Coix seed oil alleviates synovial angiogenesis through suppressing HIF-1α/VEGF-A signaling pathways via SIRT1 in collagen-induced arthritis rats.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by symmetric arthritis. Coix Seed Oil (CSO) has been shown to reduce inflammation in collagen induced arthritis (CIA) rats. However, the effect of CSO on synovial angiogenesis in RA is unknown. In this study, we aimed to explore whether CSO could inhibit RA synovial angiogenesis and elucidate the underlying mechanisms. METHODS: CIA rat models were established and subjected to different doses of CSO treatments for four weeks in vivo. Arthritis index, paw swelling, and weight were recorded to assess clinical symptoms. Hematoxylin and Eosin staining, Safarnin O fast green staining, Micro-CT, Immunohistochemical, and Immunofluorescence (IF) staining were performed to examined changes in synovial and joint tissues. The serum HIF-1α and VEGF-A levels were evaluated through enzyme-linked immunosorbent assay. Fibroblast-like synoviocytes (FLS) of rats was stimulated with tumor necrosis factor-α (TNF-α) for developing inflammatory model in vitro. Optimal concentrations of CSO and TNF-α for stimulation were measured through Cell Counting Kit-8 test. Wound healing and Transwell migration experiments were employed to determine FLS migratory ability. IF staining was performed to assess HIF-1α nuclear translocation in FLS. Protein levels of SIRT1, HIF-1α, VEGF-A, and CD31 were assessed through Western blot. The isolated aortic rings were induced with recombinant rat VEGF-A 165 (VEGF-A165) to observe the CSO inhibitory impact on angiogenesis ex vivo. RESULTS: CSO attenuated the progression of arthritis in CIA rats, mitigated histopathological deterioration in synovial and joint tissues, significantly inhibited immature vessels labeled with CD31+/αSMA-, and reduced the micro-vessels in VEGF-A165 induced aortic rings. Moreover, it upregulated SIRT1 protein levels in CIA rats and TNF-α induced FLS, but decreased HIF-1α and VEGF-A protein levels. Furthermore, CSO inhibited the migration ability and HIF-1α nuclear translocation of TNF-α induced FLS. Finally, suppressing SIRT1 levels in TNF-α induced FLS enhanced their migration ability, HIF-1α nuclear translocation, and the protein levels of HIF-1α, VEGF-A, and CD31, whereas the inhibitory effect of CSO on TNF-α induced FLS was severely constrained. CONCLUSIONS: This study indicates that CSO can alleviate synovial angiogenesis through suppressing HIF-1α/VEGF-A signaling pathways via SIRT1 in CIA rats.

Intestinal microbiota changes in Graves' disease: a prospective clinical study.

Graves' disease (GD) occurs due to an autoimmune dysfunction of thyroid gland cells, leading to manifestations consistent with hyperthyroidism. Various studies have confirmed the link between autoimmune conditions and changes in the composition of intestinal microbial organisms. However, few studies have assessed the relationship between the GD and the changes in intestinal microbiota. Therefore, the present study aimed to investigate changes in intestinal flora that may occur in the setting of GD. Thirty-nine patients with GD and 17 healthy controls were enrolled for fecal sample collection. 16S rRNA sequencing was used to analyze the diversity and composition of the intestinal microbiota. High-throughput sequencing of 16S rRNA genes of intestinal flora was performed on Illumina Hiseq2500 platform. Comparing to healthy individuals, the number of Bacilli, Lactobacillales, Prevotella, Megamonas and Veillonella strains were increased, whereas the number of Ruminococcus, Rikenellaceae and Alistipes strains were decreased among patients with GD. Furthermore, patients with GD showed a decrease in intestinal microbial diversity. Therefore, it indicates that the diversity of microbial strains is significantly reduced in GD patients, and patients with GD will undergo significant changes in intestinal microbiota, by comparing the intestinal flora of GD and healthy controls. These conclusions are expected to provide a preliminary reference for further researches on the interaction mechanism between intestinal flora and GD.

Trends in incidence of esophageal and gastric cardia cancer in high-risk areas in China.

Incidence rates have risen for gastric cardia adenocarcinoma, whereas rates have remained stable for esophageal squamous cell carcinoma in many western countries. The aim of this study was to describe and analyze trends in incidence rates for esophageal cancer and gastric cardia cancer in Cixian county, which is one of the high-risk areas for esophageal cancer in China as well as in the world. The data were obtained from the Cixian Cancer Registry, which is a population-based registry. All the data were checked and analyzed using SPSS 11.5. Between the years 1988 and 2003 there were 11,183 cases of esophageal cancer in the county. The age-standardized incidence rate was 168.55 per 100,000. In 1988, the age-standardized incidence rate for male patients was 250.76/100,000; it declined to 160.05/100,000 in 2003, representing a decrease of 36.2%. The age-standardized incidence rate for female patients was 153.86/100,000 in 1988; it declined to 82.55/100,000 in 2003, showing a decrease of 46.3%. A slight decreasing trend was observed during the period, with a yearly decrease of 3.61% in male patients and 3.39% in female patients. For gastric cardia cancer, there were 1654 cases from 1988 to 2003. The age-standardized incidence rate was 25.58 per 100,000. The age-standardized incidence rate for male patients was 13.75/100,000 in 1988; it increased to 28.55/100,000 in 2003, with a yearly increase of 7.65%. The age-standardized incidence rate for female patients was 7.12/100,000 in 1988; it increased to 12.91/100,000, with a yearly increase of 5.44%. A statistically significant increasing trend of gastric cardia cancer was observed during the study period. Cixian county is a geographical region with a very high incidence of esophageal cancer and cardia cancer. The trend in the incidence rates of esophageal cancer had decreased slightly; on the other hand, gastric cardia cancer showed a significantly increased trend in the last 16 years. Detailed epidemiological analyses of demographic trends and risk factors will help to guide future cancer control strategies.

Decrease in the esophageal cancer incidence rate in mountainous but not level parts of Cixian County, China, over 29 years.

BACKGROUND: Cixian county has one of the highest incidence rates of esophageal cancer (EC) in China, as well as the world. In 1974, the Cixian population-based cancer registry system was established, so that there is now information on esophageal cancer cases over almost 30 years. METHODS: Data from Cixian Cancer Registry were checked and analyzed using SPSS 11.5. RESULTS: From 1974 to 2002, a total of 18,471 new esophageal cancer cases were registered in Cixian, 11,068 in males and 7,403 in females. The age standardized incidence rate (ASR) for males was 208.77 per 100,000, while for females it was 120.47 per 100,000. There was a clear trend for decrease overall in the incidence rate of esophageal cancer over the 29 years (X(2)=19.94, P<0.001). As to the geographic distribution, the incidence rate in mountainous and hilly areas showed a significant decline (X(2) = 195.00 and X(2) = 46.08, respectively, both P X(2)0.001). Data for esophageal cancer incidence in level land areas in contrast were relatively steadily, with increase in recent years. CONCLUSION: Esophageal cancer has decreased in Cixian county during the last 29 years, but this is due to change in mountainous and hilly areas. Compared to other regions in the world, Cixian county still has a very high incidence of ECs.

An analysis of esophageal cancer incidence in Cixian county from 1974 to 1996.

AIM: To describe the incidence of esophageal cancer (EC) in Cixian, a county of Hebei province during 1974-1996. We analyzed the sex and age characteristics as well as the geographic distribution of EC, in order to determine the impact so that methods of preventing and controlling EC in Cixian can be put in place. METHODS: Since the early 1970s, the cancer registry system has been established, which collects the cancer incidence in Cixian county. The malignant tumors were coded according to International Classification of Disease IX (ICD-9). All the data were checked and analyzed using EPIINFO. RESULTS: The trend of the incidence rate of EC from 1974 to 1996 had declined, (229.9/100 000 vs 178.5/100 000, Odds ratio=1.47, 95 % CI:1.32-1.63, chi(2)=52.89. trend chi(2)=26.54, P<0.001). The incidence rate of males declined significantly (281.81/100 000 vs 157.96/100 000, Odds ratio=1.61, 95 % CI: 1.41-1.84, chi(2)=47.85. Trend chi(2)=44.86, P<0.001), whereas, the females remained steady (157.96/100 000 vs 133.41/100 000, odds ratio=1.28, 95 % CI:1.17-1.49, chi(2)=9.26. trend chi(2)=2.69, P>0.05). Male average annual incidence rate was 142.80/100 000 and the female's was 95.18/100 000. The sex ratio (males to females) was 1.50:1. The incidence rate was increasing along with the age. As to the geographic distribution, the incidence rate in mountainous areas and hilly areas showed a significantly declining trend (mountainous areas, trend chi(2)=149.93, P<0.001; hilly areas, trend chi(2)=42.70, P<0.001). The incidence rate of EC in plain areas had increased (trend chi(2)=22.39, P<0.001). CONCLUSION: The incidence rate of EC in Cixian county shows a trend and has declined after two decades, especially in mountainous area. But compared to other regions in the world, Cixian county still had a high incidence rate of EC.