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1.
J Exp Clin Cancer Res ; 43(1): 86, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504270

RESUMO

BACKGROUND: In clear cell renal cell carcinoma (ccRCC), first-line treatment combines nivolumab (anti-PD-1) and ipilimumab (anti-CTLA4), yielding long-term remissions but with only a 40% success rate. Our study explored the potential of enhancing ccRCC treatment by concurrently using CXCR2 inhibitors alongside immunotherapies. METHODS: We analyzed ELR + CXCL levels and their correlation with patient survival during immunotherapy. RCT001, a unique CXCR2 inhibitor, was examined for its mechanism of action, particularly its effects on human primary macrophages. We tested the synergistic impact of RCT001 in combination with immunotherapies in both mouse models of ccRCC and human ccRCC in the presence of human PBMC. RESUTS: Elevated ELR + CXCL cytokine levels were found to correlate with reduced overall survival during immunotherapy. RCT001, our optimized compound, acted as an inverse agonist, effectively inhibiting angiogenesis and reducing viability of primary ccRCC cells. It redirected M2-like macrophages without affecting M1-like macrophage polarization directed against the tumor. In mouse models, RCT001 enhanced the efficacy of anti-CTLA4 + anti-PD1 by inhibiting tumor-associated M2 macrophages and tumor-associated neutrophils. It also impacted the activation of CD4 T lymphocytes, reducing immune-tolerant lymphocytes while increasing activated natural killer and dendritic cells. Similar effectiveness was observed in human RCC tumors when RCT001 was combined with anti-PD-1 treatment. CONCLUSIONS: RCT001, by inhibiting CXCR2 through its unique mechanism, effectively suppresses ccRCC cell proliferation, angiogenesis, and M2 macrophage polarization. This optimization potentiates the efficacy of immunotherapy and holds promise for significantly improving the survival prospects of metastatic ccRCC patients.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Animais , Camundongos , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Agonismo Inverso de Drogas , Leucócitos Mononucleares/patologia , Imunoterapia
2.
Life Sci ; 338: 122405, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38176584

RESUMO

AIMS: To evaluate the effects of testosterone on endothelium-dependent vasodilation and oxidative stress in mesenteric resistance arteries. MAIN METHODS: Spontaneously hypertensive rats (SHR), aged 8 to 10 weeks, were divided into four groups: intact (SHAM), intact treated with testosterone (TTO; 3 mg/kg/day) via subcutaneous route (s.c.), intact treated with testosterone and anastrozole [aromatase enzyme inhibitor (TTO + ANA; 0.1 mg/kg/day, s.c.)] and intact treated with testosterone and finasteride [5 α-reductase enzyme inhibitor (TTO + FIN; 5 mg/kg/day, s.c.)] for four weeks. Concentration-response curves to acetylcholine (ACh, 0.1 nmol/L - 10 µmol/L) were obtained in mesenteric resistance arteries previously contracted with phenylephrine (PE, 3 µmol/L), before and after the use of selective inhibitors. Reactive oxygen species (ROS) levels were assessed in the vessels and the endothelium analyzed by scanning electron microscopy. KEY FINDINGS: TTO group showed a lower participation of nitric oxide (NO), increased oxidative stress, and participation of prostanoids and endothelium-dependent hyperpolarization (EDH), possibly to maintain the vasodilator response. Lower participation of NO and prostanoids, combined to an increased participation of EDH, were observed in the TTO + ANA group, in addition to higher levels of ROS and altered endothelial morphology. The vasodilation to ACh was impaired in TTO + FIN, along increased participation of NO, reduction of prostanoids, and greater EDH-dependent vasodilation. SIGNIFICANCE: Testosterone contributes to endothelial vasodilation by enhancing EDH through an increased participation of epoxyeicosatrienoic acids. While the decrease in NO appears to involve the participation of dihydrotestosterone, 17 ß-estradiol seems to stimulate the action of the NO pathway and prostanoids.


Assuntos
Hipertensão , Vasodilatação , Ratos , Animais , Espécies Reativas de Oxigênio/metabolismo , Testosterona/farmacologia , Testosterona/metabolismo , Hipertensão/metabolismo , Ratos Endogâmicos SHR , Inibidores Enzimáticos/farmacologia , Acetilcolina/farmacologia , Acetilcolina/metabolismo , Artérias Mesentéricas , Óxido Nítrico/metabolismo , Prostaglandinas/metabolismo , Endotélio Vascular/metabolismo
3.
Microsc Res Tech ; 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38129976

RESUMO

Antimicrobial photodynamic therapy (a-PDT) is a modality that aims to induce microorganisms through visible light, a photosensitizer, and molecular oxygen. This therapy has shown promising results in controlling cariogenic biofilm in vitro and in vivo counterparts. This study investigated bacterial viability and morphological characterization of Streptococcus mutans mature biofilms after combination of erythrosine and a high potency dental curing light. Biofilms were formed on saliva-coated hydroxyapatite disks in batch culture. The samples were performed in triplicates. Fresh medium was replaced daily for five days and treated using 40 µM of E activated by HL 288 J/cm2 and total dose of 226 J at 1200 mW/cm2 . Phosphate buffer saline and 0.12% of chlorhexidine were used as negative and positive control, respectively. After treatment, biofilms were assessed for microbial viability and morphological characterization by means of bio-volume and thickness. COMSTAT software was used for image analysis. Data were analyzed using two-way ANOVA followed by Tukey test with significance level 5%. The application of a-PDT and CHX treatments decreased S. mutans bacterial viability. The image analysis showed more red cells on biofilms when compared to other groups, demonstrating photobacterial killing. Erythrosine irradiated with a high potency curing light can potentially act as an antimicrobial tool in the treatment of cariogenic biofilms. The morphology and viability of microorganisms were impacted after treatment. Treatment with photodynamic therapy may be able to reduce the bio-volume and viability of bacteria present in biofilms. CLINICAL RELEVANCE AND RESEARCH HIGHLIGHTS: The use of the a-PDT technique has been applied in dentistry with satisfactory results. Some applications of this technique are in stomatology and endodontics. In the present study, we sought to understand the use of photodynamic therapy in the control of biofilm and the results found are compatible with the objective of microbiological control proposed by this technique, thus raising the alert for future studies in vivo using the combination of a-PDT with erythrosine, since they are easily accessible materials for the dental surgeon and can be applied in clinical practice.

4.
Nature ; 623(7986): 397-405, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37914940

RESUMO

Microglia are specialized brain-resident macrophages that arise from primitive macrophages colonizing the embryonic brain1. Microglia contribute to multiple aspects of brain development, but their precise roles in the early human brain remain poorly understood owing to limited access to relevant tissues2-6. The generation of brain organoids from human induced pluripotent stem cells recapitulates some key features of human embryonic brain development7-10. However, current approaches do not incorporate microglia or address their role in organoid maturation11-21. Here we generated microglia-sufficient brain organoids by coculturing brain organoids with primitive-like macrophages generated from the same human induced pluripotent stem cells (iMac)22. In organoid cocultures, iMac differentiated into cells with microglia-like phenotypes and functions (iMicro) and modulated neuronal progenitor cell (NPC) differentiation, limiting NPC proliferation and promoting axonogenesis. Mechanistically, iMicro contained high levels of PLIN2+ lipid droplets that exported cholesterol and its esters, which were taken up by NPCs in the organoids. We also detected PLIN2+ lipid droplet-loaded microglia in mouse and human embryonic brains. Overall, our approach substantially advances current human brain organoid approaches by incorporating microglial cells, as illustrated by the discovery of a key pathway of lipid-mediated crosstalk between microglia and NPCs that leads to improved neurogenesis.


Assuntos
Encéfalo , Colesterol , Células-Tronco Pluripotentes Induzidas , Microglia , Células-Tronco Neurais , Neurogênese , Organoides , Animais , Humanos , Camundongos , Encéfalo/citologia , Encéfalo/metabolismo , Diferenciação Celular , Células-Tronco Pluripotentes Induzidas/citologia , Microglia/citologia , Microglia/metabolismo , Organoides/citologia , Organoides/metabolismo , Colesterol/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Axônios , Proliferação de Células , Ésteres/metabolismo , Gotículas Lipídicas/metabolismo
5.
Toxics ; 11(11)2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37999563

RESUMO

Cosmetic residues have been found in water resources, especially trace elements of precursors, couplers, and pigments of hair dyes, which are indiscriminately disposed of in the sewage system. These contaminants are persistent, bioactive, and bioaccumulative, and may pose risks to living beings. Thus, the present study assessed the ecotoxicity of two types of effluents generated in beauty salons after the hair dyeing process. The toxicity of effluent derived from capillary washing with water, shampoo, and conditioner (complete effluent-CE) and effluent not associated with these products (dye effluent-DE) was evaluated by tests carried out with the aquatic organisms Artemia salina, Daphnia similis, and Danio rerio. The bioindicators were exposed to pure samples and different dilutions of both effluents. The results showed toxicity in D. similis (CE50 of 3.43% and 0.54% for CE and DE, respectively); A. salina (LC50 8.327% and 3.874% for CE and DE, respectively); and D. rerio (LC50 of 4.25-4.59% and 7.33-8.18% for CE and DE, respectively). Given these results, we can infer that hair dyes, even at low concentrations, have a high toxic potential for aquatic biota, as they induced deleterious effects in all tested bioindicators.

6.
Chemosphere ; 345: 140456, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37839740

RESUMO

Kogia sima and Kogia breviceps are apex predators of mesopelagic trophic webs being far from most anthropogenic threats. However, chemical pollutants and naturally synthesized compounds may travel long distances. This study aimed to use kogiid whales as sentinels of mesopelagic trophic webs in the Southwestern Atlantic Ocean. Persistent organic pollutants (POPs), e.g., polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT) and metabolites, mirex, hexachlorobenzene (HCB), polybrominated diphenylethers (PBDEs), pentabromoethylbenzene (PBEB) and hexabromobenzene (HBB), and the naturally produced methoxylated BDE (MeO-BDEs) were determined in the blubber of 16 K. sima and 15 K. breviceps. Among the organochlorine compounds, DDTs were the main group found in K. sima and in K. breviceps (1636.6 and 3983.3 ng g-1 lw, respective medians), followed by PCBs (425.9 and 956.1 ng g-1 lw, respectively), mirex (184.1 and 375.6 ng g-1 lw, respectively), and HCB (132.4 and 340.3 ng g-1 lw, respectively). As for the organobromine, the natural MeO-BDEs were predominant (1676.7 and 501.6 ng g-1 lw, respectively), followed by PBDEs (13.6 and 10.3 ng g-1 lw, respectively) and PBEB (2.2 and 2.9 ng g-1 lw, respectively). In general, POPs concentration was higher in K. breviceps than in K. sima. Conversely, MeO-BDEs concentration was higher in K. sima than in K. breviceps. Differences in concentrations in these sympatric odontocetes were attributed to distinct species, sampling sites, and biological parameters and suggest some level of niche segregation. It is noteworthy the long-range reach and bioaccumulation of these synthetic compounds in an unexplored habitat, that present an increasing economic interest.


Assuntos
Poluentes Ambientais , Bifenilos Policlorados , Poluentes Químicos da Água , Animais , Bifenilos Policlorados/análise , Baleias/metabolismo , Hexaclorobenzeno/metabolismo , Mirex , Éteres Difenil Halogenados/análise , Bioacumulação , Poluentes Ambientais/metabolismo , Oceano Atlântico , Monitoramento Ambiental , Poluentes Químicos da Água/análise
7.
Naturwissenschaften ; 110(5): 44, 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37682350

RESUMO

This study characterizes the osmophores and corolla traits in 18 species of Bignonieae Dumort., a Bignoniaceae tribe occurring in the Cerrado, a neotropical savanna in Brazil. To detect osmophore distribution, whole, newly opened flowers were immersed in Neutral Red Solution. Samples from the corolla tube and lobes were also fixed and analyzed micromorphologically, anatomically, and histochemically. The osmophores showed six markedly different distribution patterns that were not clearly associated with histological features. In most species, osmophores comprised papillose secretory epidermises and a few layers of subepidermal parenchyma. Starch grains, lipid droplets, and terpenes were detected in osmophores. An ornamented cuticle, cuticular folds, glandular and non-glandular trichomes, raised stomata and epicuticular wax granules are common traits in the species studied and may be useful in determining the taxonomy of the group. We found that 94% of the species visited by bees had papillose epidermises while the single hummingbird-pollinated species presented a flattened epidermis. Variations in osmophore pattern among species visited by bees, including variations within the same plant genus, are novel finding. Additionally, the Bignonieae species visited by bees presented a textured corolla surface, which has been reported as facilitating bee attachment and movement towards the floral resource. Future studies with a greater number of Bignonieae species and more detailed pollinator behavioral assays may help in the interpretation of the variations in corolla traits and functional relationships between flowers and pollinators.


Assuntos
Bignoniaceae , Animais , Abelhas , Brasil , Flores , Fenótipo , Terpenos
8.
Front Public Health ; 11: 1227899, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37546326

RESUMO

The aim of this scoping review was to map the literature related to the "Academia da Saúde" Program, including the objective and rationale of the studies, activities carried out in the program's centers, as well as the actors involved in these actions. The search for evidence was conducted in the MEDLINE, LILACS, Web of Science, Scopus, COCHRANE, and SciELO databases. Additional evidence was investigated in the Catalog of Theses and Dissertations of the Coordination of Improvement of Higher Education Personnel (CAPES-Brazil) and in the Brazilian Digital Library of Theses and Dissertations, in addition to manual searches in the references of the studies/documents. Out of 642 initial records, the information synthesis was composed of 74 studies/documents (n = 54; 73.0% scientific articles, n = 48; 64.9% with cross-sectional design, n = 45; 60.8% quantitative analysis). Nutrition (n = 24; 32.2%) and evaluation of the Program (n = 27; 36.5%) were the main themes analyzed. Regarding the participant/object analyzed in each study, users (n = 39; 52.6%) were the main actors investigated. Future studies should consider investigating the effectiveness of the actions developed in the program centers, especially physical activity and healthy eating practices.


Assuntos
Exercício Físico , Promoção da Saúde , Humanos , Brasil , Estudos Transversais , Recursos Humanos
9.
Polim Med ; 53(1): 37-46, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37260125

RESUMO

BACKGROUND: Polymethylmethacrylate (PMMA) is the most used material for the manufacturing of eye prostheses. OBJECTIVES: To investigate the cytotoxicity of different cleaning agents for ocular prostheses on human conjunctival cells. MATERIAL AND METHODS: Six groups of specimens were created (saline, soap, 4% chlorhexidine, hydrogen peroxide, 1% triclosan, and citronella oil). Three specimens were made for each disinfectant at each disinfection period (1, 7, 15, 30, 60, and 90 days), totaling 108 specimens. Thus, the specimens were disinfected, with different disinfectants, for different periods of time. After each disinfection process, the specimens were washed with sterile distilled water. A human conjunctival cell line was grown on the acrylic resin specimens and then cytotoxicity tests (MTT and Neutral Red (NR)) were performed. A negative control (untreated cell cultures) and positive control (Tween 20) were created. Two-way analysis of variance (ANOVA) and Bonferroni test were performed (p < 0.05). RESULTS: For the MTT and NR tests, when there was a significant difference between the disinfectant and negative control, the disinfectant generated a significant reduction in cell proliferation most of the time. CONCLUSIONS: All reductions in cell proliferation caused by the disinfectants were clinically acceptable. All disinfectants tested in this study were found to be non-cytotoxic to human conjunctival cells.


Assuntos
Desinfetantes , Olho Artificial , Humanos , Teste de Materiais , Desinfetantes/toxicidade , Clorexidina , Desinfecção
10.
Children (Basel) ; 10(5)2023 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-37238369

RESUMO

The individual and combined association between unhealthy lifestyle behaviors and body weight dissatisfaction in adolescents was investigated. This cross-sectional research used data from 676 students (348 female), aged between 14 and 19 years old (mean of 14.6 years old) from southern Brazil. Unhealthy lifestyle behaviors and body weight dissatisfaction were assessed through a questionnaire. Unhealthy lifestyle behaviors included smoking, excessive alcohol consumption, sedentary lifestyle, and poor diet, and were analyzed as individual factors and as combinations of behaviors. For males, smoking (OR: 2.6; 95% CI: 1.6-4.0) and the combination of smoking/excessive consumption of alcoholic beverages (OR: 2.5; 95% CI: 1.1-5.8) were directly associated with the desire to reduce body weight, whereas the combination of smoking/inadequate diet (OR: 1.3; 95% CI: 1.0-1.6) was associated with the desire to increase body weight. For females, the combinations of inadequate diet/physical inactivity (OR: 1.6; 95% CI: 1.0-2.5) and of smoking/excessive consumption of alcoholic beverages (OR: 1.9; 95% CI: 1.4-2.8) were directly associated with the desire to reduce body weight. The presence of simultaneous unhealthy lifestyle behaviors is associated with bodyweight dissatisfaction in adolescents.

11.
ACS Chem Biol ; 18(3): 484-493, 2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36775999

RESUMO

In DNA, electron excitation allows adjacent pyrimidine bases to dimerize by [2 + 2] cycloaddition, creating chemically stable but lethal and mutagenic cyclobutane pyrimidine dimers (CPDs). The usual cause is ultraviolet radiation. Alternatively, CPDs can be made in the dark (dCPDs) via chemically mediated electron excitation of the skin pigment melanin, after it is oxidized by peroxynitrite formed from the stress-induced radicals superoxide and nitric oxide. We now show that the dark process is not limited to the unusual structural molecule melanin: signaling biomolecules such as indolamine and catecholamine neurotransmitters and hormones can also be chemiexcited to energy levels high enough to form dCPDs. Oxidation of serotonin, dopamine, melatonin, and related biogenic amines by peroxynitrite created triplet-excited species, evidenced by chemiluminescence, energy transfer to a triplet-state reporter, or transfer to O2 resulting in singlet molecular oxygen. For a subset of these signaling molecules, triplet states created by peroxynitrite or peroxidase generated dCPDs at levels comparable to ultraviolet (UV). Neurotransmitter catabolism by monoamine oxidase also generated dCPDs. These results reveal a large class of signaling molecules as electronically excitable by biochemical reactions and thus potential players in deviant mammalian metabolism in the absence of light.


Assuntos
Dano ao DNA , Raios Ultravioleta , Animais , Melaninas/genética , Ácido Peroxinitroso , Dímeros de Pirimidina/química , Neurotransmissores , Hormônios , DNA/química , Mamíferos/genética , Mamíferos/metabolismo
12.
Photochem Photobiol ; 99(2): 251-276, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36681894

RESUMO

Light is one way to excite an electron in biology. Another is chemiexcitation, birthing a reaction product in an electronically excited state rather than exciting from the ground state. Chemiexcited molecules, as in bioluminescence, can release more energy than ATP. Excited states also allow bond rearrangements forbidden in ground states. Molecules with low-lying unoccupied orbitals, abundant in biology, are particularly susceptible. In mammals, chemiexcitation was discovered to transfer energy from excited melanin, neurotransmitters, or hormones to DNA, creating the lethal and carcinogenic cyclobutane pyrimidine dimer. That process was initiated by nitric oxide and superoxide, radicals triggered by ultraviolet light or inflammation. Several poorly understood chronic diseases share two properties: inflammation generates those radicals across the tissue, and cells that die are those containing melanin or neuromelanin. Chemiexcitation may therefore be a pathogenic event in noise- and drug-induced deafness, Parkinson's disease, and Alzheimer's; it may prevent macular degeneration early in life but turn pathogenic later. Beneficial evolutionary selection for excitable biomolecules may thus have conferred an Achilles heel. This review of recent findings on chemiexcitation in mammalian cells also describes the underlying physics, biochemistry, and potential pathogenesis, with the goal of making this interdisciplinary phenomenon accessible to researchers within each field.


Assuntos
Melaninas , Dímeros de Pirimidina , Animais , Melaninas/química , Fotoquímica , Raios Ultravioleta , Mamíferos
13.
J Mol Endocrinol ; 70(1)2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36476761

RESUMO

The role of androgens in vascular reactivity is controversial, particularly regarding their age-related actions. The objective of this study was to conduct a temporal evaluation of the vascular reactivity of resistance arteries of young male rats, as well as to understand how male sex hormones can influence the vascular function of these animals. Endothelium-mediated relaxation was characterized in third-order mesenteric arteries of 10-, 12-, 16-, and 18w (week-old) male rats. Concentration-response curves to acetylcholine (ACh, 0.1 nmol/L-10 µmol/L) were constructed in arteries previously contracted with phenylephrine (PE, 3 µmol/L), before and after the use of nitric oxide synthase or cyclooxygenase inhibitors. PE concentration-response curves (1 nmol/L-100 µmol/L) were also built. The levels of vascular nitric oxide, superoxide anion, and hydrogen peroxide were assessed and histomorphometry analysis was performed. The 18w group had impaired endothelium-dependent relaxation. All groups showed prostanoid-independent and nitric oxide-dependent vasodilatory response, although this dependence seems to be smaller in the 18w group. The 18w group had the lowest nitric oxide and hydrogen peroxide production, in addition to the highest superoxide anion levels. Besides functional impairment, 18w animals showed morphological differences in third-order mesenteric arteries compared with the other groups. Our data show that time-dependent exposure to male sex hormones appears to play an important role in the development of vascular changes that can lead to impaired vascular reactivity in mesenteric arteries, which could be related to the onset of age-related cardiovascular changes in males.


Assuntos
Óxido Nítrico , Superóxidos , Masculino , Ratos , Animais , Peróxido de Hidrogênio , Artérias , Hormônios Esteroides Gonadais
14.
Percept Mot Skills ; 130(1): 340-363, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36330766

RESUMO

Body weight dissatisfaction has been described as a marker for various health diseases, given its direct association with social, physical, and emotional suffering. We investigated the association between body weight dissatisfaction and health risk behaviors in adolescents. This was a cross-sectional study conducted with 668 adolescents aged 14-19 years in the city of São José, southern Brazil. Body weight satisfaction/dissatisfaction was assessed using a questionnaire validated for the investigated population. Health risk behaviors included smoking, alcohol, illicit drugs, medication, non-prescription anabolic steroids, not using seatbelt, unsafe sexual behavior and not knowing how to deal with day-to-day stress. Among males, 66.1% were dissatisfied with their body weight (32.1% due to thinness and 34.0% due to overweight). Among females, 80.0% were dissatisfied with their body weight (24.5% due to thinness and 55.5% due to overweight). There were no significant differences regarding health risk behaviors according to body weight satisfaction/dissatisfaction and sex. Compared to males who were satisfied with their body weight, those who were dissatisfied due to being overweight were more likely to be using tobacco (OR: 2.9; 95% CI: 2.1-4.2), alcohol (OR: 1.7; 95% CI: 1.5-1.9) and anabolic steroids (OR: 2.7; 95% CI: 1.2-5.7). Compared to females who were satisfied with their body weight, those who were dissatisfied due to thinness were more likely to be consuming alcoholic beverages (OR: 1.6; 95% CI: 1.2-2.0) and less likely to be consuming illicit drugs (OR: 0.5; 95% CI: 0.3-0.8). Interventions aimed at health education regarding the non-adoption of risk behaviors such as alcohol and tobacco use, as well as the non-use of anabolic steroids, and favoring the maintenance of general health, may be important for adolescents with body dissatisfaction. These data suggest that health risk behaviors such as adolescent male use of tobacco, alcohol, and anabolic steroids and the use of alcohol and drugs by female adolescents can be related to body weight dissatisfaction.


Assuntos
Insatisfação Corporal , Humanos , Masculino , Adolescente , Feminino , Peso Corporal , Sobrepeso/epidemiologia , Magreza/epidemiologia , Comportamentos de Risco à Saúde , Imagem Corporal/psicologia , Estudos Transversais , Índice de Massa Corporal
15.
Antioxidants (Basel) ; 11(11)2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36421444

RESUMO

Betaxanthins are natural products with high antioxidant and anti-inflammatory properties. Here, we describe the semisynthesis of twenty-one betaxanthins derived from proteinogenic amino acids, including the elusive betaxanthin of l-cysteine and two betaxanthins derived from l-lysine, and rationalize their antioxidant properties in mechanistic terms. The antioxidant capacity and redox potential of these betaxanthins were compared to those of model betaxanthins derived from dopamine, l-DOPA (L-3,4-dihydroxyphenylalanine), and pyrrolidine and structure-property relationships were established by using matched molecular pair analysis and a model developed using a genetic algorithm. Either a phenol or indole moiety enhance the antioxidant capacity of betaxanthins, which is overall much higher than that of their amino acid precursors and standard antioxidants, except for the cysteine-betaxanthin. The one-electron oxidation of amino acid betaxanthins produces radicals stabilized in multiple centers, as demonstrated by quantum chemical calculations.

16.
ACS Catal ; 12(19): 11761-11766, 2022 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-36249873

RESUMO

The typically low thermodynamic and kinetic stability of enzymes is a bottleneck for their application in industrial synthesis. Baeyer-Villiger monooxygenases, which oxidize ketones to lactones using aerial oxygen, among other activities, suffer particularly from these instabilities. Previous efforts in protein engineering have increased thermodynamic stability but at the price of decreased activity. Here, we solved this trade-off by introducing mutations in a cyclohexanone monooxygenase from Acinetobacter sp., guided by a combination of rational and structure-guided consensus approaches. We developed variants with improved activity (1.5- to 2.5-fold) and increased thermodynamic (+5 °C T m) and kinetic stability (8-fold). Our analysis revealed a crucial position in the cofactor binding domain, responsible for an 11-fold increase in affinity to the flavin cofactor, and explained using MD simulations. This gain in affinity was compatible with other mutations. While our study focused on a particular model enzyme, previous studies indicate that these findings are plausibly applicable to other BVMOs, and possibly to other flavin-dependent monooxygenases. These new design principles can inform the development of industrially robust, flavin-dependent biocatalysts for various oxidations.

17.
Pathogens ; 11(9)2022 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-36145406

RESUMO

The spleen plays a central role in human and canine visceral leishmaniasis, where the activation of the immune response occurs in one of the tissues where Leishmania infantum reproduces. Therefore, this organ is both a target to understand the mechanisms involved in the parasite control and a parameter for assessing the therapeutic response. In this sense, this study aimed to evaluate the main histological, immunological and parasitological aspects in the spleen of symptomatic dogs naturally infected by L. infantum treated with the therapeutic vaccine LBMPL. For this, dogs were divided into four groups: dogs uninfected and untreated (NI group); L. infantum-infected dogs that were not treated (INT group); L. infantum-infected dogs that received treatment only with monophosphoryl lipid A adjuvant (MPL group); and L. infantum-infected dogs that received treatment with the vaccine composed by L. braziliensis promastigote proteins associated with MPL adjuvant (LBMPL group). Ninety days after the therapeutics protocol, the dogs were euthanized and the spleen was collected for the proposed evaluations. Our results demonstrated a reduction of hyperplasia of red pulp and follicular area of white pulp, increased mRNA expression of IFN-γ, TNF-α, IL-12 and iNOS, and decreased IL-10 and TGF-ß1, and intense reduction of splenic parasitism in dogs treated with the LBMPL vaccine. These results possibly suggest that the pro-inflammatory environment promoted the progressive organization of the splenic architecture favoring the cellular activation, with consequent parasite control. Along with previously obtained data, our results propose the LBMPL vaccine as a possible treatment strategy for canine visceral leishmaniasis (CVL).

18.
Artigo em Inglês | MEDLINE | ID: mdl-35886538

RESUMO

OBJECTIVE: The aim of this scope review was to map the available scientific evidence on physical activity counseling for adults during the COVID-19 pandemic. METHODS: The search was performed in PubMed, Web of Science, Scopus, SPORTDiscus, LILACS, SciELO, and CINAHL databases. Studies that described the population of adults over 18 years of age that used physical activity counseling during the COVID-19 pandemic context were selected. Data extracted were author, study location, sample, age group, sex, population characteristics, design, means used for intervention, time of intervention, professionals involved, and intervention or counseling strategy. RESULTS: Physical activity counseling interventions were aimed at participants with insufficient levels of physical activity or with comorbidities; counseling was carried out in the online format; by health professionals, in the highest proportion of coaches, physicians, researchers, and nutritionists; through educational contents regarding the practice of physical activity; and using the transtheoretical model of behavior change as a reference method. CONCLUSIONS: The results of this review can provide tools for health professionals to assist in the process of coping with physical inactivity.


Assuntos
COVID-19 , Adolescente , Adulto , COVID-19/epidemiologia , Aconselhamento/métodos , Exercício Físico , Humanos , Pandemias , Comportamento Sedentário
19.
J Lasers Med Sci ; 13: e2, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35642236

RESUMO

Introduction: Bichectomy consists in the partial removal the Bichat ball (BB) of its buccal extension and smoothing the facial contour. The objective of this study is to present, by means of a clinical case, bichectomy surgery with the use of a high-power diode laser and cold scalpel on different sides of the same patient, analyzing the trans-surgical phase and the pain and edema like consequence operative of each technique and 6-month follow-up. Case Presentation: A 20-year-old female patient reported the occurrence of involuntary trauma to the cheek mucosa and rounded facial appearance. After anamnesis and clinical examination, bichectomy was proposed. For comparison, on the right side, an incision was made using a laser, while on the left side, with a cold scalpel. To assess and measure the progression of treatment, photographs and facial measurements were repeated before the procedure, 7, 14 and 28 days after the procedure, and 2, 3 and 6 months after the procedure. Conclusion: The high-power diode laser showed excellent applicability for bichectomy due to its hemostatic properties in the trans-surgical phase. In addition, it promoted greater patient comfort, with less edema and pain on the side of the face where it was used.

20.
ACS Omega ; 7(18): 16070-16079, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35571802

RESUMO

The l-DOPA dioxygenase of Amanita muscaria (AmDODA) participates in the biosynthesis of betalain- and hygroaurin-type natural pigments. AmDODA is encoded by the dodA gene, whose DNA sequence was inferred from cDNA and gDNA libraries almost 30 years ago. However, reports on its heterologous expression rely on either the original 5'-truncated cDNA plasmid or artificial gene synthesis. We provide unequivocal evidence that the heterologous expression of AmDODA from A. muscaria specimens is not possible by using the coding sequence previously inferred for dodA. Here, we rectify and reannotate the full-length coding sequence for AmDODA and express a 205-aa His-tagged active enzyme, which was used to produce the l-DOPA hygroaurin, a rare fungal pigment. Moreover, AmDODA and other isozymes from bacteria were submitted to de novo folding using deep learning algorithms, and their putative active sites were inferred and compared. The wide catalytic pocket of AmDODA and the presence of the His-His-His and His-His-Asp motifs can provide insight into the dual cleavage of l-DOPA at positions 2,3 and 4,5 as per the mechanism proposed for nonheme dioxygenases.

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