The recently published articles about the pathogenesis of osteoarthritis were reviewed.Osteoarthritis(OA)is characterized by cartilage degradation,osteophyte and involvement of the synovium.Mechanics,inflammatory mediators and aging collide studies in developmental,genetic and joint disease models indicate that Wnt/?-catenin signaling is critically involved in these processes.Many different factors contribute to the onset and progression of OA and Wnt/?-catenin signaling plays a vital role in these processes.

Objective To study the microRNA ( miRNA) regulation on the expression of housekeeping and non-house-keeping human genes from the systemic level , and to reveal the influence of conservation at 3′UTRs region for the density difference of miRNA regulatory between the two classes of genes .Methods We obtained miRNA regulation informations for the two classes of genes through the integration analysis of three sequence-based target gene prediction softwares and the conjoint analysis based on gene expression profile data .We also used phastCons-score based evolution analysis to study the conservation of 3′UTRs regions between the two classes of genes .Results Our results showed that housekeeping genes have a significantly higher density of miRNA binding sites and their 3′UTR are relatively conservative .Conclusion These findings highlight the importance of miRNA regulation in housekeeping genes , suggesting that investigating the roles of miR-NAs on the robustness of housekeeping genes expression is highly necessary .

Objective:To investigate the predictive value of KAI1 expression in colon cancer tissues for tumor recurrence.Methods:Ninety-two pathological tissue samples were collected from patients undergoing radical operation for colon cancer in Tangshan People's Hospital from August 2010 to November 2011. According to the results of follow-up, the patients were divided into recurrent group (33 cases) and non-recurrent group (59 cases). KAI1 expression in tumor tissues was detected by immunohistochemistry. χ2 test was used to analyze the relationship between KAI1 expression in colon cancer tissues and clinicopathological characteristics of patients with colon cancer. Spearman correlation test was used to analyze the relationship between KAI1 expression in colon cancer tissues and the recurrence time of patients. Cox proportional hazards model was used to analyze the related factors affecting postoperative recurrence of colon cancer. Results:KAI1 expression in tumor tissues in the recurrent group was lower than that in the non-recurrent group [39.39% (13/33) vs. 62.71% (37/59), χ2 = 4.638, P = 0.031]. KAI1 expression was not associated with patients' gender, age and tumor maximum diameter (all P > 0.05), but related to the tumor differentiation and lymphatic metastasis [high and medium differentiation vs. low differentiation: 70.3% (26/37) vs. 43.6% (24/55), χ2 = 6.324, P =0.012; lymph node metastasis vs. non-lymph node metastasis: 43.2% (19/44) vs. 64.6% (31/48), χ2 = 4.238, P = 0.039]. KAI1 expression in tumor tissues was positively correlated with tumor recurrence time ( r = 0.845, P < 0.05). Cox multivariate analysis showed that the low differentiation of the tumor, lymph node metastasis and negative expression of KAI1 in colon cancer tissues were independent risk factors for recurrence of colon cancer after surgery ( HR = 1.736, 95% CI 1.598-5.391, P = 0.019; HR =1.526, 95% CI 1.175-3.029, P = 0.037; HR = 1.799,95% CI 1.756-5.825, P = 0.013). Conclusion:Low KAI1 expression in colon cancer tissues is closely related to colon cancer recurrence, and the detection of KAI1 expression in colon cancer tissues has certain predictive value for tumor recurrence.

Objective To investigate the modulatory effect of Yulian Pills(composed of Coptidis Rhizoma and Euodiae Fructus)on splenic memory follicular T helper cell(mTfh)in mice with dextran sodium sulfate(DSS)-induced ulcerative colitis.Methods Forty BALB/c mice were randomly divided into normal group,model group,Yulian Pills group(0.5 g·kg-1)and Mesalazine group(0.3 g·kg-1),10 mice in each group.The mouse model of ulcerative colitis was induced by ad libitum drinking 3%DSS solution for 7 days.During the experiment,the mental state,faecal characteristics,blood in stool and body mass of the mice were recorded daily,and the length and mass of the colon were measured and the colon mass index was calculated;HE staining was used to observe the pathological and morphological changes of the colon tissue;ELISA was used to determine the expression levels of interleukin(IL)-6 and IL-15 in the colon tissues;flow cytometry was used to determine the mTfh cell subpopulation in the spleen tissue expression;Western Blot was used to determine the protein expression levels of Roquin-1,AMPK-α,p-AMPK-α in colon tissues.Results Compared with the normal group,the mice in the model group showed a significant decrease in body mass(P＜0.01),a significant shortening of colon length(P＜0.01),significant increase in colon mass(P＜0.05)and colon mass index(P＜0.01),and severe pathological damage to colon tissues;the expression levels of the pro-inflammatory cytokines IL-6 and IL-15 in the colon tissues were significantly increased(P＜0.01);cell expression levels of CD4+CCR7-CXCR5+CD62L+,CD4+CCR7+CXCR5+ GL7+,CD4+CCR7-CXCR5+GL7+ were significantly increased in spleen tissues(P＜0.01),whereas the expression level of CD4+CCR7+CXCR5+CD62L+ cell was significantly decreased(P＜0.01);and protein expression levels of Roquin-1,AMPK-α,p-AMPK-α were significantly reduced in the colonic tissues(P＜0.05).Compared with the model group,mice in the Yulian Pills group and Mesalazine group showed a significant increase in body mass(P＜0.05),a significant extension of colon length(P＜0.01),a significant reduction in colon mass(P＜0.05),a significant decrease in the colon mass index(P＜0.01),and a more obvious improvement in pathological damage of the colon tissues;a significant decrease in the expression levels of IL-6 and IL-15 in the colon tissues(P＜0.01);cell expression levels of CD4+CCR7-CXCR5+CD62L+,CD4+CCR7+CXCR5+GL7+,CD4+CCR7-CXCR5+GL7+ in splenic tissues was significantly reduced(P＜0.01),whereas the expression level of CD4+CCR7+CXCR5+CD62L+ cell was significantly increased(P＜0.01);the protein expression levels of Roquin-1,AMPK-α,and p-AMPK-α were significantly increased in colon tissues(P＜0.05,P＜0.01).Conclusion The therapeutic effect of Yulian Pills on DSS-induced ulcerative colitis mice can ameliorate the histopathological damage of colon,which may be related to the activation of the Roquin-1/MPK-α signalling pathway,the down-regulation of the expressions of inflammatory cytokines IL-6 and IL-15,and the modulation of the homeostasis of the mTfh cell subpopulation.

BACKGROUND: Currently, a significant number of miners are involved in mining operations at the Gejiu tin mine in Yunnan. This occupational setting is associated with exposure to dust particles, heavy metals, polycyclic aromatic hydrocarbons, and radioactive radon, thereby significantly elevating the risk of lung cancer. This study aims to investigate the involvement of leptin-mediated extracellular regulated protein kinase (ERK) signaling pathway in the malignant transformation of rat alveolar type II epithelial cells induced by Yunnan tin mine dust. METHODS: Immortalized rat alveolar cells type II (RLE-6TN) cells were infected with Yunnan tin mine dust at a concentration of 200 μg/mL for nine consecutive generations to establish the infected cell model, which was named R₂₀₀ cells. The cells were cultured normally, named as R cells. The expression of leptin receptor in both cell groups was detected using the Western blot method. The optimal concentration of leptin and mitogen-activated protein kinase kinase (MEK) inhibitor (U0126) on R₂₀₀ cells was determined using the MTT method. Starting from the 20th generation, the cells in the R group were co-cultured with leptin, while the cells in the R₂₀₀ group were co-cultured with the MEK inhibitor U0126. The morphological alterations of the cells in each group were visualized utilizing hematoxylin-eosin staining. Additionally, concanavalin A (ConA) was utilized to detect any morphological differences, and an anchorage-independent growth assay was conducted to assess the malignant transformation of the cells. The changes in the ERK signaling pathway in epithelial cells after the action of leptin were detected using the Western blot method. RESULTS: Both the cells in the R group and R₂₀₀ group express leptin receptor OB-R. Compared to the R₂₀₀ group, the concentration of leptin at 100 ng/mL shows the most significant pro-proliferation effect. The proliferation of R₂₀₀ cells infected with the virus is inhibited by 30 μmol/L U0126, and a statistically significant divergence was seen when compared to the control group (P<0.05). Starting from the 25th generation, the cell morphology of the leptin-induced R₂₀₀ group (R₂₀₀L group) underwent changes, leading to malignant transformation observed at the 30th generation. The characteristics of malignant transformation became evident by the 40th generation in the R₂₀₀L group. In contrast, the other groups showed agglutination of P40 cells, and the speed of cell aggregation increased with an increase in ConA concentration. Notably, the R₂₀₀L group exhibited faster cell aggregation compared to the U0126-induced R₂₀₀ (R₂₀₀LU) group. Additionally, the cells in the R₂₀₀L group were capable of forming clones starting from P30, with a colony formation rate of 2.25‰±0.5‰. However, no clonal colonies were observed in the R₂₀₀LU group and R₂₀₀ group. The expression of phosphorylated extracellular signal-regulated kinase (pERK) was enhanced in cells of the R₂₀₀L group. However, when the cells in the R₂₀₀L group were treated with U0126, a blocking agent, the phosphorylation level of pERK decreased. CONCLUSIONS Leptin can promote the malignant transformation of lung epithelial cells infected by mine dust, and the ERK signaling pathway may be necessary for the transformation of alveolar type II epithelial cells induced by Yunnan tin mine dust.
Rats ; Animals ; Alveolar Epithelial Cells/pathology* ; Dust ; Tin/adverse effects* ; Lung Neoplasms/pathology* ; Leptin/adverse effects* ; Receptors, Leptin ; China ; Signal Transduction ; Epithelial Cells/pathology* ; Mitogen-Activated Protein Kinase Kinases/adverse effects*