RESUMEN
Ganoderma lucidum polysaccharides (GLP) have renal protection effect but there was no study on the diabetic nephropathy. This study was designed to investigate its effect and mechanism using a diabetic rat model induced by streptozotocin (50 mg/kg, i.p.). The diabetic rats were treated with GLP (300 mg/kg/day) for 10 weeks. The blood glucose, glycated hemoglobin, body weight, and the levels of blood creatinine, urea nitrogen, and urine protein were assessed. And renal pathologies were assessed by the tissue sections stained with hematoxylin-eosin, Masson's trichome, and periodic acid-Schiff. The expression of phosphorylated phosphoinositide 3 kinase (p-PI3K), phosphorylated protein kinase B (p-Akt), and phosphorylated mammalian target of rapamycin (p-mTOR), the autophagy proteins beclin-1, LC3-II, LC3-I, and P62; the apoptosis-related proteins caspase-3 and caspase-9; and the inflammation markers IL-6, IL-1ß, and TNF-É were assessed. Results showed that GLP alleviated the impairment of renal function by reducing urinary protein excretion and the blood creatinine level and ameliorated diabetic nephropathy. The expression of p-PI3K, p-Akt, and p-mTOR in the diabetic kidney were significantly reduced in the GLP treatment group compared to the without treatment group. GLP treatment activated the autophagy indicators of beclin-1 and the ratio of LC3-II/LC3-I but reduced p62 and also inhibited the expression of caspase-3, caspase-9 and IL-6, IL-1ß, and TNF-É. In conclusion, the effect of GLP amelioration diabetic nephropathy may be via the PI3k/Akt/mTOR signaling pathway by inhibition of the apoptosis and inflammation and activation of the autophagy process.
Asunto(s)
Nefropatías Diabéticas/tratamiento farmacológico , Polisacáridos/farmacología , Reishi , Animales , Biomarcadores/metabolismo , Glucemia/efectos de los fármacos , Diabetes Mellitus Experimental , Masculino , Ratas , Transducción de Señal , EstreptozocinaRESUMEN
α-(1,6)-fucosyltransferase 8 (FUT8) is implicated in the pathogenesis of several malignancies, but its role in psoriasis is poorly understood. In this study, we show that FUT8 remodeling of EGFR plays a critical role in the development of psoriasis phenotypes. Notably, elevated FUT8 expression was associated with disease severity in the lesional epidermis of a patient with psoriasis. FUT8 gain of function promoted HaCaT cell proliferation, whereas short hairpin FUT8 reduced cell proliferation and induced a longer S phase with downregulation of cyclin A1 expression. Furthermore, cell proliferation, which is controlled by the activation of EGFR, was shown to be regulated by FUT8 core fucosylation of EGFR. Short hairpin FUT8 significantly reduced EGFR/protein kinase B signaling and slowed EGFâEGFR complex trafficking to the perinuclear region. Moreover, short hairpin FUT8 reduced ligand-induced EGFR dimerization. Overactivated EGFR was observed in the lesional epidermis of both human patient and psoriasis-like mouse model, whereas conditional knockout of FUT8 in an IL-23 psoriasis-like mouse model ameliorated disease phenotypes and reduced EGFR activation in the epidermis. These findings implied that elevated FUT8 expression in the lesional epidermis is implicated in the development of psoriasis phenotypes, being required for EGFR overactivation and leading to keratinocyte hyperproliferation.
Asunto(s)
Epidermis/patología , Receptores ErbB/metabolismo , Fucosiltransferasas/metabolismo , Psoriasis/inmunología , Animales , Estudios de Casos y Controles , Proliferación Celular/genética , Modelos Animales de Enfermedad , Epidermis/inmunología , Femenino , Fucosiltransferasas/genética , Mutación con Ganancia de Función/inmunología , Glicosilación , Células HaCaT , Voluntarios Sanos , Humanos , Interleucina-23/administración & dosificación , Interleucina-23/inmunología , Masculino , Ratones Noqueados , Cultivo Primario de Células , Multimerización de Proteína/inmunología , Psoriasis/genética , Psoriasis/patología , Transducción de Señal/genética , Transducción de Señal/inmunologíaRESUMEN
BACKGROUND: Hepatitis B surface antigen (HBsAg) and hepatitis B surface antibody (anti-HBs) were conventionally determined by enzyme immunoassays. We aimed to apply a rapid, simple, and accurate method to detect HBsAg and its antibody. METHODS: We collected 1463 serum samples from healthy volunteers, hepatitis B carriers, and children of HBsAg-positive mothers. The test card that we examined is a chromatographic immunoassay for the qualitative detection of either HBsAg or anti-HBs. We then compared the results of the test card to the results of the conventional enzyme-immunoassay method, which is regarded as a standard. RESULTS: In the use of the test card to check HBsAg, the sensitivity was 88.8% and the specificity was 100%. The median hepatitis B virus viral load was significantly higher in the true-positive group [10(3.71) copies/mL (range, 10(2)-10(9.03) copies/mL)] than in the false-negative group [10(2) copies/mL (range, 10(2)-10(3.26) copies/mL)] (p = 0.005). In those who were younger than 2 years, the diagnostic accuracy of the HBsAg test card was 100%. Then, 1272 samples were tested for anti-HBs rapid test card. The sensitivity was 91.8% and the specificity was 96.5%. The median anti-HBs titer was significantly higher in the true-positive group (295.8 mIU/mL) than in the false-negative group (42.3 mIU/mL; p < 0.001). CONCLUSION: Because of (1) the limited amount of blood sample required and (2) most of the young hepatitis B virus carriers having high viremia, and no concerns of false negativity, the test card is a good rapid screening tool for the detection of HBsAg and anti-HBs in pediatric group.
Asunto(s)
Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoensayo , Lactante , Masculino , Sensibilidad y Especificidad , TaiwánRESUMEN
BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is widely accepted as the preferred procedure to establish long-term enteral feeding. OBJECTIVE: To learn the long-term outcomes of the patients who have undergone PEG placement, we reviewed our experience with children who underwent this procedure in our institute. METHODS: A total of 83 pediatric patients (42 males and 41 females), who were aged from 3 months to 20 years, underwent PEG insertion in National Taiwan University Hospital from January 2000 to April 2011. The underlying diseases of the patients receiving PEG were neurological dysfunction (n = 67), metabolic disorders (n = 9), gastrointestinal disease (n = 2), and congenital heart disease (n = 1). This procedure was performed under intravenous sedation or under general anesthesia. Prophylactic antibiotics were administered for 1 day. Tube feeding began 24 hours after the PEG placement. The body weight of the patients was recorded 1 day before PEG placement and at least 6 months after PEG placement. RESULTS: The weight-for-age Z-score before and at 6 months after PEG placement were -1.5 ± 2.0 and -0.9 ± 2.1, respectively, which was statistically significant (paired t test, p = 0.006). The catch-up growth was recorded after PEG placement. Complications of PEG in our patients included cellulitis at the gastrostomy wound (n = 14), dislodgement of the tube (n = 17), and persistent gastrocutaneous fistula (n = 3). The PEG tube was removed permanently in seventeen patients because they resumed an adequate oral intake. During the follow-up period, 14 patients died of an underlying disease or infection. CONCLUSION: Our experience confirmed that PEG placement is a good long-term route for nutritional supply with no serious complications in children.