Current Molecular Medicine - Volume 25, Issue 10, 2025

Oxidative damage and apoptosis of lens epithelial cells (LECs) are the primary factors contributing to the development of age-related cataracts (ARC). The potential protective effects of epigallocatechin gallate (EGCG) on LECs remain unclear despite its remarkable antioxidant and anti-apoptotic properties. The aim of this study was to explore the role of serine/threonine-protein kinase (PAK1) in EGCG-mediated attenuation of H2O2-induced apoptosis of LECs in vivo and in vitro.

PAK1 expression was assessed in the anterior capsule of the lens from mice and patients with and without ARC using western blotting and immuno-histochemistry. Human lens epithelial B3 (HLE-B3) cells were pre-treated with EGCG+H2O2 or H2O2 only, and PAK1 expression was determined using qRT-PCR and western blotting. Apoptosis (following PAK1 overexpression or silencing) and cell survival were assessed using Hoechst 33342 staining and a cell counting Kit-8 assay, respectively. Cleaved caspase-3 was measured in transected cells, aged/young mice, and mice treated with EGCG via western blotting.

PAK1 expression was significantly lower in ARC LECs than in control LECs. In HLE-B3 cells, EGCG+H2O2 treatment upregulated PAK1 mRNA and protein expression when compared with H2O2 alone. PAK1 overexpression alleviated H2O2-induced apoptosis in LECs, while low expression weakened EGCG’s protective effects. PAK1 overexpression reduced cleaved caspase-3 expression in H2O2-treated cells, whereas PAK1 silencing increased its expression in EGCG+H2O2-treated cells. EGCG decreased cleaved caspase-3 expression in H2O2-treated cells. These results suggest that PAK1 inhibits cleaved caspase-3 expression, thereby enhancing EGCG’s attenuation of H2O2-induced LEC apoptosis.

The PAK1/cleaved caspase-3 pathway plays a key role in EGCG’s protective effects on the development of ARC. This provides a new therapeutic target for the use of EGCG in preventing and treating ARC.

This study aims to investigate the unique proteins in exosomes from mesenchymal stem cells derived from psoriatic lesions and compare them with those from healthy human skin. It seeks to identify potential regulatory factors that may influence the differential effects observed in these exosomes.

Dermal mesenchymal stem cell exosomes were isolated from healthy human skin (HDMSCs-EXO) and psoriatic lesion of patient (PDMSCs-EXO). The extracted exosomes were analyzed through label-free quantitative proteomics to identify differential proteins. Bioinformatics analyses, including GO and KEGG enrichment, were conducted.

The comparative analysis using HDMSCs-EXO as a control group revealed 13 differential proteins. Notably, proteins such as B2R4D5, MFGE8, and MFAP5 are associated with the inflammatory mechanisms of psoriasis.

The study identifies several differentially expressed proteins in exosomes may play roles in the development of psoriasis. These finding offer valuable insights for further exploration of the inflammatory processes in psoriasis.

Keloid formation is characterized by excessive production of extracellular matrix, leading to dysregulated fibroproliferative collagen response. N6-methyl-adenosine (m6A) modification plays an essential role in this process.

Our objective in this study was to explore the mechanism of m6A methyltransferase KIAA1429 in keloid formation.

We examined the impact of m6A methyltransferase KIAA1429 on keloid formation using qRT-PCR, Western blot, immunofluorescence, Transwell migration assay, and MeRIP-qPCR.

KIAA1429 was downregulated in keloid tissue. Overexpression of KIAA1429 suppressed fibroblast migration and reduced COL1A1 and α-SMA levels. Conversely, the knockdown of KIAA1429 promoted fibroblast migration and COL1A1 and α-SMA levels. Additionally, overexpression of KIAA1429 inhibited the TGF-β1/Smad pathway. Mechanistic experiments suggested that KIAA1429 regulated TGF-β1 m6A modification, maintained TGF-β1 mRNA stability, and participated in the regulation of keloid formation. Furthermore, TGF-β1 could reverse the effects of KIAA1429 overexpression on fibroblast migration and collagen deposition.

Taken together, our study suggested that KIAA1429 promoted keloid formation through the TGF-β1/Smad pathway, providing new insights for the treatment of keloid.

This study aimed to examine the molecular mechanisms involved in transforming growth factor-β (TGF-β)-induced epithelial-mesenchymal transition (EMT) in human lung adenocarcinoma (LUAD) A549 cells.

Proteins were extracted from cultured human LUAD A549 cells cultured under two conditions: untreated and treated with TGF-β (5 ng/ml) for 48 hours. The expression levels of EMT-related proteins, including E-cadherin, Vimentin, and α-smooth muscle actin, were assessed using western blotting. Proteomic analysis was performed using isobaric tags for relative and absolute quantification combined with two-dimensional liquid chromatography-tandem mass spectrometry. Differentially expressed proteins were subjected to bioinformatics analysis, including functional annotation and interaction network studies.

A total of 122 proteins were identified as differentially expressed between the untreated and TGF-β-treated A549 cells. Of these, 55 proteins were upregulated, while 67 were downregulated following TGF-β treatment. Bioinformatics and interaction network analyses highlighted six proteins—GAPDH, TP53, MAPK1, IGF1, SRC, and MYC—as being closely associated with the EMT in human LUAD.

This study provides new insights into the processes of invasion and metastasis in LUAD by examining the molecular mechanisms underlying TGF-β-induced EMT in A549 cells.

Among Th lineages from naïve CD4+T cells, Th17 cells producing IL-17 are strongly related to the pathogenesis of neutrophilic asthma. Leptin is involved in inflammation and immunity. Little is known about MBD2's epigenetic regulation in CD4+T cell differentiation.

Our study is intended to delve into the mode by which MBD2 interacts with Leptin to govern Th17 cell differentiation.

CD4+T cells were harvested from the spleen tissue of C57BL/6 mice. Th17 cell differentiation was determined by flow cytometry, and ELISA measured IL-17. Western blot and RT-qPCR were employed to detect the expression of MBD2, Leptin and RORγt. CO-IP was utilized to assess the relationship between MBD2 and Leptin.

Under the overexpression or silencing of the MBD2 and Leptin genes, the differentiation of Th17 cells, IL-17 secretion, and RORγt expression all manifested positive changes. Leptin expression showed a positive variance upon overexpression or silencing of the MBD2 gene; however, there was no significant disparity in the expression of MBD2 under the overexpression or silencing of the Leptin gene. MBD2 can interact directly with Leptin.

MBD2 is capable of inducing the differentiation of naïve CD4+T cells into Th17 cells by augmenting the expression of Leptin.