Glucosinolates and Their Hydrolytic Derivatives: Promising Phytochemicals With Anticancer Potential DOI Open Access
Nataša Joković, Srdjan Pešić, Jelena Vitorović

et al.

Phytotherapy Research, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 27, 2024

Recent research has increasingly focused on phytochemicals as promising anticancer agents, with glucosinolates (GSLs) and their hydrolytic derivatives playing a central role. These sulfur-containing compounds, found in plants of the Brassicales order, are converted by myrosinase enzymes into biologically active products, primarily isothiocyanates (ITCs) indoles, which exhibit significant properties. Indole-3-carbinol, diindolylmethane, sulforaphane (SFN), phenethyl isothiocyanate (PEITC), benzyl isothiocyanate, allyl have shown potent effects animal models, particularly breast, prostate, lung, melanoma, bladder, hepatoma, gastrointestinal cancers. Clinical studies further support chemopreventive SFN PEITC, detoxifying carcinogens altering biochemical markers cancer patients. compounds demonstrated good bioavailability, low toxicity, minimal adverse effects, supporting potential therapeutic application. Their mechanisms include modulation reactive oxygen species, suppression cancer-related signaling pathways, direct interaction tumor cell proteins. Additionally, semi-synthetic GSLs been developed to enhance efficacy. In conclusion, offer both warranting clinical investigation optimize application treatment.

Language: Английский

Regulation of the NLRP3 inflammasome by autophagy and mitophagy DOI
Suman Gupta,

Suzanne L. Cassel,

Fayyaz S. Sutterwala

et al.

Immunological Reviews, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 17, 2024

Summary The NLRP3 inflammasome is a multiprotein complex that upon activation by the innate immune system drives broad inflammatory response. primary initial mediators of this response are pro‐IL‐1β and pro‐IL‐18, both which in an inactive form. Formation activates caspase‐1, cleaves pro‐IL‐18 triggers formation gasdermin D pores. Gasdermin pores allow for secretion active IL‐1β IL‐18 initiating organism‐wide can be beneficial to host; however, if inappropriately activated it lead significant pathology. While components known, precise details assembly less well defined conflicting. Here, we discuss several proposed pathways inflammasome. We examine role subcellular localization reciprocal regulation autophagy. focus on roles mitochondria mitophagy activating regulating Finally, detail impact pathologic responses development manifestations pulmonary disease.

Language: Английский

Citations

5
Autophagy and Programmed Cell Death Modalities Interplay in HIV Pathogenesis DOI Creative Commons

Harpreet Kaur Lamsira,

Andrea Sabatini, Serena Ciolfi

et al.

Cells, Journal Year: 2025, Volume and Issue: 14(5), P. 351 - 351

Published: Feb. 28, 2025

Human immunodeficiency virus (HIV) infection continues to be a major global health challenge, affecting 38.4 million according the Joint United Nations Program on HIV/AIDS (UNAIDS) at end of 2021 with 1.5 new infections. New HIV infections increased during 2 years after COVID-19 pandemic. Understanding intricate cellular processes underlying pathogenesis is crucial for developing effective therapeutic strategies. Among these processes, autophagy and programmed cell death modalities, including apoptosis, necroptosis, pyroptosis, ferroptosis, play pivotal roles in host-virus interaction dynamics. Autophagy, highly conserved mechanism, acts as double-edged sword infection, influencing viral replication, immune response modulation, fate infected cells. Conversely, critical defense mechanism against spread contributes depletion CD4+ T cells, hallmark progression. This review aims dissect complex interplay between modalities HIV-induced pathogenesis. It highlights molecular mechanisms involved, their persistence dysfunction, challenges posed by reservoir drug resistance, which continue impede management pathology. Targeting pathways holds promise novel strategies mitigate chronic inflammation, ultimately improving outcomes individuals living HIV.

Language: Английский

Citations

0
The role of autophagy in the pathogenesis and treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) DOI Creative Commons
Jimmy Beckers, Philip Van Damme

Autophagy Reports, Journal Year: 2025, Volume and Issue: 4(1)

Published: March 20, 2025

Language: Английский

Citations

0
Natural Autophagy Activators to Fight Age-Related Diseases DOI Creative Commons

Vianey M. Mundo Rivera,

José Roberto Tlacuahuac Juárez,

Nadia Mireya Murillo-Melo

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(19), P. 1611 - 1611

Published: Sept. 26, 2024

The constant increase in the elderly population presents significant challenges addressing new social, economic, and health problems concerning this population. With respect to health, aging is a primary risk factor for age-related diseases, which are driven by interconnected molecular hallmarks that influence development of these diseases. One main mechanisms has attracted more attention autophagy, catabolic process removes recycles damaged or dysfunctional cell components preserve viability. autophagy can be induced deregulated response wide range internal external stimuli, such as starvation, oxidative stress, hypoxia, organelles, infectious pathogens, aging. Natural compounds promote stimulation regulatory pathways, mTOR, FoxO1/3, AMPK, Sirt1, lead increased levels essential proteins Beclin-1 LC3, well decrease p62. These changes indicate activation autophagic flux, known decreased cardiovascular neurodegeneration, cataracts. regulated administration natural offers an adjuvant therapeutic alternative diseases; however, experimental evidence needed support confirm benefits. Hence, review aims highlight potential benefits regulating pathways approach combating

Language: Английский

Citations

3
Analysis of Sigma-1 Receptor Antagonist BD1047 Effect on Upregulating Proteins in HIV-1-Infected Macrophages Exposed to Cocaine Using Quantitative Proteomics DOI Creative Commons
Omar Vélez-López, Kelvin Carrasquillo, Yadira M. Cantres-Rosario

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(9), P. 1934 - 1934

Published: Aug. 23, 2024

HIV-1 infects monocyte-derived macrophages (MDM) that migrate into the brain and secrete virus neurotoxic molecules, including cathepsin B (CATB), causing cognitive dysfunction. Cocaine potentiates CATB secretion neurotoxicity in HIV-infected MDM. Pretreatment with BD1047, a sigma-1 receptor antagonist, before cocaine exposure reduces HIV-1, secretion, neuronal apoptosis. We aimed to elucidate intracellular pathways modulated by BD1047 MDM exposed cocaine. hypothesized Sig1R antagonist prior cocaine, significantly deregulates proteins involved replication lead neurotoxicity. culture lysates from HIV-1-infected women treated were compared untreated controls using TMT quantitative proteomics, bioinformatics, Lima statistics, pathway analyses. Results demonstrate pretreatment dysregulated eighty (80) when infected group. found fifteen (15) related infection, CATB, mitochondrial function. Upregulated oxidative phosphorylation (SLC25A-31), mitochondria (ATP5PD), ion transport (VDAC2-3), endoplasmic reticulum (PHB, TMED10, CANX), cytoskeleton remodeling (TUB1A-C, ANXA1). treatment protects upregulating reduce damage, ER transport, exocytosis associated CATB-induced

Language: Английский

Citations

0
Reconstructing of the geometry of Atg13 and Atg101 molecules while assembling the complex DOI Open Access

Elijah Bulgakov,

Alexey Rayevsky

Faktori eksperimental noi evolucii organizmiv, Journal Year: 2024, Volume and Issue: 35, P. 146 - 150

Published: Sept. 25, 2024

Aim. Associated subproteins which constitute the ATG1 multi-protein complex in plants and mammals, including ULK1 humans, are orchestral protein kinase atg-units resistance to stress stimuli across their different nature. The goals of this endeavour were characterize molecular nature interaction ATG13 with ATG101, followed by silico docking catch plausible ensuing integration into a multimeric ULK1/ATG1, initiates assembly PAS-preautophagosomal structure first step autophagy initiation. Methods. Protein structures modeled homology using AlphaFold, dynamics (MD) was performed GROMACS 5.0 Charmm36. Results. By implementing computer modeling methods, for both ATG101 proteins, reflecting interface conformational properties, constructed detailed interpretation while forming forthcoming ULK1/ATG1 platform. Conclusions. This study provides high-quality model platform further sequential studies protein-protein interactions possibility reconstructing full identify ATG8 binding sites.

Language: Английский

Citations

0
Role of mitophagy in intervertebral disc degeneration: A narrative review DOI
Zuolong Wu, Yong Liu, Wei Song

et al.

Osteoarthritis and Cartilage, Journal Year: 2024, Volume and Issue: 33(1), P. 27 - 41

Published: Nov. 12, 2024

Language: Английский

Citations

0
Identification of the role of SNARE proteins in rAAV vector production through interaction with the viral membrane-associated accessory protein (MAAP) DOI Creative Commons
Çağla Aksu Küz, Kang Ning, Siyuan Hao

et al.

Molecular Therapy — Methods & Clinical Development, Journal Year: 2024, Volume and Issue: 33(1), P. 101392 - 101392

Published: Dec. 5, 2024

Adeno-associated virus (AAV) expresses a membrane-associated accessory protein (MAAP), small nonstructural protein, that facilitates AAV secretion out of the plasma membrane through an association with extracellular vesicles during egress. Here, we investigated host proteins interact AAV2 MAAP (MAAP2) using APEX2-mediated proximity labeling. We identified two SNARE proteins, Syntaxin 7 (STX7) and synaptosome-associated 23 (SNAP23), vesicle (v-)SNARE target (t-)SNARE, respectively, mediate intracellular trafficking aand exhibited associations MAAP2 in HEK293 cells. found indirectly interacted STX7 or SNAP23, knockout SNAP23 not only enhanced rAAV into media but also increased total vector yield production Thus, our study revealed practical approach for producing higher yields vectors from media, easing downstream processes manufacturing.

Language: Английский

Citations

0
Glucosinolates and Their Hydrolytic Derivatives: Promising Phytochemicals With Anticancer Potential DOI Open Access
Nataša Joković, Srdjan Pešić, Jelena Vitorović

et al.

Phytotherapy Research, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 27, 2024

Recent research has increasingly focused on phytochemicals as promising anticancer agents, with glucosinolates (GSLs) and their hydrolytic derivatives playing a central role. These sulfur-containing compounds, found in plants of the Brassicales order, are converted by myrosinase enzymes into biologically active products, primarily isothiocyanates (ITCs) indoles, which exhibit significant properties. Indole-3-carbinol, diindolylmethane, sulforaphane (SFN), phenethyl isothiocyanate (PEITC), benzyl isothiocyanate, allyl have shown potent effects animal models, particularly breast, prostate, lung, melanoma, bladder, hepatoma, gastrointestinal cancers. Clinical studies further support chemopreventive SFN PEITC, detoxifying carcinogens altering biochemical markers cancer patients. compounds demonstrated good bioavailability, low toxicity, minimal adverse effects, supporting potential therapeutic application. Their mechanisms include modulation reactive oxygen species, suppression cancer-related signaling pathways, direct interaction tumor cell proteins. Additionally, semi-synthetic GSLs been developed to enhance efficacy. In conclusion, offer both warranting clinical investigation optimize application treatment.

Language: Английский

Citations

0