Single-Stranded DNA-Binding Protein 1 Abrogates Cardiac Fibroblast Proliferation and Collagen Expression Induced by Angiotensin II.

Angiotensin II (Ang II), an effective component of renin-angiotensin system, plays a pivotal role in cardiac fibrosis, which may further contribute to heart failure. Single-stranded DNA-binding protein 1 (SSBP1), a DNA damage response protein, regulates both mitochondrial function and extracellular matrix remodeling. In this study, we aim to investigate the role of SSBP1 in cardiac fibrosis that is induced by Ang II. We infused C57BL/6J mice with vehicle or Ang II and valsartan using implanted osmotic mini-pumps. Moreover, heart function was examined by echocardiography and cardiac fibrosis was analyzed via picrosirus red staining. The expression of COL1A1, COL3A1, SSBP1, p53, Nox1, and Nox4 was analyzed via qRT-PCR and/or immunoblots. The SSBP1 expression was manipulated via SSBP1 shRNA and pcDNA3.1/SSBP1 plasmids, while the p53 expression was enhanced via AdCMV-p53 infection. The exposure to Ang II increased the mouse heart weight, systolic blood pressure, interventricular septal thickness diastolic (IVSTD) and left ventricular end posterior wall dimension diastolic (LVPWD), which were counteracted by valsartan. While cardiac fibrosis was induced with Ang II treatment, it was relieved using valsartan. Furthermore, Ang II treatment caused mitochondrial dysfunction, oxidative stress, and down-regulated SSBP1 expression. The knockdown of SSBP1 increased cardiac fibroblast proliferation, collagen expression, and decreased p53 expression, which was impeded via SSBP1 overexpression. Moreover, the forced expression of p53 abated the fibroblast proliferation and collagen expression that was induced by Ang II. To summarize, SSBP1 was down-regulated by Ang II and implicated in cardiac fibroblast proliferation and collagen expression partly via the p53 protein.

Multi-parametric MRI in cervical cancer: early prediction of response to concurrent chemoradiotherapy in combination with clinical prognostic factors.

OBJECTIVE: To investigate the prediction of response to concurrent chemoradiotherapy (CCRT) through a combination of pretreatment multi-parametric magnetic resonance imaging (MRI) with clinical prognostic factors (CPF) in cervical cancer patients. METHODS: Sixty-five patients underwent conventional MRI, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced MRI (DCE-MRI) before CCRT. The patients were divided into non- and residual tumour groups according to post-treatment MRI. Pretreatment MRI parameters and CPF between the two groups were compared and prognostic factors, optimal thresholds, and predictive performance for post-treatment residual tumour occurrence were estimated. RESULTS: The residual group showed a lower maximum slope of increase (MSIL) and signal enhancement ratio (SERL) in low-perfusion subregions, a higher apparent diffusion coefficient (ADC) value, and a higher stage than the non-residual tumour group (p < 0.001, p = 0.003, p < 0.001, and p < 0.001, respectively). MSIL and ADC were independent prognostic factors. The combination of both measures improved the diagnostic performance compared with individual MRI parameters. A further combination of these two factors with CPF exhibited the highest predictive performance. CONCLUSIONS: Pretreatment MSIL and ADC were independent prognostic factors for cervical cancer. The predictive capacity of multi-parametric MRI was superior to individual MRI parameters. The combination of multi-parametric MRI with CPF further improved the predictive performance. KEY POINTS: • Pretreatment MSI L and ADC were independent prognostic factors for post-treatment residual tumours. • The residual groups showed lower MSI L , higher ADC and higher stage. • The predictive capacity of multi-parametric MRI was superior to individual MRI parameters. • The combination of multi-parametric MRI with CPF exhibited the highest predictive performance.

Minimum apparent diffusion coefficient for predicting lymphovascular invasion in invasive cervical cancer.

PURPOSE: To investigate the diagnostic performance of minimum apparent diffusion coefficient (mini-ADC) for predicting lymphovascular invasion (LVI) in invasive cervical cancer. MATERIALS AND METHODS: Ninety-six patients with pathologically confirmed invasive cervical cancer (CC) underwent conventional preoperative magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) on a 3.0T MRI system. Tumor ADC, mini-ADC and mini-ADC ratio (mini-ADC value / tumor ADC value) were obtained and compared between LVI-positive and LVI-negative invasive CC, and correlation between LVI status and Ki-67, p16, p63, and clinical prognostic factors were analyzed. ADC thresholds and diagnostic performance were determined by receiver operating characteristic (ROC) analysis. RESULTS: Tumor ADC showed no significant difference (P = 0.300) between LVI-positive invasive CC (n = 27) and LVI-negative invasive CC (n = 69); the mini-ADC and mini-ADC ratio were significantly lower in LVI-positive invasive CC than in LVI-negative invasive CC ([0.712 ± 0.078 × 10-3 mm2 /s] vs. [0.867 ± 0.099 × 10-3 mm2 /s], P < 0.001; and [0.772 ± 0.062] vs. [0.917 ± 0.052], P < 0.001, respectively). ROC curve analysis yielded a cutoff mini-ADC value of 0.837 in the differentiation of LVI-positive and LVI-negative invasive CC, with a sensitivity of 65%, specificity of 100%, and area under the curve (AUC) of 0.885; a cutoff mini-ADC ratio of 0.875 with a sensitivity of 78%, specificity of 100%, AUC of 0.970, positive predictive value of 100%, and negative predictive value of 64%. There was a positive correlation between LVI status and Ki-67 (r = 0.241, P = 0.014) and a negative correlation between mini-ADC and LVI status (r = -0.582, P < 0.001); mini-ADC and Ki-67 (r = -0.587, P < 0.001). CONCLUSION: Mini-ADC value appears to be a simple and effective tool for the prediction of LVI status in invasive CC, and the mini-ADC ratio may be the best parameter in discriminating between LVI-positive and LVI-negative invasive CC. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 4 J. MAGN. RESON. IMAGING 2017;45:1771-1779.

[Rapid detection of Streptococcus mutans and streptococcus sobrinus in human saliva by nested polymerase chain reaction].

OBJECTIVE: To establish a simple and rapid method to detect Streptococcus mutans and streptococcus sobrinus simultaneously in human saliva. METHODS: Chromosomal DNA from the bacteria was obtained by the extraction method with phenol-chloroform. A nested PCR method with two sets of primers specific for portions of the glucosyltransferase genes (gtfB of S. mutans and gtfI of S. sobrinus), was optimized to detect S. mutans and S. sobrinus from standard strains, clinical strains and directly in human saliva. RESULTS: The first process of nested PCR was capable of amplifying DNA fragments specific for these species from chromosomal DNA extracted from 10(5) CFU cells of standard and clinical strains, or from 1 ml clinical saliva samples containing 10(5) CFU cells of either species. a second process of nested PCR, using the first PCR product as a template with new internal primers to detect 10(3) CFU of either streptococcal species in 1ml saliva samples. CONCLUSION: Nested PCR could detect S. mutans and S. sobrinus rapidly and simply in human saliva. This finding would be important to studies of elucidation the role of these two streptococcal species in the etiology of dental caries.