This work aims to improve the antiarthritic activity of (−)-epigallocatechin gallate (EGCG) and glucosamine (GA) through fabrication and optimization of casein protein nanoparticles (EGC-NPs). Optimized EGC-NPs were obtained with a EGCG/GA/casein ratio of 1:2:8 (w/w/w). The EGC-NPs gave a mean size of 186 ± 3.5 nm and an entrapment efficiency of 86.8 ± 2.7%, and they exhibited a greater inhibitory activity against human fibroblast-like synoviocytes-osteoarthritis cells and human fibroblast-like synoviocytes-rheumatoid arthritis cells compared with that of the EGCG-GA mixture by 33.5% and 20.8%, respectively. Freeze-dried EGC-NPs stored at 25 °C during 12 months showed high dispersion stability. Moreover, the redispersion of the freeze-dried EGC-NPs produced almost no significant changes in their physicochemical properties and bioactivity. Rat experiments demonstrated that the antiarthritis effect of the EGC-NPs was significantly higher than that of EGCG-GA mixture, as assessed through an analysis of anti-inflammatory efficacy, radiographic images and histopathological assessments of paw joints, and immunohistochemical changes in serum cytokines. The enchanced antiarthritic activity in vivo was consistent with that in vitro. The EGC-NPs demonstrate potential as a food supplement for the treatment of arthritis.

Aim: ASF1 is involved in tumorigenesis. However, its possible role in lung adenocarcinoma (LUAD) is unclear. This study thus explored the role of ASF1A and ASF1B in LUAD. Materials & methods: Data from The Cancer Genome Atlas and Gene Expression Omnibus were employed to investigate ASF1A and ASF1B expression and its roles in LUAD prognosis. Immunohistochemistry was applied to determine the protein expression of ASF1B of 30 LUAD patients. Results: The upregulation of ASF1B in tumor tissues is associated with worse overall survival and progress-free survival and is correlated with advanced tumor stage and tumor development. However, aberrant expression of ASF1A was not found in LUAD and ASF1A was not related to patients’ overall survival and progress-free survival. Conclusion: ASF1B could be a promising prognostic and therapeutic biomarker in LUAD.

Background The FAT atypical cadherin 1/2/3/4 (FAT1/2/3/4) has been linked to the occurrence and development of various cancers. However, the prognostic and immunological role of FAT1/2/3/4 in non-small cell lung cancer (NSCLC) has not been clarified. Methods The association of FAT1/2/3/4 mutations with tumor mutation burden (TMB), tumor immunity in the microenvironment, and response to ICIs in NSCLC was investigated. Whole-exome sequencing data of lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC) samples from the Cancer Genome Atlas (TCGA), and an immunotherapy data set comprising mutation and survival data of 75 NSCLC patients were analyzed. Two independent pan-cancer cohorts with large samples were used to validate the prognostic value of FAT1/2/3/4 mutations in immunotherapy. Results A high mutation rate of FAT1/2/3/4 (57.3%, 603/1052) was observed in NSCLC patients. TMB was significantly higher in samples with mutated FAT1/2/3/4 compared to samples with wildtype FAT1/2/3/4 ( P < .05). FAT2 mutation was found to be an independent prognostic biomarker in LUAD. FAT1/2/3/4 were aberrantly expressed in LUAD and LUSC, and high FAT2 expression strongly correlated with high PD-L1 levels in LUAD. Moreover, LUAD patients with FAT1 mutations showed significantly high activated dendritic cells infiltration, whereas those with FAT2/3/4 mutations had high infiltration of CD8+ T-cells, M1 macrophages, activated memory CD4+ T-cells, and helper follicular T-cells. It was also observed that FAT1/2/4 mutations were significantly associated with better enhanced objective response and durable clinical benefit, whereas FAT1/2/3 mutations correlated with longer progression-free survival in ICI-treated NSCLC cohort. FAT1/4 mutations were related to better overall survival in pan-cancer patients treated with ICIs. Conclusions FAT family genes are potential prognostic and immunological biomarkers and correlate with response to ICIs in NSCLC.

Background Cumulative evidence points to abnormal spindle-like microcephaly-associated (ASPM) protein being overexpressed in various cancers, and the aberrant expression of ASPM has been shown to promote cancer tumorigenicity and progression. However, its role and clinical significance in lung adenocarcinoma (LUAD) remains unclear. This study aimed to determine the expression patterns of ASPM and its clinical significance in LUAD. Methods In total, 4 original worldwide LUAD microarray mRNA expression datasets (N=1,116) with clinical and follow-up annotations were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The expression of ASPM protein in LUAD patients was detected by immunohistochemistry. Survival analysis and Cox regression analysis were used to examine the prognostic value of ASPM expression. Gene set enrichment analysis (GSEA) was performed to investigate the relationship between ASPM and LUAD. Results Dataset analyses and immunohistochemistry revealed that ASPM expression was significantly higher in the LUAD tissues compared with normal lung tissues, especially in the advanced tumor stage. Additionally, overexpression of ASPM was significantly correlated with shorter overall survival (OS) and relapse-free survival (RFS) in LUAD. Univariate and multivariate Cox regression analyses revealed that the overexpression of ASPM was a potential independent predictor of poor OS and RFS. However, ASPM overexpression was not significantly associated with predicting OS in lung squamous cell carcinoma. GSEA analysis demonstrated that ASPM was significantly enriched in the cell cycle, DNA replication, homologous recombination, RNA degradation, mismatch repair, and p53 signaling pathways. Conclusions These findings demonstrate the important role of ASPM in the tumorigenesis and progression of LUAD.

Background: Tongfu traditional Chinese medicine (TCM) preparation is a common alternative therapy for clinical treatment of patients with septic gastrointestinal dysfunction. In recent years, a number of randomized controlled trials (RCTs) have been conducted to verify the effectiveness of Tongfu TCM preparation in the treatment of sepsis gastrointestinal dysfunction, but all of them have been small sample studies, and the research conclusions have been controversial. Here, this study conducted a meta-analysis on the clinical efficacy of the treatment of septic gastrointestinal dysfunction with TCM preparation, to produce a more objective and comprehensive systematic review to guide clinical application.To evaluate the efficacy and safety of Tongfu traditional Chinese medicine (TCM) preparation in the treatment of patients with septic gastrointestinal dysfunction. Methods: Randomized controlled trials (RCTs) of Tongfu TCM preparation in the treatment of septic gastrointestinal dysfunction published before February 2021 were searched for in the Chinese databases China National Knowledge Infrastructure (CNKI), Wanfang, Chinese Biomedical Literature Disk (CBMdisc), and Chongqing VIP (CQVIP), and English databases PubMed, Web of Science, EBSCO, andThe Cochrane Library. Meta-analysis was performed using RevMan 5.3 software, and funnel plots were drawn to evaluate the bias of literatures.Results: A total of 22 RCTs involving 1,558 patients were included. There were 772 patients in the control group and 786 in the trial group. Meta-analysis results showed that: gastrointestinal dysfunction score [mean difference (MD) =−0.50, 95% confidence interval (CI): −0.61 to −0.38], Acute Physiology and Chronic Health Evaluation II (APACHE II) score (MD =−3.30, 95% CI: −3.73 to −2.86), and mortality (MD =0.34, 95% CI: 0.25-0.47) in the experimental group were significantly lower than those in the control group, and the difference was statistically significant (P<0.001). The funnel plot results showed that there was little possibility of publication bias.Discussion: Tongfu TCM preparation can effectively improve the gastrointestinal function of patients with sepsis gastrointestinal dysfunction, prevent the deterioration of the disease, and reduce the mortality; however, more evidence is required to substantiate these findings.