Changes in Metabolic and Inflammatory Markers after a Combined Exercise Program in Workers: A Randomized Controlled Trial.

PURPOSE: We investigated the effects of a 16-week combined exercise training on body composition, metabolic and inflammatory markers in sedentary middle-aged workers. We also assessed whether significant alterations in metabolic markers were associated with changes in health-related outcomes. METHODS: This randomized controlled trial involved 46 participants randomly allocated into control and exercise groups. The exercise group performed 16-week combined aerobic and resistance training for 75 min/session, 3 times/week. Fasting blood samples were collected at baseline and after 16-week intervention to determine lipid profile, metabolic and inflammatory markers as primary outcomes. RESULTS: A total of 36 participants completed the intervention (53.70 ± 6.92 years old) (n = 18 in each group). Waist circumference (interaction effect: F = 7.423, p = 0.002), fat mass (interaction effect: F = 5.070, p = 0.011), and muscle mass (interaction effect: F = 5.420, p = 0.007) were improved in the exercise group compared to the control group. Fasting glucose increased after the 16-week follow-up (time effect: F = 73.253, p < 0.001), without an intergroup difference. Insulin levels were greater in the control compared to exercise group (group effect: F = 6.509, p = 0.015). The control group tended to increase the HOMA-IR index (interaction effect: F = 3.493, p = 0.070) and to decrease the QUICKI index (interaction effect: F = 3.364, p = 0.075) to a greater extent compared to the exercise group. Exercise group reduced leptin (interaction effect: F = 11.175, p = 0.002) and adiponectin (interaction effect: F = 4.437, p = 0.043) concentrations in a greater magnitude than control group. IL-6 (time effect: F = 17.767, p < 0.001) and TNF-α (time effect: F = 9.781, p = 0.004) concentrations decreased after the intervention, without an intergroup difference. IL-17A levels increased in the control compared to exercise group (interaction effect: F = 5.010, p = 0.033). Effects on adiponectin, IL-6 and IL-17A levels seem to depend on baseline BMI, age, and sex. Percentage changes in leptin correlated positively with changes in HOMA-IR index in the exercise (r = 0.565, p = 0.015) and control (r = 0.670, p = 0.002) groups. CONCLUSIONS: A combined training program can be an effective strategy to improve body composition and inflammatory markers and prevent marked reductions in insulin sensitivity among middle-aged workers.

A Minimally Invasive Surgical Procedure to Harvest Palate Periosteum as a Source of Mesenchymal Stromal/Stem Cells for Bone Tissue Engineering.

The aim of this study is to validate a minimally invasive surgical procedure to harvest palate periosteum as a source of tissue for mesenchymal stromal/stem cells. We performed a standardized procedure to harvest the palate periosteum in ten subjects, which consisted of a 3 mm disposable punch and a Molt periosteal elevator to harvest a small full-thickness fragment of soft tissue at the hard palate area, between the upper bicuspids, 3 to 4 mm apical to the cement enamel junction. The one-third inner portion was fragmented, and following standard cell culture procedures, the adherent cells were cultured for three passages, after obtaining 70-90% confluence. Cell morphology analysis, flow cytometry analysis, and viability and osteogenic differentiation assays were performed. In all 10 cases, uneventful healing was observed, with no need for analgesic intake. The evaluation of cell morphology showed elongated spindle-shaped cells distributed in woven patterns. A high viability range was verified as well as an immunophenotype compatible with mesenchymal stem cell lineage. The differentiation assay showed the potential of the cells to differentiate into the osteogenic lineage. These results demonstrate that the minimally invasive proposed surgical technique is capable of supplying enough periosteum source tissue for stem cell culture and bone tissue engineering.

Flow Training Program: Mindfulness, Decision Making, and Mental Well-Being of Young and Adult Elite Handball Athletes.

This study aimed to analyze the effect of a flow training program based on mindfulness applied to young and adult elite handball athletes. A quantitative, quasi-experimental, descriptive data analysis approach was carried out. The sample included 105 athletes (51 female and 54 male). The athletes were divided into two groups: (i) experimental (n = 53) and (ii) control (n = 52). The results of the repeated ANOVA indicated that the experimental group achieved significant improvements compared to the control group in decision making (n2p = 0.086), mental well-being (n2p = 0.045), dispositional flow state (n2p = 0.103), non-judgment (n2p = 0.040), refocusing (n2p = 0.052), and mindful traits in daily life (n2p = 0.058). A Pearson analysis demonstrated a positive correlation between dispositional flow state and mindfulness in sport and mental well-being. The correlation analysis also showed an inverse correlation between decision making and sense of control and mindful traits in daily life. The findings revealed that the program can be effective in decision making, mental well-being, dispositional flow state, mindfulness in sport, and mindful traits in daily lives of athletes.

Metopic craniosynostosis: Dynamic cranioplasty for trigonocephaly versus fronto-orbital remodeling and advancement - A retrospective study.

The aim of this study was to compare a traditional fronto-orbital remodeling and advancement (FORA) with the dynamic cranioplasty for trigonocephaly (DCT). The authors analyzed patients who underwent surgery for trigonocephaly. Perioperative data were compared. Parents were asked to use a visual analog scale to evaluate the pre- and postoperative distance between the eyes, the forehead shape, and the global appearance of the face. A panel of observers was asked to grade pre- and postoperative photographs using a similar visual analog scale. Pre- and postoperative anthropometric data were collected and analyzed in a subset of the study population aged 9 years or older. The total sample size was 51 patients (DCT n = 39; FORA n = 12). Durations of surgery and anesthesia were shorter in the DCT group (115 vs 194 min, p = 0.001; 226 vs 289 min, p = 0.001). Patients in the DCT group received similar preoperative ratings to those in the FORA group, but significantly higher postoperative ratings by parents for all three questions. There were no significant differences in postoperative ratings by the panel or postoperative anthropometric data. DCT is safe and effective. It is preferred over FORA because it is associated with shorter durations of surgery and anesthesia, while providing higher degrees of parental satisfaction and similar aesthetic and anthropometric outcomes.

Clinical validity of the nursing diagnosis risk for unstable blood glucose level in persons with type 2 diabetes mellitus: A case-control study.

OBJECTIVE: To assess clinical-causal validity evidence of the nursing diagnosis, risk for unstable blood glucose level (00179), in individuals with type 2 diabetes mellitus. METHODS: A case-control study was conducted in 5 primary healthcare units, involving 107 subjects with type 2 diabetes mellitus, 60 in the case group and 47 in the control group. Causality was determined by the association between sociodemographic and clinical factors, risk factors related to the nursing diagnosis, and the occurrence of unstable blood glucose level. An association was considered when the risk factor had a p-value of <0.05 and odds ratio >1. RESULTS: Risk factors, such as stress, inadequate physical activity, and low adherence to therapeutic regimen, were prevalent in the sample. Time since diagnosis between 1-5 and 6-10 years, multiracial ethnicity, and the risk factor of low adherence to therapeutic regimen increased the likelihood of the outcome. Completion of high school education was identified as a protective factor. CONCLUSIONS: The clinical validation of the nursing diagnosis, risk for unstable blood glucose level, has been successfully established, revealing a clear association between sociodemographic and clinical factors and the risk factors inherent to the nursing diagnosis. IMPLICATIONS FOR NURSING PRACTICE: The results contribute to advancing scientific knowledge related to nursing education, research, and practice and provide support for the evolution of nursing care processes for individuals with type 2 diabetes mellitus.

OBJETIVO: Avaliar a evidência de validade clínico­causal do diagnóstico de enfermagem, risco para nível instável de glicose no sangue (00179), em indivíduos com diabetes mellitus tipo 2. MÉTODO: Foi realizado um estudo caso­controle em cinco unidades básicas de saúde, envolvendo 107 indivíduos com diabetes mellitus tipo 2, 60 no grupo caso e 47 no grupo controle. A causalidade foi determinada pela associação entre fatores sociodemográficos e clínicos, fatores de risco relacionados ao diagnóstico de enfermagem e a ocorrência de nível instável de glicose no sangue. Uma associação foi considerada quando o fator de risco tinha um valor de p < 0.05 e odds ratio > 1. RESULTADOS: Fatores de risco como estresse, atividade física inadequada e baixa adesão ao regime terapêutico foram predominantes na amostra. O tempo desde o diagnóstico entre 1 e 5 anos e 6 a 10 anos, a etnia parda e o fator de risco baixa adesão ao regime terapêutico aumentaram a probabilidade do resultado. A conclusão do ensino médio foi identificada como um fator de proteção. CONCLUSÕES: A validação clínica do diagnóstico de enfermagem, risco para nível instável de glicose no sangue, foi estabelecida com sucesso, revelando uma clara associação entre fatores sociodemográficos e clínicos e os fatores de risco inerentes ao diagnóstico de enfermagem. IMPLICAÇÕES PARA A PRÁTICA DE ENFERMAGEM: Os resultados contribuem para o avanço do conhecimento científico relacionado à educação, à pesquisa e à prática de enfermagem e fornecem suporte para a evolução dos processos de cuidados de enfermagem para indivíduos com diabetes.

The Source-to-Sea Landscape: A hybrid integrative territory management approach.

Whether fresh or salty, water is a unique resource, a continuum interlinked by the hydrological cycle. It forms a complex system connected to the landscape. When the landscape is altered, water flows and their benefits are impacted. Degraded land compromises water resources. The governance and management of landscape and water resources are handled in a fragmented manner and in separate contexts. The Source-to-Sea approach offers an integrative vision based on systems thinking that focuses its concerns on the interaction among parts, flows, and processes. It proposes a framework for the governance and management of freshwater and marine water but does not bring the landscape into the context of the approach. This research used an analytical-deductive method to explore the interactions and connections between the Source-to-sea approach, landscape concepts and approaches, and the guidelines of the European Landscape Convention. The main objective was to identify and assess the feasibility of integrating these elements. The integration resulted in a governance and management approach termed the S2S Landscape approach. It is grounded in systems thinking, practical learning, active participation, and adaptive governance and management, providing an integrated vision between landscape and water. The approach includes four essential steps (Comprehension, Involvement, Planning, and Execution and Monitoring) that address the complex connections that freshwater and marine water maintain in the landscape, considering physical, biological, socio-environmental, and economic aspects across all segments, from the land to the open sea. This S2S Landscape approach may be the path to address the challenges of governance and sustainable management of resources in an interconnected and constantly changing world.

Molecular epidemiology of Western equine encephalitis virus in Brazil, 2023-2024.

During the ongoing western equine encephalitis virus (WEEV) outbreak in South America, we described three fatal cases in horses from Rio Grande do Sul, Brazil. We sequenced WEEV strains and identified a novel lineage causing these cases. Continued surveillance and horse immunization are needed to mitigate the WEEV burden.

Redox conditions and biochar pyrolysis temperature affecting As and Pb biogeochemical cycles and bacterial community of sediment from mining tailings.

Despite the widespread use of biochar for soil and sediment remediation, little is known about the impact of pyrolysis temperature on the biogeochemistry of arsenic (As) and lead (Pb) and microorganisms in sediment under reducing conditions. In this study, we investigated the effects of pyrolysis temperature and the addition of glucose on the release and transformation of As and Pb, as well as their potential effects on the bacterial community in contaminated sediments. The addition of biochar altered the geochemical cycle of As, as it favors specific bacterial groups capable of changing species from As(V) to As(III) through fermentation, sulfate respiration and nitrate reduction. The carbon quality and content of N and S in solution shaped the pH and redox potential in a way that changed the microbial community, favoring Firmicutes and reducing Proteobacteria. This change played a fundamental role in the reductive dissolution of As and Pb minerals. The addition of biochar was the only efficient way to remove Pb, possibly as a function of its sorption and precipitation mechanisms. Such insights could contribute to the production or choice of high-efficiency biochar for the remediation of sediments subjected to redox conditions.

Stool Glycoproteomics Signatures of Pre-Cancerous Lesions and Colorectal Cancer.

Colorectal cancer (CRC) screening relies primarily on stool analysis to identify occult blood. However, its sensitivity for detecting precancerous lesions is limited, requiring the development of new tools to improve CRC screening. Carcinogenesis involves significant alterations in mucosal epithelium glycocalyx that decisively contribute to disease progression. Building on this knowledge, we examined patient series comprehending premalignant lesions, colorectal tumors, and healthy controls for the T-antigen-a short-chain O-glycosylation of proteins considered a surrogate marker of malignancy in multiple solid cancers. We found the T-antigen in the secretions of dysplastic lesions as well as in cancer. In CRC, T-antigen expression was associated with the presence of distant metastases. In parallel, we analyzed a broad number of stools from individuals who underwent colonoscopy, which showed high T expressions in high-grade dysplasia and carcinomas. Employing mass spectrometry-based lectin-affinity enrichment, we identified a total of 262 proteins, 67% of which potentially exhibited altered glycosylation patterns associated with cancer and advanced pre-cancerous lesions. Also, we found that the stool (glyco)proteome of pre-cancerous lesions is enriched for protein species involved in key biological processes linked to humoral and innate immune responses. This study offers a thorough analysis of the stool glycoproteome, laying the groundwork for harnessing glycosylation alterations to improve non-invasive cancer detection.

Novel Fe3O4 Nanoparticles with Bioactive Glass-Naproxen Coating: Synthesis, Characterization, and In Vitro Evaluation of Bioactivity.

Immune response to biomaterials, which is intimately related to their surface properties, can produce chronic inflammation and fibrosis, leading to implant failure. This study investigated the development of magnetic nanoparticles coated with silica and incorporating the anti-inflammatory drug naproxen, aimed at multifunctional biomedical applications. The synthesized nanoparticles were characterized using various techniques that confirmed the presence of magnetite and the formation of a silica-rich bioactive glass (BG) layer. In vitro studies demonstrated that the nanoparticles exhibited bioactive properties, forming an apatite surface layer when immersed in simulated body fluid, and biocompatibility with bone cells, with good viability and alkaline phosphatase activity. Naproxen, either free or encapsulated, reduced nitric oxide production, an inflammatory marker, while the BG coating alone did not show anti-inflammatory effects in this study. Overall, the magnetic nanoparticles coated with BG and naproxen showed promise for biomedical applications, especially anti-inflammatory activity in macrophages and in the bone field, due to their biocompatibility, bioactivity, and osteogenic potential.

Physical activity and sedentary behavior levels among individuals with mental illness: A cross-sectional study from 23 countries.

People with mental illness tend to present low levels of physical activity and high levels of sedentary behavior. The study aims to compare these levels in mental illness patients, exploring the role of socioeconomic development and treatment setting. This cross-sectional study used accelerometers and the Simple Physical Activity Questionnaire (SIMPAQ) to assess physical activity and sedentary behavior in mental illness individuals living in 23 countries. Two-way ANOVAs were used to evaluate the interaction between socioeconomic development and the treatment settings on physical activity and sedentary behavior. A total of 884 (men = 55.3%) participants, mean age of 39.3 (SD = 12.8), were evaluated. A significant interaction between socioeconomic development and treatment settings was found in sedentary behavior (F = 5.525; p = 0.019; η2p = 0.009; small effect size). Main effects were observed on socioeconomic development (F = 43.004; p < 0.001; η2p = 0.066; medium effect size) and treatment setting (F = 23.001; p < 0.001; η2p = 0.036; small effect size) for sedentary behavior and physical activity: socioeconomic development (F = 20.888; p < 0.001; η2p = 0.033; small effect size) and treatment setting (F = 30.358; p < 0.001; η2p = 0.047; small effect size), showing that HIC patients were more active, while MIC patients were more sedentary. Moreover, despite of inpatients had presented higher levels of physical activity than outpatients, they also spent more time sitting. Socioeconomic development plays an important role in sedentary behavior in patients with mental disorders, warning the need to develop new strategies to reduce these levels in this population.

Accuracy of infrared thermography evaluation in burn wound healing: a systematic review and meta-analysis.

OBJECTIVE: Accurate assessment of burn depth and burn wound healing potential is essential to determine early treatments. Infrared thermography (IRT) is a non-invasive and objective tool to do this. This systematic review evaluated the accuracy of IRT to determine burn wound healing potential. METHOD: This systematic review and meta-analysis used MEDLINE, EMBASE, CINAHL, PEDro, DiTA and CENTRAL databases. IRT data were extracted from primary studies and categorised into four cells (i.e., true positives, false positives, true negatives and false negatives). Subgroup analysis was performed according to methods used to capture thermal images. RESULTS: The search strategy identified 2727 publications; however, 15 articles were selected for review and 11 for meta-analysis. In our meta-analysis, the accuracy of IRT was 84.8% (63% sensitivity and 81.9% specificity). CONCLUSION: IRT is a moderately accurate tool to identify burn depth and healing potential. Thus, IRT should be used carefully for evaluating burn wounds.

Respiratory muscles's thermographic analysis in asthmatic youth with and without bronchospasm induced by eucapnic voluntary hyperpnea.

OBJECTIVE: To compare the thermographic pattern of regions of interest (ROI) of respiratory muscles in young asthmatics with and without bronchospasm induced by eucapnic voluntary hyperpnea (EVH). MATERIALS AND METHODS: Cross-sectional study carried out with 55 young (55% male and 45% females) aged 12.5 ± 3.3 years, divided in nine nonasthmatics, 22 asthmatics without exercise-induced bronchospasm compatible response (EIB-cr) and 24 asthmatics with EIB-cr. The diagnosis of EIB was given to subjects with a fall in forced expiratory volume in the first second (FEV1) ≥ 10% compared to baseline. Thermographic recordings of respiratory muscles were delimited in ROI of the sternocleidomastoid (SCM), pectoral, and rectus abdominis intention area. Thermal captures and FEV1 were taken before and 5, 10, 15 and 30 min after EVH. RESULTS: Twenty-four (52.1%) of asthmatics had EIB-cr. There was a decrease in temperature at 10 min after EVH test in the SCM, pectoral and rectus abdominis ROIs in all groups (both with p < 0.05). There was a decrease in temperature (% basal) in asthmatic with EIB-cr compared to nonasthmatics in the rectus abdominis area (p < 0.05). CONCLUSION: There was a decrease in temperature in the ROIs of different muscle groups, especially in asthmatics. The greater drop in FEV1 observed in individuals with EIB-cr was initially associated with a decrease in skin temperature, with a difference between the nonasthmatics in the abdominal muscle area. It is likely that this decrease in temperature occurred due to a temporary displacement of blood flow to the most used muscle groups, with a decrease in the region of the skin evaluated in the thermography.

Determinants of HIV late presentation among men who have sex with men in Portugal (2014-2019): who's being left behind?

Introduction: HIV late presentation (LP) remains excessive in Europe. We aimed to analyze the factors associated with late presentation in the MSM population newly diagnosed with HIV in Portugal between 2014 and 2019. Methods: We included 391 newly HIV-1 diagnosed Men who have Sex with Men (MSM), from the BESTHOPE project, in 17 countrywide Portuguese hospitals. The data included clinical and socio-behavioral questionnaires and the viral genomic sequence obtained in the drug resistance test before starting antiretrovirals (ARVs). HIV-1 subtypes and epidemiological surveillance mutations were determined using different bioinformatics tools. Logistic regression was used to estimate the association between predictor variables and late presentation (LP). Results: The median age was 31 years, 51% had a current income between 501-1,000 euros, 28% were migrants. 21% had never been tested for HIV before diagnosis, with 42.3% of MSM presenting LP. 60% were infected with subtype B strains. In the multivariate regression, increased age at diagnosis, higher income, lower frequency of screening, STI ever diagnosed and higher viral load were associated with LP. Conclusion: Our study suggests that specific subgroups of the MSM population, such older MSM, with higher income and lower HIV testing frequency, are not being targeted by community and clinical screening services. Overall, targeted public health measures should be strengthened toward these subgroups, through strengthened primary care testing, expanded access to PrEP, information and promotion of HIV self-testing and more inclusive and accessible health services.

Unveiling the neuroanatomy of Josephoartigasia monesi and the evolution of encephalization in caviomorph rodents.

Caviomorph rodents are an exceptional model for studying the effects of ecological factors and size relations on brain evolution. These mammals are not only speciose and ecologically diverse but also present wide body size disparity, especially when considering their fossil relatives. Here, we described the brain anatomy of the largest known rodent, Josephoartigasia monesi, uncovering distinctive features within this species regarding other taxa. Albeit resembling extant pacarana Dinomys branickii, J. monesi stands out due to its longer olfactory tract and well-developed sagittal sinus. Challenging the previous hypothesis that giant rodents possessed comparatively smaller brains, we found that J. monesi and another giant extinct rodent, Neoepiblema acreensis, are within the encephalization range of extant caviomorphs. This was unraveled while developing the a Phylogenetic Encephalization Quotient (PEQ) for Caviomorpha. With PEQ, we were able to trace brain-size predictions more accurately, accounting for species-shared ancestry while adding the extinct taxa phenotypic diversity into the prediction model. According to our results, caviomorphs encephalization patterns are not the product of ecological adaptations, and brain allometry is highly conservative within the clade. We challenge future studies to investigate caviomorphs encephalization within different taxonomic ranks while increasing the sampled taxa diversity, especially of extinct forms, in order to fully comprehend the magnitude of this evolutionary stasis.

Targeted and Self-Adjuvated Nanoglycovaccine Candidate for Cancer Immunotherapy.

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.

Unmasking the Metabolite Signature of Bladder Cancer: A Systematic Review.

Bladder cancer (BCa) research relying on Omics approaches has increased over the last few decades, improving the understanding of BCa pathology and contributing to a better molecular classification of BCa subtypes. To gain further insight into the molecular profile underlying the development of BCa, a systematic literature search was performed in PubMed until November 2023, following the PRISMA guidelines. This search enabled the identification of 25 experimental studies using mass spectrometry or nuclear magnetic resonance-based approaches to characterize the metabolite signature associated with BCa. A total of 1562 metabolites were identified to be altered by BCa in different types of samples. Urine samples displayed a higher likelihood of containing metabolites that are also present in bladder tumor tissue and cell line cultures. The data from these comparisons suggest that increased concentrations of L-isoleucine, L-carnitine, oleamide, palmitamide, arachidonic acid and glycoursodeoxycholic acid and decreased content of deoxycytidine, 5-aminolevulinic acid and pantothenic acid should be considered components of a BCa metabolome signature. Overall, molecular profiling of biological samples by metabolomics is a promising approach to identifying potential biomarkers for early diagnosis of different BCa subtypes. However, future studies are needed to understand its biological significance in the context of BCa and to validate its clinical application.

Aberrantly Glycosylated GLUT1 as a Poor Prognosis Marker in Aggressive Bladder Cancer.

Muscle-invasive bladder cancer (MIBC) remains a pressing health concern due to conventional treatment failure and significant molecular heterogeneity, hampering the development of novel targeted therapeutics. In our quest for novel targetable markers, recent glycoproteomics and bioinformatics data have pinpointed (glucose transporter 1) GLUT1 as a potential biomarker due to its increased expression in tumours compared to healthy tissues. This study explores this hypothesis in more detail, with emphasis on GLUT1 glycosylation patterns and cancer specificity. Immunohistochemistry analysis across a diverse set of human bladder tumours representing all disease stages revealed increasing GLUT1 expression with lesion severity, extending to metastasis, while remaining undetectable in healthy urothelium. In line with this, GLUT1 emerged as a marker of reduced overall survival. Revisiting nanoLC-EThcD-MS/MS data targeting immature O-glycosylation on muscle-invasive tumours identified GLUT1 as a carrier of short glycosylation associated with invasive disease. Precise glycosite mapping uncovered significant heterogeneity between patient samples, but also common glycopatterns that could provide the molecular basis for targeted solutions. Immature O-glycosylation conferred cancer specificity to GLUT1, laying the molecular groundwork for enhanced targeted therapeutics in bladder cancer. Future studies should focus on a comprehensive mapping of GLUT1 glycosites for highly specific cancer-targeted therapy development for bladder cancer.

A multivalent CD44 glycoconjugate vaccine candidate for cancer immunotherapy.

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.

Increasing the polarity of ß-lapachone does not affect its binding capacity with bovine plasma protein.

Despite ortho-quinones showing several biological and pharmacological activities, there is still a lack of biophysical characterization of their interaction with albumin - the main carrier of different endogenous and exogenous compounds in the bloodstream. Thus, the interactive profile between bovine serum albumin (BSA) with ß-lapachone (1) and its corresponding synthetic 3-sulfonic acid (2, under physiological pH in the sulphonate form) was performed. There is one main binding site of albumin for both ß-lapachones (n ≈ 1) and a static fluorescence quenching mechanism was proposed. The Stern-Volmer constant (KSV) values are 104 M-1, indicating a moderate binding affinity. The enthalpy (-3.41 ± 0.45 and - 8.47 ± 0.37 kJ mol-1, for BSA:1 and BSA:2, respectively) and the corresponding entropy (0.0707 ± 0.0015 and 0.0542 ± 0.0012 kJ mol-1 K-1) values indicate an enthalpically and entropically binding driven. Hydrophobic interactions and hydrogen bonding are the main binding forces. The differences in the polarity of 1 and 2 did not change significantly the affinity to albumin. In addition, the 1,2-naphthoquinones showed a similar binding trend compared with 1,4-naphthoquinones.