[Effect of proximal fibula osteotomy on tension of lateral knee soft tissue in patients with knee osteoarthritis].

OBJECTIVE: To evaluate the short-term efficacy of proximal fibula osteotomy in the treatment of knee osteoarthritis, and to analyze the effect of osteotomy on the tension of the lateral knee soft tissue of patients and verify the reliability of the Arch string theory. METHODS: A total of 71 patients with varus knee osteoarthritis from December 2019 to March 2022 were included, 3 patients dropped out, and 68 patients completed all trials, collected 27 males and 41 females, aged from 51 to 79 years old, with an average of (68.0±7.0 ) years old. The follow-up time ranged from 4 to 12 weeks, with an average of (3.76±1.94) weeks. After admission, the patient underwent Proximal fibula osteotomy, and the tension of lateral knee soft tissue, visual analogue scale (VAS) of pain, the western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and other indicators were recorded before surgery and 1 month after surgery in the weight-bearing state. RESULTS: According to the VAS, the curative effect of a single index was evaluated by referring to the score before and after treatment by Bao Zongzhao. Thirty seven cases were markedly effective, 27 cases were effective, and 4 cases were ineffective. After surgery, 3 patients presented with weakness of dorsalis pedis extension and 1 presented with paresthesia of dorsalis pedis, which disappeared after symptomatic treatment . The VAS and WOMAC score at 1 month after operation were lower than those before operation, and the differences were statistically significant(P<0.001). The tension of lateral knee soft tissue 1 month after operation was lower than that before operation, and the difference had statistical significance(P<0.001). CONCLUSION: Proximal fibula osteotomy is safe and effective in the treatment of varus knee osteoarthritis in the short term. One month after osteotomy, the tension of lateral knee soft tissue increases under weight-bearing state, but the long-term changes still need further observation and follow-up.

Prediction of adenocarcinoma and squamous carcinoma based on CT perfusion parameters of brain metastases from lung cancer: a pilot study.

Objectives: Predicting pathological types in patients with adenocarcinoma and squamous carcinoma using CT perfusion imaging parameters based on brain metastasis lesions from lung cancer. Methods: We retrospectively studied adenocarcinoma and squamous carcinoma patients with brain metastases who received treatment and had been pathologically tested in our hospital from 2019 to 2021. CT perfusion images of the brain were used to segment enhancing tumors and peritumoral edema and to extract CT perfusion parameters. The most relevant perfusion parameters were identified to classify the pathological types. Of the 45 patients in the study cohort (mean age 65.64 ± 10.08 years; M:F = 24:21), 16 were found to have squamous cell carcinoma. Twenty patients were with brain metastases only, and 25 patients were found to have multiple organ metastases in addition to brain metastases. After admission, all patients were subjected to the CT perfusion imaging examination. Differences in CT perfusion parameters between adenocarcinoma and squamous carcinoma were analyzed. The receiver operating characteristic (ROC) curves were used to predict the types of pathology of the patients. Results: Among the perfusion parameters, cerebral blood flow (CBF) and mean transit time (MTT) were significantly different between the two lung cancers (adenocarcinoma vs. squamous cell carcinoma: p < 0.001, p = 0.012.). Gender and tumor location were identified as the clinical predictive factors. For the classification of adenocarcinoma and squamous carcinoma, the model combined with CBF and clinical predictive factors showed better performance [area under the curve (AUC): 0.918, 95% confidence interval (CI): 0.797-0.979). The multiple organ metastasis model showed better performance than the brain metastasis alone model in subgroup analyses (AUC: 0.958, 95% CI: 0.794-0.999). Conclusion: CT perfusion parameter analysis of brain metastases in patients with primary lung cancer could be used to classify adenocarcinoma and squamous carcinoma.

Predictive Values of Blood Type I and Type II Interferon Production for Disease Activity and Clinical Response to TNF-α Blocking Therapy in Patients with Ankylosing Spondylitis.

Tumor necrosis factor-α (TNF-α) blocking therapy is recommended to treat ankylosing spondylitis for patients who fail to respond to nonsteroidal anti-inflammatory drugs (NSAIDs). Herein, we attempt to dissect whether blood type I and II interferon (IFN) production can be predictive of ankylosing spondylitis progression and treatment response to the tumor necrosis factor inhibitor (TNFi). A total of 50 ankylosing spondylitis patients receiving originator TNFi with a 6-month period were retrospectively analyzed. The patients who reached the Assessment of SpondyloArthritis international Society 40 (ASAS40) response at the 6-month interval were classified as responders (n = 29) to TNFi treatment, otherwise as non-responders (n = 21). The serum type I IFN activity, and the serum levels of IFN-α and IFN-γ in the patients at baseline were notably greater than the healthy controls. Pearson correlation analysis showed positive correlations in the patients between the serum type I IFN activity or the serum levels of IFN-α and IFN-γ, and BASDAI scores, ASDASCRP or pro-inflammatory factor production. The responders were demonstrated with reduced serum type I IFN activity concomitant with lower serum levels of IFN-α and IFN-γ compared to the non-responders after anti-TNF treatment. The serum type I IFN activity, and the serum levels of IFN-α and IFN-γ used as a test to predict responders and non-responders to anti-TNF treatment produced an area under the curve (AUC) of 0.837, 0.814, and 0.787, respectively. In conclusion, the study demonstrates that blood type I and II IFN production may be correlated with disease activity, inflammatory cytokine production, and indicative of unsatisfying response to TNFi treatment in ankylosing spondylitis patients.

Hypoxia-induced FOXO4/LDHA axis modulates gastric cancer cell glycolysis and progression.

BACKGROUND AND AIM: We previously identified forkhead box (FOX) O4 mRNA as a predictor in gastric cancer (GC). However, the underlying mechanism has yet to be elucidated. We aimed to illustrate the mechanism by which FOXO4 regulated glycolysis under hypoxia in GC. METHODS: FOXO4 protein expression was investigated by immunohistochemical staining of 252 GC and their normal adjacent tissues. We restored or silenced FOXO4 expression in GC cell lines to explore the underlying mechanisms. RESULTS: FOXO4 was downregulated in GC. Loss of FOXO4 expression was validated in univariate and multivariate survival analysis as an independent prognostic predictor for overall survival (P < 0.05) and disease-free survival (P<0.05). Restored FOXO4 expression significantly impaired the glycolysis rate in GC cells, while silencing FOXO4 expression enhanced glycolysis rate. FOXO4 expression was inversely associated with maximum standardized uptake value in mice models and patient samples. Mechanistically, FOXO4 bound to the glycolytic enzyme lactate dehydrogenase (LDH)A promoter and inactivated its activity in a dose-dependent manner (P < 0.05). Finally, we determined that FOXO4 was a transcriptional target of hypoxia-inducible factor (HIF) -1α, which is central in response to hypoxia. CONCLUSIONS: Our data suggested that FOXO4 plays a key role in the regulation of glycolysis in GC, and disrupting the HIF-1α-FOXO4-LDHA axis might be a promising therapeutic strategy for GC.

Histone deacetylase-1 as a prognostic factor and mediator of gastric cancer progression by enhancing glycolysis.

Histone deacetylase 1 (HDAC1) has been shown to be closely associated with tumor development. We investigated its effects on survival and biological behavior in gastric cancer (GC). HDAC1 expression and glycolysis activity were analyzed in a cohort of 252 samples of primary GC tumors and in vitro study. High HDAC1 (HDAC1High) staining was seen in 60.7% patients with GCs, which was significantly greater than was seen in normal epithelial cells (19.4%; P < .005). HDAC1High expression was associated with larger tumor size (P = .001), advanced T stage (P = .001), lymph node metastases (N stage; P < .001), and lymphovascular invasion (P = .005). Univariate and multivariate survival analyses showed HDAC1 expression to be an independent prognostic factor for both disease-free survival and overall survival (P < .05). In vitro studies showed a notably decreased glycolysis rate in HDAC1 knockdown cells. In patients' samples, HDAC1High expression was always accompanied with high Maximal standardized uptake value (SUVmax) value (P < .05). A hypoxia-inducible factor (HIF)-1α response element-luciferase reporter system showed HDAC1 to affect HIF1α activity in a dose-dependent manner. In conclusion, HDAC1 promotes glycolysis in GC and affects HIF-1α activity in tumor progression and metastasis. HDAC1High expression was also an independent adverse prognostic factor for overall survival and disease-free survival.

Aldolase A as a prognostic factor and mediator of progression via inducing epithelial-mesenchymal transition in gastric cancer.

Glycolysis is regarded as the hallmark of cancer development and progression, which involves a multistep enzymatic reaction. This study aimed to explore the clinicopathological significance and potential role of glycolytic enzyme aldolase A (ALDOA) in the carcinogenesis and progression of gastric cancer (GC). ALDOA was screened from three paired liver metastasis tissues and primary GC tissues and further explored with clinical samples and in vitro studies. The ALDOA protein level significantly correlated with a larger tumor diameter (P = .004), advanced T stage (P < .001), N stage (P < .001) and lymphovascular invasion (P = .001). Moreover, the expression of ALDOA was an independent prognostic factor for the 5-year overall survival and disease-free survival of patients with GC in both univariate and multivariate survival analyses (P < .05). Silencing the expression of ALDOA in GC cell lines significantly impaired cell growth, proliferation and invasion ability (P < .05). Knockdown of the expression of ALDOA reversed the epithelial-mesenchymal transition process. Mechanically, ALDOA could affect the hypoxia-inducible factor (HIF)-1α activity as demonstrated by the HIF-1α response element-luciferase activity in GC cells. Collectively, this study revealed that ALDOA was a potential biomarker of GC prognosis and was important in the carcinogenesis and progression of human GC.

Diagnostic Accuracy of Magnifying Endoscopy with Narrow Band Imaging and Its Diagnostic Value for Invasion Depth Staging in Esophageal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND AND GOALS: This study aimed to investigate the diagnostic accuracy of magnifying endoscopy with narrow band imaging (ME-NBI) and determine its value for invasion depth staging in esophageal squamous cell carcinoma. METHODS: We searched the PubMed, Embase, and Cochrane Library databases and found relevant studies published up to December 2016. Quality Assessment of Diagnostic Accuracy Studies 2 was used to evaluate the quality of the studies. We calculated sensitivity, specificity, and positive and negative likelihood values from forest plots and determined summary receiver operating characteristic (sROC) curves for ME-NBI diagnostic accuracy analysis. RESULTS: Ten studies met our criteria and were selected for this meta-analysis. A total of 1,033 patients underwent ME-NBI, and 207 of these patients received a diagnosis of staging mucosal or submucosal invasion. The pooled sensitivity, specificity, and positive and negative likelihood values of ME-NBI for the diagnostic rate were 0.90 (95% CI, 0.71-0.97), 0.90 (95% CI, 0.80-0.95), 6.74 (95% CI, 3.52-712.89), and 0.20 (95% CI, 0.10-0.42), respectively. The area under the curve (AUC) was 0.95 for all studies. CONCLUSIONS: ME-NBI provides a high diagnostic rate in evaluating the esophagus to diagnose squamous cell carcinoma. In the differentiation for invasion depth staging, ME-NBI was demonstrated to be superior to white light endoscopy and had a similar diagnostic rate compared with HF-EUS. However, HF-EUS had high positive likelihood values for invasion depth staging, suggesting that HF-EUS is a reliable method for confirming invasion depth staging.

Krüppel-Like Factor 7 is a Marker of Aggressive Gastric Cancer and Poor Prognosis.

BACKGROUND/AIMS: Krüppel-like factor (KLF) 7 protein is a member of the KLF transcription factor family, which plays important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation and metabolism. However, the role of KLF7 in gastric cancer (GC) is unknown. The aim of this study is to explore the role of KLF7 in GC and its correlation with clinicopathological characteristics and prognosis of GC patients. METHODS: We first systematically evaluated dysregulation of the KLF family in The Cancer Genome Atlas (TCGA) GC database. Then, 252 patients who underwent surgery for GC were enrolled to validate the results from the TCGA. Functional studies were also used to explore the role of KLF7 in GC. RESULTS: In the TCGA database, we found that KLF7 was an independent predictor for survival by both univariate and multivariate analysis (P<0.05). In a validation cohort, KLF7 expression was significantly increased in GC tissues compared with adjacent normal controls (P=0.013). High KLF7 expression correlated with inferior prognostic factors, such as T stage (P=0.022), N stage (P =0.005) and lymphovascular invasion (P=0.009). Furthermore, we observed a strong negative correlation between KLF7 expression and 5-year overall survival and disease-free survival in GC patients (P<0.05). Moreover, our in vitro studies showed a notable decrease in migration in KLF7 knockdown cells. CONCLUSION: KLF7 has an important role in GC progression, as it inhibits GC cell migration and may serve as a prognostic marker.

Expression of PRR11 protein and its correlation with pancreatic cancer and effect on survival.

This study aimed at finding the relationship between the level of expression of the PRR11 protein in pancreatic carcinoma, and the clinical characteristics of the tumor. PCR technique was used to analyze the expression levels of the PRR11 gene in 38 samples from pancreatic cancer patients and 10 samples from normal pancreatic tissues. Western blot analysis and immunohistochemistry were used to measure the expression of the PRR11. Additionally, the migration ability of cancerous cells expressing PRR11 and those with inhibited expression were compared using a wound healing assay. Finally, the relationships between the expression level of PRR11 protein and variables such as tumor size, tumor invasion, TNM stages, and the overall survival time of patients with pancreatic cancer were calculated. Our results showed the expression level of the PRR11 gene in pancreatic cancer tissues was significantly higher than that in normal pancreatic tissues. The detection of PRR11 protein in cancer tissues versus normal tissues was 78.9 (30/38) vs. 0 (0/10), respectively. The western blot results confirmed this by showing a significantly higher level of expression of the PRR11 protein in pancreatic cancer tissues than in normal tissues (P<0.05). Inhibiting the expression of PRR11 in cancer cells reduced the migration ability of the cells. Finally, the expression of PRR11 was positively correlated with the invasion, disease and tissue differentiation stages of the pancreatic cancer. By comparing clinical data and expression patterns in patients, we found the survival rate in those expressing the PRR11 protein by immunohistochemistry to be lower than in those with tissues negative to the PRR11 protein. Our results show, the expression of PRR11 protein in pancreatic cancer is closely related to the development of the cancer and a poor prognosis. These findings provide a theoretical and experimental basis for approaching the diagnosis and treatment of pancreatic cancer using PRR11 as a molecular target.

Shen-Cao granules formulated based on traditional Chinese medicine alleviates bone marrow suppression caused by platinum-based anticancer reagents.

BACKGROUND: The aim of this study was to evaluate effects of Shen-Cao granules for the prevention of thrombocytopenia caused by anticancer chemotherapy. METHODS: In this prospective study, a total of 200 patients with various malignant tumors were enrolled and evenly divided into a Shen-Cao granule treatment (n = 100) and a control group (n = 100). After 2 cycles chemotherapy with any combination of platinum-based drugs (cisplatin, carboplatin, and nedaplatin), the blood platelet (PLT) counts, levels of the PLT production regulator thrombopoietin (TPO), PLT aggregation rates, and the PLT activation marker CD62P expressions were monitored for 2 weeks. RESULTS: During 2 weeks of post-chemotherapy, the mean values of the minimum PLT count were 49.65 ±â€Š7.35 × 10/L in the treatment group and 31.56 ±â€Š9.32 × 10/L in the control group. The PLT count in the treatment group reached the lowest value 1.8 days later and recovered to a concentration ≥100 × 10/L 3 days earlier than in the control group. The concentrations of the TPO were 71.43 ±â€Š1.74 and 87.24 ±â€Š0.92 ng/mL in the treatment group and 65.75 ±â€Š1.39 and 67.75 ±â€Š0.67 ng/mL in the control group at 7 and 14 days post-chemotherapy, respectively. The maximum PLT aggregation rate declined after chemotherapy in the treatment group from 58.14 ±â€Š11.46% to 52.89 ±â€Š10.52%, while it increased in the control group from 56.94 ±â€Š10.55% to 61.75 ±â€Š12.26%. Coordinately, the expression of CD62P in the treatment group decreased from 6.17 ±â€Š0.59% to 4.89 ±â€Š0.72%, while it increased from 6.09 ±â€Š0.75% to 7.75 ±â€Š0.67% in the control group. CONCLUSION: Our study demonstrated that Shen-Cao granule treatment alleviated thrombocytopenia after chemotherapy, and reduced tumor-induced PLT activation and aggregation.

RNA sequencing analysis reveals protective role of kruppel-like factor 3 in colorectal cancer.

The Kruppel-like factor (KLF) family of transcription factors plays an important role in embryonic formation and cancer progression. This study was performed to determine the clinical importance of the KLF family in colorectal cancer (CRC). In total, 361 patients with CRC from The Cancer Genome Atlas (TCGA) cohort were used to comprehensively study the role of the KLF family in CRC. The results were then further validated using an in-house cohort (n=194). Univariate and multivariate Cox proportional hazards models were used to assess the risk factors for survival. In the TCGA cohort, KLF3 (hazard ratio [HR], 0.501; 95% confidence interval [CI], 0.272-0.920; P=0.025), KLF14 (HR, 1.454; 95% CI, 1.059-1.995; P=0.020), and KLF17 (HR, 1.241; 95% CI, 1.030-1.494, P=0.023) were identified as potential biomarkers in the univariate analysis, but after Cox proportional hazards analysis, only KLF3 (HR, 0.473; 95% CI, 0.230-0.831; P=0.012) was shown to be independently predictive of overall survival in patients with CRC. This finding was validated in our in-house cohort, which demonstrated that KLF3 expression was an independent predictor of both overall survival (HR, 0.628; 95% CI, 0.342-0.922; P=0.035) and disease-free survival (HR, 0.421; 95% CI, 0.317-0.697, P=0.016). KLF3 expression was inversely correlated with the N stage (P=0.015) and lymphovascular invasion (P=0.020). Collectively, loss of KLF3 was correlated with aggressive phenotypes and poor survival outcomes. KLF3 might be a potential new predictor and therapeutic target for CRC. Further study is needed for a more detailed understanding of the role of KLF3 in CRC.

FOXO4 and FOXD3 are predictive of prognosis in gastric carcinoma patients.

Forkhead box (FOX) transcription factor family plays an important role in cancer growth and metastasis. This study aimed to determine the predictive ability of FOX genes in gastric carcinoma. A total of 360 patients with gastric from The Cancer Genome Atlas (TCGA) cohorts were collected in this study. The expression profile of FOX family were obtained from the TCGA RNAseq database. Clinicopathological characteristics, including age, gender, tumor node metastasis (TNM), tumor grade, and overall survival were collected. Univariate and multivariate Cox proportional hazards model were used to assess the risk factors for survival, and the results were further validated in in-house cohort. In the TCGA cohort, FOXO4 (HR = 0.613, 95%CI 0.452-0.832) and FOXD3 (HR = 1.704, 95%CI 1.212-2.397) were shown independently predictive of overall survival in gastric cancer after Cox proportional hazards analysis. The finding was validated in our in-house cohort, which demonstrated that both FOXO4 and FOXD3 were independent predictors for overall survival (FOXO4 high, HR: 0.445, 95%CI 0.277-0.715, P = 0.001, FOXD3 high, HR: 1.927, 95%CI 1.212-3.063, P = 0.006) and disease free survival (FOXO4 high, HR: 0.628, 95%CI 0.420-0.935, P = 0.022, FOXD3 high, HR: 1.698, 95%CI 1.136-2.540, P = 0.010).Collectively, FOX family paly critical roles in gastric cancer, and FOXO4 and FOXD3 were identified as independent prognostic factors for survival outcomes of gastric cancer. Further functional study is needed to understand more about FOX family in gastric cancer.

Effect of Age on Survival Outcome in Operated and Non-Operated Patients with Colon Cancer: A Population-Based Study.

OBJECTIVE: To know the effect of age on survival outcome in operated and non-operated patients with colon cancer. METHODS: From the Surveillance, Epidemiology, and End Results database, we identified 123,356 patients with colon cancer who were diagnosed between 1996 and 2005, grouped them as older or younger than 40 years and analyzed their 5-year cancer-specific survival (CSS) data, along with some risk factors, using Kaplan-Meier methods and multivariable Cox regression models. RESULTS: The younger group had significantly higher pathological grades (P<0.001), more mucinous and signet-ring histology (P<0.001), advanced AJCC stage (P<0.001), and were more likely to undergo surgery (P<0.001). For surgically treated patients, age did not significantly affect 5-year CSS (younger: 66.7%; older: 67.3%; P = 0.86). Further analysis showed that age was an independent prognostic factor in stage I-IV disease (stage I: P = 0.001; P<0.001 for stages II-IV, in both uni- and multivariate analyses), but not for patients with unknown disease stage (P = 0.52). For non-surgically treated patients, age significantly affected 5-year CSS (younger: 16.2%; older: 12.9%; P<0.001) in univariate analysis; and was an independent prognostic factor (P<0.001) in multivariate analysis. CONCLUSION: The CSS rate for younger CC patients was at least as high as for older patients, although they presented with higher proportions of unfavorable factors and more advanced disease.

Endoplasmic reticulum stress of Kupffer cells involved in the conversion of natural regulatory T cells to Th17 cells in liver ischemia-reperfusion injury.

BACKGROUND AND AIM: Our previous studies have shown that regulatory T cells (Tregs) are reduced and Th17 cells are elevated in liver insults. Recent studies have indicated the critical role of endoplasmic reticulum (ER) stress of Kupffer cells (KCs) in evoking liver inflammation following reperfusion. The objective of this study was to investigate the role of ER stress of KCs in the conversion of Tregs to Th17 cells and the effect on liver ischemia-reperfusion injury. METHODS: The partial warm liver ischemia-reperfusion injury mouse model was adopted. ER stress of KCs and the frequency of Tregs and Th17 cells following reperfusion were analyzed. Apart from depletion and adoptive transfer of KCs, KCs were isolated from ischemic lobes and co-cultured with Tregs to study the effect of KCs on Tregs and Th17 cells. RESULTS: It was found that KCs induced ER stress, decreased natural Tregs (nTregs), and increased Th17 cells after reperfusion. Depletion of KCs modulated the reduction of nTregs and elevation of Th17 cells. Co-culture with stressed KCs led to the reduction in nTregs and elevation of Th17 cells. This effect was suppressed by anti-interleukin-6. Adoptive transfer of these stressed KCs resulted in the reduction in nTregs and elevation of Th17 cells and caused liver injury. CONCLUSION: Endoplasmic reticulum stress of KCs contributed to the conversion of nTregs to Th17 cells due to interleukin-6, resulting in the worsening of liver insult.

Relief of diabetes by duodenal-jejunal bypass sleeve implantation in the high-fat diet and streptozotocin-induced diabetic rat model is associated with an increase in GLP-1 levels and the number of GLP-1-positive cells.

A recently invented duodenal-jejunal bypass sleeve (DJBS) implanted in the duodenum and proximal jejunum has exhibited good glycemic control in diabetes mellitus. However, the specific mechanism by which DJBS placement induces the remission of diabetes is not well known. Previous studies have indicated that changes in the pattern of gut hormone secretion may play a role. The aim of the present study was to explore the role of intestinal L cells and the production of glucagon-like peptide-1 (GLP-1) by these cells in DJBS implantation-induced glycemic control in diabetic rats. A DJBS was placed in the proximal small intestine of rats with diabetes induced by a high-fat diet and low-dose streptozotocin (STZ), and the effects of the DJBS on the remission of diabetes and the GLP-1 levels of plasma and intestinal tissues were investigated 12 weeks after DJBS placement. The number of intestinal GLP-1 positive cells was also counted. When the DJBS had been in place for 12 weeks, the plasma glucose level of the DJBS-implanted rats decreased significantly from 23.33±1.56 mmol/l prior to surgery to 7.70±0.84 mmol/l and the diabetes mellitus was relieved completely; however, diabetic control rats and diabetic rats subjected to sham surgery did not show any improvement. Parallel with the remission of diabetes, the plasma and distal ileum GLP-1 levels of rats in the DJBS implantation group were also higher than those of rats in the diabetic control and sham surgery groups. The number of GLP-1-positive cells in the distal ileum was also higher in the DJBS implantation group than in the diabetic control and sham surgery groups (31.0±2.6 vs. 23.5±4.4 vs. 23.0±3.2 respectively; P<0.01). DJBS implantation effectively led to the remission of diabetes in rats with diabetes induced by a high-fat diet and low-dose STZ when implanted for 12 weeks. The remission of diabetes may be associated with the increase in the number of L cells and elevation of GLP-1 levels induced by DJBS implantation.

Derlin-1 is overexpressed in human colon cancer and promotes cancer cell proliferation.

Derlin-1 is overexpressed in many types of solid tumors and plays an important role in cancer progression. However, the expression pattern and functions of Derlin-1 in human colon cancer are not fully understood. In the present study, we examined Derlin-1 expression in colon cancer cell lines and human tissues and investigated its role in colon cancer. We found that Derlin-1 expression was increased significantly in colon cancer tissues and its overexpression correlated with the tumor differentiation, Dukes stage, invasion, lymph node metastasis, distant metastasis, and poor overall survival. The silencing of Derlin-1 by shRNA led to the growth inhibition of colon cancer cells, which were associated with the promotion of apoptosis. Furthermore, Derlin-1 silencing significantly inhibited the activation of the PI3K/AKT signaling pathway. Taken together, our results showed that Derlin-1 is overexpressed in colon cancer and promotes proliferation of colon cancer cells. Derlin-1 may be a potential therapeutic target for the treatment of colon cancer.

miR-99 inhibits cervical carcinoma cell proliferation by targeting TRIB2.

MicroRNAs (miRNAs) have significant roles in cell processes, including proliferation, apoptosis and stress responses. To investigate the involvement of miR-99 in the inhibition of HeLa cell proliferation, an miR-99 gene expression vector (pU6.1/miR-99), which overexpressed miR-99 in HeLa cells after transient transfection, was constructed. The expression of miR-99 was detected by qPCR. Cell proliferation and apoptosis were analyzed by cell viability, proliferation and apoptosis assays, as well as by electron microscopy. The results showed that overexpression of miR-99 in HeLa cells increased the HeLa cell mortality rate. Moreover, miR-99 overexpression was able to markedly inhibit HeLa cell proliferation according to the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The cell apoptosis rate was significantly higher in pU6.1/miR-99-treated cells compared with that in the control cultures. Increases in intracellular electron density, as well as the proportion of nuclear plasma, blebbing phenomena and apoptotic bodies were observed in pU6.1/miR-99-treated cells compared with control cultures according to electron microscopy analysis. The Tribbles 2 (TRIB2) 3'-untranslated region was also observed to be targeted by miR-99 and the results further demonstrated that miR-99 was able to negatively regulate TRIB2 expression in HeLa cells The results indicate that miR-99 acts as a tumor suppressor gene in HeLa cells, establishing a theoretical basis for its application in cancer therapeutics.

The associations of single nucleotide polymorphisms in miR-146a, miR-196a and miR-499 with breast cancer susceptibility.

BACKGROUND: Previous studies have investigated the association between single nucleotide polymorphisms (SNPs) located in microRNAs (miRNAs) and breast cancer susceptibility; however, because of their limited statistical power, many discrepancies are revealed in these studies. The meta-analysis presented here aimed to identify and characterize the roles of miRNA SNPs in breast cancer risk, and evaluate the associations of polymorphisms in miR-146a rs2910164, miR-196a rs11614913 and miR-499 rs3746444 with breast cancer susceptibility, respectively. METHODOLOGY/PRINCIPAL FINDINGS: The PubMed and Embases databases were searched updated to 31(st) December, 2012. The complete data of polymorphisms in miR-146a rs2910164, miR-196a rs11614913 and miR-499 rs3746444 from case-control studies for breast cancer were analyzed by odds ratios (ORs) with 95% confidence intervals (CIs) to reveal the associations of SNPs in miRNAs with breast cancer susceptibility. Totally, six studies for rs2910164 in miR-146a, involving 4225 cases and 4469 controls; eight studies for rs11614913 in miR-196a, involving 4110 cases and 5100 controls; and three studies of rs3746444 in miR-499, involving 2588 cases and 3260 controls, were investigated in the meta-analysis. The rs11614913 (TT+CT) genotype of miR-196a2 was revealed to be associated with a decreased breast cancer susceptibility compared with the CC genotypes (OR = 0.906, 95% CI: 0.825-0.995, P = 0.039); however, no significant associations were observed between rs2910164 in miR-146a (or rs3746444 in miR-499) and breast cancer susceptibility. CONCLUSIONS: This meta-analysis demonstrates the compelling evidence that the rs11614913 CC genotype in miR-196a2 increases breast cancer risk, which provides useful information for the early diagnosis and prevention of breast cancer.

Antiviral activity of recombinant mouse ß-defensin 3 against influenza A virus in vitro and in vivo.

BACKGROUND: Influenza causes significant morbidity and mortality. Mammalian ß-defensins are small peptides of about 4.5-6 kDa in mass and are effectors of the innate immune response with potent antimicrobial activity. In this paper, we focused on the anti-influenza A activity of the recombinant mouse ß-defensin 3 (rMBD-3) in vivo and in vitro. METHODS: The rMBD-3 peptide was added to Madin-Darby canine kidney (MDCK) cells at different stages of influenza A virus (IAV) A/PR/8/34 (H1N1) infection and its virus inhibitory properties were determined. Mice were infected with IAV and treated with rMBD-3 peptide from 12 h post-infection. The effect of rMBD-3 peptide was determined by pulmonary viral load, pathology and mortality. In addition, the expression of interleukin (IL)-12, interferon (IFN)-γ and tumour necrosis factor (TNF)-α genes in mice with or without rMBD-3 treatment was determined by semi-quantitative reverse transcriptase PCR. RESULTS: rMBD-3 was shown to protect MDCK cells against IAV infection and had a major role in inhibition of adsorption and uptake by cells infected with IAV. Following the addition of 100 µg/ml rMBD-3 to MDCK cells medium, approximately 80% of cells were protected from infection in vitro. rMBD-3 given by tail vein injection (10 mg/kg/day) was the most effective method to improve the survival rate of the mice. Treatment with rMBD-3 was found to up-regulate IFN-γ and IL-12 gene expression, but reduced expression of the TNF-α gene. CONCLUSIONS: These results demonstrate that rMBD-3 possesses anti-influenza virus activity both in vivo and in vitro that might be of therapeutic use.

Expression of mouse beta defensin 2 in Escherichia coli and its broad-spectrum antimicrobial activity

Mature mouse beta defensin 2 (mBD2) is a small cationic peptide with antimicrobial activity. Here we established a prokaryotic expression vector containing the cDNA of mature mBD2 fused with thioredoxin (TrxA), pET32a-mBD2. The vector was transformed into Escherichia Coli (E. coli) Rosseta-gami (2) for expression fusion protein. Under the optimization of fermentation parameters: induce with 0.6 mM isopropylthiogalactoside (IPTG) at 34ºC in 2×YT medium and harvest at 6 h postinduction, fusion protein TrxA-mBD2 was high expressed in the soluble fraction (>95%). After cleaved fusion protein by enterokinase, soluble mature mBD2 was achieved 6 mg/L with a volumetric productivity. Purified recombinant mBD2 demonstrated clear broad-spectrum antimicrobial activity for fungi, bacteria and virus. The MIC of antibacterial activity of against Staphylococcus aureus was 50 µg/ml. The MIC of against Candida albicans (C. albicans) and Cryptococcus neoformans (C. neoformans) was 12.5µg/ml and 25µg/ml, respectively. Also, the antimicrobial activity of mBD2 was effected by NaCl concentration. Additionally, mBD2 showed antiviral activity against influenza A virus (IAV), the protective rate for Madin-Darby canine kidney cells (MDCK) was 93.86% at the mBD2 concentration of 100 µg/ml. These works might provide a foundation for the following research on the mBD2 as therapeutic agent for medical microbes.