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1.
Nature ; 584(7821): 415-419, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641829

RESUMO

Sexual dimorphism arises from genetic differences between male and female cells, and from systemic hormonal differences1-3. How sex hormones affect non-reproductive organs is poorly understood, yet highly relevant to health given the sex-biased incidence of many diseases4. Here we report that steroid signalling in Drosophila from the ovaries to the gut promotes growth of the intestine specifically in mated females, and enhances their reproductive output. The active ovaries of the fly produce the steroid hormone ecdysone, which stimulates the division and expansion of intestinal stem cells in two distinct proliferative phases via the steroid receptors EcR and Usp and their downstream targets Broad, Eip75B and Hr3. Although ecdysone-dependent growth of the female gut augments fecundity, the more active and more numerous intestinal stem cells also increase female susceptibility to age-dependent gut dysplasia and tumorigenesis, thus potentially reducing lifespan. This work highlights the trade-offs in fitness traits that occur when inter-organ signalling alters stem-cell behaviour to optimize organ size.


Assuntos
Drosophila melanogaster/metabolismo , Fertilidade/fisiologia , Intestinos/crescimento & desenvolvimento , Longevidade/fisiologia , Tamanho do Órgão/fisiologia , Ovário/metabolismo , Esteroides/metabolismo , Envelhecimento , Animais , Carcinogênese , Proliferação de Células , Copulação/fisiologia , Proteínas de Ligação a DNA/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/anatomia & histologia , Drosophila melanogaster/citologia , Drosophila melanogaster/fisiologia , Ecdisona/metabolismo , Feminino , Mucosa Intestinal/anatomia & histologia , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Intestinos/anatomia & histologia , Intestinos/citologia , Intestinos/patologia , Masculino , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores de Esteroides/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Fatores de Transcrição/metabolismo
2.
Mol Biol Evol ; 41(4)2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38573520

RESUMO

Visual systems adapt to different light environments through several avenues including optical changes to the eye and neurological changes in how light signals are processed and interpreted. Spectral sensitivity can evolve via changes to visual pigments housed in the retinal photoreceptors through gene duplication and loss, differential and coexpression, and sequence evolution. Frogs provide an excellent, yet understudied, system for visual evolution research due to their diversity of ecologies (including biphasic aquatic-terrestrial life cycles) that we hypothesize imposed different selective pressures leading to adaptive evolution of the visual system, notably the opsins that encode the protein component of the visual pigments responsible for the first step in visual perception. Here, we analyze the diversity and evolution of visual opsin genes from 93 new eye transcriptomes plus published data for a combined dataset spanning 122 frog species and 34 families. We find that most species express the four visual opsins previously identified in frogs but show evidence for gene loss in two lineages. Further, we present evidence of positive selection in three opsins and shifts in selective pressures associated with differences in habitat and life history, but not activity pattern. We identify substantial novel variation in the visual opsins and, using microspectrophotometry, find highly variable spectral sensitivities, expanding known ranges for all frog visual pigments. Mutations at spectral-tuning sites only partially account for this variation, suggesting that frogs have used tuning pathways that are unique among vertebrates. These results support the hypothesis of adaptive evolution in photoreceptor physiology across the frog tree of life in response to varying environmental and ecological factors and further our growing understanding of vertebrate visual evolution.


Assuntos
Opsinas , Pigmentos da Retina , Humanos , Animais , Opsinas/genética , Anuros/genética , Duplicação Gênica , Microespectrofotometria
3.
PLoS Pathog ; 19(2): e1011149, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36780872

RESUMO

Aedes aegypti mosquitoes are the main vectors of arboviruses. The peritrophic matrix (PM) is an extracellular layer that surrounds the blood bolus. It acts as an immune barrier that prevents direct contact of bacteria with midgut epithelial cells during blood digestion. Here, we describe a heme-dependent peroxidase, hereafter referred to as heme peroxidase 1 (HPx1). HPx1 promotes PM assembly and antioxidant ability, modulating vector competence. Mechanistically, the heme presence in a blood meal induces HPx1 transcriptional activation mediated by the E75 transcription factor. HPx1 knockdown increases midgut reactive oxygen species (ROS) production by the DUOX NADPH oxidase. Elevated ROS levels reduce microbiota growth while enhancing epithelial mitosis, a response to tissue damage. However, simultaneous HPx1 and DUOX silencing was not able to rescue bacterial population growth, as explained by increased expression of antimicrobial peptides (AMPs), which occurred only after double knockdown. This result revealed hierarchical activation of ROS and AMPs to control microbiota. HPx1 knockdown produced a 100-fold decrease in Zika and dengue 2 midgut infection, demonstrating the essential role of the mosquito PM in the modulation of arbovirus vector competence. Our data show that the PM connects blood digestion to midgut immunological sensing of the microbiota and viral infections.


Assuntos
Aedes , Arbovírus , Infecção por Zika virus , Zika virus , Animais , Humanos , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/metabolismo , Peroxidase/metabolismo , Mosquitos Vetores , Heme/metabolismo , Peroxidases/metabolismo , Zika virus/metabolismo
4.
FASEB J ; 38(10): e23691, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38780525

RESUMO

Heme is a prosthetic group of proteins involved in vital physiological processes. It participates, for example, in redox reactions crucial for cell metabolism due to the variable oxidation state of its central iron atom. However, excessive heme can be cytotoxic due to its prooxidant properties. Therefore, the control of intracellular heme levels ensures the survival of organisms, especially those that deal with high concentrations of heme during their lives, such as hematophagous insects. The export of heme initially attributed to the feline leukemia virus C receptor (FLVCR) has recently been called into question, following the discovery of choline uptake by the same receptor in mammals. Here, we found that RpFLVCR is a heme exporter in the midgut of the hematophagous insect Rhodnius prolixus, a vector for Chagas disease. Silencing RpFLVCR decreased hemolymphatic heme levels and increased the levels of intracellular dicysteinyl-biliverdin, indicating heme retention inside midgut cells. FLVCR silencing led to increased expression of heme oxygenase (HO), ferritin, and mitoferrin mRNAs while downregulating the iron importers Malvolio 1 and 2. In contrast, HO gene silencing increased FLVCR and Malvolio expression and downregulated ferritin, revealing crosstalk between heme degradation/export and iron transport/storage pathways. Furthermore, RpFLVCR silencing strongly increased oxidant production and lipid peroxidation, reduced cytochrome c oxidase activity, and activated mitochondrial biogenesis, effects not observed in RpHO-silenced insects. These data support FLVCR function as a heme exporter, playing a pivotal role in heme/iron metabolism and maintenance of redox balance, especially in an organism adapted to face extremely high concentrations of heme.


Assuntos
Heme , Mitocôndrias , Oxirredução , Rhodnius , Animais , Heme/metabolismo , Rhodnius/metabolismo , Mitocôndrias/metabolismo , Receptores Virais/metabolismo , Receptores Virais/genética , Vírus da Leucemia Felina/metabolismo , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética
5.
Photochem Photobiol Sci ; 23(6): 1129-1142, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38734995

RESUMO

Bacterial infections are a global health concern, particularly due to the increasing resistance of bacteria to antibiotics. Multi-drug resistance (MDR) is a considerable challenge, and novel approaches are needed to treat bacterial infections. Photodynamic inactivation (PDI) of microorganisms is increasingly recognized as an effective method to inactivate a broad spectrum of bacteria and overcome resistance mechanisms. This study presents the synthesis of a new cationic 5,15-di-imidazolyl porphyrin derivative and the impact of n-octanol/water partition coefficient (logP) values of this class of photosensitizers on PDI efficacy of Escherichia coli. The derivative with logP = -0.5, IP-H-OH2+, achieved a remarkable 3 log CFU reduction of E. coli at 100 nM with only 1.36 J/cm2 light dose at 415 nm, twice as effective as the second-best porphyrin IP-H-Me2+, of logP = -1.35. We relate the rapid uptake of IP-H-OH2+ by E. coli to improved PDI and the very low uptake of a fluorinated derivative, IP-H-CF32+, logP ≈ 1, to its poor performance. Combination of PDI with cinnamaldehyde, a major component of the cinnamon plant known to alter bacteria cell membranes, offered synergic inactivation of E. coli (7 log CFU reduction), using 50 nM of IP-H-OH2+ and just 1.36 J/cm2 light dose. The success of combining PDI with this natural compound broadens the scope of therapies for MDR infections that do not add drug resistance. In vivo studies on a mouse model of wound infection showed the potential of cationic 5,15-di-imidazolyl porphyrins to treat clinically relevant infected wounds.


Assuntos
Acroleína , Antibacterianos , Escherichia coli , Imidazóis , Fármacos Fotossensibilizantes , Porfirinas , Escherichia coli/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/síntese química , Porfirinas/farmacologia , Porfirinas/química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Acroleína/análogos & derivados , Acroleína/farmacologia , Acroleína/química , Imidazóis/química , Imidazóis/farmacologia , Imidazóis/síntese química , Cátions/química , Cátions/farmacologia , Testes de Sensibilidade Microbiana , Animais , Camundongos , Sinergismo Farmacológico , Fotoquimioterapia
6.
J Clin Periodontol ; 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38798054

RESUMO

AIM: To investigate the effects of high-intensity interval training (HIIT) on periodontitis (PD) progression and behavioural outcomes. MATERIALS AND METHODS: Forty-eight Wistar rats were divided into four groups: non-trained (NT); non-trained with PD; HIIT with PD; and HIIT. The HIIT protocol, involving daily treadmill sessions, spanned 8 weeks, with PD induced by ligature after the 6th week. Behavioural tests were conducted to assess anxiety and memory. Post euthanasia, we evaluated the systemic inflammatory profile and oxidative stress markers in the hippocampus and amygdala. A morphological evaluation and elemental composition analysis of the mandibular alveolar bone were performed. RESULTS: PD exacerbated alveolar bone level, bone surface damage and alterations in calcium and phosphorus percentages on the bone surface (p < .05), while HIIT attenuated these changes (p < .05). HIIT improved systemic inflammatory markers altered by PD (tumour necrosis factor [TNF]-α, interleukin [IL]-10, TNF-α/IL-10 and IL-1ß/IL-10 ratios, p < .05). PD animals exhibited lower total antioxidant capacity and levels of thiobarbituric acid reactive substances in the amygdala and hippocampus, respectively (p < .05). HIIT maintained these parameters at levels similar to those in NT animals. HIIT improved anxiety and memory outcomes altered by PD (p < .05). CONCLUSIONS: HIIT attenuates systemic inflammation, anxiety and memory outcomes promoted by PD.

7.
J Chem Phys ; 160(3)2024 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-38226823

RESUMO

The immobilization of Re(I) complexes onto metal oxide surfaces presents an elegant strategy to enhance their stability and reusability toward photocatalytic CO2 reduction. In this study, the photocatalytic performance of fac-[ClRe(CO)3(dcbH2)], where dcbH2 = 4,4'-dicarboxylic acid-2,2'-bipyridine, anchored onto the surface of 1%m/m CuO/Nb2O5 was investigated. Following adsorption, the turnover number for CO production (TONCO) in DMF/TEOA increased significantly, from ten in solution to 370 under visible light irradiation, surpassing the TONCO observed for the complex onto pristine Nb2O5 or CuO surfaces. The CuO/Nb2O5 heterostructure allows for efficient electron injection by the Re(I) center, promoting efficient charge separation. At same time CuO clusters introduce a new absorption band above 550 nm that contributes for the photoreduction of the reaction intermediates, leading to a more efficient CO evolution and minimization of side reactions.

8.
Planta Med ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38631368

RESUMO

Traditional medicine is a frequently utilized method to treat cardiovascular disease and its primary risk factors, including hypertension and dyslipidemia. Aloysia polystachya is a species that is commonly employed to treat various pathological conditions, and it has already been identified as having some cardioprotective effects. This study aimed to investigate the protective effects of the essential oil extracted from the leaves of A. polystachya in a rat model that simulates multiple cardiovascular risk factors. We evaluate the acute toxicity, as well as the cardioprotective effects, by giving different doses of A. polystachya essential oil (1.47 mg/kg, 4.40 mg/kg, and 13.20 mg/kg) over a period of 42 days. The control group was treated with rosuvastatin (5 mg/kg). At the end of the treatments, the renal function, electrocardiography, blood pressure, vascular reactivity, serum biochemical profile, and organ histopathology were evaluated. The main compounds identified in the essential oil of A. polystachya using gas chromatography coupled with mass spectrometry were beta-myrcene (1.08%), limonene (40.13%), and carvone (56.47%). The essential oil of A. polystachya not only lacks acute toxicity but also mitigates the reduction in the excretion of sodium, chloride, and creatinine in urine. Furthermore, it reduces electrocardiographic abnormalities and decreases blood pressure levels. Moreover, this treatment prevents an elevation in markers of inflammation and oxidative stress in the bloodstream. Our findings indicate significant cardioprotective effects of the essential oil of A. polystachya against multiple risk factors for cardiovascular diseases in hypertensive rats.

9.
An Acad Bras Cienc ; 96(3): e20221001, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38865505

RESUMO

The objective was to evaluate the chemical composition and in vitro fermentation of spineless cactus of the genus Nopalea, F-21 (Nopalea cochenillifera Dyck), IPA-Sertânia (Nopalea cochenillifera Dyck) and Miúda (Nopalea cochenillifera Salm Dyck), in different phenophases. There was no effect (P < 0.05) of the phenological phases of spineless cactus on DM, ash, OM, EE, and CP. Varieties F-21 and Miúda presented higher values of DM and OM, whereas the CP was higher for IPA-Sertânia. The contents of NDF, ADF, and ADL, as well as the fractions of carbohydrates B2 and C were higher in the mature stage, irrespective of the variety. The Miúda variety showed higher levels of NFC and fractions A + B1 and the lower levels of pectin compared to the F-21 and IPA-Sertânia varieties, but not differ of TC to F-21. The volume of gas produced via the degradation of NFC was higher for young phenological phases. The young and intermediate stages showed a higher in vitro digestibility of DM. Based on the results, varieties IPA-Sertânia and Miúda have a high potential for use in animal feed because of their high nutritional quality. Mature cladodes showed a higher fibrous fraction and lower digestibility in all varieties.


Assuntos
Cactaceae , Fermentação , Valor Nutritivo , Cactaceae/química , Cactaceae/classificação , Cinética , Ração Animal/análise
10.
Chem Biodivers ; : e202400687, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702295

RESUMO

Rhizophora extracts have several potential biological activities, and their metabolites can be used in the pharmaceutical industry. Extracts of Rhizophora species obtained from mangroves have shown prospective activity against Staphylococcus aureus. This study aimed to investigate the chemical profile of Rhizophora mangle leaves from fringe, basin, and transition mangrove zones and their bactericidal/bacteriostatic potential against S. aureus. R. mangle leaves were collected monthly in 2018 from litterfall in three different zones of the mangrove of Guaratiba State Reserve: fringe, basin, and transition. Extracts were prepared from the material collected in October and December for LC-HRMS/MS analysis, and dereplication was performed using a molecular library search and the classical molecular networking GNPS platform. The minimum inhibitory concentrations (MICs) of the aqueous extract of R. mangle against S. aureus were determined. No S. aureus growth was observed compared to the control for extracts collected from September to December. Different compounds were annotated in each region, yet a marked presence of phenolic compounds was noted, among them glycosylated flavonoid derivatives of quercetin and kaempferol. The results suggest bactericidal/bacteriostatic activity for extracts of R. mangle leaves collected in 2018 from three mangrove forest zones.

11.
J Antimicrob Chemother ; 78(5): 1300-1308, 2023 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-36999363

RESUMO

BACKGROUND: Carbapenem-resistant Klebsiella pneumoniae (CRKP) strains are of particular concern, especially strains with mobilizable carbapenemase genes such as blaKPC, blaNDM or blaOXA-48, given that carbapenems are usually the last line drugs in the ß-lactam class and, resistance to this sub-class is associated with increased mortality and frequently co-occurs with resistance to other antimicrobial classes. OBJECTIVES: To characterize the genomic diversity and international dissemination of CRKP strains from tertiary care hospitals in Lisbon, Portugal. METHODS: Twenty CRKP isolates obtained from different patients were subjected to WGS for species confirmation, typing, drug resistance gene detection and phylogenetic reconstruction. Two additional genomic datasets were included for comparative purposes: 26 isolates (ST13, ST17 and ST231) from our collection and 64 internationally available genomic assemblies (ST13). RESULTS: By imposing a 21 SNP cut-off on pairwise comparisons we identified two genomic clusters (GCs): ST13/GC1 (n = 11), all bearing blaKPC-3, and ST17/GC2 (n = 4) harbouring blaOXA-181 and blaCTX-M-15 genes. The inclusion of the additional datasets allowed the expansion of GC1/ST13/KPC-3 to 23 isolates, all exclusively from Portugal, France and the Netherlands. The phylogenetic tree reinforced the importance of the GC1/KPC-3-producing clones along with their rapid emergence and expansion across these countries. The data obtained suggest that the ST13 branch emerged over a decade ago and only more recently did it underpin a stronger pulse of transmission in the studied population. CONCLUSIONS: This study identifies an emerging OXA-181/ST17-producing strain in Portugal and highlights the ongoing international dissemination of a KPC-3/ST13-producing clone from Portugal.


Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos , Infecções por Klebsiella , Humanos , Klebsiella pneumoniae , Filogenia , Portugal/epidemiologia , beta-Lactamases/genética , Proteínas de Bactérias/genética , Carbapenêmicos , Genômica , Testes de Sensibilidade Microbiana , Infecções por Klebsiella/epidemiologia , Antibacterianos/farmacologia , Chaperonas Moleculares/genética , Proteínas Supressoras de Tumor/genética
12.
Eur J Clin Microbiol Infect Dis ; 42(12): 1405-1423, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37897520

RESUMO

In recent years, multidrug-resistant Acinetobacter baumannii has emerged globally as a major threat to the healthcare system. It is now listed by the World Health Organization as a priority one for the need of new therapeutic agents. A. baumannii has the capacity to develop robust biofilms on biotic and abiotic surfaces. Biofilm development allows these bacteria to resist various environmental stressors, including antibiotics and lack of nutrients or water, which in turn allows the persistence of A. baumannii in the hospital environment and further outbreaks. Investigation into therapeutic alternatives that will act on both biofilm formation and antimicrobial resistance (AMR) is sorely needed. The aim of the present review is to critically discuss the various mechanisms by which AMR and biofilm formation may be co-regulated in A. baumannii in an attempt to shed light on paths towards novel therapeutic opportunities. After discussing the clinical importance of A. baumannii, this critical review highlights biofilm-formation genes that may be associated with the co-regulation of AMR. Particularly worthy of consideration are genes regulating the quorum sensing system AbaI/AbaR, AbOmpA (OmpA protein), Bap (biofilm-associated protein), the two-component regulatory system BfmRS, the PER-1 ß-lactamase, EpsA, and PTK. Finally, this review discusses ongoing experimental therapeutic strategies to fight A. baumannii infections, namely vaccine development, quorum sensing interference, nanoparticles, metal ions, natural products, antimicrobial peptides, and phage therapy. A better understanding of the mechanisms that co-regulate biofilm formation and AMR will help identify new therapeutic targets, as combined approaches may confer synergistic benefits for effective and safer treatments.


Assuntos
Acinetobacter baumannii , Antibacterianos , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Biofilmes , Percepção de Quorum , Farmacorresistência Bacteriana Múltipla/genética
13.
Exp Mol Pathol ; 134: 104870, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37690528

RESUMO

Bisphenol A (BPA) is an endocrine-disrupting chemical with a potential role in endocrine cancers. However, the effects of BPA on the salivary glands have been barely explored. We investigated the impact of in vivo sub-chronic exposure to BPA and its in vitro effects on human salivary gland mucoepidermoid carcinoma cell lines. Male and female mice were exposed to BPA (30 mg/kg/day). Sublingual and submandibular salivary glands from an estrogen-deficiency model were also analyzed. BPA concentration in salivary glands was evaluated by gas chromatography coupled to ion trap mass spectrometry. Immunohistochemical analysis using anti-p63 and anti-α-SMA antibodies was performed on mouse salivary gland tissues. Gene expression of estrogen receptors alpha and beta, P63 and α-SMA was quantified in mouse salivary gland and/or mucoepidermoid (UM-HMC-1 and UM-HMC-3A) cell lines. Cell viability, p63 and Ki-67 immunostaining were evaluated in vitro. BPA disrupted the tissue architecture of the submandibular and sublingual glands, particularly in female mice, and increased the expression of estrogen receptors and p63, effects that were accompanied by significant BPA accumulation in these tissues. Conversely, ovariectomy slightly impacted BPA-induced morphological changes. In vitro, BPA did not affect the proliferation of neoplastic cells, but augmented the expression of p63 and estrogen receptors. The present data highlight a potential harmful effect of BPA on salivary gland tissues, particularly in female mice, and salivary gland tumor cells. Our findings suggest that estrogen-dependent pathways may orchestrate the effects of BPA in salivary glands.


Assuntos
Neoplasias das Glândulas Salivares , Glândulas Salivares , Humanos , Animais , Camundongos , Masculino , Feminino , Estrogênios , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Linhagem Celular Tumoral , Neoplasias das Glândulas Salivares/induzido quimicamente
14.
J Oral Pathol Med ; 52(5): 402-409, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36149755

RESUMO

BACKGROUND: While the relevance of the World Health Organization histopathological grading system as a prognostic tool for oral squamous cell carcinoma has received many critics, other histopathological features such as tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding are displaying promising results. Here, we evaluated the prognostic impact of the incorporation of tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding into World Health Organization histopathological grading for patients with oral squamous cell carcinoma. METHODS: A total of 95 patients with early-stage oral squamous cell carcinoma were enrolled in the study, and World Health Organization tumor grading, tumor-stroma ratio, tumor-infiltrating lymphocytes, and tumor budding were evaluated in surgical slides stained with hematoxylin and eosin. Survival analyses for cancer-specific survival and disease-free survival were performed using Cox regression models, and receiver operating characteristic curves were applied for assessment of the performance of the combinations. RESULTS: Tumor-stroma ratio (stroma-rich) was significantly and independently associated with both shortened cancer-specific survival and poor disease-free survival, individually and in combination with World Health Organization histopathological grading. The combination of tumor-stroma ratio with World Health Organization grading did not improve the discriminatory ability compared to tumor-stroma ratio alone. Although low tumor-infiltrating lymphocytes were associated with shortened cancer-specific survival, the association did not withstand multivariate analysis. However, in combination with World Health Organization grading, low tumor-infiltrating lymphocytes were independently associated with poor cancer-specific survival. The combination of tumor-infiltrating lymphocytes and World Health Organization histopathological grading displayed a better discrimination of poor cancer-specific survival than tumor-infiltrating lymphocytes alone, but not at a significant level. CONCLUSION: Our findings support tumor-stroma ratio as a potential prognostic marker for patients with oral squamous cell carcinoma, and the incorporation of tumor-infiltrating lymphocytes into the World Health Organization grading system improves the prognostic ability of the tumor grading alone.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Neoplasias Bucais/patologia , Linfócitos do Interstício Tumoral , Prognóstico , Gradação de Tumores , Organização Mundial da Saúde , Neoplasias de Cabeça e Pescoço/patologia , Estudos Retrospectivos , Estadiamento de Neoplasias
15.
BMC Public Health ; 23(1): 534, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36944943

RESUMO

BACKGROUND: Litigation for health care, also known as health judicialization, is frequent in Brazil. It involves recourse to the court system to access health services. The study aimed to evaluate whether cancer patients in Belo Horizonte, Minas Gerais, Brazil, increased their overall survival by increasing access to certain drugs or treatments through litigation, controlling for the effect of demographic and disease-related variables. METHODS: A retrospective cohort study was conducted. Patients with breast, prostate, brain, lung, or colon cancers from 2014 to 2019 were included. Survival analysis was performed using the Cox proportional hazards model. RESULTS: In the multivariate analysis, litigation was significantly associated with increased survival in cancers of breast (HR = 0.51, 95%CI 0.33-0.80), prostate (HR = 0.50, 95%CI 0.30-0.85), colon (HR = 0.59, 95%CI 0.38-0.93), and lung (HR = 0.36, 95%CI 0.22-0.60). Five-year survival rates of patients who sued for treatment were 97.8%, 88.7%, 59.3%, and 26.0%, compared to median survival of 95.7%, 78.7%, 41.2%, and 2.4%, respectively, among patient that did not resort to court action. The study suggests that litigation for access to cancer treatment may represent a step forward in obtaining more effective treatment. This study´s main limitations are the lack of patients´ clinical information for use as control variables and the lack of variables to assess patients´ quality of life. The study also found that many cases involved claims that could have been solved by administrative rather than legal action. Some claims thus reflect the lack of adequate administrative procedures. CONCLUSION: When based on scientific evidence, access to new therapies, combined with other technologies already available, can favor patient survival. Access to new therapies through litigation may increase health inequalities since low-income patients have limited access to legal recourse against the State to meet their needs. The timely approval of new effective therapies can mitigate the judicialization of cancer treatment.


Assuntos
Neoplasias , Saúde Pública , Masculino , Humanos , Brasil/epidemiologia , Estudos Retrospectivos , Qualidade de Vida , Análise de Sobrevida , Neoplasias/terapia
16.
Mem Inst Oswaldo Cruz ; 117: e220109, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36700579

RESUMO

BACKGROUND: The human immunodeficiency virus type 1, F1 sub-subtype (HIV-1 F1) circulates in three continents: Africa, Europe, and South America. In Brazil, this sub-subtype co-circulates with subtypes B and C and several recombinant forms, mainly BF1 variants. OBJECTIVES: This study aimed to reconstruct the dynamic history of HIV-1 F1 in Brazil. METHODS: HIV-1 near full-length genome and pol gene nucleotide sequences available in public databases were assembled in two datasets (POL671 and NFLG53) to cover the largest number of F1 sub-subtype sequences. Phylodynamic and temporal analyses were performed. FINDINGS: Two main strains of the F1 sub-subtype are circulating worldwide. The first (F1.I) was found among Brazilian samples (75%) and the second (F1.II) among Romanian (62%) and other European and African isolates. The F1 subtype epidemic in Brazil originated from a single entry into the country around 1970. This ancestral sample is related to samples isolated in European countries (France, Finland, and Belgium), which are possibly of African origin. Moreover, further migration (1998 CI: 1994-2003) of strains from Brazil to Europe (Spain and the UK) was observed. Interestingly, all different recombinant BF patterns found, even those from outside Brazil, present the same F1 lineage (F1.I) as an ancestor, which could be related to the acquisition of adaptive advantages for the recombinant progenies. MAIN CONCLUSIONS: These findings are important for the understanding of the origin and dynamics of the F1 sub-subtype and a consequent better and greater understanding of the HIV-1 F1 and BF epidemic that still spreads from Brazil to other countries.


Assuntos
HIV-1 , Filogenia , Humanos , Brasil , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética
17.
Int J Mol Sci ; 24(3)2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36769264

RESUMO

Classically, osteopontin (OPN) has been described as a secreted glycophosprotein. Indeed, most data concerning its physiological and pathological roles are mainly related to the secreted OPN (sOPN). However, there are several instances in which intracellular OPN (iOPN) has been described, presenting some specific roles in distinct experimental models, such as in the immune system, cancer cells, and neurological disorders. We herein aimed to highlight and discuss some of these secreted and intracellular roles of OPN and their putative clinical and biological impacts. Moreover, by consolidating data from the OPN protein database, we also analyzed the occurrence of signal peptide (SP) sequences and putative subcellular localization, especially concerning currently known OPN splicing variants (OPN-SV). Comprehending the roles of OPN in its distinct cellular and tissue environments may provide data regarding the additional applications of this protein as biomarkers and targets for therapeutic purposes, besides further describing its pleiotropic roles.


Assuntos
Osteopontina , Splicing de RNA , Osteopontina/genética , Osteopontina/metabolismo
18.
Int J Paediatr Dent ; 33(1): 89-98, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35838202

RESUMO

BACKGROUND: Selective outcome reporting (SOR) is a bias that occurs when the primary outcome of a randomised clinical trial (RCT) is omitted or changed. AIM: To evaluate the prevalence of SOR in RCTs on restorative treatment in primary teeth. DESIGN: We conducted an electronic search on ClinicalTrials.gov and the World Health Organization platform (International Clinical Trials Registry Platform) on 1st of April 2021, with no registry time or language restrictions. We included RCT protocols that evaluated restorative treatments in primary teeth and excluded trials that did not have a complete publication in a scientific journal. The chi-squared test was used to identify the association between SOR and variables as a discrepancy in the follow-up period, the timing of registration, the type of sponsorship and the type of study design (α = 5%). RESULTS: Of the 294 identified protocols, 30 were included in the study. 83.3% of trials were registered retrospectively. SOR was observed in 53.3% (n = 16) of the published trials and was significantly associated with a discrepancy in the follow-up period (p = .017). CONCLUSIONS: The high prevalence of SOR in RCTs on restorative treatment proves that this is a prominent threat. A proper preregistered protocol, declaration of any protocol deviation and allowance of stakeholders to compare the protocol with that of the submitted papers will achieve transparency.


Assuntos
Odontopediatria , Projetos de Pesquisa , Criança , Humanos , Resultado do Tratamento
19.
Molecules ; 28(14)2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37513277

RESUMO

Gallesia integrifolia, a notable species in the Atlantic Forest, has been traditionally employed in folk medicine for treating rheumatism, asthma, and worms. This study investigated the cellular antioxidant, antiproliferative, and anti-inflammatory activities of the essential oils (EOs) and crude extracts (CEs) from G. integrifolia flowers, fruits, and leaves. The chemical identification of EOs was performed by GC-MS and CEs by UHPLC-MS. Cellular antioxidant and anti-inflammatory activities were assessed through mouse macrophage cell culture. In addition, the antiproliferative potential was evaluated in gastric, colorectal, breast, and lung tumor cell lines and non-tumor VERO cells. EOs predominantly contained organosulfur compounds in flowers (96.29%), fruits (94.94%), and leaves (90.72%). We found the main compound is 2,2'-Disulfanediyldiethanethiol in the EOs of flowers (47.00%), leaves (41.82%), and fruits (44.39%). Phenolic compounds were identified in CEs. The EOs and CEs demonstrated potential against the tumor cell lines tested (GI50 between 51 and 230 µg/mL). The selectivity index values were greater than 1.0 (1.01 to 3.37), suggesting a relative safety profile. Moreover, the anti-inflammatory activity IC50 ranged from 36.00 to 268 µg/mL, and the cellular oxidation inhibition ranged from 69% to 82%. The results suggest that oils and extracts derived from G. integrifolia have potential for use in various industrial sectors.


Assuntos
Antioxidantes , Óleos Voláteis , Camundongos , Animais , Chlorocebus aethiops , Antioxidantes/farmacologia , Antioxidantes/análise , Frutas , Células Vero , Folhas de Planta/química , Flores/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/análise , Óleos Voláteis/química , Extratos Vegetais/química
20.
J Food Sci Technol ; 60(12): 2916-2926, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37786599

RESUMO

Starches and proteins are two major types of biopolymer components in many foods. The interactions of protein with starches greatly influence the matrix structure and properties of starch-based food systems. In this study, the physical-chemical properties and the effect of the commercial whey protein concentrate in the texture and rheological properties of jackfruit starch gels were evaluated. The experimental design was completely randomized, using a 4 × 4 complete factorial scheme, with four levels of starch (3, 6, 9 and 12%) and four levels of protein (0, 2, 4 and 6%). In higher concentrations of starch the addition of proteins delayed the beginning of gelatinization, led to an increase in G' and G″ and decrease in the tan (δ) values, characterizing the gel as strong, e.g., the gel network became more structured. However, in the treatment with 6% starch the addition of protein led to a decrease in gel strength. For gels with 9% starch the increase in protein concentration, led a slight increase in the hardness and cohesiveness, characterizing a more rigid and cohesive gel. Overall, gels with 3 and 6% of starch showed characteristic behavior of a weak gel and with 9 and 12% of strong gel. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05793-1.

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