Yan-Ning Yang

Increased Expression of RelA/Nuclear Factor-κB Protein Correlates with Colorectal Tumorigenesis

Objective: To identify the role of RelA/nuclear factor-ĸB, an important inhibitor of apoptosis in colorectal tumorigenesis, we examined the expression of RelA in normal colorectal mucosa (n = 10), colorectal adenomas (n = 30) and colorectal adenocarcinomas (n = 30). Furthermore, the association of RelA expression with tumor cell apoptosis, proliferation, and expression of Bcl-2/Bcl-xL was also studied. Methods: Paraffin sections were stained with monoclonal antibodies directed against RelA, Bcl-2, Bcl-xL, and Ki-67 to assess protein expression patterns in normal, adenomatous and colon cancer tissue. Apoptotic cells were detected by terminal deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labeling (TUNEL) using an in situ detection kit. Results: The results of immunohistochemical staining revealed that expression of RelA, Bcl-2, Bcl-xL, and Ki-67 labeling index (LI) significantly increased in the transition from adenoma with low dysplasia to adenocarcinoma. This transition was associated with a significant decrease in the apoptotic index (AI) and a significant increase in the Ki-67 LI. The expression of RelA correlated inversely with the AI and correlated positively with the expression of Bcl-2, Bcl-xL, and Ki-67 LI in the transition from low-grade dysplasia to adenocarcinoma. Conclusion: Our results suggest that increased expression of RelA/nuclear factor-ĸB plays an important role in the transition from colorectal adenoma with low-grade dysplasia to adenocarcinoma in the pathogenesis of colon cancer in humans.

The effects of acetylsalicylic acid on proliferation, apoptosis, and invasion of cyclooxygenase-2 negative colon cancer cells

Background Acetylsalicylic acid (ASA, aspirin), the most common nonsteroidal anti‐inflammatory drug (NSAID), has been shown to have a protective effect against the incidence and mortality of colorectal cancer. However, the mechanism of its anticancer function remains unclear. The aim of this study was to determine the effects of acetylsalicylic acid on proliferation, apoptosis, and invasion in human cyclooxygenase‐2 (COX‐2) negative colorectal cancer cell lines.

Matrix metalloproteinases (MMP-2 and 9) and tissue inhibitors of matrix metalloproteinases (TIMP-1 and 2) during the course of experimental necrotizing herpetic keratitis

To determine the distribution and activities of metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) during the course of experimental herpes simplex virus (HSV) type-1 keratitis, BALB/c mice were corneally infected with 10(5) plaque-forming units (PFU) of HSV-1 (KOS strain) and then observed for the clinical signs of keratitis. Corneas were harvested at days 0, 2, 7 and 14 post-infection (p.i.). MMP-2, MMP-9, MMP-8, TIMP-1 and TIMP-2 were detected by immunohistochemistry and the Western blot technique. The enzymatic activities were analyzed by zymography. Epithelial HSV keratitis was present at day 2 after corneal infection and healed by day 5 p.i. While the expression and activity of MMP-2, MMP-8 and MMP-9 increased in the corneas at day 2 p.i., it was reduced at day 7 p.i. TIMP-1 and -2 were expressed in the corneas before and seven days after infection. Necrotizing stromal keratitis with corneal ulceration and dense polymorphonuclear leukocyte (PMN) infiltration was present at day 14 p.i. This correlated with increased expression of MMP-2, MMP-8 and MMP-9 in the corneas. MMP-8, MMP-9 and MMP-2 staining was particularly intense in the proximity of the ulcers and in areas of PMN infiltration. At day 14 p.i., MMP-2, -8 and -9 activities were upregulated, and TIMP-2 was expressed. These data suggest that MMPs produced by resident corneal cells and PMNs may possibly play a role in early epithelial keratitis and in the ulcerative process in the late phase after corneal HSV-1 infection. The ratio of MMPs to TIMPs may be important for the course of necrotizing HSV keratitis. TIMPs might participate in the repair process.

Increased abundance of cyclooxygenase-2 correlates with vascular endothelial growth factor-A abundance and tumor angiogenesis in gastric cancer

To understand the role of cyclooxygenase-2 (COX-2) in gastric cancer, we examined the abundance of COX-2, vascular endothelial growth factor-A (VEGF-A), and CD34 in 45 surgically resected human gastric cancers and paired normal gastric mucosa by immunohistochemical analysis. In addition, the message RNA (mRNA) expression of COX-2 and VEGF-A was evaluated in ten fresh surgically resected human gastric cancers and paired normal gastric mucosas using semi-quantitative reverse transcriptional polymerase chain reaction analysis. Our results confirmed an increased abundance of COX-2 and VEGF-A, and the microvessel density, which was assessed by CD34 abundance, in gastric cancer tissues compared with normal paired mucosa. Abundance of COX-2 and VEGF-A was significantly associated with tumor-node-metastasis (TNM) stage (P<0.05) and lymph node metastasis (P<0.001). In addition, abundance of VEGF-A associates with distance metastasis. A significant correlation was found between COX-2 and VEGF-A abundances (P<0.001). Both abundance of COX-2 and VEGF-A were significantly correlated with microvessel density (P<0.001, respectively). In six of ten cancerous tissues and in one of ten paired normal mucosas, the mRNA expression of COX-2 and VEGF-A was detected in the same specimen. In one other cancerous tissue, only COX-2 mRNA was detected. This study indicates that COX-2 is related to tumor angiogenesis in gastric cancer. VEGF-A might play a main role in the COX-2 angiogenic pathway.

Increased expression of nuclear factor-κB/RelA is correlated with tumor angiogenesis in human colorectal cancer

Background and aimsRecent studies have shown that nuclear factor-κ B/RelA (NF-κ B/RelA) is involved in tumor angiogenesis. This study examined whether NF-κ B/RelA expression is associated with vascular endothelial growth factor (VEGF) expression and microvessel density in human colorectal cancer.Materials and methodsTen specimens from normal colorectal mucosa and 52 colorectal adenocarcinomas were obtained by surgery or endoscopy. Immunohistochemical expression of NF-κ B/RelA, VEGF, and CD34 was detected on paraffin-embedded tissue sections.ResultsNF-κ B/RelA and VEGF were significantly overexpressed and associated with microvessel density in colorectal cancer. A significant association was found between NF-κ B/RelA and VEGF expression. Clinicopathological features were not correlated with NF-κ B/RelA, VEGF expression, or microvessel density.ConclusionOur results suggest that increased expression of NF-κ B/RelA contributes to tumor angiogenesis in colorectal cancer. VEGF may play an important role in mediating the NF-κ B/RelA angiogenic pathway.

TNF-α stimulates MMP-2 and MMP-9 activities in human corneal epithelial cells via the activation of FAK/ERK signaling.

Aims: Herpes simplex virus type-1-induced herpes simplex keratitis (HSK) is a common immunological cornea disease. While previous studies have addressed the role of tumor necrosis factor (TNF)-α and matrix metalloproteinases (MMPs) in HSK, the mechanistic link between TNF-α and MMPs in the pathogenesis of HSK remains elusive. Methods: We first established a HSK mice model and measured the levels of TNF-α, MMP-2 and MMP-9 in the corneas at different time points by ELISA. Next, we employed cultured human corneal epithelial (HCE) cells as an in vitro model and performed gelatin zymography analysis. Results: We observed that the change in the TNF-α level shared a similar pattern to that of MMP-2 and MMP-9 in the HSK mice model. Furthermore, TNF-α stimulated MMP-2 and MMP-9 activities in a dose-dependent manner, but either knockdown of focal adhesion kinase (FAK) by short interference RNA or inhibition of extracellular regulated protein kinase (ERK) by chemical inhibitor could block TNF-α-stimulated MMP-2 and MMP-9 activities in vitro. Taken together, our results provide in vivo evidence that the TNF-α level is positively correlated with MMP-2 and MMP-9 levels in a HSK model and in vitro evidence that TNF-α stimulates MMP-2 and MMP-9 activities via the activation of FAK/ERK signaling in HCE cells. Conclusions: Our findings shed new light on the pathogenesis of HSK and open up new possibility of modulating the TNF-α-FAK-ERK signaling cascade to pursue therapeutic measures for HSK.

Inhibition of cytosolic phospholipase A2 mRNA expression: a novel mechanism for acetylsalicylic acid-mediated growth inhibition and apoptosis in colon cancer cells

Acetylsalicylic acid (ASA) has been confirmed to inhibit proliferation and to induce apoptosis in human colorectal cancer cells in vitro. However, the mechanism by which ASA exhibits antiproliferative and proapoptotic effects in cyclooxygenase 2 (COX-2)-negative cells remains to be further elucidated. In the present study, SW480, a COX-2-negative colon cancer cell line, was treated with various concentrations of ASA (0, 2.5, 5, and 10 mM). The antiproliferative and proapoptotic effects of ASA were confirmed by MTT assay, flow cytometry of propidium iodide (PI)-stained cells, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. After treatment with ASA, intracellular cyclic AMP (cAMP) levels were increased and the production of prostaglandin E2 (PGE2) was decreased. RT-PCR analysis revealed that treatment of ASA induced a concentration-dependent downregulation of cytosolic phospholipase A2 (cPLA2) mRNA expression in SW480 cells and also in two other colorectal cancer cell lines, Colo320 and HT-29 cells. Intracellular calcium levels were unaffected by ASA treatment. Our results indicate that the ASA-induced downregulation of cytosolic phospholipase A2 mRNA expression might be a novel mechanism for ASA-mediated growth inhibition and apoptosis in colon cancer cells.

Prevalence of infectious keratitis in Central China

BackgroundThe baseline data pertaining to the national epidemiological survey of infectious keratitis remain scarce in China, and currently there is no corneal blindness control strategy developed by the nation.MethodsGeographically defined cluster sampling was used to randomly select a cross-section of residents from representative urban and rural populations in Hubei Province. Participants were selected from village registers, followed by door-to-door household visits. The assessment items included a structured interview, visual acuity testing, external eye examination, and anterior segment examination using slit lamp. Causes and sequelae of corneal disease were identified according to uniform customized protocol.ResultsThe prevalence of presenting corneal diseases was 0.8% (211/26 305), while the prevalence of infectious keratitis was 0.148% (39/26 305). The prevalences of viral, bacterial, and fungal keratitis were 0.065, 0.068, and 0.015%, respectively. There were no significant differences found between the prevalences of viral (accounting for 43.6%) and bacterial (accounting for 46.2%) corneal ulcers. cases of Acanthamoeba keratitis were not found. Infectious keratitis was the leading cause of corneal blindness (85.7%), and the prevalence of blindness in at least one eye resulting from infected corneas was 0.091% (95% CI: 0.067-0.127%).ConclusionsViral and bacterial mechanisms constitute the most important risk factors for infectious corneal ulcers in Central China. To reduce the rate and severity of infectious keratitis, he public health care policy should be focused on designing cost-effective strategies and operational programs for the prevention and prompt treatment of infectious corneal ulcers.

Risk Factors for Dry Eye Syndrome: A Retrospective Case-Control Study.

Purpose To investigate the independent risk factors of dry eye syndrome (DES) in Chinese. Methods A hospital-based age- and sex-matched population was enrolled with a case-control ratio of 1:2, with 789 DES case patients and 1119 healthy family members. Both groups underwent standard ophthalmologic examinations, including slit-lamp evaluation of the anterior segment, measurement of tear film breakup time, Schirmer test, and corneal fluorescein staining. Data on demographic characteristics and lifestyle habits were collected using a questionnaire. Dry eye syndrome risk factors were identified by univariate and multivariate logistic regression analyses. Results The following independent risk factors showed significant association with DES: diabetes (odds ratio [OR], 1.408; 95% confidence interval [CI], 1.031 to 1.924), hepatitis C (OR, 3.326; 95% CI, 1.632 to 6.776); connective tissue disease (OR, 2.157; 95% CI, 1.679 to 2.771), benign prostatic hyperplasia (OR, 3.892; 95% CI, 2.476 to 6.116), rosacea (OR, 3.747; 95% CI, 1.972 to 7.120), posttraumatic stress disorder (OR, 1.449; 95% CI, 1.043 to 2.013), hematopoietic stem cell transplantation (OR, 7.269; 95% CI, 2.312 to 22.849), head and neck radiotherapy (OR, 8.776; 95% CI, 3.096 to 24.873), postmenopausal estrogen therapy (OR, 1.912; 95% CI, 1.160 to 3.151), antihistamines (OR, 2.040; 95% CI, 1.516 to 2.746), antidepressants (OR, 1.982; 95% CI, 1.077 to 3.647), contact lenses (OR, 2.366; 95% CI, 1.266 to 4.423), and video display terminal exposure for more than 6 h/d (OR, 2.275; 95% CI, 1.451 to 3.568). Potentially protective factors against DES were vitamin supplements (OR, 0.716; 95% CI, 0.528 to 0.972) and &OHgr;-3 fatty acid–rich diet (OR, 0.514; 95% CI, 0.332 to 0.796). Conclusion Several known risk factors of DES are applicable to Chinese, and some distinctive dietary factors may be protective in this population.

Assessment of visual outcomes of cataract surgery in Tujia nationality in Xianfeng County, China

AIM To evaluate the visual outcome and factors influencing visual outcome of manual small incision cataract surgery (MSICS) in the rural area in the Xianfeng County. METHODS Eighty-two eyes of 82 patients who underwent cataract surgery performed by using MSICS technique were identified. Data collected included each patients age, gender, the level of education. Uncorrected and corrected distance visual acuity (UDVA and CDVA) at presentation and at 1, 6, 8wk postoperatively, pre-existing eye disease, operative findings and complications, the risk factors were evaluated. RESULTS In 82 patients, the average age was 69.6±0.6y, illiterate were 52 (63.4%). Of 82 eyes, pseudophakia was present in 77 eyes (93.9%). At 1wk postoperatively, 47 eyes (57.3%) had the UDVA of ≥6/18, and 52 eyes (63.4%) had the CDVA of ≥6/18. At 6 to 8wk postoperatively, 50 eyes (61.0%) had UDVA of ≥6/18, and 57 eyes (69.5%) had the CDVA of ≥6/18. Postoperative visual status was significantly related to the co-morbidities, such as corneal pathology, glaucoma (P<0.001). Operative complications, such as posterior capsule opacity and cystoid macular edema were main operative cause for the poor visual outcome. CONCLUSION MSICS provides a good visual recovery in our study but the vision outcome did not fulfill the standards proposed by WHO, which highlights the need for an improvement in local socioeconomic understanding, population education and surgery quality.