CASQ2 alleviates lung cancer by inhibiting M2 tumor‐associated macrophage polarization and JAK/STAT pathway DOI
Yan Ding, Xiaoliang Yuan, Ying Wang

et al.

Journal of Biochemical and Molecular Toxicology, Journal Year: 2024, Volume and Issue: 38(8)

Published: Aug. 1, 2024

Lung cancer (LC) is a major inducer of cancer-related death. We aim to reveal the effect Calsequestrin2 (CASQ2) on macrophage polarization and Janus kinase/signal transducer activator transcription (JAK/STAT) pathway in LC. Hub genes were determined from protein-protein interaction networks based GSE21933 GSE1987 data sets using bioinformatic analysis. Expression hub was verified by real-time quantitative polymerase chain reaction (RT-qPCR). Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, wound-healing, colony formation, transwell assays performed assess impact CASQ2 LC cells. A xenograft mouse model evaluated hematoxylin-eosin, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining investigate The role regulating JAK/STAT western blot andRT-qPCR. screened out 155 common differentially expressed sets. Myomesin-2, tyrosine kinase, sex determining region Y-box 2, platelet endothelial cell adhesion molecule 1, matrix metallopeptidase 9, claudin-5, caveolin-1, CASQ2, recombinant ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 (ATP2A2), ankyrin repeat domain 1 identified as with high prediction value. selected pivotal regulator In vitro experiments models revealed that overexpression suppressed proliferation, migration, invasion cells, tumor growth vivo. Additionally, promoted expression M1 markers (cluster differentiation 80 [CD80], interleukin [IL]-12, inducible nitric oxide synthase [iNOS]), while decreasing M2 (CD163, IL-10, Arg1) tumor-associated macrophages tissues. Finally, we found inhibited pathway. novel biomarker, which can alleviate via inhibiting

Language: Английский

Similarities and differences between brain and skin GNAQ p.R183Q driven capillary malformations DOI
Sana Nasim, Colette A. Bichsel, Anna Pinto

et al.

Angiogenesis, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 29, 2024

Language: Английский

Citations

4
Oroxylin A Attenuates Homocysteine-Induced Blood–Brain Barrier (BBB) Dysfunction by Reducing Endothelial Permeability and Activating the CREB/Claudin-5 Signaling Pathway DOI

Yilu Bao,

Baiyang Sheng,

Ping Lv

et al.

ACS Chemical Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

Recent reports have indicated that elevated levels of homocysteine (Hcy) are closely linked to blood-brain barrier (BBB) dysfunction in neurological disorders. Oroxylin A (OA) is a key bioactive flavonoid has been reported regulate brain functions. However, the role OA Hcy-related BBB less reported. In this study, we aimed elucidate and molecular mechanism Hcy-mediated using both vivo vitro investigations. Our findings indicate expression tight junction (TJ) protein Claudin-5 declined, diffusion sodium fluorescein brains Hcy-challenged mice. These effects were notably rescued by administration OA. bEnd.3 microvascular endothelial cells, increased permeability, reduced trans-endothelial electrical resistance (TEER), downregulated observed. significantly reversed 25 50 μM Interestingly, treatment restored dephosphorylation CREB at Ser133 induced Hcy. addition kinase A/cAMP-response element binding (PKA/CREB) inhibitor H89 counteracted protective on inhibiting permeability promoting expression. Together, demonstrate protects against Hcy-induced maintaining integrity barriers. This effect achieved through activation CREB/Claudin-5 signaling pathway, highlighting potential therapeutic value addressing BBB-related

Language: Английский

Citations

0
Claudins as diagnostic tools and therapeutic targets—Glimpse of the horizon DOI Creative Commons
Keiji Sugiyama, Ian Chau

Cancer Treatment Reviews, Journal Year: 2025, Volume and Issue: 133, P. 102888 - 102888

Published: Jan. 17, 2025

Language: Английский

Citations

0
Catechin-Based Polyphenol Nanoparticles Ameliorated Ferroptosis to Alleviate Brain Injury after Intracerebral Hemorrhage DOI
Yu Zeng, Jian Li,

Zhuo Kong

et al.

ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Spontaneous intracerebral hemorrhagic stroke (ICH) is a highly aggressive disease, with high incidence and mortality rate. Iron deposition following ICH leads to oxidative damage motor dysfunction, significantly impacting the overall quality of life for those affected. Here, polyphenolic nanomedicine, catechin-based polyphenol nanoparticles surface-modified by thiol-terminated poly(ethylene glycol) (CNPs@PEG), was developed through polymerization self-assembly catechin, natural compound in tea. Due its potent antioxidant metal-chelating properties, CNPs@PEG effectively maintained blood-brain barrier integrity, reduced brain edema, increased survival rate mice cerebral hemorrhage markedly improved neurological deficits after ICH. Mechanistically, accomplishes this chelating iron, enhancing tissue capacity, reducing stress, inhibiting iron deposition. This approach holds promise as targeted therapeutic strategy addressing other conditions associated overload.

Language: Английский

Citations

0
Clinical and laboratory significance of soluble claudin-5 and VEGF in ovarian cancer DOI Creative Commons
Н. Е. Кушлинский,

S. Kulikova,

Frol A. Gugnin

et al.

Advances in molecular oncology, Journal Year: 2025, Volume and Issue: 12(1), P. 67 - 75

Published: April 15, 2025

Introduction. Claudin 5 is belongs to a family of transmembrane proteins mediating formation tight junctions between cells, maintenance cell polarity in epithelial and endothelial layers, regulation membrane permeability, control signal transduction inside the cells. Results small number studies show that vascular growth factor (VEGF) also affects junctions, particular through claudin expression. In addition their physiological functions, VEGF play an important role pathogenesis various diseases including malignant neoplasms. Aim. To study levels serum patients with ovarian cancer evaluate clinical significance. Materials methods. total, 123 (median age 54 years) 32 group healthy women were examined. measured prior treatment using Human CLDN5 (Claudin 5) ELISA Kit (Elabscience, China) Immunoassay (Quantikine®, R&D Systems, uSA) accordance manufacturer’s instructions. Statistical analysis obtained data was performed GraphPad Prizm v. 10 software. The values compared correlations quantified nonparametric Mann–Whitney, Kruskal–Wallis tests Spearman’s rank correlation coefficient. Overall survival analyzed Kaplan–Meier method. Results. found 97 % 94 women. Median (1st quartile (Q1) – 3rd (Q3)) level 0.77 (0.48–1.17) ng/mL, 0.95 (0.43–1.77) mg/mL. ROC informational value showed unsatisfactory diagnostic accuracy model (area under curve (AuC) 0.613 (95 confidence interval (CI) 0.513–0.713); p = 0.049): for median threshold ng/mL assay had sensitivity 50 specificity 60 %. all women; (Q1–Q3) 45.6 (13.3–89.09) pg/mL statistically significantly lower than cancer: 274.7 (199.0–472.5). good (AuC 0.942 CI 0.886–0.997); <0.0001) which allows use as criterion. best results (71 100 %, respectively) at 226.2 pg/mL. Serum are associated progression. However, not significant prognostic markers this disease. Conclusion. higher positively correlate each other. Additionally, has relatively characteristics group. presence distant metastases points potential tumor research stage, these cannot be recommended or criteria require further study.

Language: Английский

Citations

0
Recovery from Heart Failure is a Vascular Recovery DOI Open Access
Rajul Ranka,

Krishan Lal Gupta,

Felix Naegele

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 26, 2024

Abstract Heart failure (HF) remains a major cause of morbidity and mortality worldwide, with limited treatment options. transplantation is an end stage option but by donor availability. Left-ventricular assist device (LVAD) implantation serves as bridging strategy for patients awaiting transplant. Intriguingly, LVAD support (typically 6-12 months before heart transplantation) often associated some level improvement in cardiac function histology. In rare cases, can improve sufficiently to avoid after removal. The underlying mechanisms this are not understood. Here, we provide evidence that the post-LVAD reduction fibrosis increase capillary density. This recovery (HFR) also angiogenic cell fate transition. We observed distinct pro-angiogenic phenotype non-myocytes isolated from hearts. Single-nuclei RNA sequencing pre- tissue reveals fibroblast subtype undergoes mesenchymal endothelial transition (MEndoT), potentially facilitating HFR. murine model HFR, lineage tracing studies confirm MEndoT density perfusion during summary, our results new concept HFR interstitial fibrosis, perfusion, due part Our work represents shift conceptual framework regarding therapeutic avenue exploration.

Language: Английский

Citations

0
CASQ2 alleviates lung cancer by inhibiting M2 tumor‐associated macrophage polarization and JAK/STAT pathway DOI
Yan Ding, Xiaoliang Yuan, Ying Wang

et al.

Journal of Biochemical and Molecular Toxicology, Journal Year: 2024, Volume and Issue: 38(8)

Published: Aug. 1, 2024

Lung cancer (LC) is a major inducer of cancer-related death. We aim to reveal the effect Calsequestrin2 (CASQ2) on macrophage polarization and Janus kinase/signal transducer activator transcription (JAK/STAT) pathway in LC. Hub genes were determined from protein-protein interaction networks based GSE21933 GSE1987 data sets using bioinformatic analysis. Expression hub was verified by real-time quantitative polymerase chain reaction (RT-qPCR). Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, wound-healing, colony formation, transwell assays performed assess impact CASQ2 LC cells. A xenograft mouse model evaluated hematoxylin-eosin, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining investigate The role regulating JAK/STAT western blot andRT-qPCR. screened out 155 common differentially expressed sets. Myomesin-2, tyrosine kinase, sex determining region Y-box 2, platelet endothelial cell adhesion molecule 1, matrix metallopeptidase 9, claudin-5, caveolin-1, CASQ2, recombinant ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 (ATP2A2), ankyrin repeat domain 1 identified as with high prediction value. selected pivotal regulator In vitro experiments models revealed that overexpression suppressed proliferation, migration, invasion cells, tumor growth vivo. Additionally, promoted expression M1 markers (cluster differentiation 80 [CD80], interleukin [IL]-12, inducible nitric oxide synthase [iNOS]), while decreasing M2 (CD163, IL-10, Arg1) tumor-associated macrophages tissues. Finally, we found inhibited pathway. novel biomarker, which can alleviate via inhibiting

Language: Английский

Citations

0