Progress in Pluronic F127 Derivatives for Application in Wound Healing and Repair.

Pluronic F127 hydrogel biomaterial has garnered considerable attention in wound healing and repair due to its remarkable properties including temperature sensitivity, injectability, biodegradability, and maintain a moist wound environment. This comprehensive review provides an in-depth exploration of the recent advancements in Pluronic F127-derived hydrogels, such as F127-CHO, F127-NH2, and F127-DA, focusing on their applications in the treatment of various types of wounds, ranging from burns and acute wounds to infected wounds, diabetic wounds, cutaneous tumor wounds, and uterine scars. Furthermore, the review meticulously examines the intricate interaction mechanisms employed by these hydrogels within the wound microenvironment. By elucidating the underlying mechanisms, discussing the strengths and weaknesses of Pluronic F127, analyzing the current state of wound healing development, and expanding on the trend of targeting mitochondria and cells with F127 as a nanomaterial. The review enhances our understanding of the therapeutic effects of these hydrogels aims to foster the development of effective and safe wound-healing modalities. The valuable insights provided this review have the potential to inspire novel ideas for clinical treatment and facilitate the advancement of innovative wound management approaches.

NUCKS1 promotes the progression of colorectal cancer via activating PI3K/AKT/mTOR signaling pathway.

Nuclear ubiquitous casein and cyclin-dependent kinase substrate 1 (NUCKS1) is highly expressed in a variety of malignant tumors and functions as an oncogene; however, its role in colorectal cancer (CRC) remains unclear. We aimed to explore the function and regulatory mechanisms of NUCKS1 and potential therapeutic agents targeting NUCKS1 in CRC. We knocked down and overexpressed NUCKS1 in CRC cells and explored its effects in vitro and in vivo. Flow cytometry, CCK-8, Western blotting, colony formation, immunohistochemistry, in vivo tumorigenic, and transmission electron microscopy analyses were performed to determine the effects of NUCKS1 on CRC cell function. LY294002 was used to examine the mechanism of NUCKS1 expression in CRC cells. Potential therapeutic agents for NUCKS1-high CRC patients were analyzed using the CTRP and PRISM datasets, and the function of selected agents was determined by CCK-8 and Western blotting. We revealed that NUCKS1 was highly expressed in CRC tissues and clinically correlated with poor prognosis in CRC patients. NUCKS1 knockdown induces cell cycle arrest, inhibits CRC cell proliferation, and promotes apoptosis and autophagy. These results were reversed when NUCKS1 was overexpressed. Mechanistically, NUCKS1 exerts a cancer-promoting function by activating the PI3K/AKT/mTOR signaling pathway. This was reversed when LY294002 was used to inhibit the PI3K/AKT pathway. Furthermore, we determined that mitoxantrone exhibited high drug sensitivity in NUCKS1-overexpressing CRC cells. This work demonstrated NUCKS1 plays a crucial role in CRC progression via the PI3K/AKT/mTOR signaling pathway. Additionally, mitoxantrone may be a potential therapeutic agent for CRC treatment. Therefore, NUCKS1 represents a promising anti-tumor therapeutic target.

AKR7A3 modulates the metastasis of pancreatic ductal adenocarcinoma through regulating PHGDH-suppressed autophagy.

AKR7A3 is a member of the aldo-keto reductase (AKR) protein family, whose primary purpose is to reduce aldehydes and ketones to generate primary and secondary alcohols. It has been reported that AKR7A3 is downregulated in pancreatic cancer (PC). However, the mechanism underlying the effects of AKR7A3 in PC remains largely unclarified. Here, we explored the biological function, molecular mechanism and clinical relevance of AKR7A3 in pancreatic ductal adenocarcinoma (PDAC). AKR7A3 expression was downregulated in PDAC compared with adjacent normal tissues, and the lower AKR7A3 expression was related to poor prognosis. In addition, our results demonstrated that AKR7A3 could be a potential diagnostic marker for PDAC, especially in the early stages. Knockdown of AKR7A3 promoted PDAC progression and chemoresistance, while inhibiting autophagy flux. Mechanistically, AKR7A3 affected the metastasis, autophagy, and chemoresistance of PDAC by regulating PHGDH. Overall, the present study suggests that AKR7A3 inhibits PDAC progression by regulating PHGDH-induced autophagy. In addition, AKR7A3 inhibits chemoresistance via regulating PHGDH and may serve as a new therapeutic target for PDAC.

Comprehensive Analysis of 5-Methylcytosine (m5C) Regulators and the Immune Microenvironment in Pancreatic Adenocarcinoma to Aid Immunotherapy.

Background: Pancreatic adenocarcinoma (PAAD) is one of the most malignant cancers and has a poor prognosis. As a critical RNA modification, 5-methylcytosine (m5C) has been reported to regulate tumor progression, including PAAD progression. However, a comprehensive analysis of m5C regulators in PAAD is lacking. Methods: In the present study, PAAD datasets were obtained from the Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and ArrayExpress databases. The expression pattern of m5C regulators were analyzed and patients were divided into different m5C clusters according to consensus clustering based on m5C regulators. Additionally, m5C differentially expressed genes (DEGs) were determined using Limma package. Based on m5C DEGs, patients were divided into m5C gene clusters. Moreover, m5C gene signatures were derived from m5C DEGs and a quantitative indicator, the m5C score, was developed from the m5C gene signatures. Results: Our study showed that m5C regulators were differentially expressed in patients with PAAD. The m5C clusters and gene clusters based on m5C regulators and m5C DEGs were related to immune cell infiltration, immune-related genes and patient survival status, indicating that m5C modification play a central role in regulating PAAD development partly by modulating immune microenvironment. Additionally, a quantitative indicator, the m5C score, was also developed and was related to a series of immune-related indicators. Moreover, the m5C score precisely predicted the immunotherapy response and prognosis of patients with PAAD. Conclusion: In summary, we confirmed that m5C regulators regulate PAAD development by modulating the immune microenvironment. In addition, a quantitative indicator, the m5C score, was developed to predict immunotherapy response and prognosis and assisted in identifying PAAD patients suitable for tailored immunotherapy strategies.

Role of TFRC as a Novel Prognostic Biomarker and in Immunotherapy for Pancreatic Carcinoma.

Objective: To explore the expression of the transferrin receptor (TFRC) gene in pancreatic cancer and to analyze the pathogenesis and immunotherapy of TFRC in patients using bioinformatics methods. Methods: We used public data from the cancer genome atlas (TCGA) and gene expression omnibus databases to explore the expression level of the TFRC gene in pancreatic cancer patients. At the same time, we analyzed the correlation between the TFRC gene expression and patient survival, and further analyzed the correlation between TFRC and survival time of patients with different clinicopathological characteristics. Co-expressed genes and pathway enrichment analyses were used to analyze the mechanism of the TFRC in the occurrence and development of pancreatic cancer. Ultimately, we used the R software to examine the relationship between TFRC and immune phenotypes and immune cell infiltration using the TCGA database. Results: The results of the study showed that TFRC is highly expressed in pancreatic cancer tissue. The upregulated expression of TFRC was negatively correlated with the survival in patients with pancreatic cancer. The bioinformatics analysis showed that TFRC plays a role in the occurrence and development of pancreatic cancer mainly through signaling pathways (including cell adhesion molecule binding, condensed chromosomes, chromosome segregation, and cell cycle checkpoints). Finally, TFRC is associated with immune phenotypes and immune cell infiltration, which may influence immunotherapy. Conclusion: TFRC is significantly increased in pancreatic cancer and is associated with a poor prognosis. Moreover, research on TFRC may generate new ideas for the immunotherapy of pancreatic cancer.

TMEM43 promotes pancreatic cancer progression by stabilizing PRPF3 and regulating RAP2B/ERK axis.

BACKGROUND: Transmembrane protein 43 (TMEM43), a member of the transmembrane protein subfamily, plays a critical role in the initiation and development of cancers. However, little is known concerning the biological function and molecular mechanisms of TMEM43 in pancreatic cancer. METHODS: In this study, TMEM43 expression levels were analyzed in pancreatic cancer samples compared with control samples. The relationship of TMEM43 expression and disease-free survival (DFS) and overall survival (OS) were assessed in pancreatic cancer patients. In vitro and in vivo assays were performed to explore the function and role of TMEM43 in pancreatic cancer. Coimmunoprecipitation (co-IP) followed by protein mass spectrometry was applied to analyze the molecular mechanisms of TMEM43 in pancreatic cancer. RESULTS: We demonstrated that TMEM43 expression level is elevated in pancreatic cancer samples compared with control group, and is correlated with poor DFS and OS in pancreatic cancer patients. Knockdown of TMEM43 inhibited pancreatic cancer progression in vitro, decreased the percentage of S phase, and inhibited the tumorigenicity of pancreatic cancer in vivo. Moreover, we demonstrated that TMEM43 promoted pancreatic cancer progression by stabilizing PRPF3 and regulating the RAP2B/ERK axis. CONCLUSIONS: The present study suggests that TMEM43 contributes to pancreatic cancer progression through the PRPF3/RAP2B/ERK axis, and might be a novel therapeutic target for pancreatic cancer.

Comprehensive Analysis of m6A RNA Methylation Regulators and the Immune Microenvironment to Aid Immunotherapy in Pancreatic Cancer.

Pancreatic cancer (PAAD) is one of the most malignant cancers and immune microenvironment has been proved to be involved in pathogenesis of PAAD. m6A modification, related to the expression of m6A regulators, participates in the development of multiple cancers. However, the correlation between m6A regulators and immune microenvironment was largely unknown in PAAD. And because of the small sample size of pancreatic cancer in the TCGA database, it is not enough to draw a convincing conclusion. In the present study, we downloaded seven pancreatic cancer datasets with survival data and removed batch effects among these datasets to be used as the PAAD cohort to analyze the immune landscape of PAAD and the expression pattern of m6A regulators and divided the integrated dataset into cluster 1 and cluster 2 by consensus clustering for m6A regulators. Lower m6A regulators were found to be related to higher immune cell infiltration and a better survival. Moreover, we identified six m6A regulators and constructed the prognostic signature of m6A regulators. Patients with low-risk score had a higher response to immune checkpoint inhibitor and a longer overall survival. To figure out the underlying mechanism, we analyzed the cancer immunity cycle, most altered genes, gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) in risk subtypes. In summary, the present study proved m6A regulators modulated the PAAD immune microenvironment. And risk scores served as predictive indicator for immunotherapy and played a prognostic role for PAAD patients. Our study provided novel therapeutic targets to improve immunotherapy efficacy.

Ese-3 Inhibits the Proliferation, Migration, and Invasion of HaCaT Cells by Downregulating PSIP1 and NUCKS1.

OBJECTIVE: Epithelium-specific ETS protein 3 (Ese-3) is a member of the ETS family that is associated with tumor progression. However, there is little knowledge about Ese-3 in skin cancer. This study was conducted to explore the effects of Ese-3 on clinical prognosis in skin cancer and the functions of HaCaT cells. MATERIALS AND METHODS: Gene expression and clinical data were collected from The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx), and three GSE datasets (GSE15605, GSE46517, and GSE114445). Comparison of data between groups was performed by Student's t-test and chi square test. Survival analysis was performed using log-rank test. Univariate and multivariate analyses were performed using Cox proportional hazards models. Enrichment analysis was used to predict Ese-3 related functions. Cell proliferation assays, colony formation assays, and flow cytometry were used to assess cell proliferation, while Transwell assays analyzed cell migration and invasion. RESULTS: Compared with normal tissues, the Ese-3 mRNA in cutaneous malignant melanoma (CMM) patients was downregulated (P<0.0001). Ese-3 mRNA was associated with the T stage (χ 2=10.015, P=0.018), clinical stage (χ 2=4.122, P=0.042), and prognosis in CMM patients (P=0.0219) and was an independent prognostic predictor in CMM (HR=1.878, P=0.048). Enrichment analysis showed that differentially expressed proteins were associated with "protein kinase B (AKT) binding." CONCLUSION: Ese-3 inhibited the proliferation, migration, and invasion of HaCaT cells by downregulating PSIP1 and NUCKS1 expression levels to inactivate the phosphorylation of AKT.

Ese-3 contributes to colon cancer progression by downregulating EHD2 and transactivating INPP4B.

Epithelium-specific Ets protein 3 (Ese-3), a member of the Ets family of transcription factors, plays an important role in the development of cancers. However, little is known concerning its role in colon cancer (CC). In this study, we demonstrate that the expression of Ese-3 is upregulated in CC tissues and elevated Ese-3 expression is relationship with advanced T stage (P=0.037) and poor disease-free survival (DFS, P=0.044). Univariate and multivariate cox regression analyses show that Ese-3 expression may be an independent prognostic value for CC patients. Moreover, Ese-3 knockdown suppresses CC cell proliferation in vitro and in vivo, while Ese-3 overexpression has the opposite result. Further, we first demonstrate that EHD2 and INPP4B are the downstream genes of Ese-3. Subsequent investigation find that EHD2 is downregulated in CC tissues and knockdown of EHD2 significantly increase CC cell proliferation in vitro and vivo. Our findings reveal that Ese-3 promotes CC cell proliferation by downregulating EHD2 and transactivating INPP4B, and targeting the pathway may be a promising therapeutic target for CC patients.

Forkhead box P3 promotes breast cancer cell apoptosis by regulating programmed cell death 4 expression.

Forkhead box P3 (FOXP3), an X-linked tumor suppressor gene, plays an important role in breast cancer. However, the biological functions of FOXP3 in breast cancer apoptosis remain unclear. To investigate the underlying genes and networks regulated by FOXP3 in breast cancer, RNA sequencing was performed to compare FOXP3-overexpressing MDA-MB-231 cells and control MDA-MB-231 cells. Differentially expressed genes were identified, and functional enrichment analysis comparing the two groups was performed. The differentially expressed genes were mainly enriched in phagosomes, oxytocin, serotonergic synapses and the phospholipase D signaling pathway. Furthermore, gene set enrichment analysis revealed the enrichment of a gene signature associated with apoptosis in FOXP3-overexpressing MDA-MB-231 cells compared with wild-type cells. Further analysis showed that programmed cell death 4 (PDCD4), a key molecule involved in apoptosis, was overexpressed in FOXP3-MDA-MB-231 cells. Reverse transcription-quantitative PCR and western blotting showed that FOXP3 upregulated the expression of PDCD4 in breast cancer cells. Clinical sample analysis using a public database showed that the expression level of PDCD4 was associated with breast cancer clinical stages. Overall, the present study suggested that FOXP3 can promote the apoptosis of breast cancer cells by upregulating the expression of PDCD4, thus exerting a tumor suppressive function.