RESUMEN
INTRODUCTION: Hyperphosphatemia in chronic kidney disease (CKD) patients is positively associated with mortality. Ferric citrate is a potent phosphorus binder that lowers serum phosphorus level and improves iron metabolism. We compared its efficacy and safety with active drugs in Chinese CKD patients with hemodialysis. METHODS: Chinese patients undergoing hemodialysis were randomized into two treatment groups in a 1:1 ratio, receiving either ferric citrate or sevelamer carbonate, respectively, for 12 weeks. Serum phosphorus levels, calcium concentration, and iron metabolism parameters were evaluated every 2 weeks. Frequency and severity of adverse events were recorded. RESULTS: 217 (90.4%) patients completed the study with balanced demographic and baseline characteristics between two groups. Ferric citrate decreased the serum phosphorus level to 0.59 ± 0.54 mmol/L, comparable to 0.56 ± 0.62 mmol/L by sevelamer carbonate. There was no significant difference between two groups (p > 0.05) in the proportion of patients with serum phosphorus levels reaching the target range, the response rate to the study drug, and the changes of corrected serum calcium concentrations, and intact-PTH levels at the end of treatment. The change of iron metabolism indicators in the ferric citrate group was significantly higher than those in the sevelamer carbonate group. There are 47 (40.5%) patients in the ferric citrate group, and 26 (21.3%) patients in the sevelamer carbonate group experienced drug-related treatment emergent adverse events (TEAEs); most were mild and tolerable. Common drug-related TEAEs were gastrointestinal disorders, including diarrhea (12.9 vs. 2.5%), fecal discoloration (14.7 vs. 0%), and constipation (1.7 vs. 7.4%) in ferric citrate and sevelamer carbonate group. CONCLUSION: Ferric citrate capsules have good efficacy and safety in the control of hyperphosphatemia in adult patients with CKD undergoing hemodialysis. Efficacy is not inferior to sevelamer carbonate. The TEAEs were mostly mild and tolerated by the patients.
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Hiperfosfatemia , Insuficiencia Renal Crónica , Adulto , Humanos , Hiperfosfatemia/tratamiento farmacológico , Hiperfosfatemia/etiología , Sevelamer/efectos adversos , Calcio , Quelantes/efectos adversos , Diálisis Renal/efectos adversos , Compuestos Férricos/efectos adversos , Insuficiencia Renal Crónica/terapia , Insuficiencia Renal Crónica/tratamiento farmacológico , Fósforo , Hierro/uso terapéutico , ChinaRESUMEN
Tremella fuciformis is an edible white jelly mushroom with medicinal qualities. The formation of T. fuciformis fruiting bodies is highly dependent on the presence of Annulohypoxylon stygium under natural conditions and during artificial cultivation. A lack of efficient transformation systems restricts the ability of researchers to functionally characterize the genes in these two interacting fungi. In this study, we tested the utility of the Agrobacterium tumefaciens-mediated transformation of T. fuciformis and A. stygium protoplasts. A. tumefaciens strain EHA105 cells harboring the pTrGEH plasmid, which contains genes for enhanced green fluorescent protein (egfp) and hygromycin B phosphotransferase (hph), was co-cultured with T. fuciformis protoplasts. Meanwhile, EHA105 cells harboring the pAnGRH plasmid, which contains the red fluorescent protein (rfp) and hph genes, was co-cultured with A. stygium protoplasts. The egfp, rfp, and hph genes were under the control of the promoter for gpd, which encodes glyceraldehyde-3-phosphate dehydrogenase. Optimal co-cultivation was achieved with a 1:1 mixture of bacteria (OD600 0.4-0.6) and fungal protoplasts (105/mL) incubated at 25°C in a medium containing 200 µM acetosyringone. The subsequent selection on hygromycin B-containing medium yielded 45 and 187 stable transformants per 105 protoplasts for T. fuciformis and A. stygium, respectively. The integration of the transformed DNA into the two fungal genomes was confirmed by polymerase chain reaction (PCR), Southern blot analysis, fluorescence imaging, and a quantitative real-time PCR. All results confirmed the feasibility of our transformation approach, which may facilitate future functional analyses of T. fuciformis and A. stygium genes.
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Agaricales/genética , Agrobacterium tumefaciens/genética , Ascomicetos/genética , Proteínas Fúngicas/genética , Transformación Genética , Southern Blotting , Proteínas Fluorescentes Verdes , Proteínas Luminiscentes , Plásmidos/genética , Regiones Promotoras Genéticas , Protoplastos , Proteína Fluorescente RojaRESUMEN
Lentinus tuber-regium is a sclerotium-forming basidiomycetous mushroom. It has increasingly aroused people's attention for its medicinal effects. In this study, we investigated the applicability of the Agrobacterium tume-faciens-mediated transformation (ATMT) method in L. tuber-regium. A. tumefaciens strain GV 3101 harboring the vector pPEH was used to transform the mycelium of L. tuber-regium strain ACCC50657. The genes for hygromycin B phosphotransferase (hph) and enhanced green fluorescent protein (egfp) under the control of the glyceraldehyde-3-phosphate dehydrogenase (gpd) gene promoter of Pleurotus ostreatus were employed as the selection marker and reporter gene, respectively. The optimal cocultivation temperature and time for transformation were 3 days and 4 days at 25°C and 20°C, respectively. Southern blot analysis showed the variation in the copy number and position of hph, which indicated random integration of hph. Polymerase chain reaction and fluorescence microscopy indicated that the P. ostreatus gpd promoter can drive the fused hph-egfp gene expression in L. tuber-regium. This is the first report that the ATMT method was successfully applied to L. tuber-regium. This reliable and efficient transformation method could be a powerful tool for strain genetic improvement and gene function study in L. tuber-regium.
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Agrobacterium tumefaciens/genética , Lentinula/genética , Regulación Fúngica de la Expresión Génica , Vectores Genéticos , Proteínas Fluorescentes Verdes , Lentinula/fisiología , Regiones Promotoras Genéticas , Transformación GenéticaRESUMEN
BACKGROUND: In China, mesangial proliferative glomerulonephritis (MsPGN) is one of the most common kidney diseases. In this study, we treated a rat model of chronic anti-Thy-1 MsPGN with Shenhua Tablet and evaluated whether the tablet was able to protect the kidney function. Thirty-six Wistar rats were randomly divided into six groups: (1) Sham surgery (Sham); (2) anti-Thy-1 nephritis model (Thy-1); (3) anti-Thy-1 nephritis model + irbesartan-treated (Irb); (4) anti-Thy-1 nephritis model + low-dose of Shenhua Tablet (SHL); (5) anti-Thy-1 nephritis model + medium-dose of Shenhua Tablet (SHM); (6) anti-Thy-1 nephritis model + high-dose of Shenhua Tablet (SHH). RESULTS: Thirteen weeks after drug treatment, urinary proteins were quantified and renal pathological changes were thoroughly examined at the time point of 24 h. Meanwhile, the expression levels of p-Erk1/2, cyclin D1 and p21 at the renal cortex were also tested. The levels of urinary proteins and total cholesterol in the blood were significantly reduced in rats treated with any drug tested in this study. The level of triglyceride was significantly reduced in all three Shenhua Tablet-treated groups. Renal pathomorphological scores were significantly improved in groups of Irb, SHM and SHH. Mesangial cell proliferation was significantly inhibited in any drug-treated group. p-Erk1/2 and cyclin D1 were downregulated whereas p21 was upregulated in the renal cortex. CONCLUSIONS: Our study indicated that Shenhua Tablet is able to inhibit the abnormal proliferation of mesangial cells and to prevent kidney damage, which is likely associated with downregulation of p-Erk1/2 and reduced activity of its downstream target-cyclin D1.
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Proliferación Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Glomerulonefritis Membranoproliferativa/tratamiento farmacológico , Isoanticuerpos , Células Mesangiales/efectos de los fármacos , Animales , Enfermedad Crónica , Ciclina D1/análisis , Medicamentos Herbarios Chinos/uso terapéutico , Glomerulonefritis Membranoproliferativa/patología , Masculino , Proteína Quinasa 1 Activada por Mitógenos/análisis , Ratas Wistar , Reproducibilidad de los Resultados , Albúmina Sérica/análisis , Comprimidos , Factores de Tiempo , Quinasas p21 Activadas/análisisRESUMEN
BACKGROUND: In China, mesangial proliferative glomerulonephritis (MsPGN) is one of the most common kidney diseases. In this study, we treated a rat model of chronic anti-Thy-1 MsPGN with Shenhua Tablet and evaluated whether the tablet was able to protect the kidney function. Thirty-six Wistar rats were randomly divided into six groups: (1) Sham surgery (Sham); (2) anti-Thy-1 nephritis model (Thy-1); (3) anti-Thy-1 nephritis model + irbesartan-treated (Irb); (4) anti-Thy-1 nephritis model + low-dose of Shenhua Tablet (SHL); (5) anti-Thy-1 nephritis model + medium-dose of Shenhua Tablet (SHM); (6) anti-Thy-1 nephritis model + high-dose of Shenhua Tablet (SHH). RESULTS: Thirteen weeks after drug treatment, urinary proteins were quantified and renal pathological changes were thoroughly examined at the time point of 24 h. Meanwhile, the expression levels of p-Erk1/2, cyclin D1 and p21 at the renal cortex were also tested. The levels of urinary proteins and total cholesterol in the blood were significantly reduced in rats treated with any drug tested in this study. The level of triglyceride was significantly reduced in all three Shenhua Tablet-treated groups. Renal pathomorphological scores were significantly improved in groups of Irb, SHM and SHH. Mesangial cell proliferation was significantly inhibited in any drug-treated group. p-Erk1/2 and cyclin D1 were downregulated whereas p21 was upregulated in the renal cortex. CONCLUSIONS: Our study indicated that Shenhua Tablet is able to inhibit the abnormal proliferation of mesangial cells and to prevent kidney damage, which is likely associated with downregulation of p-Erk1/2 and reduced activity of its downstream target-cyclin D1.
Asunto(s)
Animales , Masculino , Medicamentos Herbarios Chinos/farmacología , Glomerulonefritis Membranoproliferativa/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Células Mesangiales/efectos de los fármacos , Isoanticuerpos , Factores de Tiempo , Albúmina Sérica/análisis , Medicamentos Herbarios Chinos/uso terapéutico , Glomerulonefritis Membranoproliferativa/patología , Enfermedad Crónica , Reproducibilidad de los Resultados , Ratas Wistar , Proteína Quinasa 1 Activada por Mitógenos/análisis , Ciclina D1/análisis , Computadoras de Mano , Quinasas p21 Activadas/análisisRESUMEN
BACKGROUND: Laparoscopic cholecystectomy is the gold standard treatment for cholecystectomy. Recently, single-incision laparoscopic cholecystectomy (SILC) has been suggested as an alternative technique. METHODS: Six databases were searched and reference lists of retrieved articles were checked to identify eligible studies. Data from randomized clinical trials related to the safety and effectiveness of SILC versus conventional laparoscopic cholecystectomy (CLC) were extracted by 2 independent reviewers. Odds ratio and mean differences were calculated with 95% confidence intervals based on intention-to-treat analyses whenever possible. RESULTS: Fifteen studies with 1113 patients met the eligibility criteria. Methodologic quality was unclear in most trails. Operating time was significantly longer in the single-incision laparoscopic surgery group compared with the CLC group (P<0.00001). Cosmesis was improved in single-incision laparoscopic patients at 1 month (P<0.00001). The pooled mean difference in pain scores at 24 hours was -0.75 in favor of the SILC technique (P=0.04). There was no significant difference in the conversion rates, adverse events, analgesia requirements, or the length of hospital stay between the 2 groups. CONCLUSIONS: The current evidence shows that patients with uncomplicated cholelithiasis or polypoid lesions of the gallbladder who prefer a better cosmetic outcome, SILC offers a safe alternative to CLC. Further high-powered randomized trials are need to determine whether SILC truly offer any advantages, especially be focused on failure of technique, adverse events, cosmesis, and quality of life.