The role of the histone ubiquitination-related gene in the cisplatin resistance of lung adenocarcinoma (LUAD) remains an intricate subject.
We accessed transcriptome data of both wild type and ...cisplatin-resistant cells from the GSE108214 dataset, and garnered transcriptome and clinical data of LUAD patients from The Cancer Genome Atlas (TCGA) database. Utilizing the R software, we analyzed these public datasets in depth. Real-time Quantitative PCR (qPCR) was used to detect the RNA level of CUL4B. Effect of CUL4B on cell proliferation was evaluated using CCK8 and colony formation assay. Effect of CUL4B on cell invasion was evaluated using transwell assay. Cisplatin sensitivity was evaluated by calculating IC50.
Our analysis shed light on the significance of the histone ubiquitination-related gene, CUL4B, in relation to cisplatin resistance and the overall survival rates of LUAD patients. Notably, CUL4B was found to be overexpressed in both lung cancer tissues and cells. Meanwhile,
experiments indicated can CUL4B significantly promote the proliferation, invasion and migration of lung cancer cells. Furthermore, suppressing CUL4B expression led to a noticeable reduction in the IC50 value of cisplatin in lung cancer cells. A deep dive into biological enrichment analysis revealed that among patients exhibiting high CUL4B expression, there was a pronounced activation of the G2M checkpoint and the PI3K/AKT/mTOR signaling pathways. Immune microenvironment analysis has revealed that patients with elevated CUL4B expression may exhibit increased infiltration of M2 macrophages, coupled with a reduced infiltration of CD8
T cells and activated NK cells. Notably, we observed higher CUL4B expression among those who responded positively to immunotherapy.
These findings underscore the significance of CUL4B in the resistance to cisplatin in lung cancer, highlighting its potential as a therapeutic target.
Myocardial infarction (MI) stands out as a highly lethal disease that poses a significant threat to global health. Worldwide, heart failure resulting from MI remains a leading cause of human ...mortality. Mesenchymal stem cell (MSC) therapy has emerged as a promising therapeutic approach, leveraging its intrinsic healing properties. Nevertheless, pervasive issues, including a low cell retention rate, suboptimal survival rate, and incomplete differentiation of MSCs, present formidable challenges for further research. The introduction and advancement of biomaterials have offered a novel avenue for the exploration of MSC therapy in MI, marking considerable progress thus far. Notably, hydrogels, among the representative biomaterials, have garnered extensive attention within the biomedical field. This review delves into recent advancements, specifically focusing on the application of hydrogels to augment MSC therapy for cardiac tissue regeneration in MI.
•Combining MSC therapy for MI with the tissue engineering potential of hydrogel.•Highlight the mechanism of hydrogel improving the therapeutic effect of MSCs for MI.•Combining clinical and basic research to analyze the pros and cons of current therapy.•Objective analysis of the challenges and opportunities faced by future for co therapy.
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•A self-association zwitterionic hydrogel was prepared by simple copolymerization.•The hydrogel had suitable elasticity and electrical excellent ionic conductivity.•The hydrogel ...enhanced the maturation and functionalization of cardiomyocytes.•The hydrogel promoted electrical signal transfer and cell synchronous contraction.•The hydrogel derived cardiac patches improved the restoration of cardiac function.
In recent years, engineered cardiac patch (ECP) with electrical conductivity has been developed for cardiac repair after injury or infarction. However, the application of traditional conductive polymers in ECP is still limited due to their toxicity and difficulty in dispersing and degradation. Herein, a self-association crosslinked conductive zwitterionic hydrogel was developed by simple copolymerization of zwitterionic monomer carboxybetaine methacrylate (CBMA) and a biocompatible monomer hydroxyethyl methacrylate (HEMA). The fabricated p(CBMA-co-HEMA) hydrogel possessed excellent ionic conductivity, suitable compressive and stretchable properties, self-healing and mechanical sensory capability. In vitro, the zwitterionic hydrogel significantly enhanced the functionalization of the cardiomyocytes, resulting in excellent synchronous contraction by increasing the expression of cardiac-related factor α-actinin and transmission electrical signal-relevant Connexin-43 (CX-43). In vivo, the hydrogel-derived functional patch effectively promoted the transmission of electrophysiological signals, improved revascularization in infarcted area and then remarkably restored the cardiac function. These data indicated that our developed conductive zwitterionic hydrogel has good promise in repairing myocardial tissue injury.
Conductive cardiac patches have been proven to promote angiogenesis in infarcted myocardium; however, their conductive integrity, elasticity, and vascularization potential have not yet been ...optimized. The prevascularization of conductive elastic cardiac patches could be an effective strategy for building a substantial connection between the patch and the infarcted heart. Here, a coronary artery casting is introduced into a holey graphene oxide/polypyrrole‐incorporated polyhydroxyethyl methacrylate prefabricated gel to form a vascularized conductive elastic patch. The engineered patches are able to rebuild functional vascular anastomoses and provide strong electrical integration with infarcted hearts, resulting in effective myocardial infarction repair in vivo. RNA sequencing analyses further reveal that the conductive elastic patches under dynamic culture conditions upregulated cardiac muscle contraction‐ and ATP biosynthesis‐related mRNA expression in vitro. Together, this study demonstrates that the fabricated patches have versatile conductivity, elasticity, and vascularization properties, and could therefore be a promising candidate for heart repair.
The integrity of conductivity, elasticity, and full vascularization into a cardiac patch remains challenging. Here, the authors report a vascularized conductive elastic patch and demonstrate its vascular anastomoses and electrical integration with the infarcted heart, resulting in effective repair for myocardial infarction.
Heart failure caused by acute myocardial infarction (MI) still remains the main cause of death worldwide. Development of conductive hydrogels provided a promising approach for the treatment of ...myocardial infarction. However, the therapeutic potential of these hydrogels is still limited by material toxicity or low conductivity. The latter directly affects the coupling and the propagation of electrical signals between cells. Here, a functional conductive hydrogel by combining hydrophilic and biocompatible poly(vinyl alcohol) (PVA) with conductive melanin nanoparticles under physical crosslinking conditions is prepared. The composite hydrogels prepared by a facile fabrication process of five freeze/thaw cycles possessed satisfying mechanical properties and conductivity close to those of the natural heart. The physical properties and biocompatibility are evaluated in vitro experiments, showing that the introduction of melanin particles successfully improved the elasticity, conductivity, and cell adhesion of PVA hydrogel. In vivo, the composite hydrogels can enhance the cardiac repair effect by reducing MI area, slowing down ventricular wall thinning, and promoting the vascularization of infarct area in MI rat model. It is believed that the melanin/PVA composite hydrogel may be a suitable candidate material for MI repair.
A physical crosslinking composite hydrogel fabricated with poly(vinyl alcohol) (PVA) and melanin possesses good conductivity, suitable compressive properties and Young's modulus comparable with natural mammalian heart. The introduction of melanin enhanced cardiomyocytes (CMs) maturation in vitro. The hydrogel implantation in vivo can remarkably improve the restoration of cardiac function and revascularization of infarcted myocardium in rats.
Tumour self-seeding by circulating tumour cells (CTCs) enhances tumour progression and recurrence. Previously, we demonstrated that tumour self-seeding by CTCs occurs in osteosarcoma and revealed ...that interleukin-6 (IL-6) may promote CTC attraction. Here, we investigated the underlying mechanisms of IL-6 in tumour self-seeding by CTCs. IL-6 suppression inhibited in vitro cell proliferation, migration, and invasion. In addition, rhIL-6 activated the Janus-activated kinase/signal transducers and activators of transcription 3 (JAK/STAT3) and mitogen-activated protein kinase/extracellular-signal regulated kinase1/2 (MAPK/ERK1/2) pathways in vitro. Both pathways increased cell proliferation, but only the JAK/STAT3 pathway promoted migration. Suppressing IL-6 inhibited in vivo tumour growth and metastasis. IL-6 suppression or JAK/STAT3 pathway inhibition reduced CTC seeding in primary tumours. Collectively, IL-6 promotes tumour self-seeding by CTCs in a nude mouse model. This finding may provide a novel strategy for future therapeutic interventions to prevent osteosarcoma progression and recurrence.
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