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Keywords = gelatin zymography

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10 pages, 975 KiB  
Communication
Tryptophan Metabolite ITE Attenuates LPS-Induced MMP-9 via NF-κB/AP-1 in Monocytes
by Fatemah Bahman, Nadeem Akhter, Shihab Kochumon, Fahd Al-Mulla and Rasheed Ahmad
Int. J. Mol. Sci. 2025, 26(12), 5663; https://doi.org/10.3390/ijms26125663 - 13 Jun 2025
Viewed by 451
Abstract
Matrix metalloproteinase-9 (MMP-9) and lipopolysaccharide (LPS) levels are known to be elevated in obesity and contribute to metabolic dysfunction. 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), an endogenous ligand of the aryl hydrocarbon receptor (AhR), has been implicated in the regulation of inflammatory responses. This [...] Read more.
Matrix metalloproteinase-9 (MMP-9) and lipopolysaccharide (LPS) levels are known to be elevated in obesity and contribute to metabolic dysfunction. 2-(1′H-indole-3′-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE), an endogenous ligand of the aryl hydrocarbon receptor (AhR), has been implicated in the regulation of inflammatory responses. This study aimed to determine whether ITE can inhibit LPS-induced MMP-9 expression in monocytic cells and to explore the underlying signaling mechanisms involved. Human monocytic THP-1 cells and primary human monocytes were treated with LPS in the presence or absence of ITE. MMP-9 mRNA and protein levels were assessed using quantitative real-time PCR and ELISA, respectively, while gelatin zymography was employed to evaluate MMP-9 enzymatic activity. Chromatin immunoprecipitation followed by qPCR (ChIP-qPCR) was performed to assess NF-κB and AP-1 binding to the MMP-9 promoter region. Our findings demonstrate that ITE significantly suppresses LPS-induced MMP-9 gene and protein expression. This suppression is associated with a marked reduction in LPS-induced NF-κB and AP-1 transcriptional activity. ChIP-qPCR confirmed that ITE attenuates the recruitment of NF-κB and AP-1 to the MMP-9 promoter, thereby inhibiting its transcription. In summary, ITE downregulates LPS-induced MMP-9 expression by interfering with NF-κB/AP-1 signaling, suggesting a potential anti-inflammatory mechanism that could be relevant in the context of MMP-9-driven inflammatory conditions. Full article
(This article belongs to the Section Molecular Endocrinology and Metabolism)
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18 pages, 3138 KiB  
Article
Aspergillusidone G Exerts Anti-Neuroinflammatory Effects via Inhibiting MMP9 Through Integrated Bioinformatics and Experimental Analysis: Implications for Parkinson’s Disease Intervention
by Fangfang Ban, Longjian Zhou, Zhiyou Yang, Yayue Liu and Yi Zhang
Mar. Drugs 2025, 23(5), 181; https://doi.org/10.3390/md23050181 - 23 Apr 2025
Viewed by 724
Abstract
Natural products have extensive attractiveness as therapeutic agents due to their low toxicity and high efficiency. Our previous study has identified a depside-type Aspergillusidone G (Asp G) derived from Aspergillus unguis DLEP2008001, which shows excellent neuroprotective activity for 1-methyl-4-phenylpyridinium (MPP+)-induced primary [...] Read more.
Natural products have extensive attractiveness as therapeutic agents due to their low toxicity and high efficiency. Our previous study has identified a depside-type Aspergillusidone G (Asp G) derived from Aspergillus unguis DLEP2008001, which shows excellent neuroprotective activity for 1-methyl-4-phenylpyridinium (MPP+)-induced primary cortical neurons and anti-neuroinflammatory property, promising to be a potential therapeutic agent for Parkinson’s disease (PD). To further explore the anti-PD potential and mechanisms of Asp G, we employed network pharmacology, cellular experiments, and various biological techniques for analysis and validation. The analysis of network pharmacology suggested that Asp G’s anti-PD potential might be attributed to its modulation of inflammation. The data from nitric oxide (NO) detection, qRT-PCR, and Western blot confirmed that Asp G dose-dependently inhibited lipopolysaccharide (LPS)-stimulated NO production, with 40 μM Asp G suppressing 90.54% of the NO burst compared to the LPS group, and suppressed the overproduction of inflammatory-related factors in LPS-induced BV2 cells. Further protein–protein interaction analysis indicated that matrix metalloproteinase 9 (MMP9), a promising target for PD intervention, was the most likely anti-PD target of Asp G, and the results of gelatin zymography, qRT-PCR, and Western blot validated that Asp G could inhibit the active and inactive forms of MMP9 directly and indirectly, respectively. Notably, the inhibition of 67 kDa-MMP9 by Asp G is expected to compensate for the inability of TIMP-1 to inhibit this form. Furthermore, a selective inhibitor of MMP9 (20 μM SB-3CT) further potentiated the anti-inflammatory effects of Asp G (20 μM), with inhibition rate on NO increasing from 27.57% to 63.50% compared to LPS group. In summary, our study revealed that Asp G exerts anti-neuroinflammatory effects by inhibiting MMP9, which provides a valuable lead compound for the development of anti-neuroinflammatory drugs and offers insights into the intervention of PD-associated neuroinflammation. Future studies will further investigate the upstream regulatory mechanisms of Asp G-mediated MMP9 inhibition and its effects in in vivo PD models. Full article
(This article belongs to the Special Issue Chemoinformatics for Marine Drug Discovery)
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16 pages, 2140 KiB  
Article
Anticancer Activity of Melittin-Containing Bee Venom Fraction Against Glioblastoma Cells In Vitro
by Agata Małek, Maciej Strzemski, Lucyna Kapka-Skrzypczak and Jacek Kurzepa
Int. J. Mol. Sci. 2025, 26(6), 2376; https://doi.org/10.3390/ijms26062376 - 7 Mar 2025
Cited by 1 | Viewed by 2034
Abstract
Previous observations indicating a lower incidence of various types of cancer in beekeepers suggest that greater exposure to stings reduces the risk of cancer development. However, it is not known which of the active compounds of the bee venom (BV) may be responsible [...] Read more.
Previous observations indicating a lower incidence of various types of cancer in beekeepers suggest that greater exposure to stings reduces the risk of cancer development. However, it is not known which of the active compounds of the bee venom (BV) may be responsible for the observed properties. The aim of this study is to evaluate the anti-glioblastoma effect of the main BV fractions. In addition, the effect of BV fractions on the activity of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) was assessed. Commercially available BV was divided into three fractions containing one of the main BV components: apamin (fraction #1), phospholipase A2 (fraction #2), or melittin (fraction #3). The viability of glioblastoma lines (LN18 and LN229) compared to a physiological line (human MO3.13) was assessed using the MTT. MMP-2 and MMP-9 activity was assessed using gelatin zymography. Tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) levels in cell culture media were measured with the ELISA method. The fraction containing apamin did not show cytotoxic activity up to a concentration of 100 µg/mL. The fraction containing phospholipase A2 partially reduced the cells’ viability at a concentration of 100 µg/mL. The greatest activity was demonstrated by the melittin-containing fraction which completely reduced the viability of glioma cells from a concentration of 2.5 μg/mL and inhibited the activity of the assessed metalloproteinases in a dose-dependent manner. After 72 h of incubation, the highest concentrations of TIMP-1 and TIMP-2 (approximately 150 ng/mL and 100 ng/mL, respectively) were observed in the LN229 line. In all tested lines, fraction #3, crude BV, and melittin reduced the secretion of both inhibitors into the medium in a dose-dependent manner. The melittin-containing fraction possessed anti-glioma properties in vitro, suggesting that melittin may be the main anticancer compound of BV. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
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18 pages, 11491 KiB  
Article
Targeting MAPK Signaling: Loureirins A and B from Dracaena Loureiri Inhibit Epithelial–Mesenchymal Transition and Invasion in Non-Small Cell Lung Cancer Cell Lines
by Xiaomin Huang, Punnida Arjsri, Kamonwan Srisawad, Sonthaya Umsumarng, Supachai Yodkeeree and Pornngarm Dejkriengkraikul
Life 2025, 15(3), 396; https://doi.org/10.3390/life15030396 - 3 Mar 2025
Viewed by 972
Abstract
Metastasis remains the leading cause of death among patients with non-small cell lung cancer (NSCLC), emphasizing the urgent need for safer and more effective therapeutic options. Mitogen-activated protein kinase (MAPK) pathways play a crucial role in regulating EMT, migration, and invasion in NSCLC. [...] Read more.
Metastasis remains the leading cause of death among patients with non-small cell lung cancer (NSCLC), emphasizing the urgent need for safer and more effective therapeutic options. Mitogen-activated protein kinase (MAPK) pathways play a crucial role in regulating EMT, migration, and invasion in NSCLC. Targeting these molecular mechanisms has become a key strategy in inhibiting NSCLC metastasis. Loureirin A and Loureirin B, flavonoids derived from the Thai traditional herb Dracaena loureiri, have shown potential pharmacological effects; however, their roles in NSCLC metastasis remain unexplored. This study aimed to elucidate the mechanisms by which Loureirin A and Loureirin B suppress EMT, migration, and invasion in NSCLC cells via the MAPK signaling pathway. The sulforhodamine B (SRB) assay showed that Loureirin A and Loureirin B, at concentrations ranging from 0 to 140 μM, were non-toxic to both A549 and H1299 cells. Additionally, Loureirins A and B exhibited no cytotoxic effects on primary human dermal fibroblast cells and did not induce hemolysis in red blood cells (RBCs). The wound-healing and trans-well assays were used to evaluate the anti-migratory and anti-invasion properties of Loureirin A and Loureirin B in NSCLC cell lines. Gelatin zymography was employed to investigate the activity of MMP-2 (gelatinase A) and MMP-9 (gelatinase B), while Western blot analysis was used to examine the expression of EMT markers and invasive proteins, and the phosphorylation of MAPK signaling molecules. Our results demonstrate that both Loureirin A and Loureirin B significantly suppressed the migration and invasion of A549 and H1299 cells. These compounds suppressed the activity of matrix metalloproteinases MMP-2 and MMP-9 and downregulated the expression of key invasive proteins including uPA, uPAR, and MT1-MMP. Additionally, they effectively suppressed the expression of EMT markers such as N-cadherin, Vimentin, and Fibronectin. Mechanistically, Loureirin A and Loureirin B inhibited the MAPK signaling pathway by downregulating the phosphorylation of ERK, JNK, and p38 proteins. In conclusion, these findings demonstrate that Loureirin A and Loureirin B exhibit potent anti-invasive properties and no cytotoxic effect on NSCLC cell lines, suggesting their potential as promising candidates for anti-cancer drug development. Furthermore, they may pave the way for the exploration of combination therapies with other anti-cancer drugs for clinical translation. Full article
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19 pages, 4942 KiB  
Article
The Therapeutic Potential of Kiwi Extract as a Source of Cysteine Protease Inhibitors on DNCB-Induced Atopic Dermatitis in Mice and Human Keratinocyte HaCaT Cells
by Hye Ryeon Yang, Most Nusrat Zahan, Du Hyeon Hwang, Ramachandran Loganathan Mohan Prakash, Deva Asirvatham Ravi, Il-Hwa Hong, Woo Hyun Kim, Jong-Hyun Kim, Euikyung Kim and Changkeun Kang
Int. J. Mol. Sci. 2025, 26(4), 1534; https://doi.org/10.3390/ijms26041534 - 12 Feb 2025
Viewed by 1174
Abstract
The discovery of effective cysteine protease inhibitors with crude protein kiwi extracts (CPKEs) has created novel challenges and prospects for pharmaceutical development. Despite extensive research on CPKEs, limited research has been conducted on treating atopic dermatitis (AD). Therefore, the objective of this work [...] Read more.
The discovery of effective cysteine protease inhibitors with crude protein kiwi extracts (CPKEs) has created novel challenges and prospects for pharmaceutical development. Despite extensive research on CPKEs, limited research has been conducted on treating atopic dermatitis (AD). Therefore, the objective of this work was to investigate the anti-inflammatory effects of CPKEs on TNF-α activation in a HaCaT cell model and in a DNCB (1-chloro-2, 4-dinitrochlorobenzene)-induced atopic dermatitis animal model. The molecular weight of the CPKE was determined using SDS-PAGE under non-reducing (17 kDa and 22 kDa) and reducing conditions (25 kDa, 22 kDa, and 15 kDa), whereas gelatin zymography was performed to examine the CPKE’s inhibitory impact on cysteine protease (actinidin and papain) activity. Moreover, the CPKE remains stable at 60 °C, with pH levels varying from 4 to 11, as determined by the azocasein assay. CPKE treatment decreased the phosphorylation of mitogen-activated protein kinase (MAPK) and Akt, along with the activation of nuclear factor-kappa B (NF-κB)-p65 in tumor necrosis factor-α (TNF-α)-stimulated HaCaT cells. Five-week-old BALB/c mice were treated with DNCB to act as an AD-like animal model. The topical application of CPKE to DNCB-treated mice for three weeks substantially decreased clinical dermatitis severity and epidermal thickness and reduced eosinophil infiltration and mast cells into ear and skin tissues. These findings imply that CPKE derived from kiwifruit might be a promising therapy option for inflammatory skin diseases such as AD. Full article
(This article belongs to the Special Issue Mast Cells in Human Health and Diseases—3rd Edition)
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15 pages, 2017 KiB  
Article
Cannabinoid-2 Receptor Activation Attenuates Sulfur Mustard Analog 2-Chloroethyl-Ethyl-Sulfide-Induced Acute Lung Injury in Mice
by Gregory Nicholson, Nicholas Richards, Janette Lockett, My Boi Ly, Raj V. Nair, Woong-Ki Kim, K. Yaragudri Vinod and Nagaraja Nagre
Pharmaceuticals 2025, 18(2), 236; https://doi.org/10.3390/ph18020236 - 10 Feb 2025
Viewed by 1191
Abstract
Background: Exposure to sulfur mustard (SM; 2,2′-dichlorodiethyl sulfide) causes toxicity in the human body, particularly the lungs. The molecular mechanisms of SM-induced lung damage are elusive, and no effective treatments exist. This study explores the anti-inflammatory potential of cannabinoid receptor 2 (CB2R) activation [...] Read more.
Background: Exposure to sulfur mustard (SM; 2,2′-dichlorodiethyl sulfide) causes toxicity in the human body, particularly the lungs. The molecular mechanisms of SM-induced lung damage are elusive, and no effective treatments exist. This study explores the anti-inflammatory potential of cannabinoid receptor 2 (CB2R) activation in mitigating acute lung injury (ALI) and inflammation induced by 2-chloroethyl ethyl sulfide (CEES), a structural analog of SM. Methods: C57BL/6J mice were exposed to CEES via intratracheal administration to model ALI. CB2R activation was achieved through the intraperitoneal administration of HU308, a selective synthetic agonist. ALI and inflammation were evaluated at 48 h post-exposure to CEES. Bronchoalveolar lavage fluid (BALF) was collected to measure total cells, protein, and cytokines. Lung injury, inflammatory signaling in alveolar macrophages (AMs), and matrix metalloproteinase-9 (MMP-9) activity were assessed via histological analysis, immunoblotting, and gelatin zymography, respectively. Results: CEES exposure led to an increase in immune cell infiltration, pro-inflammatory cytokines (IL-6 and TNF-α), and pro-MMP9 levels in the BALF, which were significantly decreased by HU308 treatment. The activation of CB2R attenuated CEES-induced NF-κB activation and reduced pro-inflammatory M1 markers (iNOS, and Cox-2) but did not alter the increase in the M2 marker arginase-1. CB2R activation mitigated CEES-induced oxidative stress, as evidenced by lower levels of heme oxygenase-1 (HO-1) and reactive oxygen species (ROS) in mouse AMs. Additionally, 4-hydroxynonenal (4-HNE) levels were reduced in the lungs of HU308-treated mice but were elevated after CEES exposure. Conclusions: These findings suggest that CB2R activation alleviates CEES-induced ALI and inflammation in mice, supporting its potential as a therapeutic approach for vesicant-induced pulmonary injury. Full article
(This article belongs to the Special Issue Innovative Applications and Therapeutic Potential of Cannabinoids)
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13 pages, 2365 KiB  
Article
Irisin and Metastatic Melanoma: Selective Anti-Invasiveness Activity in BRAF Wild-Type Cells
by Simona Serratì, Roberta Zerlotin, Michele Manganelli, Roberta Di Fonte, Manuela Dicarlo, Angela Oranger, Graziana Colaianni, Letizia Porcelli, Amalia Azzariti, Stefania Guida, Maria Grano, Silvia Concetta Colucci and Gabriella Guida
Int. J. Mol. Sci. 2025, 26(2), 652; https://doi.org/10.3390/ijms26020652 - 14 Jan 2025
Viewed by 1273
Abstract
Irisin is a newly discovered 12 kDa messenger protein involved in energy metabolism. Irisin affects signaling pathways in several types of cancer; however, the role of irisin in metastatic melanoma (MM) has not been described yet. We explored the biological effects of irisin [...] Read more.
Irisin is a newly discovered 12 kDa messenger protein involved in energy metabolism. Irisin affects signaling pathways in several types of cancer; however, the role of irisin in metastatic melanoma (MM) has not been described yet. We explored the biological effects of irisin in in vitro models of MM cells (HBLwt/wt, LND1wt/wt, Hmel1V600K/wt and M3V600E/V600E) capable of the oncogenic activation of BRAF. We treated MM cells with different concentrations of r-irisin (10 nM, 25 nM, 50 nM, 100 nM) for 24 h–48 h. An MTT assay highlighted that r-irisin did not affect the proliferation of MM cells. We subsequently treated MM cells with 10 nM r-irisin, corresponding to the dose exhibiting biological activity in vitro. Irisin reduced the invasive ability of only LND1wt/wt (p < 0.05), which highly expressed αv gene levels, but did not affect the invasion of BRAFmut cells. Gelatin zymography analysis showed a reduction in the enzymatic activity of MMP-2 and MMP-9 in BRAFwt/wt cells treated with 10 nM r-irisin. Moreover, gene expression analysis (qPCR) of MMP-2 and MMP-9 and of the fibrinolytic system (uPAR, uPA and PAI-1) highlighted a crucial role of 10 nM r-irisin treatment in the inhibition of pro-invasive systems in BRAFwt/wt. In conclusion, our results may suggest a possible differential role of irisin in melanoma cells. Full article
(This article belongs to the Special Issue Skin Diseases: From Molecular Mechanisms to Pathology)
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20 pages, 6959 KiB  
Article
Dissecting Cytophagalysin: Structural and Biochemical Studies of a Bacterial Pappalysin-Family Metallopeptidase
by Eva Estevan-Morió, Juan Sebastián Ramírez-Larrota, Enkela Bushi and Ulrich Eckhard
Biomolecules 2024, 14(12), 1604; https://doi.org/10.3390/biom14121604 - 16 Dec 2024
Viewed by 1230
Abstract
Cytophaga is a genus of Gram-negative bacteria occurring in soil and the gut microbiome. It is closely related to pathogenic Flavobacterium spp. that cause severe diseases in fish. Cytophaga strain L43-1 secretes cytophagalysin (CPL1), a 137 kDa peptidase with reported collagenolytic and gelatinolytic [...] Read more.
Cytophaga is a genus of Gram-negative bacteria occurring in soil and the gut microbiome. It is closely related to pathogenic Flavobacterium spp. that cause severe diseases in fish. Cytophaga strain L43-1 secretes cytophagalysin (CPL1), a 137 kDa peptidase with reported collagenolytic and gelatinolytic activity. We performed highly-confident structure prediction calculations for CPL1, which identified 11 segments and domains, including a signal peptide for secretion, a prosegment (PS) for latency, a metallopeptidase (MP)-like catalytic domain (CD), and eight immunoglobulin (Ig)-like domains (D3–D10). In addition, two short linkers were found at the D8–D9 and D9–D10 junctions, and the structure would be crosslinked by four disulfide bonds. The CPL1 CD was found closest to ulilysin from Methanosarcina acetivorans, which assigns CPL1 to the lower-pappalysin family within the metzincin clan of MPs. Based on the structure predictions, we aimed to produce constructs spanning the full-length enzyme, as well as PS+CD, PS+CD+D3, and PS+CD+D3+D4. However, we were successful only with the latter three constructs. We could activate recombinant CPL1 by PS removal employing trypsin, and found that both zymogen and mature CPL1 were active in gelatin zymography and against a fluorogenic gelatin variant. This activity was ablated in a mutant, in which the catalytic glutamate described for lower pappalyins and other metzincins was replaced by alanine, and by a broad-spectrum metal chelator. Overall, these results proved that our recombinant CPL1 is a functional active MP, thus supporting the conclusions derived from the structure predictions. Full article
(This article belongs to the Collection Feature Papers in 'Biomacromolecules: Proteins')
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12 pages, 8840 KiB  
Article
Mycobacteria Treatment Inhibits Bladder Cancer Cell Migration, Invasion, and Anchorage-Independent Growth
by Marc Bach-Griera, Alba Hernández and Esther Julián
Int. J. Mol. Sci. 2024, 25(23), 12997; https://doi.org/10.3390/ijms252312997 - 3 Dec 2024
Viewed by 1220
Abstract
Bladder cancer (BC) is a highly recurrent and invasive malignancy, with Mycobacterium bovis BCG serving as the primary immunotherapy, particularly for non-muscle-invasive bladder cancer (NMIBC). However, the mechanisms underlying BCG’s antitumor effects and the potential of non-tuberculous mycobacteria like Mycobacterium brumae remain unclear. [...] Read more.
Bladder cancer (BC) is a highly recurrent and invasive malignancy, with Mycobacterium bovis BCG serving as the primary immunotherapy, particularly for non-muscle-invasive bladder cancer (NMIBC). However, the mechanisms underlying BCG’s antitumor effects and the potential of non-tuberculous mycobacteria like Mycobacterium brumae remain unclear. This study investigates the antitumor effects of M. bovis BCG and M. brumae on BC cell migration, invasion, and anchorage-independent growth. BC cell lines representing different stages of tumor differentiation were treated with either M. bovis BCG or M. brumae. Cell migration was assessed through wound healing and transwell assays, invasiveness by transwell invasion assays, MMP-9 production by gelatin zymography, and anchorage-independent growth via soft agar colony formation. Both mycobacteria inhibited individual cell migration across all BC lines, while collective migration was only reduced in intermediate-grade cells. Both treatments also reduced invasiveness, associated with decreased MMP-9 production. Furthermore, M. brumae inhibited anchorage-independent growth across all BC lines, while M. bovis BCG had a more selective effect, primarily inhibiting growth in high-grade cells. In conclusion, both mycobacteria reduce migration, invasion, and anchorage-independent growth of BC cells, with their effectiveness varying by species and tumor differentiation grade. Full article
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17 pages, 2834 KiB  
Article
The Anti-Metastatic Potential of Aronia Leaf Extracts on Colon Cancer Cells
by Katarzyna Owczarek, Miłosz Caban, Dorota Sosnowska, Dominika Kajszczak and Urszula Lewandowska
Nutrients 2024, 16(23), 4110; https://doi.org/10.3390/nu16234110 - 28 Nov 2024
Cited by 1 | Viewed by 2082
Abstract
Background/Objectives: Numerous studies have demonstrated the health benefits of polyphenols found in aronia fruits; however, little is known about how aronia leaf polyphenols impact colorectal cancer (CRC). This study aimed to evaluate the in vitro anti-metastatic and anti-invasive activity of crude aronia leaf [...] Read more.
Background/Objectives: Numerous studies have demonstrated the health benefits of polyphenols found in aronia fruits; however, little is known about how aronia leaf polyphenols impact colorectal cancer (CRC). This study aimed to evaluate the in vitro anti-metastatic and anti-invasive activity of crude aronia leaf extract (ACE) and purified phenolic-rich aronia leaf extract (APE) against two CRC cell lines (SW-480 and HT-29). Methods: Migration and invasion potential of ACE and APE were evaluated. Moreover, ELISA and gelatin zymography were performed to detect translational and activity changes in CRC cells after aronia extracts treatment. Results: We found that a 100 µg/mL concentration of ACE and APE almost entirely downregulated the migration and invasion of SW-480 cells, showing greater effectiveness than HT-29 cells. The observed inhibition was concentration-dependent and statistically significant. Additionally, extracts reduced the product of MMP-2 and MMP-9 gene expression at the protein level and simultaneously inhibited the activity of both MMPs. An APE at 300 µg/mL for SW-480 and 600 µg/mL for HT-29 resulted in a notable reduction in MMP-2 protein synthesis by 72% and 50%, respectively. In contrast, MMP-9 protein synthesis decreased by 48% and 59% in HT-29 cells treated with 300 µg/mL and 600 µg/mL of ACE, respectively. The levels of gelatinase activity were similar for both CRC lines, and the APE tested at a concentration of 300 µg/mL reached almost the IC50 value after 48 h of incubation. Conclusions: Based on the presented results, we provided an experimental foundation for future in vitro and in vivo studies on the potential effects and activities of aronia leaves. Full article
(This article belongs to the Section Phytochemicals and Human Health)
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17 pages, 1529 KiB  
Article
Exploring the Bioactive Potential of Taraxacum officinale F.H. Wigg Aerial Parts on MDA Breast Cancer Cells: Insights into Phytochemical Composition, Antioxidant Efficacy, and Gelatinase Inhibition within 3D Cellular Models
by Valentina Laghezza Masci, Elisa Ovidi, William Tomassi, Daniela De Vita and Stefania Garzoli
Plants 2024, 13(19), 2829; https://doi.org/10.3390/plants13192829 - 9 Oct 2024
Viewed by 2189
Abstract
In this work, aerial parts of Taraxacum officinale F.H. Wigg. produced in Umbria, Italy, were chemically investigated by solid-phase microextraction/gas chromatography–mass spectrometry (SPME/GC-MS) to describe their volatile profile. The results obtained showed the preponderant presence of monoterpenes, with limonene and 1,8-cineole as the [...] Read more.
In this work, aerial parts of Taraxacum officinale F.H. Wigg. produced in Umbria, Italy, were chemically investigated by solid-phase microextraction/gas chromatography–mass spectrometry (SPME/GC-MS) to describe their volatile profile. The results obtained showed the preponderant presence of monoterpenes, with limonene and 1,8-cineole as the main components. Further analyses by GC/MS after derivatization reaction were performed to characterize the non-volatile fraction highlighting the presence of fatty acids and di- and triterpenic compounds. T. officinale methanol and dichloromethane extracts, first analyzed by HRGC/MS, were investigated to evaluate the antioxidant activity, cytotoxicity, and antiproliferative properties of MDA cells on the breast cancer cell line and MCF 10A normal epithelial cells as well as the antioxidant activity by colorimetric assays. The impact on matrix metalloproteinases MMP-9 and MMP-2 was also explored in 3D cell systems to investigate the extracts’ efficacy in reducing cell invasiveness. The extracts tested showed no cytotoxic activity with EC50 > 250 µg/mL on both cell lines. The DPPH assay revealed higher antioxidant activity in the MeOH extract compared with the DCM extract, while the FRAP assay showed a contrasting result, with the DCM extract exhibiting slightly greater antioxidant capacity. After treatment for 24 h with a non-cytotoxic concentration of 500 µg/mL of the tested extracts, gelatin zymography and Western blot analyses demonstrated that both MeOH and DCM extracts influenced the expression of MMP-9 and MMP-2 in MDA cells within the 3D cell model, leading to a significant decrease in the levels of these gelatinases, which are crucial markers of tumor invasiveness. Full article
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16 pages, 3269 KiB  
Article
Galectin-8 Contributes to Human Trophoblast Cell Invasion
by Janko Legner, Milica Jovanović Krivokuća, Aleksandra Vilotić, Andrea Pirković, Mirjana Nacka-Aleksić and Žanka Bojić-Trbojević
Int. J. Mol. Sci. 2024, 25(18), 10096; https://doi.org/10.3390/ijms251810096 - 20 Sep 2024
Cited by 2 | Viewed by 1735
Abstract
Galectins are a class of lectins that are extensively expressed in all organisms. Galectins are involved in a range of functions, including early development, tissue regeneration, cancer and inflammation. It has been shown that galectin-8 is expressed in the villous and extravillous trophoblast [...] Read more.
Galectins are a class of lectins that are extensively expressed in all organisms. Galectins are involved in a range of functions, including early development, tissue regeneration, cancer and inflammation. It has been shown that galectin-8 is expressed in the villous and extravillous trophoblast (EVT) cells of the human placenta; however, its physiological role in pregnancy establishment has not been elucidated. Taking these factors into account, we investigated the functional role of galectin-8 in HTR-8/SVneo cells—a human EVT cell line—and human primary cytotrophoblast cells isolated from a first-trimester placenta. We analyzed the effects of recombinant human galectin-8 (rh galectin-8) on the adhesion, migration and invasion of HTR-8/SVneo cells. We used qPCR, cell-based ELISA (cELISA) and gelatin zymography to study the effects of galectin-8 on mediators of these processes, such as integrin subunits alpha-1 and beta-1 and matrix metalloproteinases (MMPs)-2 and -9, on the mRNA and protein levels. Further, we studied the effects of galectin-8 on primary cytotrophoblast cells’ invasion. Galectin-8 stimulated the adhesion, migration and invasion of HTR-8/SVneo cells, as well as the invasion of primary cytotrophoblasts. In addition, the MMP-2 and -9 levels were increased, while the expression of integrins alpha-1 and beta-1 was not affected. Galectin-8 has the ability to positively affect EVTs’ invasion, so it can be considered a significant factor in the trophoblast cell invasion process. Full article
(This article belongs to the Special Issue Galectins (Gals))
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10 pages, 1223 KiB  
Article
Zinc Iodide Dimethyl Sulfoxide Reduces Collagen Deposition by Increased Matrix Metalloproteinase-2 Expression and Activity in Lung Fibroblasts
by Michael Roth, Bo Han, Chong Teck S’ng, Ba Xuan Hoang and Christopher Lambers
Biomedicines 2024, 12(6), 1257; https://doi.org/10.3390/biomedicines12061257 - 5 Jun 2024
Cited by 1 | Viewed by 3101
Abstract
Chronic inflammatory lung diseases are characterized by disease-specific extracellular matrix accumulation resulting from an imbalance of matrix metalloproteinases (MMPs) and their inhibitors. Zinc is essential for the function of MMPs, and zinc deficiency has been associated with enhanced tissue remodeling. This study assessed [...] Read more.
Chronic inflammatory lung diseases are characterized by disease-specific extracellular matrix accumulation resulting from an imbalance of matrix metalloproteinases (MMPs) and their inhibitors. Zinc is essential for the function of MMPs, and zinc deficiency has been associated with enhanced tissue remodeling. This study assessed if zinc iodide (ZnI) supplementation through dimethyl sulfoxide (DMSO) modifies the action of MMPs in isolated human lung fibroblasts. The expression and activity of two gelatinases, MMP-2 and MMP-9, were determined by gelatin zymography and enzyme-linked immuno-sorbent assay (ELISA). Collagen degradation was determined by cell-based ELISAs. Collagen type I and fibronectin deposition was stimulated by human recombinant tumor growth factor β1 (TGF-β1). Untreated fibroblasts secreted MMP-2 but only minute amounts of MMP-9. TGF-β1 (5 ng/mL) reduced MMP-2 secretion, but stimulated collagen type I and fibronectin deposition. All the effects of TGF-β1 were significantly reduced in cells treated with ZnI-DMSO over 24 h, while ZnI and DMSO alone had a lower reducing effect. ZnI-DMSO alone did not increase MMP secretion but enhanced the ratio of active to inactive of MMP-2. ZnI alone had a lower enhancing effect than ZnI-DMSO on MMP activity. Furthermore, MMP-2 activity was increased by ZnI-DMSO and ZnI in the absence of cells. Soluble collagen type I increased in the medium of ZnI-DMSO- and ZnI-treated cells. Blocking MMP activity counteracted all the effects of ZnI-DMSO. Conclusion: The data suggest that the combination of ZnI with DMSO reduces fibrotic processes by increasing the degradation of collagen type I by up-regulating the activity of gelatinases. Thus, the combination of ZnI with DMSO might be considered for treatment of fibrotic disorders of the lung. DMSO supported the beneficial effects of ZnI. Full article
(This article belongs to the Section Drug Discovery, Development and Delivery)
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14 pages, 2998 KiB  
Article
Exploration of the Molecular Mechanism by Which Caveolin-1 Regulates Changes in Blood–Brain Barrier Permeability Leading to Eosinophilic Meningoencephalitis
by An-Chih Chen, Shih-Chan Lai, Cheng-You Lu and Ke-Min Chen
Trop. Med. Infect. Dis. 2024, 9(6), 124; https://doi.org/10.3390/tropicalmed9060124 - 24 May 2024
Cited by 1 | Viewed by 1947
Abstract
Angiostrongylus cantonensis, a zoonotic parasite, can invade the human central nervous system (CNS) and cause acute eosinophilic meningitis or eosinophilic meningoencephalitis. Mice infected with A. cantonensis show elevated levels of pro-inflammatory cytokines, plasminogen activators, and matrix metalloproteinase-9, resulting in disruption of the [...] Read more.
Angiostrongylus cantonensis, a zoonotic parasite, can invade the human central nervous system (CNS) and cause acute eosinophilic meningitis or eosinophilic meningoencephalitis. Mice infected with A. cantonensis show elevated levels of pro-inflammatory cytokines, plasminogen activators, and matrix metalloproteinase-9, resulting in disruption of the blood–brain barrier (BBB) and immune cell infiltration into the CNS. Caveolin-1 (Cav-1) regulates the permeability of the BBB, which affects immune cells and cerebrospinal fluid. This intricate interaction ultimately fuels the progression of brain damage and edema. This study aims to investigate the regulatory role of Cav-1 in the pathogenesis of meningoencephalitis induced by A. cantonensis infection. We investigated pathological alterations by triphenyl-tetrazolium chloride, brain water content, BBB permeability, Western blot analysis, and gelatin zymography in BALB/c mice after A. cantonensis. The study evaluates the critical role of Cav-1 regulation through the TLR4/MyD88 signaling pathway, modulates tight junction proteins, influences BBB permeability, and contributes to brain damage in A. cantonensis-induced meningoencephalitis. Full article
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19 pages, 6977 KiB  
Article
Deflamin Attenuated Lung Tissue Damage in an Ozone-Induced COPD Murine Model by Regulating MMP-9 Catalytic Activity
by Elia Ana Baltazar-García, Belinda Vargas-Guerrero, Ana Lima, Ricardo Boavida Ferreira, María Luisa Mendoza-Magaña, Mario Alberto Ramírez-Herrera, Tonatiuh Abimael Baltazar-Díaz, José Alfredo Domínguez-Rosales, Adriana María Salazar-Montes and Carmen Magdalena Gurrola-Díaz
Int. J. Mol. Sci. 2024, 25(10), 5063; https://doi.org/10.3390/ijms25105063 - 7 May 2024
Cited by 4 | Viewed by 1806
Abstract
Chronic obstructive pulmonary disease (COPD) is comprised of histopathological alterations such as pulmonary emphysema and peribronchial fibrosis. Matrix metalloproteinase 9 (MMP-9) is one of the key enzymes involved in both types of tissue remodeling during the development of lung damage. In recent studies, [...] Read more.
Chronic obstructive pulmonary disease (COPD) is comprised of histopathological alterations such as pulmonary emphysema and peribronchial fibrosis. Matrix metalloproteinase 9 (MMP-9) is one of the key enzymes involved in both types of tissue remodeling during the development of lung damage. In recent studies, it was demonstrated that deflamin, a protein component extracted from Lupinus albus, markedly inhibits the catalytic activity of MMP-9 in experimental models of colon adenocarcinoma and ulcerative colitis. Therefore, in the present study, we investigated for the first time the biological effect of deflamin in a murine COPD model induced by chronic exposure to ozone. Ozone exposure was carried out in C57BL/6 mice twice a week for six weeks for 3 h each time, and the treated group was orally administered deflamin (20 mg/kg body weight) after each ozone exposure. The histological results showed that deflamin attenuated pulmonary emphysema and peribronchial fibrosis, as evidenced by H&E and Masson’s trichrome staining. Furthermore, deflamin administration significantly decreased MMP-9 activity, as assessed by fluorogenic substrate assay and gelatin zymography. Interestingly, bioinformatic analysis reveals a plausible interaction between deflamin and MMP-9. Collectively, our findings demonstrate the therapeutic potential of deflamin in a COPD murine model, and suggest that the attenuation of the development of lung tissue damage occurs by deflamin-regulated MMP-9 catalytic activity. Full article
(This article belongs to the Special Issue Natural Compounds in Health and Disease)
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