Increased expression of sialic acid in cervical biopsies with squamous intraepithelial lesions

<p>Abstract</p> <p>Background</p> <p>Altered sialylation has been observed during oncogenic transformation. Sialylated oligosaccharides of glycoproteins and glycolipids have been implicated in tumor progression and metastases. In the cervical cancer high levels of sialic acid have been reported in the patients serum, and an increased of total sialic acid concentration has been reported for the cervical neoplasia and cervical cancer. This study investigates the changes in expression and distribution of α2,3-linked sialic acid and α2,6- linked sialic acid in low and high squamous intraepithelial lesions and in normal tissue.</p> <p>Methods</p> <p>Lectin histochemistry was used to examine the expression and distribution of sialic acid in different grades of cervical neoplasia. We applied <it>Maackia amurensis </it>lectin, which interacts with α2,3-linked sialic acid and <it>Sambucus nigra </it>lectin specific for α2,6-linked sialic acid.</p> <p>Results</p> <p>The histochemical analysis showed that α2,3-linked sialic acid and α2,6- linked sialic acid increased in intensity and distribution in concordance with the grade of squamous intraepithelial lesion (SIL). These results are in concordance with a previous study that reports increased RNAm levels of three sialyltransferases.</p> <p>Conclusions</p> <p>These results show that the change in sialylation occurs before cancer development and may play an important role in cellular transformation. These findings provide the basis for more detailed studies of the possible role of cell surface glycoconjugates bearing sialic acid in the cellular cervix transformation.</p

Detection of hepatitis C virus RNA in saliva of patients with active infection not associated with periodontal or liver disease severity

BACKGROUND: Hepatitis C virus (HCV) is mainly transmitted by parenteral route, being blood transfusion and intravenous drug use the most frequent risk factors. However, it has been suggested that there are other routes of transmission. There are several studies where HCV RNA has been detected in saliva of patients infected with HCV, and epidemiological studies have proposed the dental treatments as possible risk factors for HCV transmission. The purpose of this study was to detect the presence of HCV RNA in saliva of patients with active infection and associating with periodontal or liver disease. METHODS: Patients with quantifiable HCV-RNA in serum were enrolled in the study. Periodontal disease was assessed using the modified gingival index (MGI). Presence of dental plaque was assessed with the use of disclosing tablets. Patients were clinically and laboratory evaluated to identify the stage of liver disease, the HCV RNA was determinate in saliva by nested RT-PCR. To determine associations between different parameters univariate and multivariate analysis were used. RESULTS: A total of 45 patients were included. Of these patients, 21 (46.6%) had hepatitis, 23 (51.1%) had cirrhosis and one patient (2.4%) presented hepatocellular carcinoma (HCC). Viral loads in serum ranged from 2.31–6.68 log IU/ml with a mean of 5.46 log IU/ml (95% CI 5.23–5.70). HCV RNA was positive in saliva of 29 patients (64.4%) and was not detected in 16 (35.6%). For univariate analysis three independent variables were associated with the detection of HCV-RNA in saliva: gender, viral load and dental plaque and multivariate analysis only one independent variable viral load >5.17 log IU/mL remained significantly associated with the detection of HCV in saliva (p = 0.0002). A statistical difference was observed when viral load was analyzed, log 5.85 IU/mL (95% CI 5.67–6.02) for patients with HCV in saliva vs. log 4.77 IU/mL (95% CI 4.35–5.19) for patients without HCV in saliva (p = 0.0001). The detection of HCV-RNA in saliva was more frequent in patients with relatively high serum viral loads. CONCLUSION: HCV-RNA in saliva was associated with the level of serum viral load but not with periodontal or liver disease severity

Quantitative analysis of interferon alpha receptor subunit 1 and suppressor of cytokine signaling 1 gene transcription in blood cells of patients with chronic hepatitis C

<p>Abstract</p> <p>Background</p> <p>Interferon (IFN)-α receptor 1 (<it>ifnar1</it>) and suppressor of cytokine signaling 1 (<it>socs1</it>) transcription levels were quantified in peripheral blood mononuclear cells (PBMC) of 59 patients infected with hepatitis C virus (HCV) and 17 non-infected individuals. Samples were obtained from patients infected with HCV that were either untreated or treated with IFN-α2 plus ribavirin for 1 year and divided into responders and non-responders based on viral load reduction 6 months after treatment. <it>Ifnar1 </it>and <it>socs1 </it>transcription was quantified by real-time RT-PCR, and the fold difference (2^-ΔΔCT) with respect to <it>hprt </it>housekeeping gene was calculated.</p> <p>Results</p> <p><it>Ifnar1 </it>transcription increased significantly in HCV-infected patients either untreated (3.26 ± 0.31), responders (3.1 ± 0.23) and non-responders (2.18 ± 0.23) with respect to non-infected individuals (1 ± 0.34; <it>P </it>= 0.005). <it>Ifnar1 </it>transcription increased significantly (<it>P </it>= 0.003) in patients infected with HCV genotypes 1a (4.74 ± 0.25) and 1b (2.81 ± 0.25) but not in 1a1b (1.58 ± 0.21). No association was found of <it>Ifnar1 </it>transcription with disease progress, initial viral load or other clinical factors. With respect to <it>socs1 </it>transcription, values were similar for non-infected individuals (1 ± 0.28) and untreated patients (0.99 ± 0.41) but increased in responders (2.81 ± 0.17) and non-responder patients (1.67 ± 0.41). Difference between responder and non-responder patients was not statistically significant. <it>Socs1 </it>transcription increased in patients infected with HCV genotypes 1a and 1b (2.87 ± 0.45 and 2.22 ± 0.17, respectively) but not in 1a1b (1.28 ± 0.40). <it>Socs1 </it>transcript was absent in three patients infected with HCV genotype 1b. A weak correlation between <it>ifnar1 </it>and <it>socs1 </it>transcription was found, when Spearman's correlation coefficient was calculated.</p> <p>Conclusion</p> <p>Our results suggest that HCV infection may up-regulate <it>ifnar1 </it>transcription. HCV genotypes differ in their capacity to affect <it>ifnar1 </it>and <it>socs1 </it>transcription, as well as in the ability to evade the antiviral response.</p

Comparison of Health-Related Quality of Life Between Patients With Different Metatarsalgia Types and Matched Healthy Controls: A Cross-Sectional Analysis

[Abstract] BACKGROUND: Metatarsalgia can be considered to be a common complaint in clinical practice. The aim of this study was to compare quality of life (QoL) between participants with different metatarsalgia types and matched-paired healthy controls. DESIGN AND SETTING: A cross-sectional analysis on a sample of 124 participants of median age ± interquartile range of 55 ± 22 years was carried out in the University Clinic of Podiatric Medicine and Surgery, Ferrol, Spain. They presented primary (n = 31), secondary (n = 31) or iatrogenic (n = 31) metatarsalgia, or were matched-paired healthy controls (n = 31). METHODS: Self-reported domain scores were obtained using the Foot Health Status Questionnaire (FHSQ) and were compared between the participants with metatarsalgia and between these and the healthy controls. RESULTS: Statistically significant differences were shown in all FHSQ domains (P ≤ 0.001). Post-hoc analyses showed statistically significant differences (P < 0.05) between the metatarsalgia types in relation to the matched healthy control group, such that the participants with metatarsalgia presented impaired foot-specific and general health-related QoL (lower FHSQ scores). CONCLUSION: This study demonstrated that presence of metatarsalgia had a negative impact on foot health-related QoL. Foot-specific health and general health were poorer among patients with metatarsalgia, especially among those with secondary and iatrogenic metatarsalgia, in comparison with matched healthy controls

Hepatitis C virus infection in blood donors from the state of Puebla, Mexico

<p>Abstract</p> <p>Background</p> <p>Worldwide, 130 million persons are estimated to be infected with HCV. Puebla is the Mexican state with the highest mortality due to hepatic cirrhosis. Therefore, it is imperative to obtain epidemiological data on HCV infection in asymptomatic people of this region. The objective of present study was to analyze the prevalence of antibodies and genotypes of hepatitis C virus (HCV) in blood donors from Puebla, Mexico.</p> <p>Results</p> <p>The overall prevalence was 0.84% (515/61553). Distribution by region was: North, 0.86% (54/6270); Southeast, 1.04% (75/7197); Southwest, 0.93% (36/3852); and Central, 0.79% (350/44234). Ninety-six donors were enrolled for detection and genotyping of virus, from which 37 (38.5%) were HCV-RNA positive. Detected subtypes were: 1a (40.5%), 1b (27.0%), mixed 1a/1b (18.9%), undetermined genotype 1 (5.4%), 2a (2.7%), 2b (2.7%), and mixed 1a/2a (2.7%). All recovered donors with S/CO > 39 were HCV-RNA positive (11/11) and presented elevated ALT; in donors with S/CO < 39 HCV-RNA, positivity was of 30.4%; and 70% had normal values of ALT. The main risk factors associated with HCV infection were blood transfusion and surgery.</p> <p>Conclusions</p> <p>HCV prevalence of donors in Puebla is similar to other Mexican states. The most prevalent genotype is 1, of which subtype 1a is the most frequent.</p

Identification of Human Papillomavirus genotypes in juvenile laryngeal papillomatosis. Three-year experience in a concentration hospital in Puebla, Mexico

uvenile laryngeal papillomatosis (JLP) is a chronic benign disease of viral etiology, with an aggressive clinical course. In Mexico, the genotypes of the Human Papilloma Virus (HPV) that cause the disease have been poorly studied. The aim of this study was to identify HPV genotypes in PLJ patients. A descriptive and retrospective study was carried out, the records of patients with PLJ treated in a hospital in Mexico were reviewed, in the period 2018-2021. HPV was identied in all patients for genomes 6, 11, 16, and 18. nine patients were included, 56% women, mean age 9.5 ± 5.7 years; seven patients registered positivity for HPV-11 and 2 for HPV-6. The average age at diagnosis was 2.35 ± 1.77 years, with an average of 12 ± 11.56 surgical procedures. In conclusion, the most frequent genotypes in patients with PLJ were HPV-6 and HPV-11, with the latter predominating

Cross-hybridization between HPV genotypes in the Linear Array Genotyping Test confirmed by Next-Generation Sequencing

Background: Linear Array Genotyping Test (LA) is one of the gold standards used for Human Papillomavirus (HPV) genotyping, however, since its launching in 2006, new HPV genotypes are still being characterized with the use of high specificity techniques such as Next-Generation Sequencing (NGS). Derived from a previous study of the IMSS Research Network on HPV, which suggested that there might be cross-reaction of some HPV genotypes in the LA test, the aim of this study was to elucidate this point. Methods: Double stranded L1 fragments (gBlocks) from different HPVs were used to perform LA test, additionally, 14 HPV83+ and 26 HPV84+ cervical samples determined with LA, were individually genotyped by NGS. Results: From the LA HPV83+ samples, 64.3% were truly HPV83+, while 42.9% were found to be HPV102+. On the other hand, 69.2% of the LA HPV84+ samples were HPV84+, while 3.8, 11.5 and 30.8% of the samples were indeed HPV 86, 87 and 114 positive, respectively. Additionally, novel nucleotide changes in L1 gene from HPV genotypes 83, 84, 87, 102 and 114 were determined in Mexican cervical samples, some of them lead to changes in the protein sequence. Conclusions: We demonstrated that there is cross-hybridization between alpha3-HPV genotypes 86, 87 and 114 with HPV84 probe in LA strips and between HPV102 with HPV83 probe; this may be causing over or under estimation in the prevalence of these genotypes. In the upcoming years, a switch to more specific and sensitive genotyping methods that detect a broader spectrum of HPV genotypes needs to be implemented

Specialized proresolving mediators protect against experimental autoimmune myocarditis by modulating Ca2+ handling and NRF2 activation

Specialized proresolving mediators and, in particular, 5(S), (6)R, 7-trihydroxyheptanoic acid methyl ester (BML-111) emerge as new therapeutic tools to prevent cardiac dysfunction and deleterious cardiac damage associated with myocarditis progression. The cardioprotective role of BML-111 is mainly caused by the prevention of increased oxidative stress and nuclear factor erythroid-derived 2-like 2 (NRF2) down-regulation induced by myocarditis. At the molecular level, BML-111 activates NRF2 signaling, which prevents sarcoplasmic reticulum–adenosine triphosphatase 2A down-regulation and Ca2+ mishandling, and attenuates the cardiac dysfunction and tissue damage induced by myocarditis.This work was supported by the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (SAF-2017-84777R), Instituto de Salud Carlos III (ISCIII) (PI17/01093, PI17/01344, and PI20/01482), Sociedad Española de Cardiología, Proyecto Traslacional 2019 and Asociación del Ritmo Cardiaco (SEC, España), Proyecto Asociación Insuficiencia Cardiaca (Trasplante Cardiaco) 2020, Fondo Europeo de Desarrollo Regional, Fondo Social Europeo, and CIBERCV, a network funded by ISCIII, Spanish Ministry of Science, Innovation and Universities (PGC2018-097019-B-I00), Ministerio de Economía, Industria y Competitividad/Agencia Estatal de Investigación 10.13039/501100011033 PID2020-113238RB-I00, PID2019-105600RB-I00, the Instituto de Salud Carlos III (Fondo de Investigación Sanitaria grant PRB3 [PT17/0019/0003-ISCIII-SGEFI/ERDF, ProteoRed]), and “la Caixa” Foundation (project code HR17-00247). The Centro Nacional de Investigaciones Cardiovasculares is supported by the ISCIII, the Ministerio de Ciencia, Innovación y Universidades. Dr Ruiz-Hurtado is Miguel Servet I researcher of ISCIII (CP15/00129 Carlos III Health Institute). Dr Tamayo and R.I. Jaén, and M. Gil-Fernández were or currently are PhD students funded by the Formación de Profesorado Universitario program of the Spanish Ministry of Science, Innovation and Universities (FPU17/06135; FPU16/00827, FPU1901973)

Specialized proresolving mediators protect against experimental autoimmune myocarditis by modulating Ca2+ handling and NRF2 activation

Preclinical research[Abstract] Specialized proresolving mediators and, in particular, 5(S), (6)R, 7-trihydroxyheptanoic acid methyl ester (BML-111) emerge as new therapeutic tools to prevent cardiac dysfunction and deleterious cardiac damage associated with myocarditis progression. The cardioprotective role of BML-111 is mainly caused by the prevention of increased oxidative stress and nuclear factor erythroid-derived 2-like 2 (NRF2) down-regulation induced by myocarditis. At the molecular level, BML-111 activates NRF2 signaling, which prevents sarcoplasmic reticulum–adenosine triphosphatase 2A down-regulation and Ca2+ mishandling, and attenuates the cardiac dysfunction and tissue damage induced by myocarditis.Ministerio de Economía y Competitividad (España); SAF-2017-84777RInstituto de Salud Carlos III; PI17/01093Instituto de Salud Carlos III; PI17/01344Instituto de Salud Carlos III; PI20/01482Ministerio de Ciencia, Innovación y Universidades (España); PGC2018-097019-B-I00Ministerio de Economía, Industria y Competitividad (España); 10.13039/501100011033Ministerio de Industria, Economía y Competitividad; PID2020-113238RB-I00Ministerio de Industria, Economía y Competitividad (España); PID2019-105600RB-I00Fundación La Caixa; HR17-0024