Intratumoral expression of genes encoding Cytochrome P450 enzymes (CYP) might play a critical role not only in cancer development but also in the metabolism of anticancer drugs. The purpose of this study was to compare the mRNA expression patterns of seven representative CYPs in paired tumor and normal tissue of child patients with rabdomyosarcoma (RMS). Using real time quantitative RT-PCR, the gene expression pattern of CYP1A1, CYP1A2, CYP1B1, CYP2E1, CYP2W1, CYP3A4, and CYP3A5 were analyzed in tumor and adjacent non-tumor tissues from 13 child RMS patients. Protein concentration of CYPs was determined using Western blot. The expression levels were tested for correlation with the clinical and pathological data of the patients. Our data showed that the expression levels of CYP1A1 and CYP1A2 were negligible. Elevated expression of CYP1B1 mRNA and protein was detected in most RMS tumors and adjacent normal tissues. Most cancerous samples exhibit higher levels of both CYP3A4 and CYP3A5 compared with normal tissue samples. Expression of CYP2E1 mRNA was found to be significantly higher in tumor tissue, however no relation was found with protein levels. CYP2W1 mRNA and/or protein are mainly expressed in tumors. In conclusion, we defined the CYP gene expression profile in tumor and paired normal tissue of child patients with RMS. The overexpression of CYP2W1, CYP3A4 and CYP3A5 in tumor tissues suggests that they may be involved in RMS chemoresistance; furthermore, they may be exploited for the localized activation of anticancer prodrugs.
26 August 2016 in Human Vaccines & Immunotherapeutics
A quadrivalent, inactivated, split-virion influenza vaccine containing a strain from both B lineages (IIV4) has been developed, but its safety and immunogenicity in young children has not been described. This was a phase III, randomized, double-blind, active-controlled, multi-center study to examine the immunogenicity and safety of IIV4 in children 3–8 y of age (EudraCT no. 2011-005374-33). Participants were randomized 5:1:1 to receive the 2013/2014 Northern Hemisphere formulation of IIV4, an investigational trivalent comparator (IIV3) containing the B/Victoria lineage strain, or the licensed Northern Hemisphere IIV3 containing the B/Yamagata lineage strain. Participants who had not previously received a full influenza vaccination schedule received 2 doses of vaccine 28 d apart; all others received a single dose. 1242 children were included. For all 4 strains, IIV4 induced geometric mean haemagglutination inhibition titres non-inferior to those induced by the IIV3 comparators. For both B strains, geometric mean antibody titres induced by IIV4 were superior to those induced by the IIV3 with the alternative lineage strain. Similar proportions of participants vaccinated with IIV4 and IIV3 reported solicited injection-site reactions, solicited systemic reactions, and vaccine-related adverse events. A single vaccine-related serious adverse event, thrombocytopenia, was reported 9 d after vaccination with IIV4 and resolved without sequelae. In conclusion, in children aged 3–8 y who received one dose or 2 doses 28 d apart, IIV4 had an acceptable safety profile, was as immunogenic as IIV3 for the shared strains, and had superior immunogenicity for the additional B strain.
Coronavirus disease 2019 (COVID-19) presents with various symptoms, and some patients develop post-COVID-19 condition (PCC). Vitamin D has shown therapeutic potential in COVID-19 and may offer benefits for PCC. The aim of this study was to evaluate the differences associated with two supplementation strategies (bolus and daily) on interleukin-6 (IL-6) levels, glutathione peroxidase (GPx) activity, and clinical outcomes in PCC patients, regardless of whether target 25 (OH) D levels reached the ideal range. We conducted a self-controlled study in which 54 participants with PCC were supplemented with vitamin D3 (n = 28 bolus and n = 26 daily) for 2 months. Blood samples were collected to measure IL-6 levels and GPx activity using spectrophotometric methods. The Hospital Anxiety and Depression Scale (HADS) was used to assess mental function. Both bolus and daily vitamin D supplementation were significantly associated with increased GPx activity and decreased IL-6 levels. Daily supplementation was additionally associated with a significant reduction in anxiety and depression scores. However, neither regimen was associated with improvements in cough, dyspnea, or fatigue. These findings suggest a potential association between vitamin D supplementation and improvements in antioxidant and neuropsychiatric parameters in PCC, possibly mediated by its immunomodulatory and antioxidant properties. Further placebo-controlled trials are warranted to determine whether these observed associations reflect causal relationships.
31 January 2010 in The Journal of Thoracic and Cardiovascular Surgery
Background: Appendicitis is the most common abdominal emergency in pediatrics and is suggested as a quality indicator for timely access to care in time-sensitive conditions. Despite advances in diagnostics, the incidence of complicated appendicitis (CA) remains high due to delays in pediatric surgical care, which can increase disease severity. Social vulnerability has been associated with surgical access, particularly in low- and middle-income populations. This study examines the relationship between surgical delay and social determinants of complicated appendicitis in children without social security in the Metropolitan Zone of México.Methods: This retrospective cohort study was conducted in a pediatric public hospital. Consecutive cases from 2018 to 2021 with confirmed appendicitis diagnoses were included. The primary outcome variable was the type of appendicitis (acute/complicated), while two independent variables were the time of evolution (patient and hospital timing) and socioeconomic factors associated with social vulnerability. A logistic regression analysis assessed the relationship between appendicitis type and covariates.Results: A total of 943 pediatric cases of appendicitis were included. Out of these, 62.67% presented CA, with a mean age 10 ± 4 years. 60.9% were well-nourished, and 16% had at least one comorbidity. Most subjects (76%) met at least two criteria for social vulnerability, and 74.7% of families held unskilled jobs. The median symptom-to-admission time was 2 days, with a median hospital-to-surgery time of 19.5 h (p25–p75). Prehospital delays affected 57.8% of cases (n = 545), and 39% (n = 365) experienced intrahospital delays. In the multivariable logistic regression, prehospital delay ≥48 h (OR 3.27, 95% CI 2.43–4.39) and children under 5 years (OR 1.76, 95% CI 1.09–2.84) were associated with higher odds of CA.Conclusion: The high frequency of CA in uninsured children at a public hospital is due to surgical delays of two or more days. Social vulnerabilities, as observed globally, hinder access to quality care. Thus, appendicitis should be recognized as both a medical and social issue, requiring a comprehensive approach that addresses social vulnerability.
Cardiovascular diseases (CVDs) have become one of the major global health crises of the last century, causing millions of deaths each year, and are the leading cause of disability worldwide. The pharmacological management of these conditions demands new alternative or complementary therapies due to the multiple long-term side effects experienced by patients. In this context, exopolysaccharides (EPSs) have emerged as a promising alternative due to their numerous functional properties and favorable biotechnological and medical applications for health. This review provides an overview of the properties of EPSs as bioactive agents in cardiovascular diseases, highlighting the cellular signaling mechanisms in their role as cardioprotective agents, with a primary focus on their roles as antioxidants, antihypertensives, and cholesterol regulators, and their regenerative effects on vascular epithelia, positioning EPSs as promising biomolecules for CVD prevention.