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The multiple biological activities of hyperoside: from molecular mechanisms to therapeutic perspectives in neoplastic and non-neoplastic diseases.

In recent years, hyperoside (quercetin 3-O-β-D-galactopyranoside) has garnered significant attention due to its diverse biological effects, which include vasoprotective, antioxidant, anti-inflammatory, and anti-tumor properties. Notably, hyperoside has shown remarkable potential in cancer therapy by targeting multiple mechanisms; it induces apoptosis, inhibits proliferation, blocks angiogenesis, and reduces the metastatic potential of cancer cells. Furthermore, hyperoside enhances the sensitivity of cancer cells to chemotherapy by modulating key signaling pathways. Beyond neoplastic diseases,

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… This conversion is crucial for the formation of autophagosomes, making LC3-II a widely used marker for assessing autophagosome abundance and autophagy levels ( Mizushima and Yoshimori, 2007 ; Jiang and Mizushima, 2015 ; Schaaf et al., 2016 ). … The observed increase in LC3-II levels further supports the conclusion that hyperoside induces cytotoxicity by promoting autophagosome formation. …

Tumor biomarkers for diagnosis, prognosis and targeted therapy.

Tumor biomarkers, the substances which are produced by tumors or the body's responses to tumors during tumorigenesis and progression, have been demonstrated to possess critical and encouraging value in screening and early diagnosis, prognosis prediction, recurrence detection, and therapeutic efficacy monitoring of cancers. Over the past decades, continuous progress has been made in exploring and discovering novel, sensitive, specific, and accurate tumor biomarkers, which has significantly promoted personalized medicine and improved the outcomes of cancer patients, especially advances in molecu

Prognostic Value of PSMB5 and Correlations with LC3II and Reactive Oxygen Species Levels in the Bone Marrow Mononuclear Cells of Bortezomib-Resistant Multiple Myeloma Patients.

Proteasome inhibitors (PIs) constitute the most common type of induction treatment for multiple myeloma. Interactions between the proteasome, autophagy, and reactive oxygen species (ROS) have been shown in the past, thus emphasizing the need for a better understanding of the underlying pathophysiology. For this study, bone marrow mononuclear cells from 110 myeloma patients were collected at different disease stages. PSMB5 and LC3I/II protein levels were determined using Western blot, proteasome proteolytic activity (PPA) with spectrofluorometry, and ROS with flow cytometry. PSMB5 accumulation

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… The main linking molecules are molecular chaperones that direct ubiquitin-labeled polypeptides to the autophagosomes and transcription factors that co-activate the two distinct pathways. … CRIP1 was found to promote PI resistance by enhancing the maturation of the autophagosomes that act as substitutes for the impaired UPS [ 82 ]. …

The role of Rhizoma Paridis saponins on anti-cancer: The potential mechanism and molecular targets.

Cancer is a disease characterized by uncontrolled cell proliferation, leading to excessive growth and invasion that can spread to other parts of the body. Traditional Chinese medicine has made new advancements in the treatment of cancer, providing new perspectives and directions for cancer treatment. Rhizoma Paridis is a widely used Chinese herbal medicine with documented anti-cancer effects dating back to ancient times. Modern research has shown that Rhizoma Paridis saponins (RPS) have various pharmacological activities. RPS can inhibit cancer in multiple ways, such as suppressing tumor growt

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… As autophagosomes form, cytosolic LC3-I binds to PE and is transferred to the double-membrane of autophagosomes, forming the membrane-bound LC3-II [ 110 ]. The conversion from LC3-I to LC3-II is a crucial step in the autophagy process. … It is widely believed that LC3 promotes the formation of autophagosomes and activates the Atg5-Atg12 complex, thereby facilitating the binding of LC3I. …

The Anti-Cancer Effect of Polyphenols against Breast Cancer and Cancer Stem Cells: Molecular Mechanisms.

The high incidence of breast cancer in developed and developing countries, and its correlation to cancer-related deaths, has prompted concerned scientists to discover novel alternatives to deal with this challenge. In this review, we will provide a brief overview of polyphenol structures and classifications, as well as on the carcinogenic process. The biology of breast cancer cells will also be discussed. The molecular mechanisms involved in the anti-cancer activities of numerous polyphenols, against a wide range of breast cancer cells, in vitro and in vivo, will be explained in detail. The in

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… Down-regulation of mTOR activity, and the subsequent formation of autophagosomes by quercetin treatment, have been evidenced [ 140 ]. … This can be explained by the role of SQSTM1 protein in interacting with LC3, which has a pivotal role in vesicle formation in autophagosomes [ 147 ]. …

Mitochondrial Determinants of Anti-Cancer Drug-Induced Cardiotoxicity.

Mitochondria are key organelles for the maintenance of myocardial tissue homeostasis, playing a pivotal role in adenosine triphosphate (ATP) production, calcium signaling, redox homeostasis, and thermogenesis, as well as in the regulation of crucial pathways involved in cell survival. On this basis, it is not surprising that structural and functional impairments of mitochondria can lead to contractile dysfunction, and have been widely implicated in the onset of diverse cardiovascular diseases, including ischemic cardiomyopathy, heart failure, and stroke. Several studies support mitochondrial t

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… In general, autophagy represents the main degradation mechanism in cells and uses autophagosome vesicles to deliver cytoplasmic elements to the lysosomes. … Notably, LC-3, i.e., the microtubule-associated protein 1 light chain, has been identified by Kabeya et al. as the first mammalian protein associated with the membranes of autophagosomes [ 78 ]. …

Pharmaceutical Chaperones and Proteostasis Regulators in the Therapy of Lysosomal Storage Disorders: Current Perspective and Future Promises.

Different approaches have been utilized or proposed for the treatment of lysosomal storage disorders (LSDs) including enzyme replacement and hematopoietic stem cell transplant therapies, both aiming to compensate for the enzymatic loss of the underlying mutated lysosomal enzymes. However, these approaches have their own limitations and therefore the vast majority of LSDs are either still untreatable or their treatments are inadequate. Missense mutations affecting enzyme stability, folding and cellular trafficking are common in LSDs resulting often in low protein half-life, premature degradatio

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… Macroautophagy occur with encapsulating denatured macromolecules or damaged organelle with membranous structures generating autophagosomes that fuses with lysosomes to initiate the digestion process. … Alterations in the autophagy function contribute to the pathogenesis of many LSDs which leads to the accumulation of autophagosomes in affected cells and activation of cell death pathways. …

Recent Insights into the Creation of Histone Deacetylase Inhibitors for the Treatment of Human Diseases.

This review examines publications over the past two years devoted to histone deacetylase inhibitors for the treatment of cancer, diseases of the nervous, cardiovascular, digestive, and respiratory systems, and autoimmune diseases. The review covers various classes of histone deacetylase inhibitors depending on the zinc-binding group, in particular hydroxamic acids, benzamides, hydrazides, carboxylic acids, and cyclic peptides. The review pays special attention to the mechanisms of development of pathologies involving various isoforms of histone deacetylases. The review shows that, for the trea

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… Ubiquitinated parkin activates autophagy transition proteins such as nuclear dot protein 52 (NDP52) and anchors damaged mitochondria in autophagosomes by binding to microtubule-associated protein 1 light chain 3 (LC3), which is degraded in the lysosome. … with LC3 “grabber”, II—fusion of autophagosomes with damages mitochondria, III—autophagosome binds to lysosomes, IV—lysosomal degradation of damaged mitochondria. …

Different Strategies to Overcome Resistance to Proteasome Inhibitors-A Summary 20 Years after Their Introduction.

Proteasome inhibitors (PIs), bortezomib, carfilzomib, and ixazomib, are the first-line treatment for multiple myeloma (MM). They inhibit cytosolic protein degradation in cells, which leads to the accumulation of misfolded and malfunctioned proteins in the cytosol and endoplasmic reticulum, resulting in cell death. Despite being a breakthrough in MM therapy, malignant cells develop resistance to PIs via different mechanisms. Understanding these mechanisms drives research toward new anticancer agents to overcome PI resistance. In this review, we summarize the mechanism of action of PIs and how M

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… This pathway relies on accumulating unwanted proteins in aggresomes followed by sequestering the aggresomes with double membranes, which results in the formation of autophagosomes. The maturation of autophagosomes is associated with acidification of their contents and lysis with lysosomal enzymes. … They impede the fusion of lysosomes with autophagosomes, preventing lysis of the latter’s cargo. After promising results in cell lines, both drugs were tested in clinical trials in combination with PIs. …

Targeting Metal Ion Homeostasis for Regulated Cell Death-Amplified Tumor Nanomedicine.

Amidst escalating global health challenges, neoplastic diseases remain a predominant cause of morbidity and mortality, exerting complex and far-reaching effects on human health and societal well-being. The advent of precision medicine has ushered in an era of tailored therapeutic strategies, leveraging individual genetic profiles, tumor microenvironmental features, and exogenous factors to redefine oncology care. Central to these advances is the understanding of cell death, a fundamental biological process encompassing both programmed and non-programmed forms. Programmed cell death is orchestr

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… Adapted from Ref 28 ( B ): Formation of autophagosomes through encapsulation of damaged organelles or protein aggregates by autophagic membrane via a circular structure. … Adapted from Ref 28 ( B ): Formation of autophagosomes through encapsulation of damaged organelles or protein aggregates by autophagic membrane via a circular structure. …

Targeting the two-pore channel 2 in cancer progression and metastasis.

The importance of Ca2+ signaling, and particularly Ca2+ channels, in key events of cancer cell function such as proliferation, metastasis, autophagy and angiogenesis, has recently begun to be appreciated. Of particular note are two-pore channels (TPCs), a group of recently identified Ca2+-channels, located within the endolysosomal system. TPC2 has recently emerged as an intracellular ion channel of significant pathophysiological relevance, specifically in cancer, and interest in its role as an anti-cancer drug target has begun to be explored. Herein, an overview of the cancer-related functions

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… Overexpression of TPC2, but not an inactive mutant form of TPC2, in Hela cervical cancer and 4T1 breast cancer cells decreased autophagosomal-lysosomal fusion, resulting in the accumulation of autophagosomes [ 29 , 65 ]. … Conversely, TPC2 knockdown in mouse embryonic stem cells promoted autophagosomal-lysosomal fusion [ 65 ], and autophagy-related gene 5 ( ATG5 ) knockdown, but not mTOR activity inhibition, abolished the TPC2-induced accumulation of autophagosomes [ 65 ]. …

Emerging strategies and therapies for treatment of Paget's disease of bone.

Paget's disease of bone (PDB) is a progressive monostotic or polyostotic metabolic bone disease characterized by focal abnormal bone remodeling, with increased bone resorption and excessive, disorganized, new bone formation. PDB rarely occurs before middle age, and it is the second most frequent metabolic bone disorder after osteoporosis, affecting up to 3% of adults over 55 years of age. One of the most striking and intriguing clinical features is the focal nature of the disorder, in that once the disease is established within a bone, there is only local spread within that bone and no systemi

Analysis of microRNA expression profiles in exosomes derived from acute myeloid leukemia by p62 knockdown and effect on angiogenesis.

ObjectivesIn this study, we aimed to investigate the effect of p62 on angiogenesis and microRNA (miRNA) expression profiles in acute myeloid leukemia (AML) exosomes.MethodsAn Exiqon v19.0 microRNA MicroArray was used to profile miRNAs in exosomes derived from parental and p62-knockdown U937 cells. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to predict the biological functions and potential mechanisms of differentially expressed miRNAs in AML exosomes. Endothelial cell tube formation assays using human umbilical vein endothelial cells (HUVECs) w

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… The PB1 domain of p62 promotes packaging of ubiquitinated substrates by self-oligomerization and transports packaged substrates to the autophagy pathway to participate in autophagosome formation ( Ichimura et al., 2008 ). … P62 interacts with LC3, an autophagosome marker protein, to form a complex through its LIR domain that is degraded in autophagosomes as an autophagy-specific substrate ( Pankiv et al., 2007 ). …

Paeoniflorin Ameliorates BiPN by Reducing IL6 Levels and Regulating PARKIN-Mediated Mitochondrial Autophagy.

BACKGROUND: Bortezomib-induced peripheral neuropathy (BiPN) is a common complication of multiple myeloma (MM) treatment that seriously affects the quality of life of patients. The purpose of the present study was to explore the therapeutic effect of paeoniflorin on BiPN and its possible mechanism. METHODS: ELISA was used to measure the level of interleukin-6 (IL6) in the plasma of MM patients, and bioinformatics analysis was used to predict the mechanism underlying the effect of paeoniflorin on peripheral neuropathy. Cell and animal models of BiPN were constructed to evaluate mitochondrial fu

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

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… Pathological α-Syn activates microglia, which then engulf α-Syn into autophagosomes for degradation. p62, encoded by sequestosome 1 (SQSTM1), acts as a bridge between ubiquitinated proteins and autophagosomes within cells. … Ubiquitinated mutant α-Syn binds to p62, which is subsequently transported to autophagosomes and degraded following lysosomal fusion. Pathological α-Syn interacts with TLR4 on the microglial surface, enhancing p62/SQSTM1 transcription via the NF-κB signaling pathway. …

Identification of Long Non-Coding RNAs Deregulated in Multiple Myeloma Cells Resistant to Proteasome Inhibitors.

While the clinical benefit of proteasome inhibitors (PIs) for multiple myeloma (MM) treatment remains unchallenged, dose-limiting toxicities and the inevitable emergence of drug resistance limit their long-term utility. Disease eradication is compromised by drug resistance that is either present de novo or therapy-induced, which accounts for the majority of tumor relapses and MM-related deaths. Non-coding RNAs (ncRNAs) are a broad class of RNA molecules, including long non-coding RNAs (lncRNAs), that do not encode proteins but play a major role in regulating the fundamental cellular processes

Нейрозащитный и терапевтический потенциал ресвератрола для травм спинного мозга: систематический обзор.

Травматические травмы спинного мозга являются частыми повреждениями CNS, которые происходят в таких обстоятельствах, как падение или несчастные случаи. Травматические травмы спинного мозга чаще встречаются в более старшей возрастной группе и у мужчин, причем высокая заболеваемость и распространенность этого заболевания объясняются отсутствием эффективного фармакологического или нейрохирургического лечения. Травматический СКИ может быть отнесен к категории первичных или вторичных травм, которые в конечном счете могут привести к смерти или физической зависимости. Resveratrol - это экстракт из по

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… Switching from autophagy to apoptosis During the phase of secondary SCI injury, the process of autophagy is gradually blocked evidenced by the building up of autophagy substrate protein p62, accumulation of LC3-II positive autophagosomes, and the drop down of lysosomal proteases such as cathepsin D … This conversion is vital for the formation of autophagosomes and plays a significant role in activating autophagy (Zhiya [ 13 ]. Fig. 5 Resveratrol mediates neuroprotection through SIRT1/AMPK pathway. …

Antimitotic drugs in the treatment of cancer.

Cancer is a complex disease since it is adaptive in such a way that it can promote proliferation and invasion by means of an overactive cell cycle and in turn cellular division which is targeted by antimitotic drugs that are highly validated chemotherapy agents. However, antimitotic drug cytotoxicity to non-tumorigenic cells and multiple cancer resistance developed in response to drugs such as taxanes and vinca alkaloids are obstacles faced in both the clinical and basic research field to date. In this review, the classes of antimitotic compounds, their mechanisms of action and cancer cell res

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… Autophagy Autophagy is a form of cell death where organelles and proteins are degraded resulting in energy that is packaged into double membrane vesicles known as autophagosomes [ 56 ]. … In MCF-7 and SK-BR-3 cells that were not undergoing mitosis because of mitotic slippage, paclitaxel prevented autophagy by hindering autophagosome trafficking [ 55 ]. Classes of antimitotic drugs Taxanes Taxanes are commonly used as chemotherapy treatment for breast cancer [ 57 ]. …

Noncanonical SQSTM1/p62-Nrf2 pathway activation mediates proteasome inhibitor resistance in multiple myeloma cells via redox, metabolic and translational reprogramming.

Multiple Myeloma (MM) is a B-cell malignancy characterized by the accumulation of clonal plasma cells in the bone marrow, with drug resistance being a major cause of therapeutic failure. We established a carfilzomib-resistant derivative of the LP-1 MM cell line (LP-1/Cfz) and found that the transcription factor NF-E2 p45-related factor 2 (Nrf2; gene symbol NFE2L2) contributes to carfilzomib resistance. The mechanism of Nrf2 activation involved enhanced translation of Nrf2 as well as its positive regulator, the autophagy receptor sequestosome 1 (SQSTM1)/p62. The eukaryotic translation initiatio

Митохондриальная дисфункция, накопление железа, пероксидация липидов и воспаленная активация в клеточных моделях, полученных от пациентов с множественным склерозом.

Множественный склероз (MS) является воспалительным заболеванием центральной нервной системы (CNS). Несмотря на успехи в борьбе с вновь возникающими активными заболеваниями, эффективное лечение необратимого постепенного сокращения НР остается ограниченным. Исследования с использованием фибробатластов кожи, полученные от пациентов с неврологическими расстройствами, выявили изменения в путях клеточного стресса и биоэнергетики. Однако исследований с использованием моделей клеток MS, разработанных пациентами, мало. В этом исследовании мы собрали фибробласты из two Пациенты MS для изучения клеточных

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… Autophagy and MS Our results also showed impaired lysosomal acidification, leading to autophagosomes accumulation and increased expression levels of LAMP1, a membrane lysosomal marker, as well as increased autophagy-related proteins expression levels. … These results suggest that autophagosomes and lysosomes are accumulated because lysosomal acidification deficiency disrupts autophagy process. Autophagy has the property of a double-edged sword in MS in that it may have both beneficial and detrimental effects on MS neuropathology [ 56 ]. …