As a kind of tumor commonly seen, no effective treatment is available for esophageal squamous cell carcinoma (ESCC). Therefore, seeking a new treatment is urgent. Demethylzeylasteral (T-96) isolated from Tripterygium wilfordii root bark embraces outstanding good antitumor activity. However, as for the mechanism of T-96 work on ESCC cells, it is rarely reported. In this study, we found that T-96 has inhibition when ESCC cells are proliferating, migrating and cloning. Moreover, relevant effects are influenced by dose and time. And T-96 can result in the stop of G2/M phase and induce apoptosis of ESCC cells. In addition, the expressions of Cyclin B1, Cyclin D1, Bcl-2, PARP1 and Survivin were decreased after starch demethylation. Despite of this, Bax and PARP1's expressions went up. To add up, there was an obvious increase in the expression of E-cadherin, while that of N-cadherin, Vimentin and MMP9 decreased after T-96 treatment. Moreover, the expression of Wnt/β-Catenin pathway, which concerns proteins β-Catenin, c-Myc and Wnt3a decreased. Our study shows that T-96 inhibits the proliferation and migration of esophageal cancer cells through Wnt/β-catenin pathway. Moreover, it gives rise to cell cycle arrest and apoptosis. According to the research results, T-96 tends to be put into use when treating ESCC patients, thus laying the experimental foundation for clinical research.
BackgroundEpidemiological studies of ours and other groups have reported an inverse association between dietary and serum Mg with knee radiographic osteoarthritis (OA) [1–4].ObjectivesTo investigate the effects of dietary magnesium supplementation and intra-articular MgSO4 on the development of experimental rat osteoarthritis, and explore the underlying potential molecular mechanisms by mRNA and lncRNA expression profiles screening.MethodsRat osteoarthritis model was induced by surgery. Articular cartilage damage was evaluated by modified Mankin score system after intervention of dietary magnesium supplementation or intra-articular MgSO4 injection. Microarray was performed to reveal alteration of expression profiles of mRNA and lncRNA after intervention of MgSO4 on human osteoarthritis chondrocytes. Bioinformatics analyses including gene ontology analysis, pathway analysis, target gene predictions and network analysis were used.ResultsComparing with normal diet, dietary Mg supplementation showed significantly ameliorated cartilage damage at the medial femoral condyle, lateral tibial plateau and medial tibial plateau (P≤0.05), and approaching significance at the lateral femoral condyle (P=0.06). All four locations exhibited mitigated cartilage damage in the intra-articular MgSO4 group compared with intra-articular saline (P≤0.05). 1767 lncRNAs and 2558 mRNAs were upregulated while 994 lncRNAs and 1512 mRNAs were downregulated in chondrocytes with intervention of 50mM MgSO4 compared with control group (fold change ≥2.0). The top 6 lncRNAs which showed the largest difference were ENST00000425914.2, ENST00000419881.1, ENST00000561231.1, ENST00000609062.1, TCONS_00029212 and ENST00000429530.1. Bioinformatics analyses indicated that the differentially expressed lncRNA target genes of chondrocyte after intervention of 50mM MgSO4 are enriched in negative regulation of phosphatidylinositol 3-kinase signaling.ConclusionsBoth dietary magnesium supplementation and intra-articular MgSO4 injection may exert cartilage protective effects by causing widespread changes in the profile of lncRNAs and mRNAs of chondrocytes.References Hunter DJ. Evidence of altered bone turnover, vitamin D and calcium regulation with knee osteoarthritis in female twins. Rheumatology 2003;42(11):1311–6.Zeng C, Wei J, Li H, Yang T, Zhang FJ, Pan D, et al. Relationship between Serum Magnesium Concentration and Radiographic Knee Osteoarthritis. J Rheumatol 2015;42(7):1231–6.Qin B, Shi X, Samai PS, Renner JB, Jordan JM, He K. Association of dietary magnesium intake with radiographic knee osteoarthritis: Results from a population-based study. Arthritis Care & Research 2012;64(9):1306–11.Zeng C, Li H, Wei J, Yang T, Deng Z, Yang Y, et al. Association between Dietary Magnesium Intake and Radiographic Knee Osteoarthritis. PLOS ONE 2015;10(5):e127666. Disclosure of InterestNone declared
Lung cancer is one of the most prevalent, fatal, and highly heterogeneous diseases that, seriously threaten human health. Lung cancer is primarily caused by the aberrant expression of multiple genes in the cells. Lung cancer treatment options include surgery, radiation, chemotherapy, targeted therapy, and immunotherapy. In recent decades, significant progress has been made in developing therapeutic agents for lung cancer as well as a biomarker for its early diagnosis. Nonetheless, the alternative applications of traditional pre-clinical models (cell line models) for diagnosis and prognosis prediction are constrained by several factors, including the lack of microenvironment components necessary to affect cancer biology and drug response, and the differences between laboratory and clinical results. The leading reason is that substantial shifts accrued to cell biological behaviors, such as cell proliferative, metastatic, invasive, and gene expression capabilities of different cancer cells after decades of growing indefinitely in vitro. Moreover, the introduction of individualized treatment has prompted the development of appropriate experimental models. In recent years, preclinical research on lung cancer has primarily relied on the patient-derived tumor xenograft (PDX) model. The PDX provides stable models with recapitulate characteristics of the parental tumor such as the histopathology and genetic blueprint. Additionally, PDXs offer valuable models for efficacy screening of new cancer drugs, thus, advancing the understanding of tumor biology. Concurrently, with the heightened interest in the PDX models, potential shortcomings have gradually emerged. This review summarizes the significant advantages of PDXs over the previous models, their benefits, potential future uses and interrogating open issues.
Objective. Previous studies suggested that the level of bone turnover markers (BTMs) could be altered in patients with nonalcoholic fatty liver disease (NAFLD). We aim to provide a comprehensive understanding on the associations between BTMs and NAFLD in adults with a meta-analysis. Methods. Articles published up to January 31, 2023, were systematically searched in PubMed, Web of Science, Cochrane database, Embase, and CNKI. The search formula is as follows: “nonalcoholic fatty liver disease” combined with the terms that bone turnover markers such as “osteocalcin,” “collagen type I trimeric cross-linked peptide,” and “procollagen type I N-terminal peptide.” Stata 15.0 software was used to calculate the pooled OR (95% CI) and perform the heterogeneity test, sensitivity analysis, and publication bias. Results. We identified 18 studies with a total of 12,310 participants. Statistical differences were found between patients with NAFLD compared to the control group for osteocalcin (n = 15 studies; SMD: −0.69; 95% CI: −0.73–−0.64; P = 0.002 ), procollagen type I N-terminal propeptide (n = 5 studies; SMD: −0.40; 95% CI: −0.80−−0.00; P = 0.049 ), and collagen type I cross-linked C-telopeptide (n = 7 studies; SMD: −0.16; 95% CI: −0.23−−0.09); P < 0.001 ). Conclusion. Bone turnover markers were lower in patients with NAFLD compared to the control group.
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