Bone marrow-derived mesenchymal stem cells attenuate myocardial ischemia-reperfusion injury via upregulation of splenic regulatory T cells.

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) is the main pathological manifestation of cardiovascular diseases such as myocardial infarction. The potential therapeutic effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) and the participation of regulatory T cells (Tregs) in MIRI remains to be defined. METHODS: We used the experimental acute MIRI that was induced in mice by left ascending coronary ischemia, which were subsequently randomized to receive immunoglobulin G (IgG) or anti-CD25 antibody PC61 with or without intravenously injected BM-MSCs. The splenectomized mice underwent prior to experimental MIRI followed by intravenous administration of BM-MSCs. At 72 h post-MIRI, the hearts and spleens were harvested and subjected to cytometric and histologic analyses. RESULTS: CD25+Foxp3+ regulatory T cells were significantly elevated after MIRI in the hearts and spleens of mice receiving IgG + BM-MSCs and PC61 + BM-MSCs compared to the respective control mice (all p < 0.01). This was accompanied by upregulation of interleukin 10 and transforming growth factor ß1 and downregulation of creatinine kinase and lactate dehydrogenase in the serum. The post-MIRI mice receiving BM-MSCs showed attenuated inflammation and cellular apoptosis in the heart. Meanwhile, splenectomy compromised all therapeutic effects of BM-MSCs. CONCLUSION: Administration of BM-MSCs effectively alleviates MIRI in mice through inducing Treg activation, particularly in the spleen.

The value of p16ink4a expression by fluorescence in situ hybridization in triage for high risk HPV positive in cervical cancer screening.

OBJECTIVES: The aim of this study is to evaluate the effect of fluorescence in situ hybridization (FISH) detection for p16ink4a expression as an alternative triage for high risk HPV positive women in cervical cancer screening. METHODS: Totally 191 cervical cell specimens from women with HPV positive were collected. The p16ink4a expression by FISH and liquid-based thin-layer cytology was performed and followed by colposcopy with or without biopsied histologic examination for all participants. The relationship between p16ink4a expression and histologic diagnosis, as well as cytology was analyzed. RESULTS: The positive rate of p16ink4a was 5.35% in normal or inflammation cases, 56.67% in CIN 1, 83.78% in CIN 2-3, 100.00% in carcinoma, respectively, with a significance between

Application of hTERC in thinprep samples with mild cytologic abnormality and HR-HPV positive.

OBJECTIVE: Amplification of hTERC is found to be an important genetic event in the progression from cervical dysplasia to cervical cancer. The hTERC value in predicting high-grade cervical intraepithelial neoplasia (CIN) or squamous cell carcinoma (SCC), in high-risk HPV (HR-HPV) positive thinprep samples with atypical squamous cells (ASC) or a low-grade squamous intraepithelial lesion (LSIL) was explored in this study. METHODS: A total of 300 thinprep cytology specimens (129 of ASC-US, 82 of LSIL, and 89 of ASC-H) with positive HR-HPV DNA was detected by a two-probe dual-color FISH panel, targeting hTERC and the centromeric region of chromosome 3 (CSP3). Using >2 signals for hTERC together with ≥2 signals for CSP3 to define abnormal nucleus, and the cutoff value was set at 6.5 per random 200 nuclei displayed increased hTERC signals and/or tumor ploidy. Statistical analyses were based on histologic findings of colposcopy biopsies, allowing CIN2 or worse (CIN2+) as the positive criterion. RESULTS: The FISH results were systematically analyzed among groups, based on histologic diagnosis, cytologic finding, HR-HPV viral load, and age status. hTERC presented good consistency with histology, and had satisfactory sensitivity, specificity, and accuracy among different groups, with less difference intergroup. The individual hTERC positive nuclei ratio was generally increased with severity of the cervical lesions. CONCLUSIONS: hTERC could be a stable predictor in assuring the risk of high-grade CIN in women with mild cytologic abnormality and positive HR-HPV, and the individual positive nuclei ratio of it might be helpful in identifying morbid grade for cervical lesions.

Detection of human telomerase RNA gene in cervical cancer and precancerous lesions: comparison with cytological and human papillomavirus DNA test findings.

OBJECTIVES: The aims of this study were to compare the findings of fluorescence in situ hybridization (FISH) detection of human telomerase RNA gene (hTERC) amplification with that of cytological and human papillomavirus (HPV) DNA tests and explore the possibility to improve the accuracy of the diagnoses of high-grade cervical intraepithelial neoplasia (CIN) and cervical cancer. METHODS: A total of 201 specimens of liquid-based thin-layer cytological examination findings were collected and detected by HPV DNA test and hTERC detected by FISH. All women underwent colposcopy and histological examination of biopsy specimen if needed. The 3 screening methods were compared based on histological examination of colposcopic biopsies. RESULTS: The amplification of hTERC showed 6.06% in normal or inflammation cases, 10.00% in CIN 1, 66.67% in CIN 2, 72.50% in CIN 3, and 100.00% in carcinoma, with significant difference between the low- (or=CIN 2 or >or=atypical squamous cells in which high-grade squamous intraepithelial lesion cannot be excluded) cervical lesions (P < 0.001). The hTERC amplification rate was consistent with abnormal rates of cytological and histological diagnoses. The detection of hTERC amplification had a much higher accuracy (87.56%) than the cytological (80.10%) and HPV DNA test (77.61%) findings. CONCLUSIONS: Using FISH to detect the amplification of hTERC had a much higher specificity and accuracy for the diagnoses of high-grade CIN and cervical cancer than cytological and HPV DNA test findings, suggesting that this detection might be a useful and specific screening method in cervical cancer and precancerous lesions.