Green Nanotechnology Through Papain Nanoparticles: Preclinical in vitro and in vivo Evaluation of Imaging Triple-Negative Breast Tumors.

Background: Recent advancements in nanomedicine and nanotechnology have expanded the scope of multifunctional nanostructures, offering innovative solutions for targeted drug delivery and diagnostic agents in oncology and nuclear medicine. Nanoparticles, particularly those derived from natural sources, hold immense potential in overcoming biological barriers to enhance therapeutic efficacy and diagnostic accuracy. Papain, a natural plant protease derived from Carica papaya, emerges as a promising candidate for green nanotechnology-based applications due to its diverse medicinal properties, including anticancer properties. Purpose: This study presents a novel approach in nanomedicine and oncology, exploring the potential of green nanotechnology by developing and evaluating technetium-99m radiolabeled papain nanoparticles (99mTc-P-NPs) for imaging breast tumors. The study aimed to investigate the efficacy and specificity of these nanoparticles in breast cancer models through preclinical in vitro and in vivo assessments. Methods: Papain nanoparticles (P-NPs) were synthesized using a radiation-driven method and underwent thorough characterization, including size, surface morphology, surface charge, and cytotoxicity assessment. Subsequently, P-NPs were radiolabeled with technetium-99m (99mTc), and in vitro and in vivo studies were conducted to evaluate cellular uptake at tumor sites, along with biodistribution, SPECT/CT imaging, autoradiography, and immunohistochemistry assays, using breast cancer models. Results: The synthesized P-NPs exhibited a size mean diameter of 9.3 ± 1.9 nm and a spherical shape. The in vitro cytotoxic activity of native papain and P-NPs showed low cytotoxicity in HUVEC, MDA-MB231, and 4T1 cells. The achieved radiochemical yield was 94.2 ± 3.1% that were sufficiently stable (≥90%) for 6 h. The tumor uptake achieved in the 4T1 model was 2.49 ± 0.32% IA/g at 2 h and 1.51 ± 0.20% IA/g at 6 h. In the spontaneous breast cancer model, 1.19 ± 0.20% IA/g at 2 h and 0.86 ± 0.31% IA/g at 6 h. SPECT/CT imaging has shown substantial tumor uptake of the new nanoradiopharmaceutical and clear tumor visualization. 99mTc-P-NPs exhibited a high affinity to tumoral cells confirmed by ex vivo autoradiography and immunohistochemistry assays. Conclusion: The findings underscore the potential of green nanotechnology-driven papain nanoparticles as promising agents for molecular imaging of breast and other tumors through SPECT/CT imaging. The results represent a substantial step forward in the application of papain nanoparticles as carriers of diagnostic and therapeutic radionuclides to deliver diagnostic/therapeutic payloads site-specifically to tumor sites for the development of a new generation of nanoradiopharmaceuticals.

Electrical Stimulation Prevents Muscular Atrophy and the Decrease of Interleukin-6 in Paralyzed Muscles after Spinal Cord Injury in Rats.

Objective To analyze the muscle trophism and expression of interleukin-6 in the biceps brachii muscle of rats with incomplete cervical spinal cord injury treated with neuromuscular electrical stimulation (NMES). Methods Adult rats underwent C5-C7 spinal cord hemisection and a 5-week NMES protocol. Trophism of the biceps brachii was assessed using muscle weight/body weight ratio and histological analysis. Interleukin-6 expression from biceps brachii was measured using the enzyme-linked immunosorbent assay technique. Results Preservation of the biceps brachii muscle trophism was found in the NMES treated group, along with prevention of the reduction of interleukin-6 levels. Conclusion Spinal cord injury causes muscle atrophy and decreases interleukin-6 levels. These alterations are partially prevented by NMES. The results suggest a possible NMES action mechanism and underscore the clinical use of this therapeutic tool.

[1-7-NαC]-Crocaorb A1 and A2, orbitides from the latex of Croton campanulatus.

Two new heptapeptides, [1-7-NαC]-crocaorbs A1 (1) and A2 (2), were isolated from the latex of Croton campanulatus. Their structures were determined using NMR spectroscopic techniques, ESI-HRMS data, Marfey's method, and further refined using molecular dynamics with simulated annealing (MD/SA). Molecular dynamics calculations of peptides 1 and 2 demonstrated greater stability in simulations using a biological solvent compared to those using DMSO. Compound 1, the most abundant peptide in latex, was assessed for NO production, antiplasmodial and cytotoxicity activities. The peptide significantly increased nitric oxide (NO) production at concentrations of 40, 20 or 10 µM (17.932 ± 1.1, 18.270 ± 0.9, 18.499 ± 0.7, respectively). Its antiplasmodial activity exhibited limited efficacy, with only 5% inhibition of Plasmodium falciparum 3D7 growth at a concentration of 50 µM. Also, it exhibited no cytotoxic effects in the J774A.1 murine macrophages cell line. This study represents the first report of a phytochemical investigation of the species C. campanulatus, which showed orbitides with distinctive sequences in contrast to other peptides described for the genus Croton and contributes to the study of structural diversity within this particular class of compounds.

Different Proteomic Profiles Regarding Antihypertensive Therapy in Preeclampsia Pregnant.

Preeclampsia (PE) is a hypertensive pregnancy syndrome associated with target organ damage and increased cardiovascular risks, necessitating antihypertensive therapy. However, approximately 40% of patients are nonresponsive to treatment, which results in worse clinical outcomes. This study aimed to compare circulating proteomic profiles and identify differentially expressed proteins among 10 responsive (R-PE), 10 nonresponsive (NR-PE) patients, and 10 healthy pregnant controls (HP). We also explored correlations between these proteins and clinical data. Plasma protein relative quantification was performed using mass spectrometry, followed by bioinformatics analyses with the UniProt database, PatternLab for Proteomics 4.0, and MetaboAnalyst software (version 6.0). Considering a fold change of 1.5, four proteins were differentially expressed between NR-PE and R-PE: one upregulated (fibronectin) and three downregulated (pregnancy-specific beta-1-glycoprotein 1, complement C4B, and complement C4A). Between NR-PE and HP, six proteins were differentially expressed: two upregulated (clusterin and plasmin heavy chain A) and four downregulated (apolipoprotein L1, heparin cofactor II, complement C4B, and haptoglobin-related protein). Three proteins were differentially expressed between R-PE and HP: one downregulated (transthyretin) and two upregulated (apolipoprotein C1 and hemoglobin subunit beta). These findings suggest a complex interplay of these proteins involved in inflammatory, immune, and metabolic processes with antihypertensive therapy responsiveness and PE pathophysiology.

Specific Biomarkers in Spinocerebellar Ataxia Type 3: A Systematic Review of Their Potential Uses in Disease Staging and Treatment Assessment.

Spinocerebellar ataxia type 3 (SCA3) is the most common type of disease related to poly-glutamine (polyQ) repeats. Its hallmark pathology is related to the abnormal accumulation of ataxin 3 with a longer polyQ tract (polyQ-ATXN3). However, there are other mechanisms related to SCA3 progression that require identifying trait and state biomarkers for a more accurate diagnosis and prognosis. Moreover, the identification of potential pharmacodynamic targets and assessment of therapeutic efficacy necessitates valid biomarker profiles. The aim of this review was to identify potential trait and state biomarkers and their potential value in clinical trials. Our results show that, in SCA3, there are different fluid biomarkers involved in neurodegeneration, oxidative stress, metabolism, miRNA and novel genes. However, neurofilament light chain NfL and polyQ-ATXN3 stand out as the most prevalent in body fluids and SCA3 stages. A heterogeneity analysis of NfL revealed that it may be a valuable state biomarker, particularly when measured in plasma. Nonetheless, since it could be a more beneficial approach to tracking SCA3 progression and clinical trial efficacy, it is more convenient to perform a biomarker profile evaluation than to rely on only one.

Trophic plasticity of tetra-fish, Psalidodon aff. fasciatus (Cuvier, 1819) (Characidae), in an Atlantic Forest stream of Northeast Brazil.

Trophic plasticity is a distinctive feature of freshwater fishes, representing an essential strategy for fish living in resource-variable environments. We analyzed the stomach contents of individuals sampled in two Atlantic Forest streams to identify the primary food sources consumed by Psalidodon aff. fasciatus and verify the existence of spatial, seasonal, and ontogenetic variations. The diet was determined by analyzing the stomach contents using the Volume Method to quantify the importance of food items. In general, Psalidodon aff. fasciatus was classified as an omnivorous species, consuming mainly insects, plant material, and filamentous algae. The results also showed significant effects for all factors considered (spatial, seasonal, and ontogenetic). Finally, Psalidodon aff. fasciatus demonstrated considerable trophic plasticity, which can result in better use of available resources in the environment and improved resource partitioning, reducing intraspecific and interspecific competition.

Mitigating jaw osteonecrosis: bioactive glass and pericardial membrane combination in a rat model.

Objectives: Bisphosphonates (BFs) show clinical effectiveness in managing osteoporosis and bone metastases but pose risks of bisphosphonate-related jaw osteonecrosis (BRONJ). With no established gold standard for BRONJ treatment, our focus is on symptom severity reduction. We aimed to assess the preventive effects of bioactive glass and/or pericardial membrane in a preclinical BRONJ model, evaluating their potential to prevent osteonecrosis and bone loss post-tooth extractions in zoledronic acid (ZA)-treated animals. Methods: Rats, receiving ZA or saline biweekly for four weeks, underwent 1st and 2nd lower left molar extractions. Pericardial membrane alone or with F18 bioglass was applied post-extractions. Microarchitecture analysis and bone loss assessment utilized computerized microtomography (CT) and positron emission tomography (PET) with 18F-FDG and 18F-NaF tracers. Histological analysis evaluated bone injury. Results: Exclusive alveolar bone loss occurred post-extraction in the continuous ZA group, inducing osteonecrosis, osteolysis, osteomyelitis, and abscess formation. Concurrent pericardial membrane with F18 bioglass application prevented these outcomes. Baseline PET/CT scans showed no discernible uptake differences, but post-extraction 18F-FDG tracer imaging revealed heightened glucose metabolism at the extraction site in the ZA-treated group with membrane, contrasting the control group. Conclusion: These findings suggest pericardial membrane with F18 bioglass effectively prevents BRONJ in the preclinical model.

Nanoemulsion with wine lees: a green approach.

Bioactive substances can be found in wine lees, a waste from the winemaking industry. This work developed two formulations, a nanoemulsion with coconut oil (NE-OC) and a nanoemulsion with coconut oil and 0.5% of wine lees extract (NE-OC-Ext), to investigate their effect on untreated, bleached, and bleached-colored hair. The oil-in-water (O/W) nanoemulsions were prepared with coconut oil, TweenTM 80, SpanTM 80, AristoflexTM AVC, Conserve NovaMit MFTM, wine lees extract, and deionized water. The hydration measurements were carried out using a Corneometer® CM 825 with the capacitance method. Scanning electron microscopy (SEM) was used to characterize the effect of formulations on hair fibers. Differential Thermal Analysis (DTA) was to assess the thermal stability and compatibility of wine lees and coconut oil in formulations. Compared to NE-OC, NE-OC-Ext showed a greater hydration effect on bleached-colored hair. DTA showed that NE-OC-Ext presented a smaller number of exothermic degradation events than those of NE-OC, suggesting good interaction and compatibility of the wine lees extract in this formulation. This study highlights the value of wine lees, a residue from the winemaking process, and its possibility of use as raw material for the cosmetic hair industry since it shows a greater moisturizing potential in colored hair.

Two decades of clear-cutting threats in the Brazilian Amazonian protected areas around the Jirau, Santo Antônio, and Belo Monte large dams.

Deforestation rates in the Amazon have markedly increased in the last few years, affecting non-protected and protected areas (PAs). Brazil is a hotspot of Protected Area Downgrading, Downsizing, and Degazettement (PADDD) events, with most events associated with infrastructure projects. Despite the threats dams impose on PAs, there is a knowledge gap in assessing deforestation in PAs around large dams in the Amazon. This study investigates how deforestation affects Biodiversity Protection Areas (BioPAs) and Indigenous Lands around the Jirau and Santo Antônio (JSA) dams (Madeira River, Rondônia) and Belo Monte dam (Xingu River, Pará) in the Brazilian Amazon. We compared clear-cutting between PAs and control areas and the annual rates of forest change between pre-dam and post-dam periods. We discussed deforestation-related factors (e.g., PADDD events and the presence of management plans or councils). Our results show an increase in deforestation after the operation of the dams when environmental control from licensing agencies decreases and other political and economic factors are in practice. Indigenous Lands experienced a significant increase in deforestation around the Belo Monte dam, which is associated with the demarcation process and land conflicts. Surrounding the JSA dams, sustainable use BioPAs showed high deforestation rates, and 27 PADDD events were reported, four directly related to dams. In addition to dams, deforestation was associated with the crisis of Brazilian democracy and the weakening of environmental policies. In conclusion, the weak environmental control from environmental licensing agencies during dam operation and PADDD events have contributed to increased deforestation rates and additional stresses in the Amazon.

Treponema pallidum PCR with blood and cerebrospinal fluid of newborns exposed and not exposed to syphilis during pregnancy.

INTRODUCTION: Congenital syphilis (CS) has severe adverse outcomes, including abortion and death. Diagnosis of CS in asymptomatic newborns remains difficult. This study aims to evaluate an in-house polymerase chain reaction (PCR) on cerebrospinal fluid (CSF) and blood samples (BS) to identify T. pallidum DNA in newborns. METHODOLOGY: We performed an exploratory cross-sectional study that included newborns exposed to syphilis during pregnancy (SEG) and non-exposed (SNEG) newborns, between 2019 and 2020. In-house conventional PCR for T. pallidum targeting the tpp47 gene was used to analyze CSFS and dried blood spots. RESULTS: BS was obtained from 54 newborns (33 SEG/21 SNEG) and CSF from 55 newborns (33 SEG/22 SNEG). Twenty-five (71.4%) SEG newborns had reactive BS rapid plasmatic reagins (RPR), and all of them had RPR titers less than or equal to the corresponding maternal titers. All RPR CSF tests were negative. PCR for T. pallidum DNA was positive in 19/33 (57.6%) BS, and in 22/33 CSF. The only SEG newborn with clinical signs of early CS had a positive CSF PCR and a negative BS PCR. Conversely, among SNEG newborns, PCR was positive in 2/21 BS and 5/22 (22.7%) CSF. CONCLUSIONS: T. pallidum DNA was identified using our PCR tests. The exposed group did not present abnormalities that would indicate CS. This prevented conclusions regarding sensitivity and specificity. Dried spot permitted bedside collection, easy transportation, and storage. Further research is needed to evaluate and improve the accuracy of CS low-cost PCR tests, especially for limited resource settings.

Female rats present higher oxidative damage and inflammation during goitrogenesis.

Thyroid disorders affect more women than men, but the underlying mechanisms contributing to this disparity remain incompletely understood. Thyrotropin (TSH), the primary regulator of thyroid oxidative hormonogenesis, has been implicated as a risk factor for proliferative thyroid diseases and a predictor of malignancy. In this study, we aimed to evaluate the impact of sustained elevated TSH levels on thyroid redox homeostasis, inflammatory markers, and DNA damage response in both male and female rats. Rats were treated with methimazole for 7 or 21 days, and hormonal measurements were conducted. H2O2 levels were evaluated in thyroid membrane fractions, while enzymatic activities were assessed in total thyroid homogenates. Sex-specific differences emerged, with females displaying higher reactive oxygen species levels - increased transiently NOX and sustained DUOX activities. Lipid peroxidation marker 4-hydroxynonenal (4-HNE) was elevated in females at both time points, contrasting with males just at 21 days. Sexual dimorphism was observed in DNA damage response, with females showing higher γH2AX levels at 21 days. Elevated IL-1ß, TNF-α, CD11b mRNA, and phospho-NF-κB levels at 7 days indicated a distinct inflammatory profile in females. Notably, both sexes exhibited upregulated antioxidant enzymes. Our data suggest that females are more susceptible to oxidative damage and inflammation in our goiter model, which may be associated with higher ROS production and a less-efficient antioxidant defense system. These findings provide insights into the sex-specific mechanisms underlying thyroid dysfunction and highlight the importance of considering sex disparities in thyroid disorder research.

Poverty-Food Insecurity Nexus in the Post-Construction Context of a Large Hydropower Dam in the Brazilian Amazon.

Within the 2030 Sustainable Development Agenda, large hydropower dams are positioned as a sustainable energy source, notwithstanding their adverse impacts on societies and ecosystems. This study contributed to ongoing discussions about the persistence of critical social issues, even after the investments of large amounts of resources in areas impacted by the construction of large hydropower dams. Our study focused on food insecurity and evaluated this issue in the city of Altamira in the Brazilian Amazon, which has been profoundly socially and economically impacted by the construction, between 2011 and 2015, of Brazil's second-largest dam, namely, Belo Monte. A survey in Altamira city featured a 500-household random sample. Structural equation modeling showed conditioning factors of 60% of the population experiencing varying food insecurity degrees. Poverty, female-led households, lower education, youth, and unemployment were strongly linked to higher food insecurity. Crowded, officially impacted, and resettled households also faced heightened food insecurity. Our findings underscore the food insecurity conditions in the region impacted by the Belo Monte dam, emphasizing the need to take into account this crucial issue while planning and implementing hydropower dams.

COVID-19 is more lethal in hemodialysis chronic kidney disease patients with low physical capacity.

INTRODUCTION: The mortality rate in patients on maintenance hemodialysis (HD) is high and is associated with low functional capacity (FC). We analyzed the association of FC and COVID-19 lethality among HD patients. METHODS: A cohort study that included evaluations of FC in patients on HD was underway, and the association between FC and lethality was included as an ad-hoc outcome. RESULTS: One hundred and twelve patients were submitted to a physical, 31 patients contracted symptomatic COVID-19, 20 recovered and 11 died (lethality rate of 35.5%). There was a difference between survivors and non-survivors on six-minutes-walking-test (6MWT) 386.1 ± 112.8 versus 296.9 ± 103.3 meters (p = 0.04), 30 s sit-to-stand test (30CST) score 11.7 ± 3.1 versus 7.7 ± 4.1 (p = 0.006), and timed up and go test (TUG) 9.4 versus 13.6 s (p = 0.009). There was also an association between percentages of predicted 6MWT, 30CST, and TUG with COVID-19 lethality. CONCLUSION: Patients on maintenance HD with poorer physical performance presented the worst prognosis from COVID-19 pandemic.

Maternal depression and child development at 3 years of age: a longitudinal study in a Brazilian child development promotion program.

BACKGROUND: We tested the hypothesis that children of non-depressed mothers perform better in a developmental test at 3 years than children of depressed mothers. METHOD: Longitudinal analysis from a trial to assess the impact of a child development promotion program in 30 Brazilian municipalities. Mothers and children were appraised at first-year post-partum, 1 and 3 years after enrollment. Child development was assessed through the Ages and Stages Questionnaire (ASQ3) and maternal depression through the Edinburgh Postnatal Depression Scale (EPDS). Crude and adjusted beta coefficients were obtained by linear regression before and after multiple imputation. RESULTS: In total, 2098 mother/child dyads were included and 8.2% of the mothers had persistent depressive symptoms. There was a decrease in ASQ3 as the number of follow-ups with EPDS ≥ 10 increased (p for trend <0.001). In adjusted analysis, the direction of the association persisted but lost statistical significance. After multiple imputation, children from mothers with EPDS ≥ 10 in three follow-ups presented a decrease of about 14 points in ASQ3 (adjusted beta coefficient = -13.79; -22.59 to -5.00) (p for trend = 0.001). CONCLUSIONS: Identification of women at increased risk of depression should be among the primary health care sector priorities in maternal and child health in Brazil. IMPACT: In our population study, almost one in every ten women presented persistent depression symptoms across the first 3 years postpartum. In adjusted analysis there was a detrimental impact of persistent maternal depression on child development at 3 years of age. The persistent exposure to maternal depression across early childhood negatively influences children's development. Considering its prevalence, identification of women at increased risk of depression should be among the primary health care sector priorities in maternal and child health in Brazil.

Electrical Stimulation Prevents Muscular Atrophy and the Decrease of Interleukin-6 in Paralyzed Muscles after Spinal Cord Injury in Rats / A estimulação elétrica previne a atrofia muscular e a diminuição da interleucina-6 em músculos paralisados após lesão da medula espinal em ratos

Abstract Objective To analyze the muscle trophism and expression of interleukin-6 in the biceps brachii muscle of rats with incomplete cervical spinal cord injury treated with neuromuscular electrical stimulation (NMES). Methods Adult rats underwent C5-C7 spinal cord hemisection and a 5-week NMES protocol. Trophism of the biceps brachii was assessed using muscle weight/body weight ratio and histological analysis. Interleukin-6 expression from biceps brachii was measured using the enzyme-linked immunosorbent assay technique. Results Preservation of the biceps brachii muscle trophism was found in the NMES treated group, along with prevention of interleukin-6 level reduction. Conclusion Spinal cord injury causes muscle atrophy and decreases interleukin-6 levels. These alterations are partially prevented by NMES. The results suggest a possible NMES action mechanism and underscore the clinical use of this therapeutic tool.

Resumo Objetivo Analisar o trofismo muscular e a de interleucina-6 no músculo bíceps braquial de ratas com lesão medular cervical incompleta tratados com estimulação elétrica neuromuscular (EENM). Métodos Ratas adultas foram submetidas à hemissecção da medula espinal em C5-C7 e a um protocolo de EENM de 5 semanas. O trofismo do bíceps braquial foi avaliado pela relação peso muscular/peso corporal e análise histológica. A expressão de interleucina-6 no bíceps braquial foi medida usando ensaio de imunoabsorção enzimática. Resultados O grupo tratado com EENM apresentou preservação do trofismo muscular, assim como prevenção da redução dos níveis de interleucina-6. Conclusão A lesão da medula espinal causa atrofia muscular e diminui a expressão de interleucina-6. Essas alterações são parcialmente prevenidas pela EENM. Os resultados sugerem um possível mecanismo de ação da EENM e ressaltam o uso clínico desta ferramenta terapêutica.

Home range overlap between small Indian mongooses and free roaming domestic dogs in Puerto Rico: implications for rabies management.

The small Indian mongoose (Urva auropunctata) is the primary terrestrial wildlife rabies reservoir on at least four Caribbean islands, including Puerto Rico. In Puerto Rico, mongooses represent a risk to public health, based on direct human exposure and indirectly through the transmission of rabies virus to domestic animals. To date, the fundamental ecological relationships of space use among mongooses and between mongooses and domestic animals remain poorly understood. This study is the first to report mongoose home range estimates based on GPS telemetry, as well as concurrent space use among mongooses and free roaming domestic dogs (FRDD; Canis lupus familiaris). Mean (± SE) home range estimates from 19 mongooses in this study (145 ± 21 ha and 60 ± 14 ha for males and females, respectively) were greater than those reported in prior radiotelemetry studies in Puerto Rico. At the scale of their home range, mongooses preferentially used dry forest and shrubland areas, but tended to avoid brackish water vegetation, salt marshes, barren lands and developed areas. Home ranges from five FRDDs were highly variable in size (range 13-285 ha) and may be influenced by availability of reliable anthropogenic resources. Mongooses displayed high home range overlap (general overlap index, GOI = 82%). Home range overlap among mongooses and FRDDs was intermediate (GOI = 50%) and greater than home range overlap by FRDDs (GOI = 10%). Our results provide evidence that space use by both species presents opportunities for interspecific interaction and contact and suggests that human provisioning of dogs may play a role in limiting interactions between stray dogs and mongooses.

Optimization of Plasmodium vivax infection of colonized Amazonian Anopheles darlingi.

Obtaining Plasmodium vivax sporozoites is essential for in vitro culture of liver stage parasites, not only to understand fundamental aspects of parasite biology, but also for drug and vaccine development. A major impediment to establish high-throughput in vitro P. vivax liver stage assays for drug development is obtaining sufficient numbers of sporozoites. To do so, female anopheline mosquitoes have to be fed on blood from P. vivax-infected patients through an artificial membrane-feeding system, which in turns requires a well-established Anopheles colony. In this study we established conditions to provide a robust supply of P. vivax sporozoites. Adding a combination of serum replacement and antibiotics to the membrane-feeding protocol was found to best improve sporozoite production. A simple centrifugation method appears to be a possible tool for rapidly obtaining purified sporozoites with a minimal loss of yield. However, this method needs to be better defined since sporozoite viability and hepatocyte infection were not evaluated.

Pyroglutamination-Induced Changes in the Physicochemical Features of a CXCR4 Chemokine Peptide: Kinetic and Structural Analysis.

We investigate the physicochemical effects of pyroglutamination on the QHALTSV-NH2 peptide, a segment of cytosolic helix 8 of the human C-X-C chemokine G-protein-coupled receptor type 4 (CXCR4). This modification, resulting from the spontaneous conversion of glutamine to pyroglutamic acid, has significant impacts on the physicochemical features of peptides. Using a static approach, we compared the transformation in different conditions and experimentally found that the rate of product formation increases with temperature, underscoring the need for caution during laboratory experiments to prevent glutamine cyclization. Circular dichroism experiments revealed that the QHALTSV-NH2 segment plays a minor role in the structuration of H8 CXCR4; however, its pyroglutaminated analogue interacts differently with its chemical environment, showing increased susceptibility to solvent variations compared to the native form. The pyroglutaminated analogue exhibits altered behavior when interacting with lipid models, suggesting a significant impact on its interaction with cell membranes. A unique combination of atomic force microscopy and infrared nanospectroscopy revealed that pyroglutamination affects supramolecular self-assembly, leading to highly packed molecular arrangements and a crystalline structure. Moreover, the presence of pyroglumatic acid has been found to favor the formation of amyloidogenic aggregates. Our findings emphasize the importance of considering pyroglutamination in peptide synthesis and proteomics and its potential significance in amyloidosis.

Quercetin improves white adipose tissue redox homeostasis in ovariectomized rats.

Estrogen deficiency is a well-known hallmark of menopause and is associated with oxidative stress and metabolic dysfunction. Quercetin (Q), a flavonoid found in fruits and vegetables, has demonstrated anti-inflammatory effects in experimental models of metabolic disorders. In this study, we aimed to investigate the effects of quercetin on retroperitoneal white adipose tissue (rWAT) redox homeostasis and systemic metabolic parameters in ovariectomized (OVX) rats. Female Wistar rats at 3 months old were divided into the following experimental groups: sham-operated treated with vehicle (DMSO 10% + PBS - 1 mL/kg); OVX (vehicle treated) and OVX-Q (25 mg/kg) - via oral gavage, daily for 5 weeks. Q did not prevent weight gain but improved glucose tolerance and blood cholesterol profile, and attenuated uterine atrophy in OVX rats. Furthermore, Q had a protective effect on rWAT, once the OVX-Q group presented lower oxidative stress levels, and reduced levels of the pro-inflammatory cytokine tumor necrosis factor alpha, compared to the OVX group. Q improved antioxidant enzyme activities such as superoxide dismutase and catalase and decreased reactive oxygen species production, in OVX-Q rats. It was followed by increased levels of total thiol content and lower lipid peroxidation. Moreover, Q reduced senescent-related genes p16INK4a and p19ARF expression which were higher in the OVX group. In conclusion, quercetin supplementation improved redox homeostasis and reduced senescence-related markers, and inflammation in rWAT, which was reflected in preserved systemic metabolic health parameters in OVX rats. These findings suggest that quercetin may have therapeutic potential for the management of metabolic disorders associated with menopause-induced estrogen deficiency.

Transmission-blocking activity of antimalarials for Plasmodium vivax malaria in Anopheles darlingi.

Malaria is caused by parasite of the genus Plasmodium and is still one of the most important infectious diseases in the world. Several biological characteristics of Plasmodium vivax contribute to the resilience of this species, including early gametocyte production, both of which lead to efficient malaria transmission to mosquitoes. This study evaluated the impact of currently used drugs on the transmission of P. vivax. Participants received one of the following treatments for malaria: i) chloroquine [10 mg/kg on day 1 and 7.5 mg/kg on day 2 and 3] co-administered with Primaquine [0.5 mg/kg/day for 7 days]; ii) Chloroquine [10 mg/kg on day 1 and 7.5 mg/kg on day 2 and 3] co-administered with one-dose of Tafenoquine [300 mg on day 1]; and iii) Artesunate and Mefloquine [100 mg and 200 mg on day 1, 2 and 3] co-administered with Primaquine [0.5 mg/kg/day for 14 days]. Patient blood was collected before treatment and 4 h, 24 h, 48 h and 72 h after treatment. The blood was used to perform a direct membrane feeding assay (DMFA) using Anopheles darlingi mosquitoes. The results showed 100% inhibition of the mosquito infection after 4 h using ASMQ+PQ, after 24 h for the combination of CQ+PQ and 48 h using CQ+TQ. The density of gametocytes declined over time in all treatment groups, although the decline was more rapid in the ASMQ+PQ group. In conclusion, it was possible to demonstrate the transmission-blocking efficacy of the malaria vivax treatment and that ASMQ+PQ acts faster than the two other treatments.