Protein profile study of clinical samples of ovarian cancer using high-performance liquid chromatography-laser induced fluorescence (HPLC-LIF)

New techniques for the early detection of cancer are fast emerging. This is essential for more effective diagnosis and control of the disease. We have used a High Performance Liquid Chromatography-Laser Induced Fluorescence (HPLCLIF) technique to record chromatograms of proteins in serum and ovarian tissue samples. The recorded chromatograms of normal, benign and malignant samples were analyzed using statistical (Principal Component Analysis) methods. It is shown that chromatograms of the samples can be classified into sets, and a model based on such a classification can be used to analyze protein profiles of test samples of serum and ovarian tissue for the detection of malignancies

Nanoencapsulation of the omega-3 EPA:DHA 6:1 formulation enhances and sustains NO-mediated endothelium-dependent relaxations in coronary artery rings and NO formation in endothelial cells

International audienceThe eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) formulation with a ratio of 6:1 is a potent stimulator of the endothelial formation of nitric oxide (NO). The aim of the study was to investigate whether nanoencapsulation of EPA:DHA 6:1 followed by coating with gum increases its biological activity. Vascular reactivity was assessed using porcine coronary artery rings, the formation of NO in cultured endothelial cells (ECs) using DAF-FM and indirectly by platelet aggregation studies. Coated EPA:DHA 6:1 nanoparticles induced sustained relaxations of coronary artery rings that were greater in rings with than in those without endothelium, and more pronounced than with the native form. Treatment of ECs with coated EPA:DHA 6:1 nanoparticles caused greater and more sustained formation of NO and enhanced their anti-aggregatory effects. Thus, nanoencapsulation of EPA:DHA 6:1 is an attractive strategy to enhance the beneficial effect at the vascular endothelium

Cardiac diastolic dysfunction in angiotensin II treated hypertensive rats is associate with endothelial upregulation of SGLT1/2 in the macro and microcirculation: Protective effect of empagliflozin

Background: /Introduction: The angiotensin II (Ang II)/AT1R/NADPH oxidase-prooxidant pathway has been shown to upregulate the expression of SGLT1 and 2 and to induce premature endothelial dysfunction in coronary endothelial cells. Since all these effects are prevented by the dual SGLT1/2 inhibitor sotagliflozin (sota) and the SGLT2 inhibitor empagliflozin (empa), SGLT1 and 2 are involved in the induction of endothelial dysfunction. Purpose: The aim of the study was to evaluate the role of SGLT1 and 2 in the Ang II-induced hypertensive response leading to cardiac and vascular endothelial dysfunction. Methods: Male Wistar rats received empa (30 mg/kg/day) provided in the diet for 5 weeks. After 1 week, rats underwent sham surgery (sham rats) or surgery with implantation of an osmotic mini-pump infusing Ang II (0.4 mg/kg/d) for 4 weeks. Systolic blood pressure (SBP) was assessed by plethysmography, the cardiac function using echocardiography, the expression level of target proteins by immunofluorescence staining, fibrosis by Sirius red staining, the function of SGLT1 and 2 indirectly by the uptake of glucose-conjugated anthocyanins, and the level of oxidative stress using dihydroethidium staining. Results: The administration of Ang II to rats caused an increased systolic blood pressure from about 140 to 180 mmHg, which was not affected by empa. In the heart, the hypertensive response resulted in an increased left ventricle mass and a diastolic dysfunction as indicated by an elevated E/e' and a decreased IVRT, fibrosis and increased collagen I and ANP expression levels. In the secondary branch of the mesenteric artery, it resulted in an increased level of oxidative stress, AT1R, collagen I and of endothelial ACE, VCAM-1, MCP-1, MMP-2, MMP-9 associated with a down-regulation of eNOS. It was also associated with an increased endothelial expression level of SGLT1 in the aorta, mesenteric resistance vessel and coronary microcirculation. Moreover, an increased uptake of anthocyanins is observed in the aorta predominantly in the endothelium and this effect is markedly reduced by sota and empa. All of the above parameters were markedly reduced in the Ang II plus empa group whereas the empa treatment alone had little effect compared to the control group. Conclusion: The findings indicate that Ang II-induced hypertension promoting left ventricle cardiac dysfunction, and both macro and microvascular endothelial dysfunction are associated with an up-regulation of SGLT1 and 2 in endothelial cells. They further indicate that empa prevents the noxious impact of Ang II on the heart and vasculature despite persistent hypertension

Anthocyanin-rich blackcurrant intake by old rats improves blood pressure, vascular oxidative stress and endothelial dysfunction associated with SGLT1- and 2-mediated vascular uptake of anthocyanin

Introduction Aging-related endothelial dysfunction and vascular oxidative stress affect early arterial sites at risk. Anthocyanins uptake via sodium-glucose co-transporter 1 (SGLT1) are potent inducers of endothelial formation of nitric oxide (NO). Aims This study examined if anthocyanin-rich blackcurrant (ARB) improves the endothelial function in old rats. Method Male Wistar rats (22-month old) received ARB (60 and 120 mg/kg/d) orally for 2 weeks. Systolic blood pressure (SBP) was assessed by tail-cuff sphygmomanometry, vascular reactivity using organ chambers, protein expression by immunofluorescence, oxidative stress using dihydroethidium, and anthocyanin uptake by Neu reagent. Results Old rats showed increased SBP, abolished endothelium-dependent hyperpolarization-mediated relaxation and increased contractile response to phenylephrine in the mesenteric artery, which were improved by ARB. Old aorta showed increased oxidative stress and expression levels of eNOS, which were improved by ARB. SGLT1 immunofluorescence predominantly in the endothelium was more pronounced in the aortic arch than the aorta and higher in old than young rats, whereas the SGLT2 signal was low. The ARB treatment induced a dose-dependent accumulation of anthocyanins in the aorta and aortic arch. An ARB purified extract promoted ex vivo greater anthocyanins uptake mostly in the endothelium in the aortic arch than aorta, and in old compared to young rats. The anthocyanins uptake was inhibited to a greater extent by a dual SGLT1/2 inhibitor than by a selective SGLT2 inhibitor in the aorta of young and old rats. Both SGLT inhibitors reduced also ex vivo the age-related vascular oxidative stress. Conclusion The upregulation of SGLT1, and the greater SGLT1 and SGLT2-mediated uptake of anthocyanins predominantly in the endothelium at arterial sites at risk in old rats suggest that anthocyanins appear as interesting natural products to protect the endothelial function with increasing age

2020 list of human papillomavirus assays suitable for primary cervical cancer screening

Background: Only clinically validated HPV assays can be accepted in cervical cancer screening. Objectives: To update the list of high-risk HPV assays that fulfil the 2009 international validation criteria (Meijer-2009). Data Sources: PubMed/Medline, Embase, Scopus, references from selected studies; published in January 2014 to August 2020. Study eligibility criteria: HPV test validation studies and primary screening studies, involving testing with an index HPV test and a comparator HPV test with reporting of disease outcome (occurrence of histologically confirmed cervical precancer; CIN2+). Participants: Women participating in cervical cancer screening. Interventions: Testing with an index and a comparator HPV test of clinician-collected cervical specimens and assessment of disease outcome ( Results: Seven hrHPV DNA tests consistently fulfilled all validation criteria in multiple studies using predefined test positivity cut-offs (Abbott RealTime High Risk HPV, Anyplex II HPV HR Detection, BD Onclarity HPV Assay, Cobas 4800 HPV Test, HPV-Risk Assay, PapilloCheck HPV-Screening Test and Xpert HPV). Another assay (Alinity m HR HPV Assay) was fully validated in one validation study. The newer Cobas 6800 HPV Test, was validated in two studies against Cobas 4800. Other tests partially fulfilled the international validation criteria (Cervista HPV HR Test, EUROArray HPV, Hybribio's 14 High-Risk HPV, LMNX Genotyping Kit GP HPV, MALDI-TOF, RIATOL qPCR and a number of other in-house developed assays) since the non-inferior accuracy was reached after a posteriori cut-off optimization, inconsistent accuracy findings in different studies, and/or insufficient reproducibility assessment. The APTIMA HPV Assay targeting E6/E7 mRNA of hrHPV was fully validated in one formal validation study and showed slightly lower pooled sensitivity but higher specificity than the standard comparator tests in seven screening studies. However, the current international validation criteria relate to DNA assays. The additional requirement for longitudinal performance data required for non-DNA based HPV assays was not assessed in this review. Conclusions: Eleven hrHPV DNA assays fulfil all requirements for use in cervical cancer screening using clinician-collected specimens. Marc Arbyn, Clin Microbiol Infect 2021;27:1083 (c) 2021 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/)