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Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.

Protein folding is a fundamental process ensuring that polypeptide chains acquire the correct three-dimensional structures required for biological function. This complex journey from nascent polypeptides to mature proteins is tightly regulated by the cellular proteostasis network-an integrated system of molecular chaperones, folding enzymes, and degradation machineries. Disruptions in this network lead to dysproteostasis, a pathological state implicated in a growing list of human diseases, including neurodegenerative disorders, metabolic syndromes, and cancer. In this review, we provide a comp

Biosensors, Artificial Intelligence Biosensors, False Results and Novel Future Perspectives.

Medical biosensors have set the basis of medical diagnostics, and Artificial Intelligence (AI) has boosted diagnostics to a great extent. However, false results are evident in every method, so it is crucial to identify the reasons behind a possible false result in order to control its occurrence. This is the first critical state-of-the-art review article to discuss all the commonly used biosensor types and the reasons that can give rise to potential false results. Furthermore, AI is discussed in parallel with biosensors and their misdiagnoses, and again some reasons for possible false results

The metabolites from traditional Chinese medicine targeting ferroptosis for cancer therapy.

Cancer is a major disease with ever-increasing morbidity and mortality. The metabolites derived from traditional Chinese medicine (TCM) have played a significant role in combating cancers with curative efficacy and unique advantages. Ferroptosis, an iron-dependent programmed death characterized by the accumulation of lipid peroxide, stands out from the conventional forms of cell death, such as apoptosis, pyroptosis, necrosis, and autophagy. Recent evidence has demonstrated the potential of TCM metabolites targeting ferroptosis for cancer therapy. We collected and screened related articles publ

Pro-inflammatory cytokine-mediated anemia: regarding molecular mechanisms of erythropoiesis.

Anemia of cancer and chronic inflammatory diseases is a frequent complication affecting quality of life. For cancer patients it represents a particularly bad prognostic. Low level of erythropoietin is considered as one of the causes of anemia in these pathologies. The deficiency in erythropoietin production results from pro-inflammatory cytokines effect. However, few data is available concerning molecular mechanisms involved in cytokine-mediated anemia. Some recent publications have demonstrated the direct effect of pro-inflammatory cytokines on cell differentiation towards erythroid pathway,

:: разработка системы запретов на использование кинжалов на основе капсаицина для модуляции взаимодействия киназы A/PHB2 и митофагии в раковых клетках.

A/AURKA — киназа серена/трионина, часто перевоплощающаяся в рак. Недавние открытия указывают на подклеточные пулы АУРКА, в том числе в митохондрии. Там AURKA вызывает расчистку органеллой митофагией вместе с автоматическим посредником LC3 и его рецептором PHB2. Здесь мы показываем, что натуральный продукт капсаицин изменяет взаимодействие AURKA/PHB2. Мы синтезируем 16 Аналоговые аналоги капсаицина и передача энергии/флюоресценция Förster's Energy Transport/Fluorescence Life Time Imageing Microscope (FRET/FLIM) в клетках рака груди показывают, что соединения 12 и 13 :: расширение взаимодействия

Fructosamine-3-Kinase as a Potential Treatment Option for Age-Related Macular Degeneration.

Age-related macular degeneration is the leading cause of blindness in the developed world. Since advanced glycation end products (AGEs) are implicated in the pathogenesis of AMD through various lines of evidence, we investigated the potential of fructosamine-3-kinase (FN3K) in the disruption of retinal AGEs, drusenoid material and drusenoid lesions in patients with AMD. AGE-type autofluorescence was measured to evaluate the effects of FN3K on glycolaldehyde-induced AGE-modified neural porcine retinas and unmodified human neural retinas. Eye pairs from cigarette-smoke- and air-exposed mice were

Окисляющий/нетрозирующий стресс, апоптоз и сигнализация " Redox " : основные игроки в нейродегенеративных заболеваниях.

Нейродегенеративные заболевания представляют собой серьезную проблему для здоровья, которая оказывает глубокое воздействие на качество и продолжительность жизни миллионов людей. Эти заболевания характеризуются патологическими изменениями в различных областях мозга, конкретными генетическими мутациями, связанными с болезнью, залежами аномальных белков и дегенерацией неврологических клеток. Поскольку нейродегенеративные расстройства различаются по своим эпидемиологическим характеристикам и степени уязвимости нейронов, лечение этих заболеваний обычно направлено на замедление развития заболеваний.

Vitamin C-Sources, Physiological Role, Kinetics, Deficiency, Use, Toxicity, and Determination.

Vitamin C (L-ascorbic acid) has been known as an antioxidant for most people. However, its physiological role is much larger and encompasses very different processes ranging from facilitation of iron absorption through involvement in hormones and carnitine synthesis for important roles in epigenetic processes. Contrarily, high doses act as a pro-oxidant than an anti-oxidant. This may also be the reason why plasma levels are meticulously regulated on the level of absorption and excretion in the kidney. Interestingly, most cells contain vitamin C in millimolar concentrations, which is much highe

Protein breakdown in muscle wasting: role of autophagy-lysosome and ubiquitin-proteasome.

Skeletal muscle adapts its mass as consequence of physical activity, metabolism and hormones. Catabolic conditions or inactivity induce signaling pathways that regulate the process of muscle loss. Muscle atrophy in adult tissue occurs when protein degradation rates exceed protein synthesis. Two major protein degradation pathways, the ubiquitin-proteasome and the autophagy-lysosome systems, are activated during muscle atrophy and variably contribute to the loss of muscle mass. These degradation systems are controlled by a transcription dependent program that modulates the expression of rate-lim

Carfilzomib Induced Microangiopathy due to Accumulation With Paxlovid.

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… The results of the plasma assessment of the alternative complement pathway were as follows: the complement factor proteins were within normal range values (total hemolytic complement 96%, C3 899 mg/l, C4 257 mg/l, factor H 99 %, factor I 83%), the expression of membrane cofactor protein was reduced ( …

Chloroquine Restores eNOS Signaling in Shunt Endothelial Cells via Inhibiting eNOS Uncoupling.

Pulmonary arterial hypertension (PAH) is characterized by increased lung vascular stiffness and impaired vessel relaxation, primarily due to reduced nitric oxide (NO) production in endothelial cells. Recent studies indicate that chloroquine, an autophagy inhibitor, may help lower pulmonary arterial pressure and enhance lung vascular function. This study investigates the mechanisms underlying the chloroquine-mediated restoration of NO bioavailability in endothelial cells derived from aortopulmonary shunt lambs, a relevant model for congenital heart defect (CHD)-associated PAH. We found that NO

Hematology

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What should rheumatologists know about Gaucher disease and Fabry disease? Connecting the dots for an overview.

Gaucher and Fabry diseases are lysosomal storage disorders in which deficient enzyme activity leads to pathological accumulation of sphingolipids. These diseases have a broad phenotypic presentation. Musculoskeletal symptoms and pain complaints are frequently reported by patients. Thus, rheumatologists can be contacted by these patients, contributing to the correct diagnosis, earlier indication of appropriate treatment and improvement of their prognosis. This review describes important concepts about Gaucher and Fabry diseases that rheumatologists should understand to improve patients' quality

Cellular and molecular mechanisms of muscle atrophy.

Skeletal muscle is a plastic organ that is maintained by multiple pathways regulating cell and protein turnover. During muscle atrophy, proteolytic systems are activated, and contractile proteins and organelles are removed, resulting in the shrinkage of muscle fibers. Excessive loss of muscle mass is associated with poor prognosis in several diseases, including myopathies and muscular dystrophies, as well as in systemic disorders such as cancer, diabetes, sepsis and heart failure. Muscle loss also occurs during aging. In this paper, we review the key mechanisms that regulate the turnover of co

Impact of Alterations in Homocysteine, Asymmetric Dimethylarginine and Vitamins-Related Pathways in Some Neurodegenerative Diseases: A Narrative Review.

Hyperhomocysteinemia (HHcy) influences the development and progression of neurodegenerative disorders in different ways. Homocysteine (Hcy) metabolism is related to that of asymmetric dimethylarginine (ADMA) and group B vitamins. The breakdown of the pathway involving nitric oxide (NO) and ADMA can be considered one of the causes of endothelial alteration that represents a crucial step in the development of several neurodegenerative disorders. Deficiencies of vitamins other than group B ones, such as D and A, have also been associated with central nervous system disorders. The aim of this narr

Comprehensive Review of Methodology to Detect Reactive Oxygen Species (ROS) in Mammalian Species and Establish Its Relationship with Antioxidants and Cancer.

Evidence suggests that reactive oxygen species (ROS) mediate tissue homeostasis, cellular signaling, differentiation, and survival. ROS and antioxidants exert both beneficial and harmful effects on cancer. ROS at different concentrations exhibit different functions. This creates necessity to understand the relation between ROS, antioxidants, and cancer, and methods for detection of ROS. This review highlights various sources and types of ROS, their tumorigenic and tumor prevention effects; types of antioxidants, their tumorigenic and tumor prevention effects; and abnormal ROS detoxification in

Triple-Negative Breast Cancer: Basic Biology and Immuno-Oncolytic Viruses.

Triple-negative breast cancer (TNBC) is the most lethal subtype of breast cancer. TNBC diagnoses account for approximately one-fifth of all breast cancer cases globally. The lack of receptors for estrogen, progesterone, and human epidermal growth factor 2 (HER-2, CD340) results in a lack of available molecular-based therapeutics. This increases the difficulty of treatment and leaves more traditional as well as toxic therapies as the only available standards of care in many cases. Recurrence is an additional serious problem, contributing substantially to its higher mortality rate as compared to

Processes and therapeutic perspectives of acylation modifications of lysine and cysteine in tumors.

Acylation modification plays a crucial role in tumor progression through altering protein homeostasis and localization. However, a comprehensive summary of these processes is lacking. Protein acylation modifications are comprehensively summarized and categorized based on the amino acids that are modified. This review focuses on modifications of the lysine (acetylation, succinylation, crotonylation, malonylation, and glutarylation) and cysteine (myristoylation and palmitoylation) groups. The key enzymes involved in the occurrence and erasure of different modifications, as well as their effects

The Complosome: An Emerging Intracellular Complement Network in Cancer Development and Therapy.

The complement system is traditionally recognized as a major effector of innate immunity, essential for pathogen clearance, inflammation and the maintenance of tissue homeostasis. In recent years, however, its role in cancer has been substantially redefined. Beyond its canonical extracellular activity, complement has emerged as a multifaceted regulator of tumor biology, acting not only within the tumor microenvironment but also intracellularly through the recently described intracellular complement system (complosome). While extracellular complement primarily shapes immune responses and the tu

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… Expression of Membrane Cofactor Protein (MCP, CD46) in Human Liver Diseases. Br. J. Cancer. 1999;80:1820–1825. doi: 10.1038/sj.bjc.6690604. 67. Barilla-LaBarca M.L., Liszewski M.K., Lambris J.D., Hourcade D., Atkinson J.P. … Role of Membrane Cofactor Protein (CD46) in Regulation of C4b and C3b Deposited on Cells. J. Immunol. 2002;168:6298–6304. doi: 10.4049/jimmunol.168.12.6298. 68. Ninomiya H., Sims P.J. The Human Complement Regulatory Protein CD59 Binds to the Alpha-Chain of C8 and to the “b”Domain of C9. J. Biol. …

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