Evaluation of cytokine expressions in patients with recurrent aphthous stomatitis: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to evaluate the expression levels of various T helper (Th) cell-secreted cytokines in recurrent aphthous stomatitis (RAS). Case-control studies comparing the serum or salivary levels of cytokines between RAS patients and healthy controls were searched in PubMed, EMBASE, Web of Science, and Google Scholar prior to September 30, 2023. Cytokines produced by Th1 (interleukin [IL]-1, IL-2, IL-8, IL-12, tumor necrosis factor alpha [TNF-α], interferon gamma [IFN-γ]), Th2 (IL-4, IL-5, IL-6, IL-10, IL-13), and Th17 (IL-17A) cells were investigated. The standard mean difference (SMD) with 95% confidence interval (CI) was calculated to detect the difference. A total of 20 studies comprising 1070 RAS patients and 536 healthy controls were included. RAS patients had significantly higher salivary levels of IL-2 (SMD = 4.15, 95%CI 0.83-7.48), IL-5 (SMD = 0.53, 95%CI 0.05-1.00), IL-6 (SMD = 0.48, 95%CI 0.12-0.84), IL-12 (SMD = 0.94, 95%CI 0.18-1.71), and TNF-α (SMD = 1.31, 95%CI 0.44-2.18) compared to healthy controls. Serum levels of IL-6 (SMD = 0.48, 95%CI 0.30-0.66), TNF-α (SMD = 0.70, 95%CI 0.22-1.17), and IFN-γ (SMD = 0.72, 95%CI 0.17-1.28) were significantly increased, while serum IL-10 levels (SMD = -2.25, 95%CI -3.99 to -0.52) were reduced in RAS patients. Patients diagnosed with major RAS had markedly elevated serum IL-8 levels (SMD = 0.39, 95%CI 0.07-0.71) and a trend toward higher serum IL-6 levels (SMD = 0.51, 95%CI -0.02 to 1.04) than those with minor RAS. In conclusion, Th1/Th2-related cytokines, especially IL-2, IL-6, and TNF-α, are involved in the pathogenesis of RAS development and progression and are potential therapeutic targets for RAS.

Safflor yellow treating angina pectoris: A pharmacoeconomic evaluation and network meta-analysis.

BACKGROUND: Coronary heart disease (CHD) is a cardiovascular disease caused by myocardial ischemia. In China, safflor yellow and artemisinin-based combination therapies have been extensively used to treat angina pectoris. METHODS: Efficacies were provided by a network meta-analysis following the PRISMA 2020 checklist. Cost-effectiveness analysis was based on patient perspectives. Two-way and probabilistic sensitivity analyses were conducted to assess the robustness of the study results. RESULTS: Conventional treatment combined with safflower is a better choice against angina pectoris. Sensitivity analysis showed that the model was sensitive to the treatment efficacy rather than the drug cost. CONCLUSION: Conventional treatment combined with safflower injection is suggested to treat angina pectoris. Low molecular weight heparin or compound Danshen-dropping pills can be used to increase the recovery rate of angina pectoris, according to conventional treatment combined with safflower injection.

Association between common polymorphisms in IL-1 and TNFα and risk of peri-implant disease: A meta-analysis.

BACKGROUND: Pro-inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor α (TNFα) play important roles in host immune response and bone metabolism during dental implant osseointegration. Whether the functional polymorphisms in IL-1α, IL-1ß and TNFα were associated with peri-implant disease was unclear, and we performed the present meta-analysis for this purpose. METHODS: Eligible studies investigating IL-1α C-889T, IL-1ß C+3954T and C-511T, TNFα G-308A, composite genotype of IL-1α C-889T and IL-1ß C+3954T for association with peri-implant disease, including peri-implantitis (PI), marginal bone loss (MBL) and implant failure/loss (IF/IL), were searched on several literature databases prior to April 30, 2021. Odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated for each polymorphism in different genetic models and for composite genotype comparing carriers to non-carriers. RESULTS: Twenty-seven studies (1324 cases with peri-implant disease and 1808 controls with healthy implants) were included. There was significant correlation between IL-1α C-889T and peri-implant disease in all genetic models. IL-1ß C+3954T was associated with peri-implant disease risk in allelic (OR = 1.66, 95%CI 1.17-2.35, p = 0.004) and dominant model (OR = 1.74, 95%CI 1.19-2.53, p = 0.004), and in subgroups of Asians, Caucasians, non-smokers, IF/IL and PI. TT genotype of IL-1ß C-511T increased the risk of peri-implant disease (OR = 1.68, 95%CI 1.15-2.43, p = 0.007) and MBL (OR = 4.33, 95%CI 1.72-10.9, p = 0.002) compared to CC+CT genotypes. We did not observed a significant association between TNFα G-308A and peri-implant diseases in overall or subgroups analysis. Carriers of positive composite genotype of IL-1α C-889T and IL-1ß C+3954T had 1.95-fold (95%CI 1.35-2.80, p<0.001) risk of peri-implant disease and 1.76-fold (95%CI 1.05-2.95, p = 0.032) risk of IF/IL than non-carriers. CONCLUSION: Functional polymorphisms of IL-1α (C-889T), IL-1ß (C+3954T, C-511T) and composite genotype of IL-1 can be used as predictive markers for peri-implant disease, whereas TNFα G-308A polymorphism was not associated with peri-implant disease.

Nobiletin selectively inhibits oral cancer cell growth by promoting apoptosis and DNA damage in vitro.

OBJECTIVES: The aim of this study was to investigate whether nobiletin (NOB) can inhibit the proliferation of oral squamous cell carcinoma (OSCC) cells by promoting apoptosis, oxidative stress (reactive oxygen species [ROS]), and DNA damage. STUDY DESIGN: OSCCs were treated with different concentrations of NOB (25, 50, and 100 µM) for different amounts of time (0, 24, 48, and 72 hours). The viability of NOB was assessed by using MTT-based cell viability assays. Flow cytometry was used to assess cell apoptosis, and the expressions of capase-3 and poly (adenosine diphosphate-ribose) polymerase (PARP) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses. The intensity of ROS fluorescence was measured by using a spectrophotometer. The expression of γH2AX and 8-Oxo-20-deoxyguanosine (8-oxodG) were assessed to determine the degree of DNA damage. RESULTS: We observed that NOB decreased OSCC cell viability in a dose- and time-dependent manner but had little effect on primary normal human oral epithelial cells (H0 ECs). Moreover, with the increase in NOB concentration and treatment time, capase-3, PARP messenger RNA (mRNA), and protein levels gradually increased, as did annexin V- and 7 adducin (ADD)-mediated apoptosis. In addition, NOB also increased the levels of ROS and DNA damage in a concentration- and time-dependent manner. CONCLUSIONS: NOB can inhibit OSCC cell by promoting apoptosis, ROS production, and DNA damage.

LPS-miR-34a-CCL22 axis contributes to regulatory T cell recruitment in periapical lesions.

Regulatory T cells (Tregs) have been shown to regulate the immune response and to control the defense against infection in periapical lesions, but the underlying mechanisms by which Tregs are recruited to these lesions remain unknown. Here we demonstrate that expression of the gene encoding CCL22 (also known as macrophage-derived chemokine), the major chemoattractant that recruits Tregs, is upregulated in periapical tissue during the progression of experimental periapical lesions; this upregulation positively correlated with the number of Tregs that accumulated in the lesions. In terms of mechanism, we determined that lipopolysaccharide (LPS) up-regulates Ccl22 expression in macrophages by suppressing miR-34a. These findings suggest that the LPS-miR-34a-CCL22 axis may contribute to the recruitment of Tregs in periapical lesions, providing a potential therapeutic target for controlling this disease.