Baseline and change in serum lipid and uric acid level over time and incident of nonalcoholic fatty liver disease (NAFLD) in Chinese adults.

Observational studies have shown that non-alcoholic fatty liver disease (NAFLD) is strongly associated with metabolic dysfunction. However, there is a paucity of research on whether changes in indicators of serum metabolism contribute to the development of NAFLD. This study was conducted with 4084 participants who underwent healthy physical examinations at Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China, in 2022 and 2023. Baseline and follow-up measurements, including anthropometric data, abdominal ultrasound and blood samples were collected. The diagnosis of NAFLD was based on the 2010 Chinese Guidelines on Diagnosis and Treatment of NAFLD. Multiple logistic regression was utilized to analyze the odds ratios (ORs) for the 1-year risk of NAFLD in connection with both baseline metabolic indicators and changes in metabolic indicators observed over the course of 1 year. A total of 3425 study participants who were free of NAFLD at baseline, including 1146 men and 2279 women, were included in the final analysis. The mean age was 34.43 ± 7.20 years. Participants who developed NAFLD were older, male and had higher levels of body mass index (BMI), blood pressure, fasting blood glucose (FBG), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), free triiodothyronine (fT3), uric acid (UA), alanine aminotransferase (ALT) and aspartate aminotransferase (AST); and lower levels of high-density lipoprotein cholesterol (HDL-C) and free thyroxine (fT4) (all P values < 0.05). The multivariable model showed that baseline BMI, diastolic blood pressure (DBP), TG, TC, HDL-C, LDL-C, UA, fT4, fT3, ALT and changes in TG, HDL-C, and UA were associated with the 1-year risk of developing NAFLD. The risk of NAFLD increased by 56% [OR 1.56, 95% Confidence Interval (CI) 1.32-1.87] and 40% (OR 1.40, 95% CI 1.19-1.64) for each standard deviation (SD) increase in altered TG values (1.01 mmol/L) and altered UA values (55 µmol/L) respectively. Conversely, for each SD (0.27 mmol/L) increase in HDL-C change, the 1-year risk of incident NAFLD was reduced by 50% (OR 0.50, 95% CI 0.40-0.62). The present study suggested that increases in TG and UA, and decreases in HDL-C, significantly increase the risk of developing NAFLD. Therefore, more attention should be paid to these factors in the management and prevention of NAFLD.

Prognostic value of Beclin 1, EGFR and ALK in non-squamous non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is one of the most malignant tumors. The study was carried out to investigate the prognostic value of Beclin 1, EGFR and ALK for this cancer. Patients diagnosed with non-squamous NSCLC and admitted to our hospital from January 2011 to September 2016 were analyzed. Expression of Beclin 1 and mutation of EGFR and ALK were assessed using polymerase chain reaction (PCR) and fluorescent in situ hybridization (FISH) and analyzed for their relationship with demographic and clinical characteristics of the patients. Multivariate Cox regression models were applied to analyze the risk factors associated with survival and receiver response curves (ROC) were plotted to determine the prognostic value of Beclin 1, EGFR and ALK for patients with non-squamous NSCLC. Compared with adjacent normal tissue, Beclin 1 expression was elevated in the cancer tissue significantly; assessments of EGFR and ALK mutations showed that out of the 480 patients, 233 (48.5%) and 75 (12.6%) patients had EGFR and ALK mutations. Univariate analysis revealed that Beclin 1 level, EGFR and ALK mutations were associated with lymph node metastasis, TNM stage, tumor differentiation and prognosis, but not with gender, age and smoking status. The Kaplan-Meier survival analysis indicated that low Beclin 1 expression and positive EGFR and ALK rearrangements were associated with higher survival rate and longer progress-free survival (PFS). Multivariate Cox regression analysis showed that Beclin 1, EGFR, ALK mutations, tumor differentiation grade, TNM stage and lymph node metastasis were independently associated with PFS. ROC analysis showed that Beclin 1, EGFR and ALK were significant predictors for PFS; the areas under curve (AUC) for Beclin 1, EGFR and ALK were 0.812 (P = 0.018, cut-off value: 1.2), 0.781 (P = 0.011, cut-off value: 15%) and 0.722 (P = 0.010, cut-off value: 11%), respectively, suggesting that they have significant prognostic value for lung cancer patients. Our data indicate that Beclin 1, EGFR and ALK genes are associated with the prognosis of patients with non-squamous NSCLC. High Beclin 1 expression and negative EGFR and ALK mutations predict a poor prognosis with PFS.

Establishing an 8-gene immune prognostic model based on TP53 status for lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) results in a majority of cancer burden worldwide. TP53 is the most commonly mutated in LUAD. This study aimed to reveal the relation between TP53 and tumor microenvironment (TME) for improving LUAD treatment. METHODS: Differentially expressed genes (DEGs) related to immunity were analyzed between TP53-WT and TP53-MUT groups. Least absolute shrinkage and selection operator (LASSO) Cox regression was applied to screen prognostic DEGs. Two independent datasets were included to evaluate the robustness of the prognostic model. RESULTS: An 8-gene prognostic model containing ANLN, CCNB1, DLGAP5, FAM83A, GJB2, NAPSA, SFTPB, and SLC2A1 was established based on DEGs. LUAD samples were classified into high- and low-risk groups with differential overall survival in the two datasets. M0 macrophages, M1 macrophages, and activated memory CD4 T cells were more enriched in high-risk group. Immune checkpoints of PDCD1, LAG3, and CD274 were also high-expressed in high-risk group. CONCLUSION: The study improved the understanding of the role of TP53 in the TME modulation. The 8-gene model had robust performance to predict LUAD prognosis in clinical practice. In addition, the eight prognostic genes may also serve as potential targets for designing therapeutic drugs for LUAD patients.

Prognostic Factors of IIIAN2 Non-Small-Cell Lung Cancer after Complete Resection: A Systemic Review and Meta-analysis.

METHODS: An extensive data search was conducted from all leading databases including PubMed, Google Scholar, Embase, and Cochrane. Fifteen studies were selected according to the PRISMA model of data selected to conduct this systemic review meta-analysis. RESULTS: Total 4444 patients were evaluated among fifteen selected studies. A number of lymph nodes involved (n = 3965), level of lymph nodes (n = 3422), and complete tumor resection (n = 3255) were the most reported prognostic factors. CONCLUSION: This study exhibits the overall significance of all prognostic factors of NSCLC IIIAN2 pathology for better patient management. However, other management strategies also play a significant contribution to achieving a better survival rate and less recurrence possibility.

LncRNA WT1-AS downregulates lncRNA UCA1 to suppress non-small cell lung cancer and predicts poor survival.

BACKGROUND: LncRNA WT1-AS inhibits gastric cancer, while its role in other cancers is unknown. We investigated the role of WT1-AS in non-small cell lung cancer (NSCLC). METHODS: Sixty-six NSCLC patients (40 males and 26 females; 36 to 68 years old; mean age 52.7 ± 6.4 years old) were selected from the 178 NSCLC patients operated on for lung cancer between 2010 and 2013. RT-qPCR was used to analyze the expression of lncRNA. Overexpression experiments were performed to assess interactions between lncRNAs. CCK-8 assay was carried to evaluate the roles of WT1-AS and UCA1 in regulating cell proliferation. Cell invasion and migration assays were performed to assess the roles of WT1-AS and UCA1 in regulating cell invasion and migration. Western-blot was performed to illustrate the effect of WT1-AS and UCA1 in EMT. RESULTS: WT1-AS was downregulated in NSCLC and was correlated with poor survival. The expression of WT1-AS in NSCLC was not correlated with clinical stages. LncRNA UCA1 was upregulated in cancer tissues and inversely correlated with WT1-AS. Overexpression of UCA1 did not affect WT1-AS, while overexpression of WT1-AS led to inhibited expression of UCA1. Overexpression of UCA1 resulted in increased proliferation, EMT, migration and invasion of NSCLC cells, while overexpression of WT1-AS showed opposite effects. In addition, overexpression of UCA1 inhibited the role of overexpression of WT1-AS. CONCLUSIONS: Therefore, overexpression of WT1-AS may inhibit the cell proliferation and EMT to decrease cell migration and invasion of NSCLC cells by downregulating UCA1.

Expression Analysis, Functional Marker Development and Verification of AgFNSI in Celery.

Apigenin is one of the primary flavonoids in celery, which has a high medicinal value. Flavone synthase I (FNSI) is the last step enzyme in apigenin biosynthesis. In this study, the 1492 bp promoter sequence before AgFNSI initiation codon (ATG) of celery was obtained, which included methyl jasmonate (MeJA) responsive elements, light responsive elements, anaerobic induction elements and five MYB binding sites. AgFNSI was sensitive to temperature, UV-B, water deficit and MeJA. Comparative analysis of AgFNSI genome and promoter sequences among celery accessions with different apigenin content showed that there were four allelic variations in AgFNSI, and four accessions with high apigenin content belonged to AgFNSIa, and five accessions with low apigenin content belonged to AgFNSIc. Three pairs of dominant complementary markers were designed based on the single-nucleotile polymorphisms (SNPs) of the AgFNSIa and AgFNSIc genomes and promoter sequences. Three pairs of functional markers were validated by 112 celery accessions. The results showed that AFPA1/AFPB1 detected significant differences in apigenin content between different genotypes. Therefore, marker AFPA1/AFPB1 is associated with apigenin content in celery and could be used for the genetic improvement of apigenin content in celery.

Comparative Transcriptome Analysis of Celery Leaf Blades Identified an R2R3-MYB Transcription Factor that Regulates Apigenin Metabolism.

Apigenin has been proven to possess many pharmacological properties, but the mechanism of regulation of apigenin biosynthesis in plants remains unclear. Apigenin is the main flavonoid in celery and is mainly accumulated in the middle stage of leaf blade development. In this study, comparative transcriptomic analysis revealed a large number of structural genes and transcription factor genes that may be involved in the apigenin metabolic pathway. On the basis of the apigenin content in different celery accessions, an R2R3-MYB transcription factor gene, named AgMYB1, was isolated from the high apigenin celery accession C014. Bioinformatics analysis indicated that AgMYB1 may be involved in flavonoid metabolism. AgMYB1 expression showed a positive relation with the expression of the apigenin accumulation marker gene FNSI and with the apigenin content in different celery tissues. Moreover, overexpression and antisense expression of AgMYB1 in transgenic celery plants significantly increased and reduced the expression of apigenin biosynthetic genes and the apigenin content, respectively. These findings suggest that AgMYB1 is involved in positive regulation of apigenin metabolism in celery.

Anti-tumor activity of biodegradable polymer-paclitaxel conjugate micelles on Lewis lung cancer mice models.

Two kinds of paclitaxel (PTX) conjugate nanomicelles were prepared for cell apoptosis and anti-tumor activity evaluation on Lewis lung cancer mice models. One (PTX micelles) was prepared by self-assembling the PTX-conjugate co-polymer, poly(ethylene glycol)-b-poly(L-lactide-co-2-methyl-2-carboxyl-propylene carbonate/PTX), and the other (FA-PTX micelles) was by co-assembling a mixture of the folic acid (FA)-carrying co-polymer poly(ethylene glycol)-b-poly(L-lactide-co-2,2-dihydroxylmethyl-propylene carbonate/FA) (PEG-b-P(LA-co-DHP/FA)), and the PTX-conjugate co-polymer. At 7 and 14 days after tail intravenous injection, the mice were killed. The inhibition rates of tumor growth for PTX and FA-PTX micelles were 50 and 90%, respectively, on the day 7, and 33 and 71%, respectively, on the day 14 after drug injection. Flow cytometry analysis showed that the cell apoptosis rates were 43, 54 and 72% for the control group, PTX micelles group and FA-PTX micelles group, respectively, on the day 7, and 16, 25 and 42 on the day 14. With the TUNEL assay, the grey values of PTX micelles and FA-PTX micelles groups were determined to be 61-62% and 43-44%, of that of the control group, on day 7 or day 14, respectively. Therefore, the PTX micelles and the FA-PTX composite micelles significantly inhibited the subcutaneously inoculated Lewis lung cancer and effectively induced the cell apoptosis, and the FA-PTX composite micelles displayed a better efficacy than the PTX-micelles, implying the contribution of the folate-mediated targeting and endocytosis effect.