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Талидомид взаимодействует с воспалением в идиопатическом фиброзе легких.

" Трагедия Талидомида " является важной вехой в истории фармацевтической промышленности. Несмотря на ограниченные клинические испытания, прилагаются постоянные усилия по изучению Талидомида в качестве лекарства от рака и подстрекательских заболеваний, таких, как ревматуидный артрит, проказа, и COVID-19. В рамках этого обзора основное внимание уделяется возможностям борьбы с воспалением путем повторного использования талидомида для лечения идиопатического фиброза легких (ИПФ). Статьи были найдены в базе данных Scopus, сортированы и рассмотрены отдельные статьи. Содержание включает в с

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… The activation of AMPK also decreased the endoplasmic reticulum stress and unfolded protein response, both of which are driving factors for the development of fibrosis by inducing tissue injury in the alveolar epithelium (Choi et al. 2016 ; Burman et al. 2018 ). …

Investigating the Interplay between Myeloma Cells and Bone Marrow Stromal Cells in the Development of Drug Resistance: Dissecting the Role of Epigenetic Modifications.

Multiple Myeloma (MM) is a malignancy of plasma cells infiltrating the bone marrow (BM). Many studies have demonstrated the crucial involvement of bone marrow stromal cells in MM progression and drug resistance. Together with the BM microenvironment (BMME), epigenetics also plays a crucial role in MM development. A variety of epigenetic regulators, including histone acetyltransferases (HATs), histone methyltransferases (HMTs) and lysine demethylases (KDMs), are altered in MM, contributing to the disease progression and prognosis. In addition to histone modifications, DNA methylation also plays

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… For example, HDAC inhibitors have been shown to disrupt proteostasis by targeting the unfolded protein response (UPR) pathway [ 168 ] and may alter other proteins important for MM pathogenesis, such as p53, Hsp90 and the aggresome [ 169 ]. …

Overcoming Drug Resistance in Advanced Prostate Cancer by Drug Repurposing.

Prostate cancer (PCa) is the second most common cancer in men. Common treatments include active surveillance, surgery, or radiation. Androgen deprivation therapy and chemotherapy are usually reserved for advanced disease or biochemical recurrence, such as castration-resistant prostate cancer (CRPC), but they are not considered curative because PCa cells eventually develop drug resistance. The latter is achieved through various cellular mechanisms that ultimately circumvent the pharmaceutical's mode of action. The need for novel therapeutic approaches is necessary under these circumstances. An

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… It also induced ER stress and activated all three Unfolded Protein Response (UPR) pathways, resulting in indirect suppression of protein translation and subsequent reduction in the amounts of G1/S cyclins, resulting in G1 cell cycle arrest. …

T-Type Calcium Channels: A Mixed Blessing.

The role of T-type calcium channels is well established in excitable cells, where they preside over action potential generation, automaticity, and firing. They also contribute to intracellular calcium signaling, cell cycle progression, and cell fate; and, in this sense, they emerge as key regulators also in non-excitable cells. In particular, their expression may be considered a prognostic factor in cancer. Almost all cancer cells express T-type calcium channels to the point that it has been considered a pharmacological target; but, as the drugs used to reduce their expression are not complete

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… For example, in glioblastoma and melanoma, mibefradil and NNC 55-0396 seemed to activate IRE1 alpha (Inositol-Requiring Enzyme 1), and the unfolded protein response (UPR) system, leading to the mobilization of calcium from the endoplasmic reticulum, inducing apoptosis [ 107 , 112 ]. … protein response UPS | Ubiquitin-proteasome system USP5 | Ubiquitin-specific cysteine protease 5 VEGF | Vascular-Endothelial Growth Factor Author Contributions Conceptualization, D.M., A.F., S.C. and I.R.; writing—original draft preparation, D.M., A.F., S.C. and G.A.M.; writing—review and editing, …

Cyclic Peptides in Modern Drug Discovery: Trends and Therapeutic Directions.

Peptide therapeutics are an important drug modality due to their high specificity, favorable safety, and expanding design potential. Among them, cyclic peptides occupy a space between small molecules and biologics, offering improved rigidity, stability, and target engagement. This report analyzes trends in cyclic peptide research using data from the CAS Content Collection over the past two decades. Results show a steady rise in academic publications and patents, reflecting growing interest across discovery and development. Notably, oral administration is gaining attention, indicating progress

Decoding VEXAS syndrome: emerging insights into pathogenesis and clinical management.

Purpose of reviewVEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a newly discovered, adult-onset, hemato-inflammatory disease driven by clonal dominance of pro-inflammatory hematopoietic cells bearing a somatic mutation in the UBA1 gene. This review aims to integrate and discuss the most recent insights into the evolving understanding of VEXAS pathogenesis and clinical management.Recent findingsAn interplay between inflammation and clonal dominance of UBA1 mutant hematopoietic clones underlies the pathogenesis of VEXAS syndrome. Mutant cells both generate and susta

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… Direct comparison of mutant versus wild-type HSPCs within VEXAS patients shows in mutant clones stronger induction of inflammatory signatures, proteotoxic stress, activation of stress-adaptive strategies, including the unfolded protein response (UPR), and a global reduction of protein translation [ 30 …

Проверьте оптические датчики на основе молекулярного распознавания SSWNT для воспламенительного цитокина TNF-α.

TNF-α (Tumor Necrosis Factor) — цитокиновый цитокин, который усиливает подстрекательскую реакцию и поощряет вербовку лейкоцитов. TNF-α производится главным образом с помощью активированных макрофагов, в частности, в ответ на инфекцию, воспаление или повреждение тканей. С учетом его центральной роли в нормальном и ненормальном иммунном реагировании он является объектом целого ряда терапевтических средств, таких, как адалимумаб и этицерцеп. TNF-α также является прогнозирующим и диагностическим биомаркером, связанным с Rheumatoid Artritis, болезнью Альцгеймера, множественным склерозом, нескольким

Breaking Therapy Resistance: An Update on Oncolytic Newcastle Disease Virus for Improvements of Cancer Therapy.

Resistance to therapy is a major obstacle to cancer treatment. It may exist from the beginning, or it may develop during therapy. The review focusses on oncolytic Newcastle disease virus (NDV) as a biological agent with potential to break therapy resistance. This avian virus combines, upon inoculation into non-permissive hosts such as human, 12 described anti-neoplastic effects with 11 described immune stimulatory properties. Fifty years of clinical application of NDV give witness to the high safety profile of this biological agent. In 2015, an important milestone was achieved, namely the succ

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… A stressful cellular state is coupled to the activation of the PERK/eIF2α/ATF4/CHOP pathway of the unfolded protein response (UPR). PKR, an interferon stimulated gene, upon detection of nonself dsRNA, coupled with eIF2α phosphorylation, induce stress granule (SG) formation. …

Outcome of transforaminal epidural steroid injection for lumbar radiculopathy: initial three-year experience at Upendra Devkota Memorial-National Institute of Neurological and Allied Sciences, Nepal.

INTRODUCTION: Additional risk minimisation measures (aRMMs) for medicinal products are necessary to address specific important safety issues which may not be practically achieved through routine risk management measures alone. The implementation and determination of effectiveness for aRMMs can be a challenge as it involves multiple stakeholders. It is therefore important to have concise objectives to avoid undue burden on patients, healthcare professionals and the healthcare system. AIM: The aim of this study was to examine how aRMMs are implemented and how effectiveness is assessed in the Eu

Sorcin: a novel potential target in therapies of cancers.

Soluble resistance-related calcium-binding protein (sorcin) is a member of the penta-EF-hand protein family. Sorcin is widely distributed in normal human tissues, such as the brain, heart, lymphocytes, kidneys, breast and skin. Findings suggest that sorcin is associated with the regulation of calcium homeostasis, cell cycle and vesicle trafficking. It has been reported that many types of non-neoplastic diseases such as diabetes, viral infection, infertility, and nervous system diseases were affected by the expression of sorcin. One of the main issues is the role of sorcin in neoplastic disease

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… In the meantime, some researchers proposed that sorcin can also influence the unfolded protein response. 19 Being associated with the regulation, calcium channels or exchangers are being studied, such as cardiac ryanodine receptors (RyR 2 ), L-type Ca 2+ channels, Na + /Ca 2+ exchanger (NCX) 23 – 25 …

Ageing, Cellular Senescence and Neurodegenerative Disease.

Ageing is a major risk factor for developing many neurodegenerative diseases. Cellular senescence is a homeostatic biological process that has a key role in driving ageing. There is evidence that senescent cells accumulate in the nervous system with ageing and neurodegenerative disease and may predispose a person to the appearance of a neurodegenerative condition or may aggravate its course. Research into senescence has long been hindered by its variable and cell-type specific features and the lack of a universal marker to unequivocally detect senescent cells. Recent advances in senescence mar

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… Senescent cells exhibit increased unfolded protein response (UPR), indicative of endoplasmic reticulum (ER) stress [ 76 , 77 ]. … protein response 53BP1 | p53-binding protein 1 Funding This research received no external funding. …

Proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells.

Head and neck cancer (HNC) has frequently an aggressive course for the development of resistance to standard chemotherapy. Thus, the use of innovative therapeutic drugs is being assessed. Bortezomib is a proteasome inhibitor with anticancer effects. In vitro antitumoral activity of Bortezomib was investigated employing human tongue (SCC-15, CAL-27), pharynx (FaDu), salivary gland (A-253) cancer cell lines and a murine cell line (SALTO-5) originated from a salivary gland adenocarcinoma arising in BALB-neuT male mice transgenic for the oncogene neu. Bortezomib inhibited cell proliferation, trigg

Relapsed/Refractory Multiple Myeloma in 2020/2021 and Beyond.

Despite the challenges imposed by the COVID-19 pandemic, exciting therapeutic progress continues to be made in MM. New drug approvals for relapsed/refractory (RR)MM in 2020/2021 include the second CD38 monoclonal antibody, isatuximab, the first BCMA-targeting therapy and first-in-class antibody-drug conjugate (ADC) belantamab mafodotin, the first BCMA-targeting CAR T cell product Idecabtagen-Vicleucel (bb2121, Ide-Cel), the first in-class XPO-1 inhibitor selinexor, as well as the first-in-class anti-tumor peptide-drug conjugate, melflufen. The present introductory article of the Special Issue

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… Novel Strategies to Target the UPR Proteasome inhibitors target the MM-specific vulnerability of aberrant protein turnover and thereby normalize the imbalance of proteasome degradative capacity and proteasome load by inducing the terminal unfolded protein response (UPR), and subsequent cell death [ … Proteasome Inhibitors Induce a Terminal Unfolded Protein Response in Multiple Myeloma Cells. Blood. 2006;107:4907–4916. doi: 10.1182/blood-2005-08-3531. 125. Song Y., Ray A., Li S., Das D.S., Tai Y.T., Carrasco R.D., Chauhan D., Anderson K.C. …

Уровень амилиновой сыворотки у пациентов с множественным склерозом: перекрестное исследование сечения.

Амилин — это поджелудочный нейроэндокринный пестид, который связывает периферическое метаболическое регулирование с центральными гомеостатическими и нейродегенеративными путями. Однако его значение для подстрекательских и демиелионирующих процессов, лежащих в основе множественного склероза (МС), остается неясным. До настоящего времени роль амилина в РС не была расследована. В ходе этого исследования были исследованы уровни сыворотки амилина у пациентов с MS и их связь с состоянием болезни. Это межсекторальное тематическое исследование включало в себя 62 пациенты, встречающиеся 2017 Критерии Mc

Gaucher disease: the hematologist's perspective of a multisystemic disorder.

Gaucher disease (GD) exemplifies how a single genetic mutation can give rise to a complex multisystem disorder with profound hematological implications. Central to its pathophysiology is the lysosomal accumulation of glucosylceramide due to deficient glucocerebrosidase activity, together with abnormal folding and trafficking of the enzyme that induce endoplasmic reticulum stress and cellular dysfunction. These processes disrupt reticuloendothelial homeostasis and interfere with hematopoiesis. As a consequence, macrophage activation and chronic inflammation contribute to the cytopenias, splenom

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… Accumulation of misfolded GCase induces chronic ER stress and activation of the unfolded protein response (UPR), a compensatory pathway that attempts to restore proteostasis but may also disrupt cellular homeostasis by promoting calcium release and oxidative stress [ 17 ]. … -6 38649404 PMC11035702 Pornsukjantra T, Saikachain N, Sutjarit N, Khongkrapan A, Tubsuwan A, Bhukhai K, Tim-Aroon T, Anurathapan U, Hongeng S, Asavapanumas N (2024) An increase in ER stress and unfolded protein response in iPSCs-derived neuronal cells from neuronopathic Gaucher disease patients. …

High-throughput drug screening reveals Pyrvinium pamoate as effective candidate against pediatric MLL-rearranged acute myeloid leukemia.

Pediatric MLL-rearranged acute myeloid leukemia (AML) has a generally unfavorable outcome, primarily due to relapse and drug resistance. To overcome these difficulties, new therapeutic agents are urgently needed. Yet, implementing novel drugs for clinical use is a time-consuming, laborious, costly and high-risk process. Therefore, we applied a drug-repositioning strategy by screening drug libraries, comprised of >4000 compounds that are mostly FDA-approved, in a high-throughput format on primary MLL-rearranged AML cells. Here we identified pyrvinium pamoate (pyrvinium) as a novel candidate dru

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… Pyrvinium targets the unfolded protein response to hypoglycemia and its anti-tumor activity is enhanced by combination therapy PLoS ONE 3 2008 e3951 19079611 10.1371/journal.pone.0003951 PMC2597738 Supplementary materials Image, application 1 Image, application 2 Image, application 3 Image, application …

Development of selective nanomolar cyclic peptide ligands as GBA1 enzyme stabilisers.

The stabilisation of recombinant glycosidases by exogenous ligands, known as pharmacological chaperones or enzyme stabilisers, has recently garnered great clinical interest. This strategy can prevent enzyme degradation in the blood, reducing required dosages of recombinant enzyme and extending IV injection intervals, thereby reducing side effects, improving patient lifestyles and treatment costs. While this therapeutic approach has been successfully implemented for treating Pompe and Fabry diseases, clinical studies for Gaucher disease using chaperones alone or in combination with enzyme repla

Targeted Delivery Strategies for Multiple Myeloma and Their Adverse Drug Reactions.

Currently, multiple myeloma (MM) is a prevalent hematopoietic system malignancy, known for its insidious onset and unfavorable prognosis. Recently developed chemotherapy drugs for MM have exhibited promising therapeutic outcomes. Nevertheless, to overcome the shortcomings of traditional clinical drug treatment, such as off-target effects, multiple drug resistance, and systemic toxicity, targeted drug delivery systems are optimizing the conventional pharmaceuticals for precise delivery to designated sites at controlled rates, striving for maximal efficacy and safety, presenting a promising appr

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… (b) Melflufen activates the unfolded protein response through the protein kinase RNA-like endoplasmic reticulum kinase pathway, enhancing the expression of C/EBP homologous protein and consequently inducing apoptosis [ 50 ]. … The Peptide-Drug Conjugate Melflufen Modulates the Unfolded Protein Response of Multiple Myeloma and Amyloidogenic Plasma Cells and Induces Cell Death. Hemasphere. 2022;6:e687. doi: 10.1097/HS9.0000000000000687. 51. Gebraad A., Ohlsbom R., Miettinen J.J., Emeh P., Pakarinen T. …

The long road to recognition: a historical review of amyloidosis from early pathology to disease-modifying therapy.

Within the last several decades, great strides are being made in both the diagnosis and treatment of cardiac amyloidosis, yet the condition itself has been a severely under-recognized cause of heart failure for centuries. For much of medical history, the accumulation of these insoluble fibril deposits was an enigmatic finding, observed primarily post-mortem in patients suffering from chronic inflammatory conditions. This review traces the fascinating evolution of amyloidosis: from its origins as a botanical term mistakenly applied to human pathology, through the serendipitous discoveries of hi

Restoring the Immunity in the Tumor Microenvironment: Insights into Immunogenic Cell Death in Onco-Therapies.

Immunogenic cell death (ICD) elicited by cancer therapy reshapes the tumor immune microenvironment. A long-term adaptative immune response can be initiated by modulating cell death by therapeutic approaches. Here, the major hallmarks of ICD, endoplasmic reticulum (ER) stress, and damage-associated molecular patterns (DAMPs) are correlated with ICD inducers used in clinical practice to enhance antitumoral activity by suppressing tumor immune evasion. Approaches to monitoring the ICD triggered by antitumoral therapeutics in the tumor microenvironment (TME) and novel perspective in this immune sy

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… As the ER’s role is pivotal for cell survival, a mechanism has evolved to detect and respond to stress, named the unfolded protein response (UPR). This mechanism restores protein folding capacity of ER by promoting chaperon expression and decreasing global protein activity. … UPR: unfolded protein response. CRT: Calreticulin. HMGB1: high mobility group box 1 protein. RAGE: receptor for advanced glycation endproducts. LAMP: lysosomal-associated membrane protein. HSPs: Heat shock proteins. ANXA1: annexin A1. FPR1: formyl peptide receptor 1. CG: Cardiac Glycosides. …