JAML inhibits colorectal carcinogenesis by modulating the tumor immune microenvironment.

It is necessary to explore new targets for the treatment of colon adenocarcinoma (COAD) according to the tumor microenvironment. The expression levels of JAML and CXADR were analyzed by bioinformatics analysis and validation of clinical samples. JAML over-expression CD8+ T cell line was constructed, and the proliferation activity was detected by MTT. The production of inflammatory factors was detected by ELISA. The expression of immune checkpoint PD-1 and TIM-3 was detected by Western blot. The apoptosis level was detected by flow cytometry and apoptosis markers. The AOM/DSS mouse model of colorectal cancer was constructed. The expression levels of JAML, CXADR and PD-1 were detected by PCR and Western blot, and the proportion of CD8+ T cells and exhausted T cells were detected by flow cytometry. The expression levels of JAML and CXADR were significantly decreased in colon cancer tissues. Overexpression of JAML can promote the proliferation of T cells, secrete a variety of inflammatory factors. Overexpression of CXADR can reduce the proliferation of colorectal cancer cells, promote apoptosis, and down-regulate the migration and invasion ability of tumor cells. Both JAML agonists and PD-L1 inhibitors can effectively treat colorectal cancer, and the combined use of JAML agonists and PD-L1 inhibitors can enhance the effect. JAML can promote the proliferation and toxicity of CD8+ T cells and down-regulate the expression of immune checkpoints in colon cancer. CXADR can inhibit the proliferation of cancer cells and promote the apoptosis. JAML agonist can effectively treat colorectal cancer by regulating CD8+ T cells.

Anchang Yuyang Decoction inhibits experimental colitis-related carcinogenesis by regulating PPAR signaling pathway and affecting metabolic homeostasis of host and microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: Inflammatory bowel disease (IBD) presents a risk of carcinogenesis, which escalates with the duration of IBD. Persistent histological inflammation is considered to be the driving factor of colitis carcinogenesis. Effective control of inflammation is helpful to prevent and treat colitis-related colorectal cancer (CAC). Anchang Yuyang Decoction (AYD), a traditional Chinese medicine (TCM) formula, is originated from the ancient prescription of TCM for treating colitis and colorectal cancer. AYD has demonstrated efficacy in treating IBD and potential anti-carcinogenic properties. AIM OF THE STUDY: This research aims to assess the therapeutic efficacy of AYD in ameliorating experimental colitis-related carcinogenesis induced by AOM/DSS. It further seeks to elucidate its potential mechanisms by integrating multiple omics sequencing approaches. MATERIALS AND METHODS: A rat model for colitis-related carcinogenesis was developed using azoxymethane (AOM)/dextran sulfate sodium (DSS). UPLC-MS identified AYD's chemical constituents. Rats were administered varying doses of AYD (18.37, 9.19 and 4.59 g/kg) orally for 53 days, with mesalazine as a positive control. The study evaluated anti-carcinogenic effects by examining adenoma number, adenoma load, abnormal crypt foci (ACF), histopathological damage, and tumor-related protein expression. Anti-inflammatory and reparative effects were assessed through body weight, disease activity index (DAI), colon length, spleen index, inflammatory cytokine levels, and tight junction protein expression. The effects on intestinal microbiota and host metabolism were explored through 16S rRNA sequencing, targeted short-chain fatty acid (SCFA) metabonomics, and non-targeted colon metabolomics. Potential AYD targets were identified through transcriptomic sequencing and validated by qRT-PCR and western blotting. RESULTS: AYD significantly reduced adenoma number, adenoma load, neoplasm-associated lesions, ACF, and tumor-related protein expression (e.g., p53, PCNA) in AOM/DSS-induced rats, thus impeding colitis-related carcinogenesis progression. AYD also alleviated histopathological damage and inflammation, promoting intestinal mucosal barrier repair. Furthermore, AYD modulated intestinal flora structure, enhanced SCFA production, and regulated colon metabolites. Transcriptomic sequencing revealed a significant impact on the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Subsequent qRT-PCR and western blotting experiments indicated AYD's influence in up-regulating PPAR-γ and down-regulating PPAR-α, PPAR-ß/δ, and related proteins (thrombomodulin [Thbd], fatty acid binding protein 5 [Fabp5], stearoyl-CoA desaturase 2 [Scd2], phospholipid transfer protein [Pltp]). CONCLUSIONS: This study demonstrates AYD's ability to inhibit experimental colitis-related carcinogenesis induced by AOM/DSS. Its mechanism likely involves modulation of the PPAR signaling pathway, impacting intestinal microbiota and host metabolic equilibrium.

ING3 inhibits the malignant progression of lung adenocarcinoma by negatively regulating ITGB4 expression to inactivate Src/FAK signaling.

Lung adenocarcinoma (LUAD) is the most commonly diagnosed subtype of lung cancer worldwide. Inhibitor of growth 3 (ING3) serves as a tumor suppressor in many cancers. This study aimed to elucidate the role of ING3 in the progression of LUAD and investigate the underlying mechanism related to integrin ß4 (ITGB4) and Src/focal adhesion kinase (FAK) signaling. ING3 expression in LUAD tissues and the correlation between ING3 expression and prognosis were analyzed by bioinformatics databases. After evaluating ING3 expression in LUAD cells, ING3 was overexpressed to assess the proliferation, cell cycle arrest, migration and invasion of LUAD cells. Then, ITGB4 was upregulated to observe the changes of malignant activities in ING3-overexpressed LUAD cells. The transplantation tumor model of NCI-H1975 cells in nude mice was established to analyze the antineoplastic effect of ING3 upregulation in vivo. Downregulated ING3 expression was observed in LUAD tissues and cells and lower ING3 expression predicated the poor prognosis. ING3 upregulation restrained the proliferation, migration, invasion and induced the cell cycle arrest of NCI-H1975 cells. Additionally, ITGB4 expression was negatively correlated with ING3 expression in LUAD tissue. ING3 led to reduced expression of ITGB4, Src and p-FAK. Moreover, ITGB4 overexpression alleviated the effects of ING3 upregulation on the malignant biological properties of LUAD cells. It could be also found that ING3 upregulation limited the tumor volume, decreased the expression of ITGB4, Src and p-FAK, which was restored by ITGB4 overexpression. Collectively, ING3 inhibited the malignant progression of LUAD by negatively regulating ITGB4 expression to inactivate Src/FAK signaling.

HPV prevalence and genotype distribution among women in eastern China during the Covid-19 pandemic.

Since March 2020, the pandemic caused by SARS-CoV-2 has affected nearly all aspects of daily life. In this study, we investigated the age-stratified prevalence and genotype distribution of human papillomavirus (HPV) among females in Shandong province (eastern China) and aimed to provide guidance on HPV-based cervical cancer screening and vaccination. The distribution of HPV genotypes was analyzed using PCR-Reverse Dot Hybridization. The overall infection rate of HPV was 16.4%, which was dominated by high-risk genotypes. The most prevalent genotype was HPV16 (2.9%), followed by HPV52 (2.3%), HPV53 (1.8%), HPV58 (1.5%), and HPV51 (1.3%). Among the positive cases with HPV infection, single-genotype infection was significantly higher than that of multi-genotype infection. In subgroup analyses by age (≤25, 26-35, 36-45, 46-55, >55), HPV16, 52, and 53 were consistently the three most common hrHPV genotypes in all age groups. The infection rate of multi-genotypes in the ≤25 and >55 age groups was significantly higher than that in other age groups. A bimodal distribution of HPV infection rate was observed in different age groups. Among lrHPV genotypes, HPV6, HPV11, and HPV81 were the three most common types in the ≤25 age group, while in other age groups, HPV81, HPV42, and HPV43 are the three most common lrHPV genotypes. This study provides basic information on the distribution and genotypes of HPV in the female population in eastern China, which could improve the application of HPV diagnostic probes and vaccines.

Inhibition Kinetics and Mechanism of Glutathione and Quercetin on Acrylamide in the Low-Moisture Maillard Systems.

ABSTRACT: The inhibition kinetics of glutathione (GSH) and quercetin on acrylamide (AA) formation in the low-moisture Maillard systems were investigated at 180°C. The inhibition rates in an equal-molar asparagine-glucose (Asn-Glc) system were higher than those in an asparagine-fructose (Asn-Fru) system, and the maximum inhibition rates for AA were 57.75% with 10-2 mol L-1 GSH and 51.38% with 10-1 mol L-1 quercetin. The Logistic-Index dynamic model and two consecutive simplified first-order kinetic models were well fitted to the changes of AA in the Asn-Glc system. The kinetics results suggested that the predominant inhibition effect of GSH on AA could be attributed to the competitive reaction between GSH and Asn for the consumption of Glc. The kinetic results and high-pressure liquid chromatography-tandem mass spectrometry analysis of the inhibitory effect of quercetin on AA indicated that quercetin might mitigate AA through the binding reaction of quercetin decomposition products and Maillard intermediate products. These experimental results provide theoretical data that may be useful to control the formation of AA during food thermal processing.

Identification of an exosomal long non-coding RNAs panel for predicting recurrence risk in patients with colorectal cancer.

Recurrence is a major cause of cancer-related deaths in colorectal cancer (CRC) patients, but the current strategies are limited to predict this clinical behavior. Our aim is to develop a recurrence prediction model based on long non-coding RNAs (lncRNAs) in exosomes of serum to improve the prediction accuracy. In discovery phase, 11 lncRNAs were found to be associated with CRC recurrence in tissues using high-throughput lncRNAs microarray and reverse transcription quantitative real-time PCR. And, 9 of them were correlated with their expression levels of serum exosomes. In training phase, a model based on 5-exosomal lncRNAs (exolncRNAs) panel was constructed, and showed high distinguish capability for recurrent CRC patients. ROC showed the panel was superior to serum CEA and CA19-9 in prediction of CRC recurrence. In both training and test sets, high-risk patients defined by the 5-exolncRNAs panel had poor recurrence free and overall survival. And, COX model showed it was an independent factor for CRC prognosis. Moreover, there was a significant relationship in detection of 5-exolncRNAs between plasma samples and paired serum samples. In summary, the 5-exolncRNAs panel robustly stratifies CRC patients' risk of recurrence, enabling more accurate prediction of prognosis.

Effect of Oil Oxidation on Acrylamide Formation in Oil-Rich Model Systems Without the Participation of Reducing Sugars.

ABSTRACT: Oil oxidation in an oil-rich system was used to investigate the effect on acrylamide formation. Three kinds of common oil, soybean oil, olive oil, and palm oil, were preheated at different temperatures (120, 150, 180, and 210°C) for different times (0, 5, 10, 15, and 20 h). The oil-rich model systems were composed of pretreated oil and asparagine. Acid value, peroxide value, p-anisidine value, and carbonyl group value were used to monitor the degree of lipid oxidation in the model system. Our results showed that the content of acrylamide increased with oil preheat time and temperature. The highest yield of acrylamide in soybean oil was 0.26 ± 0.012 µg/mL after 20 h of incubation at 210°C. Oil oxidation indices correlated significantly with the content of acrylamide. The peroxide value could provide more information for references about acrylamide formation in soybean and olive oil systems.