Quercetin, a natural flavonol existing in many food resources, has been reported to be an effective antimicrobial and anti-inflammatory agent for restricting the inflammation in periodontitis. In this study, we aimed to investigate the anti-inflammatory effects of quercetin on Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide- (LPS-) stimulated human gingival fibroblasts (HGFs). HGFs were pretreated with quercetin prior to LPS stimulation. Cell viability was evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The levels of inflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), along with chemokine interleukin-8 (IL-8), were determined by enzyme-linked immunosorbent assay (ELISA). The mRNA levels of IL-1β, IL-6, IL-8, TNF-α, IκBα, p65 subunit of nuclear factor-kappa B (NF-κB), peroxisome proliferator-activated receptor-γ (PPAR-γ), liver X receptor α (LXRα), and Toll-like receptor 4 (TLR4) were measured by real-time quantitative PCR (RT-qPCR). The protein levels of IκBα, p-IκBα, p65, p-p65, PPAR-γ, LXRα, and TLR4 were characterized by Western blotting. Our results demonstrated that quercetin inhibited the LPS-induced production of IL-1β, IL-6, IL-8, and TNF-α in a dose-dependent manner. It also suppressed LPS-induced NF-κB activation mediated by TLR4. Moreover, the anti-inflammatory effects of quercetin were reversed by the PPAR-γ antagonist of GW9662. In conclusion, these results suggested that quercetin attenuated the production of IL-1β, IL-6, IL-8, and TNF-α in P. gingivalis LPS-treated HGFs by activating PPAR-γ which subsequently suppressed the activation of NF-κB.

To investigate the role of Δ133p53 isoform in nuclear factor-κB (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC)-mediated growth inhibition of MKN45 gastric cancer cells. The growth rate of MKN45 cells after treatment with different concentrations of only PDTC or PTDC in combination with cisplatin was detected by the CCK-8 assay. mRNA expression levels of Δ133p53, p53β, and the NF-κB p65 subunit and p65 protein levels were detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence, respectively. Growth of MKN45 cells was significantly inhibited by PDTC alone in a dose-dependent manner (P < 0.01). Moreover, the inhibitory effect of cisplatin was remarkably enhanced in a dose-dependent manner by co-treatment with PDTC (P < 0.01). RT-PCR analysis revealed that mRNA expression of p65 was curbed significantly in a dose-dependent manner by treatment with only PDTC (P < 0.01), and this suppressive effect was further enhanced when co-treated with cisplatin (P < 0.01). With respect to the other p53 isoforms, mRNA level of Δ133p53 was significantly reduced in a dose-dependent manner by treatment with only PDTC or PTDC in combination with cisplatin (P < 0.01), whereas p53β mRNA expression was not altered by PDTC treatment (P > 0.05). A similar tendency of change in p65 protein expression, as observed for the corresponding mRNA, was detected by immunofluorescence analysis (P < 0.01). Pearson correlation analysis demonstrated that Δ133p53 and p65 mRNA expression levels were positively related, while no significant relationship was observed between those of p65 and p53β (r = 0.076, P > 0.01). Δ133p53 isoform (not p53β) is required in PDTC-induced inhibition of MKN45 gastric cancer cells, indicating that disturbance in the cross-talk between p53 and NF-κB pathways is a promising target in pharmaceutical research for the development of treatment strategies for gastric cancer.

Background: Numerous studies have demonstrated long noncoding RNA (lncRNA) play an important role in the occurrence and progression of cancer, and single nucleotide polymorphisms (SNPs) located in lncRNA are considered to affect cancer suspensibility. Herein, a meta-analysis was carried out to better assess the relationship of H19 polymorphisms and cancer susceptibility. Methods: A literature search was conducted through using PubMed, EMBASE, and Web of Science databases to obtain relevant publications before Aug 23, 2022. The reference lists of the retrieved studies were also investigated to identify additional relevant articles. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to appraise the risk of various cancers. Results: There appeared to be a remarkable correlation between the rs2107425 variation and decreased cancer risk among Caucasians. Nevertheless, the rs217727 polymorphism was significantly associated with an increased risk of lung cancer, hepatocellular carcinoma and oral squamous cell carcinoma. Also, we found a significant correlation between the rs2839698 polymorphism and increased cancer risk among Asians, gastric cancer, hepatocellular carcinoma, hospital-based control and larger simple size subgroups, respectively. Similarly, the rs3741219 mutation was notably related to cancer risk in higher quality score. As for rs3024270 polymorphism, the homozygous model was markedly linked to cancer risk in overall analysis and population-based controls. There was no significant association between the rs3741216 polymorphism and cancer risk. Conclusion: H19 rs2839698 and rs3024270 were closely associated with overall cancer risk. H19 rs2107425 was related to lower cancer risk among Caucasians, while the rs2839698 was related to increased cancer risk among Asians. Our results supported that H19 SNPs were significantly correlated with cancer risk.

The etiology of gastric cancer is associated with infectious, environmental and dietary factors, as well as genetic background. Additionally, emerging evidence has supported the vital role of chronic emotional stress on gastric carcinogenesis; however, the underlying mechanism remains unclear. The present study aimed to investigate the effects of chronic stress and a detrimental diet on gastric malignant epithelial transformation in rats. Therefore, 26 Wistar rats were randomly divided into the following four groups: i) Control; ii) detrimental diet (DD); iii) detrimental diet with chronic restraint (DR) and iv) detrimental diet with chronic restraint and propranolol treatment (DRP). ELISA was performed to detect the serum levels of epinephrine and norepinephrine. Epithelial cell apoptosis was analyzed using the TUNEL assay. The mRNA and protein expression levels of Akt and p53 were detected using reverse transcription quantitative PCR and western blotting, respectively. Pathological changes were analyzed using hematoxylin and eosin staining (H&E). The H&E staining results showed that dysplasia in the gastric mucosa occurred in two of eight rats in the DD group and in four of five rats in the DR group, whereas no dysplasia was detected in the DRP group. The apoptotic ratios of gastric epithelial cells were significantly decreased in all treatment groups compared with the control group. Adrenoceptor β2 (ADRB2) protein expression levels were increased significantly only in the DR group and this effect was significantly reduced in the DRP group. The mRNA expression levels of Akt and p53 were significantly upregulated in the DD group, and Akt mRNA expression was further elevated in the DR group. With regard to protein expression, the levels of Akt and p‑Akt were significantly increased in the DR group, whereas these effects were reversed in the DRP group. Furthermore, the ratio of p‑p53/p53 protein was significantly reduced in the DD or DR groups, but was reversed in the DRP group. Collectively, the findings of the present study suggested that chronic restraint stress potentially aggravates the gastric epithelial malignant transformation induced by a detrimental diet, at least partially via the Akt/p53 signaling pathway mediated via ADRB2.

The aim of the present work was to investigate the risk factors for gastric cancer‐ (GC‐) associated thrombotic diseases in a Han Chinese population. A total of 333 patients diagnosed with GC, 68 with thrombotic diseases included in the case group and the remaining 265 in the control group, were enrolled. The relevant data for the participants, including general information (gender, age, smoking, and drinking), comorbidities (diabetes, hypertension, and anemia), tumor‐related data (tumor site, histology, degree of differentiation, and clinical stage), and treatment‐related data (surgery, chemotherapy, hormones, transfusion, and peripherally inserted central venous catheter (PICC)), were collected. Statistically significant factors derived from univariate analyses were then subjected to multivariate logistic regression analyses. The results demonstrate a statistically significant difference in age, diabetes, hypertension, histology, surgery, chemotherapy, and PICC (P < 0.05), compared with control. Age, diabetes, surgery, and PICC serve as independent risk factors for GC‐associated thrombotic diseases (P < 0.05). The present work demonstrates that GC‐associated thrombotic diseases are significantly associated with age, diabetes, surgery, and PICC, suggesting a potential target for early detection and preventive strategy for GC patients with thrombophilia.