The interaction between DNA methylation and tumor immune microenvironment: from the laboratory to clinical applications.

DNA methylation is a pivotal epigenetic modification that affects gene expression. Tumor immune microenvironment (TIME) comprises diverse immune cells and stromal components, creating a complex landscape that can either promote or inhibit tumor progression. In the TIME, DNA methylation has been shown to play a critical role in influencing immune cell function and tumor immune evasion. DNA methylation regulates immune cell differentiation, immune responses, and TIME composition Targeting DNA methylation in TIME offers various potential avenues for enhancing immune cytotoxicity and reducing immunosuppression. Recent studies have demonstrated that modification of DNA methylation patterns can promote immune cell infiltration and function. However, challenges persist in understanding the precise mechanisms underlying DNA methylation in the TIME, developing selective epigenetic therapies, and effectively integrating these therapies with other antitumor strategies. In conclusion, DNA methylation of both tumor cells and immune cells interacts with the TIME, and thus affects clinical efficacy. The regulation of DNA methylation within the TIME holds significant promise for the advancement of tumor immunotherapy. Addressing these challenges is crucial for harnessing the full potential of epigenetic interventions to enhance antitumor immune responses and improve patient outcomes.

Quantification of epicardial fat volume using low-dose cardiac scan in patients with low calcium score.

Background: We investigated the accuracy of quantifying epicardial adipose tissue volume (EATV) using low-dose cardiac scan (EATVcardiac scan) and evaluated its clinical utility in predicting coronary heart disease in patients with low or mild calcification. Methods: In total, 204 patients with clinical symptoms of coronary heart disease and coronary artery calcium score (CACS) of <100 AU were enrolled in this retrospective study. After obtaining EATVcardiac scan and EATV measured using computed tomography angiography (EATVCTA), the agreement between the two measurements was evaluated using Pearson correlation coefficient and Bland-Altman analysis. Multivariate logistic regression was used to analyze the utility of EATV in predicting plaque and vulnerable plaque. Receiver operating characteristic curves were constructed. Results: The mean EATVcardiac scan (101.51±41.57 cm3) and EATVCTA (104.57±41.34 cm3) of all patients were similar, and the two measurements were strongly correlated (r=0.9596, P<0.001). The difference between EATVcardiac scan and EATVCTA was -3.0549, with only 4.9% (10/204) of patients having values outside the 95% confidence interval (CI) range (-26.15 to 20.04; P for agreement =0.0003). Further, a significant agreement was observed between EATVcardiac scan and EATVCTA in 126 patients with plaques, with an estimated difference of -3.354, and 6.35% (8/126) of patients had values outside the 95% CI range (-31.37 to 24.66; P for agreement =0.0095). After adjustment for age and sex, EATVcardiac scan and EATVCTA were significantly associated with plaque (all P values <0.001), and the areas under the curve (AUCs) were 0.662 and 0.670 (P=0.4331), respectively. In contrast, EATVcardiac scan and EATVCTA were not associated with vulnerable plaque (P>0.05), with AUCs of 0.550 and 0.530, respectively (P=0.2157). Conclusions: The study results indicate that EATVcardiac scan and EATVCTA are equivalent. In addition, both methods provide comparable values for predicting coronary arteriosclerosis in patients with low-to-mild calcification (CACS of <100 AU).

Elevated expression of ICAM-1 in synovium is associated with early inflammatory response for cartilage degeneration in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is increasingly being recognized as an independent risk factor for the onset and progression of osteoarthritis (OA). Extensive studies have focused on the contribution of obesity (excessive mechanical stress), comorbidity frequently found in T2DM, to cartilage destruction during OA development. However, a little is known about how diabetes-related inflammation may affect the local cartilage in a diabetic objective. In the present study, we were able to establish a T2DM rat model using a combination of a low dose of streptozotocin with high-fat and high-sugar diet. Although the cartilage integrity was comparable between the control and T2DM groups, the expression of matrix metalloproteinases-13 (MMP-13) was significantly upregulated in T2DM, indicating the initiation of an early cascade of cartilage degeneration. In parallel, an obvious alteration of subchondral bone remodeling (inhibition of bone formation) was observed, as evidenced by the reduction of osterix-expressing positive cells. Moreover, we demonstrated that the expression of intercellular adhesion molecule-1 (ICAM-1) in the serum and synovium of T2DM rats was elevated, accompanied by an increase of synovitis score. We also noticed that the number of F4/80-positive macrophage cells was significantly increased in the T2DM group. Mechanistically, the expression of ICAM-1 in fibroblast-like synoviocytes can be triggered by glucose and interleukin-1ß, which are the two important factors within the joint of T2DM. Given that MMP-13 expression was significantly upregulated in the T2DM cartilage, and that ICAM-1-mediated filtration of macrophage was associated with synovitis, we propose that ICAM-1 is essential for triggering a vicious cycle of inflammation within the joint, which together subsequently drivers the cartilage degradation.

Association Between c-Myc and Colorectal Cancer Prognosis: A Meta-Analysis.

Background: There is debate as to whether c-Myc predicts prognosis in colorectal cancer (CRC). In this study, we aimed to review the association between c-Myc and CRC prognosis. Methods: Pertinent studies were identified by searching electronic databases and carefully reviewing the reference lists of pertinent studies until March 2016. The summary hazard ratio (HR) and corresponding 95% confidence interval (CI) were calculated to study the association between c-Myc and CRC prognosis. Results: Eight cohort studies (including seven studies about overall survival [OS] and one study about disease free survival [DFS]) were included. The pooled HR of OS was 1.13 (95% CI: 0.66-1.95). In subgroup analysis, no significant association between c-Myc and CRC prognosis was found in the studies either from Western countries (HR: 0.87, 95% CI: 0.68-1.10) or Asian countries (HR: 1.89, 95% CI: 0.62-5.77). HRs were 0.86 (95% CI: 0.38-1.94) and 1.57 (95% CI: 0.73-3.39) for the studies using univariate analysis and multivariate analysis, respectively. HR from the studies that examined DNA level was significantly different (HR: 2.05, 95% CI: 1.22-3.46); while that about RNA level or protein level was not significantly different. Conclusion: c-Myc was not associated with CRC prognosis in this meta-analysis. However, the conclusion is preliminary and should be examined in future studies.

[Clinical observation of dog days moxibustion plaster therapy in treatment of allergic rhinitis of different patterns/syndromes].

OBJECTIVE: To explore the efficacy and feasibility of dog days moxibustion plaster therapy in treatment of allergic rhinitis of different patterns/syndromes. METHODS: Allergic rhinitis of lung deficiency and invasion of cold, spleen qi deficiency and kidney yang deficiency, 56 patients for each pattern/syndrome were randomized into a plaster therapy group and a nasal spray group, 28 cases in each one. In the plaster therapy group, according to the pattern/syndrome differentiation, with literature retrieval method, 3 acupoints of high frequency utility in clinic were selected as one group in acupoint plaster therapy. For lung deficiency and invasion of cold pattern/syndrome, Feishu (BL 13), Fengmen (BL 12) and Hegu (LI 4) were selected. For spleen qi deficiency pattern/syndrome, Pishu (BL 21), Zusanli (ST 36) and Dazhui (GV 14) were selected. For kidney yang deficiency pattern/ syndrome, Shenshu (BL 23), Dingchuan (EX-B 1) and Bailao (EX-HN 15) were selected. Separately, on July 13, 2013, July 23, 2013, August 2, 2013 and August 12, 2013, the aucpoint plaster therapy was applied, 2 to 4 h (1 to 2 h for children) each time. In the nasal spray group, beclometasone dipropionate aqueous nasal spray, 2 presses one nostril each time, 2 to 3 times a day, continuously for 4 weeks. The symptom score and efficacy were compared before and after treatment in the patients of the two groups. RESULTS: The symptom scores of 3 patterns/syndromes were all apparently improved after treatment as compared with those before treatment in the patients of the two groups (all P<0.05), and the result in the plaster therapy group was better than that of the nasal spray group (P<0.05, P<0.01). For lung deficiency and invasion of cold pattern/syndrome, the total effective rate was 87.3% (20/24) in the plaster therapy group, better than 84.6% (22/26) in the nasal spray group (P<0.05). For spleen qi deficiency pattern/syndrome, the total effective rate was 83.3% (20/24) in the plaster therapy group, obviously better than 76.9% (22/26) in the nasal spray group (P<0.05). For kidney yang deficiency pattern/syndrome, the total effective rate was 79.2% (19/24) in the plaster therapy group, better than 76.9% (22/26) in the nasal spray group (P<0.05). CONCLUSION: The dog days moxibustion plaster therapy achieves definite efficacy on allergic rhinitis at the acupoints selected based on the differentiation of different patterns/syndromes and the efficacy is better than beclometasone dipropionate aqueous nasal spray.