Influenza A (H6N6) viruses isolated from chickens replicate in mice and human lungs without prior adaptation.

The H6H6 subtype avian influenza virus (AIV) is currently prevalent in wild birds and poultry. Its host range has gradually expanded to mammals, such as swines. Some strains have even acquired the ability to bind to human-like SAα-2,6 Gal receptors, thus increasing the risk of animal to human transmission. To investigate whether the H6N6 AIV can overcome interspecies barriers from poultry to mammals and even to humans, we have assessed the molecular characteristics, receptor-binding preference, replication in mice and human lungs of three chicken-originated H6N6 strains. Among these, the A/CK/Zhangzhou/346/2014 (ZZ346) virus with the P186T, H156R, and S263G mutations of the hemagglutinin molecule showed the ability to bind to avian-like SAα-2,3 Gal and human-like SAα-2,6 Gal receptors. Moreover, H6N6 viruses, especially the ZZ346 strain, could replicate and infect mice and human lungs. Our study showed the H6N6 virus binding to both avian-like and human-like receptors, confirming its ability to cross the species barrier to infect mice and human lungs without prior adaptation. This study emphasizes the importance of continuous and intense monitoring of the H6N6 evolution in terrestrial birds.

The Long Non-Coding RNA MALAT1 Enhances Ovarian Cancer Cell Stemness by Inhibiting YAP Translocation from Nucleus to Cytoplasm.

BACKGROUND The purpose of this work was to unearth the effects and underlying mechanism of long non-coding RNA (lncRNA) MALAT1 in ovarian cancer cell stemness. MATERIAL AND METHODS Western blot, quantitative polymerase chain reaction (qPCR) and sphere forming analysis were performed to evaluate the stem-like traits of cells and MALAT1-induced effects on ovarian cancer cell stemness. Cell viability was performed to evaluate MALAT1 role in the chemoresistance of ovarian cancer cells. RNA immunoprecipitation (RIP) and luciferase reporter analysis were constructed to investigate the underlying mechanisms. RESULTS Here, qPCR assay showed that MALAT1 level was remarkably higher in non-adherent spheres formed by adherent ovarian cancer cells, as well as cisplatin-resistant ovarian cancer cells. Additionally, MALAT1 knockdown reduced ovarian cancer cell stemness, characterized as the decrease of sphere forming ability, expression of stemness regulatory masters, and attenuation of cisplatin resistance. Moreover, MALAT1 interacted with yes-associated protein (YAP), inhibited its nuclear-cytoplasm translocation, promoted YAP protein stability and expression and thus increased its activity. Notably, rescuing expression of YAP attenuated the inhibition of MALAT1 knockdown on ovarian cancer cell stemness. CONCLUSIONS In conclusion, these results demonstrate a MALAT1/YAP axis responsible for ovarian cancer cell stemness.

RNA Binding Protein RNPC1 Suppresses the Stemness of Human Endometrial Cancer Cells via Stabilizing MST1/2 mRNA.

BACKGROUND RNA binding protein RNPC1 has a tumor-suppressive role in various tumors, nevertheless, the role of RNPC1 in human endometrial cancer (EC) are never been reported. MATERIAL AND METHODS Western blot, quantitative polymerase chain reaction and sphere forming analysis were performed to evaluate the stem-like traits of cells and RNPC1-induced effects on EC cell stemness. RNA immunoprecipitation (RIP) was constructed to investigate the underlying mechanisms. RESULTS The spheres formed by EC cells, named EC spheres, exhibited a remarkably higher stemness than the parental cells, which is characterized as the increase of sphere forming ability, ALDH1 activity, stemness marker expression and migration ability. Notably, RNPC1 expression was decreased in poorly differentiated EC cells than that in EC cells with moderately differentiated. Additionally, RNPC1 expression was significantly decreased in EC spheres and RNPC1 overexpression attenuated the stemness of EC spheres. Moreover, RNPC1 overexpression decreased the migration ability of EC spheres. Mechanistic studies showed that RNPC1 overexpression activated the Hippo pathway through directly binding to MST1/2. Inhibition of MST1/2 rescued RNPC1-mediated effects on EC sphere stemness. CONCLUSIONS Therefore, our results indicate a novel RNPC1/MST1/2 signaling responsible for EC cell stemness.

Expression of Angiopoietin and VEGF in Cervical Cancer and its Clinical Significance.

OBJECTIVE: The aim of this study was to evaluate the expression of Angiopoietin-1 (Ang-1), Angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF) in cervical cancer and its clinical significance. METHODS: Immunohistochemical assay was used to examine the expression of Ang-1/2 and VEGF in tumor tissue from 56 cervical squamous cell carcinoma patients treated with operation only (SCC-O group), as well as 51 subjects with cervical squamous cell carcinoma treated with neoadjuvant radiotherapy (SCC-RCO group, n=28) or neoadjuvant chemotherapy (SCC-CO group, n=23). Both microvessel density (MVD) and lymphatic vessel density (LVD) were examined in the three groups through detection of CD34 and D2-40 expression in respective tissue samples. RESULTS: With the progression of cervical cancer, the positive expression scores of Ang-2 and VEGF were significantly increased (p<0.05). Compared with surgical intervention, neoadjuvant chemoradiotherapy significantly reduced the positive expression scores of Ang-1, Ang-2, and VEGF in cervical cancer tissues (p<0.05). The MVD values of the SCC-CO and SCC-RO groups were significantly reduced as compared to the SCC-O group (p<0.05). Similarly, the LVD values of the SCC-CO and SCC-RO groups were also significantly reduced when compared to those of the SCC-O group (p<0.05). However, LVD values of the SCC-CO and SCC-RO groups were not statistical different (p>0.05). CONCLUSION: Ang-1, Ang-2 and VEGF may play an important role in the development of cervical cancer. Mutual synergism of Ang-2 and VEGF demonstrated a close relationship with the generation of cervical blood and lymphatic vessels. Cervical cancer radiotherapy and chemotherapy could significantly inhibit the formation of blood vessels and lymphatic vessels in tumor tissue.

Characterization of ß-cell function and insulin resistance in overweight Chinese adolescents with normal glucose tolerance.

This study aimed to investigate the characteristics of insulin resistance and ß-cell secretion in healthy adolescents. A total of 124 adolescents with normal glucose tolerance (NGT) were divided according to BMI into normal weight (n=31; control), overweight (n=52) and obese (n=41) groups. Oral glucose tolerance tests were performed, and blood glucose (G0, G30 and G120) and insulin (I0, I30 and I120) levels at 0, 30 and 120 min, respectively, were measured. The homeostasis model assessment estimate of insulin resistance (HOMA-IR) and early insulin release index (IRI) were calculated to evaluate insulin sensitivity and early ß-cell secretion. The G0, G120 levels and the natural logarithm (Ln) of I30 and ΔI30/ΔG30 were similar in the overweight and obese groups, but significantly higher compared with those of the normal weight group (P<0.05). LnI0 and LnHOMA-IR progressively increased (P<0.01) in correlation with the degree of obesity among the three groups. LnΔI30/ΔG30 and LnHOMA-IR were significantly positively correlated with the indices of obesity (P<0.001 and P<0.05, respectively). LnHOMA-IR was also positively correlated with the insulin levels at 30 and 120 min (r=0.454 and 0.314, respectively; P<0.001). In healthy adolescents, insulin resistance progressively increased with increased body mass index (BMI), but the compensatory increase in early insulin secretion was limited.

One-hour after-school exercise ameliorates central adiposity and lipids in overweight Chinese adolescents: a randomized controlled trial.

BACKGROUND: The prevalence of overweight and obesity in Chinese children and adolescents was increasing during the past few decades. The goal of this study was to investigate the effects of after-school exercise with or without diet restriction on total and central obesity, fitness level, and metabolic profile in overweight Chinese adolescents. METHODS: A ten-week weight loss trial was performed using a 2 × 2 block design (exercise × diet). Ninety-three overweight adolescents (average age: (13.6 ± 0.7) years; body mass index (BMI): 22.4 - 34.1 kg/m(2)) were randomly assigned to four groups: 1) diet (D); 2) exercise (EX); 3) diet plus exercise (DEX); and 4) overweight control (C). Caloric intake recipes were enacted based on individual age and corresponding ideal body weight. One-hour after-school exercise was performed once per day, four days per week for ten weeks. Changes of anthropometry, body composition, aerobic fitness, and metabolic biomarkers were determined. RESULTS: Groups D, EX and DEX had a significant decrease in BMI (P < 0.01) after the intervention. The percentage of body and truncal fat, and waist circumference were independently reduced by exercise (P < 0.05 and P < 0.01), but not diet. The decrease in body fat percentage was positively related with the exercise compliance (r = 0.34, P = 0.01). Exercise decreased truncal fat percentage and waist circumference, suggesting a reduction of central adiposity, but did not significantly affect body weight and BMI. Exercise significantly reduced serum low-density lipoprotein cholesterol (P = 0.037), which was positively correlated with decreases of truncal fat percentage (r = 0.222, P = 0.048). No significant effects of interventions on insulin sensitivity, early insulin release index, and aerobic fitness were observed. CONCLUSION: At least twice a week of one-hour after-school exercise significantly attenuated central adiposity and had a significant impact on lipid profiles in overweight Chinese adolescents.