Advanced glycation end products promote the progression of chronic kidney diseases by targeting calpain 6.

Advanced glycation end products (AGEs) are produced by glycosylation or oxidation of proteins and lipids and are tightly involved in the chronic kidney disease (CKD) process. Calpain 6 (CAPN6) is a non-classical calpain that has been reported to be overexpressed in CKD. This study aimed to explore the effects of AGEs in CKD progress and their correlation with CAPN6. AGEs production was measured using ELISA. The CCK-8 assay was used to test cell proliferation. mRNA and protein levels were tested using qRT-PCR and western blot. The progress of glycolysis was tested by calculating the ATP and ECAR content in HK-2 cells. The expression of AGEs and CAPN6 was significantly increased in patients with CKD3, CKD4, and CKD5. AGEs treatment inhibited cell proliferation and glycolysis and accelerated apoptosis. Additionally, CAPN6 knockdown effectively reversed the effects of AGEs in HK-2 cells. In addition, overexpressed CAPN6 played similar role to AGEs, which suppressed cell proliferation and glycolysis and facilitated apoptosis. Moreover, the administration of 2-DG, a glycolysis inhibitor, counteracted the effects of CAPN6 silencing in HK-2 cells. Mechanistically, CAPN6 interacts with NF-κB and PDTC reduced CAPN6 expression in HK-2 cells. This investigation revealed that AGEs facilitate CKD development in vitro by modulating the expression of CAPN6.

[Comparative study of HR HPV E6/E7 mRNA and HR-HPV DNA in cervical cancer screening].

OBJECTIVE: To determine the performance of HR-HPV E6/E7 massager RNA (mRNA) test for detecting high-grade cervical intraepithelial neoplasia in cervical cancer screening and compare the clinical performance of HR-HPV E6/E7 mRNA test with HC-2 and Cervista HPV DNA tests for cross-sectional positivity in women with and without cervical neoplasia. METHODS: A total of 172 women underwent cytology, HR-HPV DNA test, HR-HPV E6/7 mRNA test, colposcopy and biopsy. We compared the clinical performance of HR-HPV E6/E7 mRNA test with Hybrid Capture 2 DNA test (HC-2) and Cervista HR-HPV DNA test on the cervical brush specimens during colposcopy and routine screening. The samples were histologically confirmed high-grade cervical intraepithelial neoplasia (CIN II) or worse (CIN II+) as an endpoint. RESULTS: HR-HPV E6/E7 mRNA positive rate was 37.9% in NILM, 67.9% in ASCUS and LSIL, 88.5% in ASC-H+. HR-HPV E6/E7 mRNA positive rate was 38.6% in CIN I, 77.4% in CIN II-3 and 92.5% in SCC. HR-HPV E6/E7 mRNA test showed a higher specificity than HC-2 and Cervista HPV DNA tests for high-grade lesions (61.4%, 54.3%, 55.7%, respectively, P < 0.05) and also a higher positive predictive value (75.9%, 74.8%, 74.6% respectively). Among three tests, HR-HPV E6/E7 mRNA had the largest area of ROC curve and the best diagnostic value. CONCLUSION: HR-HPV E6/E7 mRNA test has a performance more specific for detecting CIN II+ with the same sensitivity as HC-2 and Cervista HPV DNA tests. And it may serve as a more specific test for predicting the risk of progression and offer a viable tool for triage during cervical cancer screening.

Mahuang Decoction Attenuates Airway Inflammation and Remodeling in Asthma via Suppression of the SP1/FGFR3/PI3K/AKT Axis.

Background/Purpose: Mahuang decoction (MHD) is a classic famous traditional Chinese medicine and has various pharmacological effects, including anti-inflammation and anti-asthma. In this study, we aimed to investigate the potential protective effect of MHD against asthma and elucidated the underlying mechanism. Materials and Methods: A mouse model of asthma was induced by ovalbumin (OVA) treatment, and then treated with MHD to evaluate its effect on the asthma. Gain- or loss-of-function approaches were performed in SP1 and FGFR3 to study their roles in asthma via measurement of airway inflammation, airway remodeling and airway smooth muscle cell (ASMC) proliferation-related factors. Results: MHD reduced airway inflammation and remodeling. Additionally, MHD contributed to diminished expression of SP1, which was shown to repress airway inflammation and remodeling. Furthermore, SP1 bound to the FGFR3 promoter, resulting in the FGFR3 transcription promotion and ASMC proliferation. Conversely, FGFR3 knockdown abolished airway inflammation and remodeling, the mechanism of which was related to suppression of the PI3K/AKT signaling pathway. Meanwhile, MHD hindered airway inflammation and remodeling following asthma by suppressing the SP1/FGFR3/PI3K/AKT axis. Conclusion: Taken together, MHD may retard airway inflammation and remodeling by suppressing the SP1/FGFR3/PI3K/AKT axis, which contributes to an extensive understanding of asthma and may provide novel therapeutic options for this disease.

Human telomerase gene and high-risk human papillomavirus infection are related to cervical intraepithelial neoplasia.

Our aims were to evaluate the clinical performance of human telomerase RNA gene component (hTERC gene) amplification assay with high-risk human papillomavirus (HR-HPV) DNA test of Hybrid Capture 2 DNA test (HC2), for the detection of high grade cervical precancerous lesions and cancer (CIN 2+). In addition, the association shown between hTERC gene amplification and HPV DNA test positive in women with and without cervical neoplasia was assessed. There were 92 women who underwent cytology, HR-HPV DNA test, hTERC gene amplification test, colposcopy and biopsy. We compared the clinical performance of hTERC gene test along with HR-HPV DNA test of women with colposcopy and routine screening. The samples were histology- confirmed high-grade cervical intraepithelial neoplasia (CIN 2) or worse (CIN2+) as the positive criterion. The test of hTERC gene showed the hTERC gene amplification positivity increased with the severity of histological abnormality and cytological abnormality. The test of hTERC gene showed higher specificity than HR-HPV DNA test for high-grade lesions (84.4% versus 50%) and also higher positive predictive value (90.4% versus 76.5%). Our results predicted that hTERC gene amplification demonstrated more specific performance for predicting the risk of progression and offer a strong potential as a tool for triage in cervical cancer screening, with the limited sensitive as HR-HPV DNA test.

[Serum level and expression of vascular epithelial growth factor in ovarian epithelial carcinoma].

BACKGROUND & OBJECTIVE: This study was designed to examine the level of serum vascular epithelial growth factor (VEGF) and VEGF expression in the patients with ovarian epithelial carcinoma (EOC) and to evaluate the relationship between VEGF and the clinicopathological factors. METHODS: Seventy-three patients with ovarian epithelial tumor were selected as study group, including 24 benign epithelial ovarian tumor (BET), 7 borderline epithelial ovarian tumor (BOT), 42 EOC. Twenty women without obvious gynecologic diseases were selected as serum control group (CON). VEGF expression in the epithelial ovarian tumor tissues from 73 patients were analyzed immunohistochemically. Serum VEGF in 71 patients and ascite VEGF in 10 patients were detected by enzyme-linked immunosorbent assay (ELISA) and 7 cases with EOC were continuously determined after operation. RESULTS: (1) Positive immunostaining of VEGF was observed in 86.3% of EOC, which was significantly higher than that of BOT (66.67%, P < 0.005) and BET (37.5%, P < 0.005). (2) There were significant differences in serum VEGF level among BET, BOT, and EOC group (P < 0.01). Serum VEGF levels before operation in patients with EOC were significantly higher than those with BOT, BET, and CON (P < 0.01). Serum VEGF levels in EOC patients at advanced stage (stage III or IV), low differentiation (G3) were apparently higher than those at early stage (stage I or II) (P < 0.05) and high differentiation (G1, G2) (P < 0.01), respectively. Serum VEGF levels decreased after the successful removal of tumor in ovarian cancer patients. The serum VEGF levels were re-elevated during relapse in three patients. CONCLUSION: (1) The elevated serum VEGF levels and increased VEGF expression in EOC were associated with its maligment behavior. (2) Serum VEGF could be used as a marker for monitoring the clinical course of the patients with epithelial ovarian carcinoma.