Immunopathology of Schistosoma mansoni infection in rabbits: (A preliminary report)

Five rabbits infected with Schistosoma mansoni showed marked resistance, which resulted in low worm recovery and low egg production. Pathological changes appeared in liver and intestines as scattered foci of eosinophilic infiltration around immature eggs, with only occasional granulomatous formation. Antibodies to ovular and adult worm structures were demonstrated by immunofluorescence in the sera of rabbits prior to infection (natural antibodies) and specially following infection by S. mansoni. These findings point out to the peculiarities of the immunopathology of schistosomiasis in rabbits.<br>Cinco coelhos infectados experimentalmente pelo Schistosoma mansoni exibiram acentuada resistência, a qual esteve refletida na baixa recuperação dos vermes e na escassa produção de ovos. As lesões histopatológicas se limitaram a focos esparsos de infiltração eosinófila em torno de ovos imaturos e alguns raros granulomas periovulares. No soro dos coelhos normais (pré-infecção) foi detectada por imunofluorescência indireta a presença de anticorpos contra as estruturas ovulares e dos vermes adultos. Estes anticorpos se tornaram mais evidentes após a infecção pelo S. mansoni. Os achados deste estudo preliminar acentuam as pecularidades da imunopatologia da esquistossomose no coelho

Autologous dendritic cell transplantation as an adjuvant treatment in pleomorphic lung carcinoma

We embarked on autologous dendritic cells (DC) transplantation as an adjuvant therapy with chemotherapy in a pleomorphic lung carcinoma patient. DC were isolated from PBMC and primed with the autologous tumor lysate. No adverse event was noted in DC transplantation. DC administration also correlated with immunomodulation, as evidenced by an approximately 5-fold increase in serum interferon gamma after 2 months. The utility of autologous DC transplantation may offer a clinical benefit with virtually no adverse event

Autologous bone marrow-derived mesenchymal stem cells and endothelial progenitor cells transplantation showed potential benefits for type 2 diabetes mellitus Filipino patients: a case series

Introduction: Type 2 diabetes mellitus (T2DM) is a serious metabolic disorder characterized by hyperglycemia and insulin resistance. Long-standing T2DM may lead to various macro- and microvascular complications such as diabetic nephropathy, neuropathy, and retinopathy. Currently available treatments for T2DM target high plasma glucose levels but do not address T2DM-associated complications. In this report, the therapeutic application of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) transplantation in improving diabetic blood monitoring parameters among selected T2DM patients was investigated. Methods: Five Filipino patients with T2DM diagnosed for more than five years agreed to participate in the autologous bone marrow-derived stem cell transplantation. Five milliliters (mL) per kilogram (kg) of bone marrow was collected from the patients following standard procedures, and bone marrow-derived stem cells underwent quantification, genetic typing, microbial analysis, and quality control before being infused into the patients. MSCs and EPCs were intravenously transfused into the patients once a month for 6 months. Fasting blood glucose (FBG), blood urea nitrogen (BUN), glycated hemoglobin (HbA1c), and creatinine (CREA) levels were recorded pre- and post-stem cell transplantation. Results: The findings of the study revealed that the administration of autologous bone marrow-derived stem cells showed no adverse effects and improved or controlled the blood monitoring levels in most patients. Four out of five patients showed a reduction in their BUN (mean reduction = 2.246) and HbA1c (mean reduction = 0.74%) and maintained their creatinine levels within the normal range following the 6 months of infusion. Meanwhile, three out of five patients showed a decrease in FBG levels (mean reduction = 1.484 mmol/L). Conclusion: This preliminary report suggests the potential of autologous bone marrow-derived stem cell transplantation for the treatment and management of T2DM. Future studies may focus on examining other parameters such as C-peptide levels and evaluate the efficacy and safety of autologous MSCs and EPCs in the long-term management of T2DM

Characterization of Philippine drug-susceptible and multi-drug resistant mycobacterium tuberculosis isolates through combined 15-locus MIRU-VNTR genotyping and mutation analysis of drug resistance genes

Molecular genotyping, an important strategy to characterize bacterial strains infecting patients, allows identification of M. tuberculosis (MTb) complex members with varying responses to anti-mycobacterial therapy. M. tuberculosis Interspersed Repeating Units – Variable Number of Tandem Repeats (MIRU-VNTR) is a fast, reproducible and cost-effective PCR-based method capable of differentiating MTb strains. This study focused on evaluating the utility of MIRU-VNTRs to differentiate 54 MTB isolates from the Lung Center of the Philippines (LCP) through amplification of twelve MIRU-VNTRs and three Exact Tandem Repeats (ETRs). Digital codes were determined per isolate through calculation of VNTR repeats and analyzed using the MIRU-VNTRplus program (http://www.miruvntrplus.org/MIRU/index.faces). Values of the Hunter-Gaston discriminatory index (HGDI) suggest that five of fifteen (33.33%) MIRU-VNTRs are highly discriminating (\u3e0.75). All MIRU-VNTRs and ETRs except ETRC had HGDI values indicative of good resolving power (≥0.5). Among the LCP isolates, four Mtb clusters closely related to the East AfricanIndian strain family were identified on the basis of MIRU-VNTR profiles and mutation data on rpoB, katG and gyrA genes obtained through gene sequencing, which is consistent with previous reports regarding the existence of a distinct Manila family of MTb strains. The said four clusters have been designated as EAI-M1 through EAI-M4, in order of increasing propensity to develop drug resistance. Among these clusters, rpoB, katG and gyrA mutations were observed that are highly similar to those already reported in literature. Our results demonstrate that a 15-locus MIRU-VNTR genotyping strategy in combination with mutation profiling of drug resistance-related genes could serve as a molecular-epidemiology tool for characterizing and monitoring drug-susceptible and multi-drug resistant MTb strains in the Philippines

N‑Glycan and Glycopeptide Serum Biomarkers in Philippine Lung Cancer Patients Identified Using Liquid Chromatography–Tandem Mass Spectrometry

Aberrant glycosylation has been extensively reported in cancer, with fundamental changes in the glycosylation patterns of cell-surface and secreted proteins largely occurring during cancer progression. As such, serum glycan and glycopeptide biomarkers have been discovered using mass spectrometry and proposed for cancer detection. Here, we report for the first time potential serum N-glycan and glycopeptide biomarkers for Philippine lung cancer patients. The N-glycan and glycoprotein profiles of a cohort (n = 26 patients, n = 22 age- and gender-matched) of lung cancer patients were analyzed and compared to identify potential N-glycan and glycopeptide serum biomarkers using nano-QToF-MS/MS and ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry dynamic multiple monitoring methods, respectively. Statistical analyses identified differential N-glycan and glycopeptide abundances. The N-glycans were mostly sialylated and sialofucosylated branched structures. The glycopeptides involved proteins in complement and coagulation cascades (p adj = 6.418 × 10-4), innate immunity (p adj = 6.094 × 10-3), acute inflammatory response (p adj = 6.404 × 10-5), defense response (p adj = 2.082 × 10-4), complement activation pathways (p adj = 1.895 × 10-2), and immunoglobulin-mediated immune response pathways (p adj = 4.818 × 10-2). Biomarker models were constructed using serum N-glycans [area under the curve (AUC) = 0.775; 95% CI: 0.617-0.931] and glycopeptides (AUC = 0.959; 95% CI: 0.85-1.0), with glycopeptides having higher accuracies than N-glycans. The results suggest that in the Philippine lung cancer patient sera, specific N-glycans and site-specific glycans are differentially expressed between cases and controls. This report represents the first serum glycan and glycopeptide biomarkers of Philippine lung cancer patients, further demonstrating the utility of mass spectrometry-based glycomic and glycoproteomic methods

Risk of COVID-19 after natural infection or vaccinationResearch in context

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health

Risk of COVID-19 after natural infection or vaccinationResearch in context

Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health