In order to evaluate the effectiveness of everolimus vs. rapamycin in the treatment of diabetic nephropathy, 8-week old diabetic (db/db) mice received everolimus (2 mg/kg every day) or rapamycin (2 mg/kg every day) for 4 weeks or 12 weeks respectively. Blood and 24-h urine samples were collected for biochemical tests. One kidney from each mouse was homogenized for protein analysis and the other was removed for histological analysis. The expression levels of transforming growth factor-β1 (TGF-β1)and phospho-p70s6k were detected by using ELISA and Western blot, respectively in the renal tissue as well as in mesengial cell culture samples. Everolimus was significantly more effective than rapamycin in improving indexes of renal function and glomerular hypertrophy, and in decreasing accumulation and expansion of the extracellular matrix. However, everolimus inhibited TGF-β1 secretion and p70s6k phosphorylation induced by high glucose in vitro less efficiently than rapamycin at the same dose. Everolimus was more effective than rapamycin in preventing diabetic nephropathy in vivo, which may be contributed to the fact that everolimus has better bioavailability and a higher oral absorption rate.

Objective To study the expressions of DD3 mRNA and PSA mRNA in the prostate tissues and its diagnostic value in prostate cancer (PCa). Methods DD3 mRNA and PSA mRNA were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction ( FQ-RT-PCR) based on Taqman technique in the tissues of 21 cases of PCa and 39 cases of BPH. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of DD3 mRNA, PSA mRNA and DD3 mRNA/PSA mRNA. Results The expressions of DD3 mRNA and PSA mRNA, and DD3 mRNA/ PSA mRNA were significantly higher in PCa tissues than those in BPH tissues ( P 0.05 for all). The AUC-ROC of DD3 mRNA,PSA mRNA and DD3 mRNA/PSA mRNA were 0. 937 (95% CI,0. 879 -0. 995) , 0.755(95% CI,0.629 -0.880) and 0.839 (95%CI,0.738 -0.940),respectively. The sensitivity for DD3 mRNA,PSA mRNA and DD3 mRNA/PSA mRNA was 90. 5% ,81. 0% and 81. 0% , respectively, and the specificity was 85.0% ,62.0% and 66.7% at cutoff value of 1.4?105 copies/mg tissue,3.0?107 copies/ mg tissue and 5. 0?10-3,respectively. The sensitivity and specificity of simultaneous detection for DD3 mRNA and PSA mRNA were 100% and 85.0%. Conclusions Both DD3 mRNA and PSA mRNA expressions were significantly higher in PCa tissues than those in BPH tissues; and the quantitative detection of DD3 mRNA is more helpful for the diagnosis. The simultaneous detection of DD3 mRNA and PSA mRNA can improve the sensitivity in the diagnosis of PCa.

In order to evaluate the effectiveness of everolimus vs.rapamycin in the treatment of diabetic nephropathy,8-week old diabetic (db/db) mice received everolimus (2 mg/kg every day) or rapamycin (2 mg/kg every day) for 4 weeks or 12 weeks respectively.Blood and 24-h urine samples were collected for biochemical tests.One kidney from each mouse was homogenized for protein analysis and the other was removed for histological analysis.The expression levels of transforming growth factor-β1 (TGF-βl)and phospho-p70s6k were detected by using ELISA and Western blot,respectively in the renal tissue as well as in mesengial cell culture samples.Everolimus was significantly more effective than rapamycin in improving indexes of renal function and glomerular hypertrophy,and in decreasing accumulation and expansion of the extracellular matrix.However,everolimus inhibited TGF-β1 secretion and p70s6k phosphorylation induced by high glucose in vitro less efficiently than rapamycin at the same dose.Everolimus was more effective than rapamycin in preventing diabetic nephropathy in vivo,which may be contributed to the fact that everolimus has better bioavailability and a higher oral absorptionrate.

Originating but free from chromosomal DNA, extrachromosomal circular DNAs (eccDNAs) are organized in circular form and have long been found in unicellular and multicellular eukaryotes. Their biogenesis and function are poorly understood as they are characterized by sequence homology with linear DNA, for which few detection methods are available. Recent advances in high-throughput sequencing technologies have revealed that eccDNAs play crucial roles in tumor formation, evolution, and drug resistance as well as aging, genomic diversity, and other biological processes, bringing it back to the research hotspot. Several mechanisms of eccDNA formation have been proposed, including the breakage-fusion-bridge (BFB) and translocation-deletion-amplification models. Gynecologic tumors and disorders of embryonic and fetal development are major threats to human reproductive health. The roles of eccDNAs in these pathological processes have been partially elucidated since the first discovery of eccDNA in pig sperm and the double minutes in ovarian cancer ascites. The present review summarized the research history, biogenesis, and currently available detection and analytical methods for eccDNAs and clarified their functions in gynecologic tumors and reproduction. We also proposed the application of eccDNAs as drug targets and liquid biopsy markers for prenatal diagnosis and the early detection, prognosis, and treatment of gynecologic tumors. This review lays theoretical foundations for future investigations into the complex regulatory networks of eccDNAs in vital physiological and pathological processes.
Male ; Female ; Animals ; Humans ; Swine ; DNA, Circular/genetics* ; Genital Neoplasms, Female ; Semen ; DNA ; Reproduction