Treatment effect of CDKN1A on rheumatoid arthritis by mediating proliferation and invasion of fibroblast-like synoviocytes cells.

The objective of the present study was to evaluate the role of CDKN1A in rheumatoid arthritis (RA). Related gene expression data screened from Gene Expression Omnibus (GEO) were processed with network analysis. Protein-protein interaction was analysed through string database. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to measure mRNA and microRNA expression. Cell proliferation and cell cycle were tested by MTT assay and flow cytometry, respectively. Transwell migration and invasion assay was used to test cell migration and invasion. CDKN1A screened by bioinformatics methods showed differential expression in RA cells compared with healthy controls (HC), and was at an important position in the protein-protein interaction network of RA. Compared with the HC group, CDKN1A was down-regulated in human RA synovium tissues and human fibroblast-like synoviocytes (HFLS). Contrary to CDKN1A silencing, CDKN1A over-expression significantly inhibited the proliferation and invasion of HFLS-RA, arrested HFLS-RA in G0/G1 phase and down-regulated the expressions of tumour necrosis factor (TNF)-α and interleukin (IL)-6, while it up-regulated the expression of IL-10. CDKN1A over-expression could also suppress phosphorylated signal transducers and activators of transcription 1 (pSTAT-1) expression. MiR-146a, highly expressed in RA tissues, could regulate CDKN1A negatively. Anti-146a suppressed cell proliferation and invasion, and at the same time enhanced IL-10 expression but inhibited IL-6, TNF-α and pSTAT-1 expression. The results indicated that CDKN1A over-expression, which could be enhanced by miR-146a suppression, inhibited the proliferation of invasion in HFLS-RA. This was probably a result of suppressed pSTAT-1, IL-6 and TNF-α expression and enhanced IL-10 expression.

An extensive study of the mechanism of prostate cancer metastasis.

The study aimed to identify the pivotal genes and pathways involved in prostate cancer metastasis. Using the expression profile dataset GSE7930, downloaded from the Gene Expression Omnibus (GEO) database, differentially expressed genes (DEGs) between primary and highly metastatic prostate cell samples were screened, followed by functional analysis and tumor associated genes (TAG) screening. Protein-protein interaction (PPI) network of DEGs was constructed and module analysis was performed. The expression of DEGs and pathway related genes were evaluated by PCR analysis and the migra- tion ability of prostate tumor cells was observed after FABP4-siRNA blocking. Upregulated FABP4 and GK were signifi- cantly enriched in the PPAR signaling pathway, whereas downregulated IGFBP3 and THBS1 were involved in p53 signaling pathway. Among the identified DEGs, 4 downregulated genes (IGFBP3, NPP4B, THBS1, and PCDH1) and 2 upregulated genes (GJA1 and TUSC3) were TAGs. The module was associated with focal adhesion, ECM-receptor interaction, p53 signaling, and gap junction pathways with the hub node GJA1. After FABP4 silencing by siRNAs in LNcap and metastatic DU-145 cells, the numbers of migrated cells were all significantly declined. The expressions of IGFBP3, TP53 and PPAR were significantly lower in DU-145 cells than in LNcap cells. In conclusion, FABP4, IGFBP3, THBS1, and GJA1 were determined to be potential markers of prostate cancer cell metastasis, and P53, PPAR and gap junction pathways were found to play important roles in prostate cancer cell metastasis. This study may provide helpful guidelines for clinical management.

Comparison of overfeeding effects on gut physiology and microbiota in two goose breeds.

To have a better understanding of how the "gut-liver axis" mediates the lipid deposition in the liver, a comparison of overfeeding influence on intestine physiology and microbiota between Gang Goose and Tianfu Meat Goose was performed in this study. After force-feeding, compared with Gang Goose, Tianfu Meat Goose had better fat storage capacity in liver (397.94 vs. 166.54 for foie gras weight (g), P < 0.05; 6.37 vs. 2.92% for the ratio of liver to body, P < 0.05; 60.01 vs. 46.64% for fat content, P < 0.05) and the less subcutaneous adipose tissue weight (1240.96 g vs. 1440.46 g, P < 0.05). After force-feeding, the digestion-absorption capacity of Tianfu Meat Goose was higher than that of Gang Goose (5.56 vs. 3.64 and 4.63 vs. 3.68 for the ratio of villus height to crypt depth in duodenum and ileum, respectively, P < 0.05; 1394.96 vs. 782.59 and 1314.76 vs. 766.17 for the invertase activity (U/mg-prot), in duodenum and ileum, respectively, P < 0.05; 6038.36 vs. 3088.29 and 4645.29 vs. 3927.61 for the activity of maltase (U/mg-prot), in duodenum and ileum, respectively, P < 0.05). Force-feeding decreased the gene expression of Escherichia coli in the ileum of Tianfu Meat Goose; force-feeding increased the number of gut microbiota Enterobacterial Repetitive Intergenic Consensus-Polymerase Chain Reaction band in Tianfu Meat Goose and decreased the number in Gang Goose. In conclusion, compared with Gang Goose, the lipid deposition in the liver and the intestine digestion-absorption capacity and stability were higher in Tianfu Meat Goose. Thereby, Tianfu Meat Goose is the better breed for foie gras production for prolonged force-feeding; Gang Goose possesses better fat storage capacity in subcutaneous adipose tissue. However, Gang Goose has lower gut stability responding to force-feeding, so Gang Goose is suited to force-feeding in a short time to gain the body weight and subcutaneous fat as an overfed duck for roast duck.

Biotechnological implications from abscisic acid (ABA) roles in cold stress and leaf senescence as an important signal for improving plant sustainable survival under abiotic-stressed conditions.

In the past few years, the signal transduction of the plant hormone abscisic acid (ABA) has been studied extensively and has revealed an unanticipated complex. ABA, characterized as an intracellular messenger, has been proven to act a critical function at the heart of a signaling network operation. It has been found that ABA plays an important role in improving plant tolerance to cold, as well as triggering leaf senescence for years. In addition, there have been many reports suggesting that the signaling pathways for leaf senescence and plant defense responses may overlap. Therefore, the objective was to review what is known about the involvement of ABA signaling in plant responses to cold stress and regulation of leaf senescence. An overview about how ABA is integrated into sugars and reactive oxygen species signaling pathways, to regulate plant cold tolerance and leaf senescence, is provided. These roles can provide important implications for biotechnologically improving plant cold tolerance.

Effect of saw palmetto soft gel capsule on lower urinary tract symptoms associated with benign prostatic hyperplasia: a randomized trial in Shanghai, China.

PURPOSE: We determined the effect of Prostataplex in men with lower urinary tract symptoms associated with benign prostatic hyperplasia. MATERIALS AND METHODS: A total of 92 Chinese men between 49 and 75 years old with lower urinary tract symptoms were randomly assigned in this double-blind, placebo controlled trial. The 46 patients in the intervention group were given 2 Prostataplex soft gels daily for 12 weeks, while the 46 in the control group were given 2 placebo soft gels for the same time. RESULTS: The treated and control groups appeared to have more than a 95% compliance rate, as judged by counting the remaining pills in the bottle collected at the end of trial months 1 to 3. After 12 weeks of intervention the mean +/- SD maximum urinary flow rate was significantly higher in the treatment group than in the control group (14.07 +/- 2.56 vs 11.74 +/- 1.23 ml per second, p <0.001), while relative urinary resistance was significantly lower in the treatment group than in the control group (2.35 +/- 0.83 vs 3.02 +/- 1.18, p = 0.002). While there was no significant difference in mean prostate volume or International Prostate Symptom Score between the 2 groups, 18 of 46 patients (39.1%) in the treatment group showed an International Prostate Symptom Score improvement (decrease of 3 or greater) after intervention, whereas only 1 of 46 (2.2%) in the control group showed an International Prostate Symptom Score improvement (chi-square test p <0.001). CONCLUSIONS: Prostataplex may have short-term effects in improving symptoms and objective measures in Chinese men with lower urinary tract symptoms associated with benign prostatic hyperplasia.

[Molluscicidal effect of suspension concentrate of niclosamide ethanolamine salt].

Objective To evaluate the molluscicidal effect of suspension concentrate of niclosamide ethanolamine salt (SCNE) against Oncomelania hupensis snails in laboratory and field. Methods The experiment of SCNE against the snails by using the immersing and spraying methods was performed in laboratory and field, with control groups of wettable powder of niclosamide ethanolamine salt (WPN). Results In the laboratory, LC50(s) of SCNE for 24, 48 h and 72 h by using the immersion method were 0.092 6, 0.062 9 mg/L and 0.054 9 mg/L, respectively. The mortality rates of snails for 24, 48 h and 72 h by using the immersion method were all 100% with the concentrations of 0.25 mg/L. The mortality rates of snails were all 100% while spraying SCNE for 3 d in the laboratory with the concentrations of 0.25 g/m2. In Jiangling County, except 0.5 g/m3 SCNE immersing the snails for 24 h, the mortality rates of snails by using SCNE with the immersing method were all 100%. While the concentration of SCNE was 0.5 g/m3 or above, the mortality rates were all 100% after the use of it with the immersion method for 2 d in Gong'an County. In Jiangling County, the mortality rates of snails by using SCNE 0.5 g/m3 for 1 d, 3 d, and 7 d with the spraying method were 87.5%, 92.82% and 97.40% respectively. While the concentration of SCNE was 0.5 g/m3, the mortality rates were 85.94%, 86.78% and 94.21% respectively after the use of it with the spraying method for 1 d, 3 d, 7 d in Gong'an County, and the molluscicidal effect of SCNE (1.0 g/m2) was higher than that of WPN. Conclusion SCNE has a high molluscicidal effect in the laboratory and field, and it is a novel and simple formulation of niclosamide.

Reduced urinary excretion of intact osteopontin in patients with IgA nephropathy.

Osteopontin (OPN) is a phosphoprotein secreted by many cells of epithelial, mesenchymal, and hematopoietic origin. In the kidney, OPN is expressed in the renal tubules and collecting ducts and is excreted into the urine. A pathophysiologic role for urinary OPN has not been established. In this study, urinary excretion of OPN was analyzed in patients with primary glomerular diseases, including immunoglobulin A nephropathy (IgAN; n = 32), minimal change nephrotic syndrome (MCNS; n = 16), and membranous nephropathy (MN; n = 18). Compared with normal controls (n = 20), mean +/- SD of urinary OPN in IgAN patients was decreased significantly (21.4 +/- 6.2 versus 11.6 +/- 9.6 mg/g creatinine, P: < 0.001). In contrast, the levels of urinary OPN in patients with MCNS or MN did not differ significantly from normal values. Immunoblot analysis showed that OPN is present as a 55- to 60-kd molecule in normal urine. A 34-kd fragment of OPN was the major immunoreactive band in samples from IgAN patients. This fragment also was detectable in the urine from some patients with MCNS or MN but was absent in normal subjects. OPN has a thrombin-cleavage site near its central portion. Thrombin treatment of the urine from normal controls could result in 34-kd OPN fragments. Although the underlying mechanisms remain to be determined, these data provide evidence that secretion or processing (or both) of urinary OPN is altered in patients with IgAN.

Obesity, hypertension and diabetes mellitus affect complication rate of different nephrectomy techniques.

INTRODUCTION: To investigate whether obesity, hypertension, and diabetes mellitus (DM) would increase post-nephrectomy complication rates using standardized classification method. METHODS: We retrospectively included 843 patients from March 2006 to November 2012, of whom 613 underwent radical nephrectomy (RN) and 229 had partial nephrectomy (PN). Modified Clavien classification system was applied to quantify complication severity of nephrectomy. Fisher's exact or chi-square test was used to assess the relationship between complication rates and obesity, hypertension, as well as DM. RESULTS: The prevalence of obesity, hypertension, and DM was 11.51%, 30.84%, 8.78%, respectively. The overall complication rate was 19.31%, 30.04%, 35.71% and 36.36% for laparoscopic radical nephrectomy (LRN), open-RN, LPN and open-PN respectively. An increasing trend of low grade complication rate as BMI increased was observed in LRN (P=.027) and open-RN (P<.001). Obese patients had greater chance to have low grade complications in LRN (OR=4.471; 95% CI: 1.290-17.422; P=0.031) and open-RN (OR=2.448; 95% CI: 1.703-3.518; P<.001). Patients with hypertension were more likely to have low grade complications, especially grade ii complications in open-RN (OR=1.526; 95% CI: 1.055-2.206; P=.026) and open PN (OR=2.032; 95% CI: 1.199-3.443; P=.009). DM was also associated with higher grade i complication rate in open-RN (OR=2.490; 95% CI: 331-4.657; P=.016) and open-PN (OR=4.425; 95% CI: 1.815-10.791; P=.013). High grade complication rates were similar in comparison. CONCLUSIONS: Obesity, hypertension, and DM were closely associated with increased post-nephrectomy complication rates, mainly low grade complications.

CPEB1, a histone-modified hypomethylated gene, is regulated by miR-101 and involved in cell senescence in glioma.

Epigenetic mechanisms have important roles in carcinogenesis. We certified that the mRNA translation-related gene cytoplasmic polyadenylation element-binding protein 1 (CPEB1) is hypomethylated and overexpressed in glioma cells and tissues. The knockdown of CPEB1 reduced cell senescence by regulating the expression or distribution of p53 in glioma cells. CPEB1 is also regulated directly by the tumor suppressor miR-101, a potential marker of glioma. It is known that the histone methyltransferase enhancer of zeste homolog 2 (EZH2) and embryonic ectoderm development (EED) are direct targets of miR-101. We demonstrated that miR-101 downregulated the expression of CPEB1 through reversing the methylation status of the CPEB1 promoter by regulating the presence on the promoter of the methylation-related histones H3K4me2, H3K27me3, H3K9me3 and H4K20me3. The epigenetic regulation of H3K27me3 on CPEB1 promoter is mediated by EZH2 and EED. EZH2 has a role in the regulation of H3K4me2. Furthermore, the downregulation of CPEB1 induced senescence in a p53-dependent manner.

La obesidad, la hipertensión y la diabetes mellitus afectan la tasa de complicaciones de las diferentes técnicas de nefrectomía / Obesity, Hypertension and Diabetes Mellitus Affect Complication Rate of Different Nephrectomy Techniques

Introducción: Nuestro objetivo es investigar si la obesidad, la hipertensión y la diabetes mellitus (DM) aumentan la tasa de complicaciones tras nefrectomía empleando métodos de clasificación estandarizados. Métodos: Incluimos retrospectivamente 843 pacientes desde marzo de 2006 hasta noviembre de 2012, 613 de los cuales fueron sometidos a nefrectomía radical (NR) y 229 a nefrectomía parcial (NP). Se empleó el sistema de clasificación de Clavien modificado para cuantificar la gravedad de las complicaciones de la nefrectomía. Para evaluar la relación entre las tasas de complicaciones y la obesidad, la hipertensión, así como la DM, se emplearon el test exacto de Fisher y la prueba de Chi cuadrado. Resultados: La prevalencia de la obesidad, la hipertensión y la DM fue del 11,51, 30,84 y 8,78%, respectivamente. La tasa global de complicaciones fue del 19,31, 30,04, 35,71 y 36,36% para la NR laparoscópica (NRL), la NR abierta, NPL y NP abierta respectivamente. Se observó una tendencia creciente en la tasa de complicaciones leves al aumentar el IMC en la NRL (p = 0,027) y en la NR abierta (p < 0,001). Los pacientes obesos tenían más probabilidades de sufrir complicaciones leves en la NRL (OR = 4,471; IC 95%: 1,290-17,442; p = 0,031) y en la NR abierta (OR = 2,448; IC 95%: 1,703-3,518; p < 0,001). Los pacientes con hipertensión eran más propensos a sufrir complicaciones leves, especialmente complicaciones de grado II en una NR abierta (OR = 1,526; IC 95%: 1,055-2,206; p = 0,026) y en una NP abierta (OR = 2,032; IC 95%: 1,199-3,443; p = 0,009). La DM también se asoció con una mayor tasa de complicaciones de grado I en la NR abierta (OR = 2,490; IC 95%: 331-4,657; p = 0,016) y en la NP abierta (OR = 4,425; IC 95%: 1,815-10,791; p = 0,013). En comparación, las tasas de complicaciones severas fueron similares. Conclusiones: La obesidad, la hipertensión y la DM están estrechamente relacionadas con unas tasas más elevadas de complicaciones, principalmente leves, tras nefrectomía

Introduction: To investigate whether obesity, hypertension, and diabetes mellitus (DM) would increase post-nephrectomy complication rates using standardized classification method. Methods We retrospectively included 843 patients from March 2006 to November 2012, of whom 613 underwent radical nephrectomy (RN) and 229 had partial nephrectomy (PN). Modified Clavien classification system was applied to quantify complication severity of nephrectomy. Fisher's exact or chi-square test was used to assess the relationship between complication rates and obesity, hypertension, as well as DM. Results: The prevalence of obesity, hypertension, and DM was 11.51%, 30.84%, 8.78%, respectively. The overall complication rate was 19.31%, 30.04%, 35.71% and 36.36% for laparoscopic radical nephrectomy (LRN), open-RN, LPN and open-PN respectively. An increasing trend of low grade complication rate as BMI increased was observed in LRN (P = .027) and open-RN (P < .001). Obese patients had greater chance to have low grade complications in LRN (OR = 4.471; 95% CI: 1.290-17.422; P = 0.031) and open-RN (OR = 2.448; 95% CI: 1.703-3.518; P < .001). Patients with hypertension were more likely to have low grade complications, especially grade II complications in open-RN (OR = 1.526; 95% CI: 1.055-2.206; P = .026) and open PN (OR = 2.032; 95% CI: 1.199-3.443; P = .009). DM was also associated with higher grade I complication rate in open-RN (OR = 2.490; 95% CI: 331-4.657; P = .016) and open-PN (OR = 4.425; 95% CI: 1.815-10.791; P = .013). High grade complication rates were similar in comparison. Conclusions: Obesity, hypertension, and DM were closely associated with increased post-nephrectomy complication rates, mainly low grade complications

Parental origin of the supernumerary chromosome in trisomy 18.

The parental origin of an extra chromosome in Edwards syndrome has been investigated in 23 families by the combination of the VNTR probe pERT25, two microsatellite polymorphisms for D18S34 and D18S40, and several two-allele polymorphisms. Of the 23 cases, 22 were informative, with 17 (77%) being maternal and 5 (23%) paternal in origin. These results support the previous investigations, suggesting that trisomy 18 is predominantly of maternal origin, although a higher rate of paternally derived cases was observed than previously reported. A significant increase in maternal age was found to be associated with meiotic nondisjunction. Parental age was increased in both the maternally and paternally derived cases, but the size of the latter class was small and did not reach statistical significance.