopathy of unknown significance (MGUS), which then has the potential to evolve either into smouldering (asymptomatic) multiple myeloma (SMM) or into MM. Since novel drug discovery takes years to reach the clinic, drug

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… These treatments increase oxidative stress, leading to cancer cell death by triggering a process known as the Unfolded Protein Response [ 62 ]. Interestingly, our analysis showed that the ROS metabolic process was detected only in MGUS but not in sMM or MM. …

Unc-51 like kinase 3 (ULK3) contributes to autophagy and cell survival in multiple myeloma.

Despite effective therapies such as proteasome inhibitors, multiple myeloma (MM) patients relapse with refractory disease. Analysis of RNA sequencing data from CD138 + MM patient cells (n = 813) across disease stages identifies an autophagy gene signature. Particularly elevated ULK3 expression is strongly associated with disease progression. Functional studies reveal that ULK3 supports MM cell survival via the ULK-ATG13-FIP200 complex. We generate small-molecule kinase inhibitors (SG3-014/MA9-060) exhibiting nanomolar potency against ULK3, with binding confirmed by co-crystallization. While ex

Animal Models in Rheumatoid Arthritis: Is There a Correlation Between Autoantibodies in Human Pathology and Animal Models?

RA is a chronic autoimmune disease characterized by synovial inflammation and joint damage, driven by autoantibodies such as ACPA, anti-CarP and RF. These autoantibodies, influenced by genetic and environmental factors, play a crucial role in RA pathogenesis through post-translational modifications like citrullination, carbamylation, and acetylation. The early detection of ACPA provides a potential window for intervention, while anti-CarP antibodies correlate with severe disease progression and RF aids in diagnosis. Translating these findings from human pathology to animal models presents sign

Protocol for SARS-CoV-2 post-vaccine surveillance study in Australian adults and children with cancer: an observational study of safety and serological and immunological response to SARS-CoV-2 vaccination (SerOzNET).

BackgroundCancer is associated with excess morbidity and mortality from coronavirus disease 2019 (COVID-19) following infection by the novel pandemic coronavirus SARS-CoV-2. Vaccinations against SARS-CoV-2 have been rapidly developed and proved highly effective in reducing the incidence of severe COVID-19 in clinical trials of healthy populations. However, patients with cancer were excluded from pivotal clinical trials. Early data suggest that vaccine response is less robust in patients with immunosuppressive conditions or treatments, while toxicity and acceptability of COVID-19 vaccines in th

Carfilzomib boosted combination therapy for relapsed multiple myeloma.

Carfilzomib is a proteasome inhibitor that binds selectively and irreversibly to the 20S proteasome, the proteolytic core particle within the 26S proteasome, resulting in the accumulation of proteasome substrates and ultimately growth arrest and apoptosis of tumor cells. The development and ultimate approval of this medication by regulatory agencies has been an important step toward improving clinical outcomes in multiple myeloma. Although initially approved as a single agent for the treatment of multiply relapsed and/or refractory myeloma, in the USA, it is now widely used in the early relaps

Ion Channels in Multiple Myeloma: Pathogenic Role and Therapeutic Perspectives.

Ion channels are pore-forming proteins that allow ions to flow across plasma membranes and intracellular organelles in both excitable and non-excitable cells. They are involved in the regulation of several biological processes (i.e., proliferation, cell volume and shape, differentiation, migration, and apoptosis). Recently, the aberrant expression of ion channels has emerged as an important step of malignant transformation, tumor progression, and drug resistance, leading to the idea of "onco-channelopathy". Here, we review the contribution of ion channels and transporters in multiple myeloma (

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… Blocking of Transient Receptor Potential Vanilloid 1 (TRPV1) promotes terminal mitophagy in multiple myeloma, disturbing calcium homeostasis and targeting ubiquitin pathway and bortezomib-induced unfolded protein response. J. Hematol. Oncol. 2020;13:158. doi: 10.1186/s13045-020-00993-0. 64. …