The genus Lutzomyia has great importance in the New World, with some species implicated in the transmission of causal agents of leishmaniases, bartonellosis and arboviruses. From April 2003 to June ...2004 an investigation was undertaken on the richness and abundance of the sand fly fauna in the northeast area of Manacapuru county, Amazonas State. The captures were carried out, with 16 light traps CDC, in areas of forest known as terra firme along the highway Manuel Urbano. In the period of 13 months we collected a total of 10,446 sandfly specimens, 3,908 males (38%) and 6,465 females (62%), distributed in 43 species belonging to the genus Lutzomyia, 10 subgenera and six species groups. These results evidenced a diversified and abundant sand fly fauna, with some species not yet reported for Manaus county, close to the study area.
During pelagic video transects off Santo Antão, Cabo Verde, we encountered the midwater scorpionfish Ectreposebastes imus in midwater between 300 and 800 m over a bottom depth of about 1000 m. The ...fish were typically positioned vertically with their heads pointing upwards. These first midwater observations of E. imus suggest migratory (potentially feeding) behaviour into the pelagic realm and hence a possible role of this species in the trophic coupling between the pelagic and benthic habitats in the deep seas of Cabo Verde and elsewhere in its global distribution.
A male of Lutzomyia araracuarensis (Morales & Minter) and possibly six females of this same species were found in the northeastern area of Manacapuru county, Amazonas State. Samples were collected ...using light traps CDC, from April 2003 to June 2004.
Advanced-stage solid primary tumors and metastases often express mucin 16 (MUC16), carrying immature glycans such as the Tn antigen, resulting in specific glycoproteoforms not found in healthy human ...tissues. This presents a valuable approach for designing targeted therapeutics, including cancer glycovaccines, which could potentially promote antigen recognition and foster the immune response to control disease spread and prevent relapse. In this study, we describe an adjuvant-free poly(lactic-co-glycolic acid) (PLGA)-based nanoglycoantigen delivery approach that outperforms conventional methods by eliminating the need for protein carriers while exhibiting targeted and adjuvant properties. To achieve this, we synthesized a library of MUC16-Tn glycoepitopes through single-pot enzymatic glycosylation, which were then stably engrafted onto the surface of PLGA nanoparticles, generating multivalent constructs that better represent cancer molecular heterogeneity. These glycoconstructs demonstrated affinity for Macrophage Galactose-type Lectin (MGL) receptor, known to be highly expressed by immature antigen-presenting cells, enabling precise targeting of immune cells. Moreover, the glycopeptide-grafted nanovaccine candidate displayed minimal cytotoxicity and induced the activation of dendritic cells in vitro, even in the absence of an adjuvant. In vivo, the formulated nanovaccine candidate was also nontoxic and elicited the production of IgG specifically targeting MUC16 and MUC16-Tn glycoproteoforms in cancer cells and tumors, offering potential for precise cancer targeting, including targeted immunotherapies.
Contemporary challenges of prostate cancer (PCa) include overdiagnosis and overtreatment, entailing the need for novel clinical tools to improve risk stratification and therapy selection. PCa ...diagnosis and prognostication might be perfected using epigenetic biomarkers, among which aberrant DNA methylation of microRNA promoters has not been systematically explored. Herein, we identified aberrantly methylated microRNAs promoters in PCa and assessed its diagnostic and prognostic biomarker potential.
Using HumanMethylation450 BeadChip-based analysis differentially methylated CpGs in microRNA promoters were identified. Promoter methylation of six microRNAs (miR-34b/c, miR-129-2, miR-152, miR-193b, miR-663a and miR-1258) was analyzed by qMSP in three sets (180 prostatectomies, 95 urine sediments and 74 prostate biopsies). Biomarkers' diagnostic (validity estimates) and prognostic disease-free (DFS) and disease-specific survival (DSS) performance was assessed.
Significantly higher promoter methylation levels in PCa were confirmed for six candidate microRNAs. Except for miR-152, all displayed AUC values higher than 0.90, with miR-1258 and miR-193b disclosing the best performance (AUC = 0.99 and AUC = 0.96, respectively). In urine samples, miR-193b showed the best performance (91.6% sensitivity, 95.7% specificity, AUC = 0.96). Moreover, higher miR-129-2 independently predicted for shorter DSS and miR-34b/c methylation levels independently predicted for shorter DFS and DSS.
Quantitative miR-193b, miR-129-2 and miR-34b/c promoter methylation might be clinically useful PCa biomarkers for non-invasive detection/diagnosis and prognostication, both in tissue and urine samples.
Cancer presents a high mortality rate due to ineffective treatments and tumour relapse with progression. Cancer vaccines hold tremendous potential due to their capability to eradicate tumour and ...prevent relapse. In this study, we present a novel glycovaccine for precise targeting and immunotherapy of aggressive solid tumours that overexpress CD44 standard isoform (CD44s) carrying immature Tn and sialyl-Tn (sTn) O-glycans. We describe an enzymatic method and an enrichment strategy to generate libraries of well-characterized cancer-specific CD44s-Tn and/or sTn glycoproteoforms, which mimic the heterogeneity found in tumours. We conjugated CD44-Tn-derived glycopeptides with carrier proteins making them more immunogenic, with further demonstration of the importance of this conjugation to overcome the glycopeptides' intrinsic toxicity. We have optimized the glycopeptide-protein maleimide-thiol conjugation chemistry to avoid undesirable cross-linking between carrier proteins and CD44s glycopeptides. The resulting glycovaccines candidates were well-tolerated in vivo, inducing both humoral and cellular immunity, including immunological memory. The generated antibodies exhibited specific reactivity against synthetic CD44s-Tn glycopeptides, CD44s-Tn glycoengineered cells, and human tumours. In summary, we present a promising prototype of a cancer glycovaccine for future therapeutical pre-clinical efficacy validation.
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Purpose
To evaluate complete blood count (CBC) parameters in the first week of life as predictive biomarkers for the development of retinopathy of prematurity (ROP).
Methods
Multicenter, prospective, ...observational study of a cohort of preterm infants born with gestational age (GA) < 32 weeks or birth weight < 1500 g in eight Portuguese neonatal intensive care units. All demographic, clinical, and laboratory data from the first week of life were collected. Univariate logistic regression was used to assess risk factors for ROP and then multivariate regression was performed.
Results
A total of 455 infants were included in the study. The median GA was 29.6 weeks, and the median birth weight was 1295 g. One hundred and seventy-two infants (37.8%) developed ROP. Median values of erythrocytes (
p
< 0.001), hemoglobin (
p
< 0.001), hematocrit (
p
< 0.001), mean corpuscular hemoglobin concentration (
p
< 0.001), lymphocytes (
p
= 0.035), and platelets (
p
= 0.003) of the group of infants diagnosed with ROP any stage were lower than those without ROP. Mean corpuscular volume (MCV) (
p
= 0.044), red blood cell distribution width (RDW) (
p
< 0.001), erythroblasts (
p
< 0.001), neutrophils (
p
= 0.030), neutrophils-lymphocytes ratio (
p
= 0.028), and basophils (
p
= 0.003) were higher in the ROP group. Higher values of MCV, erythroblasts, and basophils remained significantly associated with ROP after multivariate regression.
Conclusion
In our cohort, the increase in erythroblasts, MCV, and basophils in the first week of life was significantly and independently associated with the development of ROP. These CBC parameters may be early predictive biomarkers for ROP.
The presence of Lutzomyia conviti Ramirez Perez, Martins & Ramirez, previously found only in Venezuela and Colombia, is recorded for the first time in Brazil. Lutzomyia conviti is now added to the ...229 species of Lutzomyia already registered in Brazil and to the 44 identified in São Gabriel da Cachoeira, Amazonas state. Both sexes of L. conviti were collected in 2007 and 2008 with CDC light traps in an environment of primary vegetation represented by firm land forest. The distribution range of the species is cited and discussed.
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