This study aims to explore the effects of silencing Zic family member 5 (ZIC5) on glucose metabolism and disulfidptosis in lung adenocarcinoma (LUAD) cells.
Data from The Cancer Genome Atlas (TCGA) was used to analyze ZIC5 expression in LUAD and its association with patient outcomes. ZIC5 was silenced in A549 and H1299 cells using siRNA. The expression of ZIC5 mRNA and protein was assessed by qRT-PCR and Western blot. Cell proliferation was evaluated through CCK-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays, while glucose uptake, lactate production, and ATP levels were measured to assess energy metabolism. Seahorse XF analysis was used to evaluate extracellular acidification rate (ECAR) and oxygen consumption rate (OCR). Disulfidptosis was assessed through NADP+/NADPH ratio, glutathione (GSH) content, GSSG/GSH ratio, and immunofluorescence staining.
ZIC5 is highly expressed in LUAD and is associated with poor patient prognosis. Silencing ZIC5 significantly reduced its mRNA and protein levels in A549 and H1299 cells, markedly inhibited cell proliferation, and led to significant decreases in glucose uptake, lactate production, ATP levels, ECAR, and OCR. Additionally, silencing ZIC5 resulted in an increased NADP+/NADPH ratio, decreased GSH levels, and a reduced GSSG/GSH ratio, alongside classic disulfidptosis features.
ZIC5 plays a crucial role in promoting LUAD cell proliferation and energy metabolism while inhibiting disulfidptosis. Silencing ZIC5 markedly suppresses these processes, indicating its potential as a therapeutic target in LUAD.

Sarcopenia, the age-related decline in muscle mass and function, poses a major health risk to the elderly population. Although dietary advanced glycation end-products (AGEs) have been implicated in worsening sarcopenia, the precise molecular mechanisms remain unclear.
A sarcopenia animal model was established by feeding a high AGE diet to C57BL/6 mice. Muscle function and mass were assessed using grip strength tests, and rotarod tests. Proteomic analysis was used to identify differentially expressed proteins. Immunoprecipitation, mass spectrometry, and co-immunoprecipitation were employed to investigate protein interactions both in vivo and in vitro. Quantitative reverse transcription PCR and Western blotting were conducted to measure gene and protein expression levels.
Our results revealed that dietary AGEs accelerated the onset of sarcopenia in mice by triggering apoptosis. Proteomic analysis showed a marked upregulation of protein arginine methyltransferase 1 (PRMT1) in the muscle tissues of mice fed a high AGE diet. PRMT1 mediated the arginine methylation of CREB-regulated transcription coactivator 3 (CRTC3) at the R534 site within its transactivation domain, leading to CRTC3 activation. The activated CRTC3, together with Forkhead box O3a (FOXO3a), transactivated the BAX (BCL2 associated X) gene, initiating Bax downstream signaling, promoting apoptosis in muscle cells, and contributing to muscle atrophy. Inhibition of PRMT1 prevented CRTC3 methylation and suppressed Bax-mediated apoptotic signaling in vitro. Moreover, in vivo treatment with PRMT1 and Bax inhibitors significantly attenuated AGE-induced sarcopenia in mice.
PRMT1-mediated CRTC3 arginine methylation plays a critical role in AGE-induced sarcopenia and suggests potential therapeutic targets for preventing sarcopenia progression.
© 2025. The Author(s).

Lung cancer is one of the most common malignant tumors in the world. In approximately 30%-40% of lung cancer patients, bone metastases ensues with osteolytic destruction. Worse still, intractable pain, pathological fracture, and nerve compression caused by bone metastases are currently the bottleneck of research, diagnosis, and treatment of lung cancer. Therefore, the present study aims at investigating the effectiveness of a new composite material made of calcium phosphate cement (CPC) and Endostar on repairing bone defects in vitro and in vivo. As indicated in results, the mechanical properties of CPC+Endostar and CPC+PLGA+Endostar do not differ from those of pure CPC. The PLGA-embedded Endostar slow-release microspheres were designed and prepared, and were combined with CPC. Poly (lactic-co-glycolic acid (PLGA) is a biodegradable polymer material in vivo, so the effect on its mechanical properties is negligible. CPC+Endostar and CPC+PLGA+Endostar have been proved to inhibit cell proliferation, promote apoptosis and block cell cycle in G2 phase; the expression levels of osteoclast-related genes CXCL2, TGF-β1, IGF-1, IL-6, and RANKL were significantly decreased while osteogenic ability and alkaline phosphatase activity observably enhanced. In vivo studies have revealed that the expression levels of TRAP, RANKL, and Caspase3 in CPC+PLGA+ENDO-treated tumor tissues after 3 weeks were higher than those in other groups with the prolongation of animal treatment time, while the expression levels of OPN and BCL2 were lower than those in other groups. In hematoxylin and eosin and TUNEL staining, 3 weeks of CPC+PLGA+ENDO-treatment yielded higher tissue necrosis and apoptosis than other groups; computed tomography and magnetic resonance imaging results showed the posterior edge bone damage reduced as a result of the CPC+PLGA+ENDO grafting in vertebral pedicle. Overall, the feasibility and reliability of CPC-loaded Endostar in the treatment of bone metastasis in lung cancer were investigated in this study, so as to promote the basic research and treatment of bone metastasis in lung cancer and other malignant tumors.
© 2024 Wiley Periodicals LLC.

Two new Ru(II) complexes, mononuclear [RuCl2(η6-p-cymene)(3,4-dmph-κN)] (1) and the binuclear complex [{RuCl(η6-p-cymene)}2(μ-Cl)(μ-3,4-dmph-κ2N,N')]Cl (2; 3,4-dmph = 3,4-dimethylphenylhydrazine), are synthesized and experimentally and theoretically structurally characterized utilizing 1H and 13C NMR and FTIR spectroscopy, as well as DFT calculations. Degradation product of 2, thus ([{RuCl(η6-p-cymene)}2(μ-Cl)(μ-3,4-dmph-κ2N,N')][RuCl3(η6-p-cymene)] (2b) was characterized with SC-XRD. In the crystals of 2b, the cationic and anionic parts interact through N-H...Cl hydrogen bridges. The spectrofluorimetric measurements proved the spontaneity of the binding processes of both complexes and HSA. Spin probing EPR measurements implied that 1 and 2 decreased the amount of bound 16-doxylstearate and implicated their potential to bind to HSA more strongly than the spin probe. The cytotoxicity assessment of both complexes against the MDA-MB-231 and MIA PaCa-2 cancer cell lines demonstrated a clear dose-dependent decrease in cell viability and no effect on healthy HS-5 cells. Determination of the malondialdehyde and protein carbonyl concentrations indicated that new complexes could offer protective antioxidant benefits in specific cancer contexts. Gel electrophoresis measurements showed the reduction in MMP9 activity and indicated the potential of 1 in limiting the cancer cells' invasion. The annexin V/PI apoptotic assay results showed that 1 and 2 exhibit different selectivity towards MIA PaCa-2 and MDA-MB-231 cancer cells. A comparative molecular docking analysis of protein binding, specifically targeting acetylcholinesterase (ACHE), matrix metalloproteinase-9 (MMP-9), and human serum albumin (HSA), demonstrated distinct binding interactions for each complex.

Dendritic cells (DCs) present exogenous antigens via major histocompatibility complex class I (MHC-I) and MHC class II (MHC-II) molecules, activating CD8+ and CD4+ T cells. A critical but poorly understood step in this process is the trafficking of peptide-loaded MHC molecules from the endocytic system to the cell surface. In this study, we demonstrate that the Golgi reassembly-stacking protein of 55 kDa (GRASP55), which has been shown to have no role in stacking, is essential for antigen presentation. Using soluble, bead-coated, and bacterial-bound antigens, we found significantly impaired exogenous antigen presentation in GRASP55-deficient bone-marrow-derived DCs (BMDCs). Notably, GRASP55 was recruited to late phagosomes, and our data suggest that it is crucial for sorting MHC-I and MHC-II molecules, facilitating their trafficking to the plasma membrane. Our findings highlight the vital role of GRASP55 in the intracellular transport of MHC molecules bound to their respective peptides during exogenous antigen presentation.
Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.