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1.
Int J Mol Sci ; 25(15)2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39125681

RESUMO

The search for bioactive compounds in natural products holds promise for discovering new pharmacologically active molecules. This study explores the anti-inflammatory potential of açaí (Euterpe oleracea Mart.) constituents against the NLRP3 inflammasome using high-throughput molecular modeling techniques. Utilizing methods such as molecular docking, molecular dynamics simulation, binding free energy calculations (MM/GBSA), and in silico toxicology, we compared açaí compounds with known NLRP3 inhibitors, MCC950 and NP3-146 (RM5). The docking studies revealed significant interactions between açaí constituents and the NLRP3 protein, while molecular dynamics simulations indicated structural stabilization. MM/GBSA calculations demonstrated favorable binding energies for catechin, apigenin, and epicatechin, although slightly lower than those of MCC950 and RM5. Importantly, in silico toxicology predicted lower toxicity for açaí compounds compared to synthetic inhibitors. These findings suggest that açaí-derived compounds are promising candidates for developing new anti-inflammatory therapies targeting the NLRP3 inflammasome, combining efficacy with a superior safety profile. Future research should include in vitro and in vivo validation to confirm the therapeutic potential and safety of these natural products. This study underscores the value of computational approaches in accelerating natural product-based drug discovery and highlights the pharmacological promise of Amazonian biodiversity.


Assuntos
Anti-Inflamatórios , Inflamassomos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Proteína 3 que Contém Domínio de Pirina da Família NLR , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Inflamassomos/antagonistas & inibidores , Inflamassomos/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Euterpe/química , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia
2.
Genet Mol Biol ; 47(3): e20230265, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39136575

RESUMO

Bladder cancer is the tenth most frequently diagnosed cancer globally. Classification of high- or low-grade tumors is based on cytological differentiation and is an important prognostic factor. LncRNAs regulate gene expression and play critical roles in the occurrence and development of cancer, however, there are few reports on their diagnostic value and co-expression levels with genes, which may be useful as specific biomarkers for prognosis and therapy in bladder cancer. Thus, we performed a marker lesion study to investigate whether gene/lncRNA expression in urothelial carcinoma tissues may be useful in differentiating low-grade and high-grade tumors. RT-qPCR was used to evaluate the expression of the JHDM1D gene and the lncRNAs CTD-2132N18.2, SBF2-AS1, RP11-977B10.2, CTD-2510F5.4, and RP11-363E7.4 in 20 histologically diagnosed high-grade and 10 low-grade tumors. A protein-to-protein interaction network between genes associated with JHDM1D gene was constructed using STRING website. The results showed a moderate (positive) correlation between CTD-2510F5.4 and CTD2132N18.2. ROC curve analyses showed that combined JHDM1D and RP11-363E7.4 predicted tumor grade with an AUC of 0.826, showing excellent accuracy. In conclusion, the results indicated that the combined expression of JHDM1D and RP11-363E7.4 may be a prognostic biomarker and a promising target for urothelial tumor therapy.

3.
Molecules ; 28(19)2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37836714

RESUMO

This study explores the potential inhibitory activity of alkaloids, a class of natural compounds isolated from Brazilian biodiversity, against the mJHBP enzyme of the Aedes aegypti mosquito. This mosquito is a significant vector of diseases such as dengue, zika, and chikungunya. The interactions between the ligands and the enzyme at the molecular level were evaluated using computational techniques such as molecular docking, molecular dynamics (MD), and molecular mechanics with generalized Born surface area (MMGBSA) free energy calculation. The findings suggest that these compounds exhibit a high binding affinity with the enzyme, as confirmed by the binding free energies obtained in the simulation. Furthermore, the specific enzyme residues that contribute the most to the stability of the complex with the compounds were identified: specifically, Tyr33, Trp53, Tyr64, and Tyr129. Notably, Tyr129 residues were previously identified as crucial in the enzyme inhibition process. This observation underscores the significance of the research findings and the potential of the evaluated compounds as natural insecticides against Aedes aegypti mosquitoes. These results could stimulate the development of new vector control agents that are more efficient and environmentally friendly.


Assuntos
Aedes , Dengue , Inseticidas , Infecção por Zika virus , Zika virus , Animais , Humanos , Controle de Mosquitos/métodos , Dengue/prevenção & controle , Brasil , Simulação de Acoplamento Molecular , Mosquitos Vetores , Inseticidas/farmacologia
4.
J Environ Sci Health B ; 58(1): 80-89, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36708186

RESUMO

Greenhouse experiments were carried out aiming to characterize-morphologically and biochemically-resistant and susceptible plants of C. sumatrensis. Two experiments were carried out to evaluate the behavior of morphological variables such as leaf area, height, and dry biomass weight, without application of paraquat (1,1'-dimethyl-4,4'-bipyridinium dichloride). Other experiments were conducted with two rates of paraquat application (0 and 800 g a.i ha-1); physiological variables were assessed at 2, 4, and 24 h after application (HAA), and plants were collected at 4 HAA for biochemical analyses of antioxidant enzymes and cell membrane peroxidation level. Without herbicide application, paraquat-resistant populations had higher dry biomass, leaf area, liquid photosynthetic rate, carboxylation efficiency, and stomatal conductance. The recovery of the photosynthetic apparatus by resistant plants after paraquat application is rapid (16 HAA) and, in general, presents physiological improvements in terms of photosynthetic rate and carboxylation efficiency. After paraquat treatment, the antioxidant system enzymes of resistant plants showed increased activity and decreased membrane peroxidation, indicating that these enzymes play an important role in the resistance mechanism of these plants.


Assuntos
Conyza , Herbicidas , Paraquat/metabolismo , Conyza/metabolismo , Antioxidantes/metabolismo , Brasil , Herbicidas/metabolismo
5.
Eur J Nucl Med Mol Imaging ; 49(3): 1063-1074, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34486070

RESUMO

PURPOSE: To combine peripheral blood indices and clinical factors in a prognostic score for metastatic castration-resistant prostate cancer (mCRPC) patients treated with radium-223 dichloride ([223Ra]RaCl2). PATIENTS AND METHODS: Baseline neutrophil-to-lymphocyte ratio (NLR), derived NLR (donor), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), Eastern Cooperative Oncology Group performance status (ECOG PS), Gleason score (GS) group, number of bone metastases, prostate-specific antigen (PSA), alkaline phosphatase (ALP), line of therapy, previous chemotherapy, and the presence of lymphadenopathies were collected from seven Italian centers between 2013 and 2020. Lab and clinical data were assessed in correlation with the overall survival (OS). Inflammatory indices were then included separately in the multivariable analyses with the prognostic clinical factors. The model with the highest discriminative ability (c-index) was chosen to develop the BIO-Ra score. RESULTS: Five hundred and nineteen mCRPC patients (median OS: 19.9 months) were enrolled. Higher NLR, dNLR, PLR, and SII and lower LMR predicted worse OS (all with a p < 0.001). The multivariable model including NLR, ECOG PS, number of bone metastases, ALP, and PSA (c-index: 0.724) was chosen to develop the BIO-Ra score. Using the Schneeweiss scoring system, the BIO-Ra score identified three prognostic groups (36%, 27.3%, and 36.6% patients, respectively) with distinct median OS (31, 26.6, and 9.6 months, respectively; hazard ratio: 1.62, p = 0.008 for group 2 vs. 1 and 5.77, p < 0.001 for group 3 vs. 1). CONCLUSIONS: The BIO-Ra score represents an easy and widely applicable tool for the prognostic stratification of mCRPC patients treated with [223Ra]RaCl2 with no additional costs.


Assuntos
Neoplasias de Próstata Resistentes à Castração , Rádio (Elemento) , Humanos , Linfócitos , Masculino , Prognóstico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Rádio (Elemento)/uso terapêutico , Estudos Retrospectivos
6.
Molecules ; 27(13)2022 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-35807321

RESUMO

Breast cancer is one of the most prevalent cancers in the world. Traditionally, medicinal plants have been used to cure various types of diseases and disorders. Based on a literature survey, the current study was undertaken to explore the anticancer potential of Foeniculum vulgare Mill. phytoconstituents against breast cancer target protein (PDB ID: 6CHZ) by the molecular docking technique. Molecular docking was done using Autodock/vina software. Toxicity was predicted by the Protox II server and drug likeness was predicted by Molinspiration. 100 ns MD simulation of the best protein-ligand complexes were done using the Amber 18 tool. The present molecular docking investigation has revealed that among the 40 selected phytoconstituents of F. vulgare, α-pinene and D-limonene showed best binding energy (-6 and -5.9 kcal/mol respectively) with the breast cancer target. α-Pinene and D-limonene followed all the parameters of toxicity, and 100 ns MD simulations of α-pinene and D-limonene complexes with 6CHZ were found to be stable. α-Pinene and D-limonene can be used as new therapeutic agents to cure breast cancer.


Assuntos
Neoplasias da Mama , Foeniculum , Neoplasias da Mama/tratamento farmacológico , Feminino , Humanos , Ligantes , Limoneno , Simulação de Acoplamento Molecular
7.
Molecules ; 27(13)2022 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-35807364

RESUMO

Dengue virus (DENV) is a danger to more than 400 million people in the world, and there is no specific treatment. Thus, there is an urgent need to develop an effective method to combat this pathology. NS2B/NS3 protease is an important biological target due it being necessary for viral replication and the fact that it promotes the spread of the infection. Thus, this study aimed to design DENV NS2B/NS3pro allosteric inhibitors from a matrix compound. The search was conducted using the Swiss Similarity tool. The compounds were subjected to molecular docking calculations, molecular dynamics simulations (MD) and free energy calculations. The molecular docking results showed that two compounds, ZINC000001680989 and ZINC000001679427, were promising and performed important hydrogen interactions with the Asn152, Leu149 and Ala164 residues, showing the same interactions obtained in the literature. In the MD, the results indicated that five residues, Lys74, Leu76, Asn152, Leu149 and Ala166, contribute to the stability of the ligand at the allosteric site for all of the simulated systems. Hydrophobic, electrostatic and van der Waals interactions had significant effects on binding affinity. Physicochemical properties, lipophilicity, water solubility, pharmacokinetics, druglikeness and medicinal chemistry were evaluated for four compounds that were more promising, showed negative indices for the potential penetration of the Blood Brain Barrier and expressed high human intestinal absorption, indicating a low risk of central nervous system depression or drowsiness as the the side effects. The compound ZINC000006694490 exhibited an alert with a plausible level of toxicity for the purine base chemical moiety, indicating hepatotoxicity and chromosome damage in vivo in mouse, rat and human organisms. All of the compounds selected in this study showed a synthetic accessibility (SA) score lower than 4, suggesting the ease of new syntheses. The results corroborate with other studies in the literature, and the computational approach used here can contribute to the discovery of new and potent anti-dengue agents.


Assuntos
Vírus da Dengue , Inibidores de Proteases , Proteínas não Estruturais Virais , Animais , Antivirais/química , Antivirais/farmacologia , Vírus da Dengue/efeitos dos fármacos , Vírus da Dengue/enzimologia , Humanos , Camundongos , Simulação de Acoplamento Molecular , Peptídeo Hidrolases/farmacologia , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , RNA Helicases/antagonistas & inibidores , RNA Helicases/química , Ratos , Serina Endopeptidases/química , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/química , Proteínas não Estruturais Virais/metabolismo
8.
Biol Sport ; 39(2): 435-441, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35309527

RESUMO

This study examined the influence of birth date, salivary testosterone [sT] concentration, sexual maturity status, and general strength on the selection process of an elite Brazilian soccer club during a 12-month period, which was a 2nd phase of a 24-month selection process. The stature, body mass, sT, sexual maturity status [Tanner scale], and hand grip strength were assessed for 143 players during 2 weeks. From these 143 players, 100 players were dismissed [DIS] and 43 players were selected to integrate the club's under-14 squad. Following 1-year training period, the under-14 team was assembled with 9 players designated as starters [STA], and then, comparisons were conducted taking into account a group of non-starters (selected; SEL = 34 players) and STA (n = 09). The DIS, SEL, STA players, and reference population, were compared for birth distribution. A greater proportion of players was born in the first trimester in the STA [75.0%], SEL [57.1%] and DIS [50.0%] groups compared to the reference population [25.8%]. One-way ANOVA showed a higher sT for STA group [516.0 ± 129.9 pmol·L-1], compared to SEL [415.5 ± 117.9 pmol·L-1] and DIS groups [390.9 ± 84.9 pmol·L-1; p = 0.003), and Kruskall-Wallis test showed a higher gonadal development for STA compared to DIS [p = 0.001]. The current findings suggest a strong influence of birth date and biological maturation on young soccer players selection process. Soccer coaches should consider these influences when making decisions about player selection of elite youth players.

9.
Future Oncol ; 17(7): 807-815, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33508980

RESUMO

Background: Radium 223 (RA223) is currently administered as part of a therapeutic sequence with the other life-prolonging agents (LPAs) for metastatic castration-resistant prostate cancer (mCRPC). Patients & methods: We retrospectively reviewed the clinical records of patients who had received at least three LPAs including RA223. Results: Median overall survival (OS) from the start of first-line treatment was 39.8 months, with the patients who completed all six planned courses of RA223 having a longer OS than those who did not (53.2 vs 29.5 months; p < 0.0001). Conclusions: Our study confirms the activity of RA223 regardless of the treatment line in which it is administered and suggests that patient selection plays a central role in maximizing this activity.


Assuntos
Antagonistas de Receptores de Andrógenos/administração & dosagem , Neoplasias Ósseas/terapia , Neoplasias de Próstata Resistentes à Castração/terapia , Compostos Radiofarmacêuticos/administração & dosagem , Rádio (Elemento)/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/secundário , Quimiorradioterapia/métodos , Seguimentos , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Seleção de Pacientes , Prostatectomia , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
10.
Aging Clin Exp Res ; 33(3): 651-658, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32358729

RESUMO

BACKGROUND: Radium-223 prolongs overall survival (OS) and delays time to the first symptomatic skeletal events in patients with symptomatic metastatic castration-resistant prostate cancer (mCRPC). There is a lack of evidence on the safety and efficacy of Radium-223 treatment in the very elderly population. AIMS: Aim of this multicentre study is to analyze mCRPC patients treated with Radium-223 in terms of OS and to assess whether there are differences between young and elderly, as well as to verify efficacy and safety in patients ≥ 75 years of age. METHODS: 430 mCRPC patients of six Italian Centres were analyzed in this multicenter retrospective study. At baseline and after each cycle were collected clinical and diagnostic patients' parameters. The whole cohort was divided into two groups based on the age of the patients (< 75 years old and ≥ 75 years old). RESULTS: 47% of the patients were < 75 years old and 53% were ≥ 75 years old. The primary outcome, OS, does not show significant differences between the two subgroups if other basal parameters are considered. Considering clinical covariates in univariate models (p < 0.05) several clinical aspects have an impact on OS, except for age (p = 0.072). Age continues to have no significant impact on the OS (p = 0.274) even in multivariate models in the two groups. The toxic effects are similar in the two groups. CONCLUSIONS: Radium-223 prolongs survival in both younger and older patients at the same baseline condition and is a good option in the symptomatic mCRPC setting compared to other agents.


Assuntos
Neoplasias Ósseas , Neoplasias de Próstata Resistentes à Castração , Idoso , Neoplasias Ósseas/radioterapia , Humanos , Itália , Masculino , Neoplasias de Próstata Resistentes à Castração/radioterapia , Rádio (Elemento) , Estudos Retrospectivos
11.
J Vasc Bras ; 20: e20200230, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630539

RESUMO

BACKGROUND: Surgical management of patients with abdominal aortic diseases associated with distal narrowing is a challenging situation. OBJECTIVES: To evaluate outcomes of unibody bifurcated endovascular stent graft repair. METHODS: This is a retrospective, observational, multi-institutional database study of a cohort of consecutive cases, approved by the local Ethics Committee. Records were reviewed of patients diagnosed from 2010 to 2020 with "shaggy" aorta, saccular aneurysm, penetrating aortic ulcer, and isolated aortic dissection located in the infrarenal abdominal aorta. All patients were treated with a unibody bifurcated stent graft. Main outcomes were technical success, procedure complications, long-term patency, and mortality in the follow-up period up to 5 years. Data on demographics, comorbidities, surgical management, and outcomes were analyzed. RESULTS: Twenty-three patients were treated with unibody bifurcated stent graft repair, including 7 cases of "shaggy" aorta, 3 isolated dissections of the abdominal aorta, 4 penetrating aortic ulcers, and 9 saccular aneurysms. Immediate technical success was achieved in 100% of cases. At follow-up, all stent grafts remained patent and there were no limb occlusions. The patients were symptom-free and reported no complications related to the procedure. There were 5 deaths during the follow-up period (median= 4 years), but none were related to the procedure and there were no aorta-related deaths. CONCLUSIONS: The present study shows that unibody bifurcated stent grafting is safe and effective in this group of patients with narrow distal abdominal aorta and complex aortic pathology. The results were similar for both infrarenal aortic aneurysms and aorto-iliac atherosclerotic disease.


CONTEXTO: O manejo cirúrgico de pacientes com doenças da aorta abdominal associadas ao estreitamento distal é desafiador. OBJETIVOS: Avaliar os desfechos do reparo endovascular com endoprótese bifurcada do tipo monobloco. MÉTODOS: Foi realizado um estudo retrospectivo, de coorte observacional, de banco de dados multi-institucional, com casos consecutivos, após aprovação pelo Comitê de Ética local. Foram analisados prontuários de pacientes com diagnóstico de shaggy aorta, aneurisma sacular, úlcera penetrante da aorta e dissecção isolada da aorta localizados na aorta abdominal infrarrenal entre 2010 e 2020; todos os pacientes foram tratados com endoprótese bifurcada do tipo monobloco. Os principais desfechos foram sucesso técnico, complicações relacionadas ao procedimento, perviedade de longo prazo e mortalidade no seguimento de até 5 anos. Foram incluídos dados demográficos, comorbidades, manejo cirúrgico e desfechos. RESULTADOS: Vinte e três pacientes foram tratados com endoprótese bifurcada do tipo monobloco, incluindo 7 casos de shaggy aorta, 3 dissecções isoladas da aorta abdominal, 4 úlceras penetrantes da aorta e 9 aneurismas saculares. Sucesso técnico imediato foi obtido em 100% dos casos. No seguimento, todas as endopróteses permaneceram pérvias e não houve oclusões de membros. Os pacientes estavam sem sintomas e não relataram complicações relacionadas ao procedimento. Ocorreram 5 óbitos durante o seguimento (mediana = 4 anos), mas nenhum relacionado ao procedimento ou à aorta. CONCLUSÕES: O presente estudo mostra que a endoprótese bifurcada do tipo monobloco é segura e eficaz neste grupo de pacientes com estreitamento distal da aorta abdominal e patologia aórtica complexa. Os resultados foram semelhantes para aneurismas da aorta infrarrenal e doença aterosclerótica aortoilíaca.

12.
Oncology ; 94(3): 161-166, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29241166

RESUMO

BACKGROUND/AIM: Prostate cancer frequently causes bone metastases and skeletal events that impair quality of life (QoL) and survival. The alpha emitter radium-223 is a new drug that improves treatment in men with castration-resistant prostate cancer (CRPC) and bone metastases. Our aim was to evaluate the effectiveness of radium-223. SUBJECTS AND METHODS: In this retrospective study we enrolled 48 subjects. Pain reduction, alkaline phosphatase (ALP), time to first symptomatic skeletal event, and QoL were the variables we evaluated. RESULTS: Radium-223 was well tolerated, with a manageable toxicity profile and a modest objective response rate. A considerable difference in serum ALP levels before and after treatment was observed, with a significant correlation between pain relief and QoL, which showed a value of R2 to 0.44 with a slope of 1.50 (p = 0.0021). CONCLUSIONS: Radium-223 showed a clinical benefit, with a reduction in pain symptoms in 58% of patients. Radium-223 was shown to be an effective and well-tolerated therapeutic option in patients with metastatic CRPC progressing after docetaxel plus prednisone treatment.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Neoplasias de Próstata Resistentes à Castração/patologia , Radioisótopos/uso terapêutico , Rádio (Elemento)/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Docetaxel , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Qualidade de Vida , Estudos Retrospectivos , Taxoides/uso terapêutico
13.
J Vasc Bras ; 17(4): 353-357, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30787957

RESUMO

Pseudoaneurysms of gluteal arteries are rare, especially involving the inferior gluteal artery. They are mainly associated with penetrating trauma, infections, or pelvic fractures. A minority of cases are caused by blunt traumas, with only six cases reported in English. We present a case of pseudoaneurysm of the right inferior gluteal artery after a bicycle fall, presenting with a large hematoma in the gluteal region, observed during clinical examination, and significantly reduced hemoglobin. CT angiography revealed a large hematoma, with contrast extravasation and pseudoaneurysm formation. Angiography revealed that the origin of the lesion was in the right inferior gluteal artery. This artery was embolized with coils. After the procedure, the patient was referred to an intensive care unit, from where he was later transferred to a different hospital, with bleeding controlled. Endovascular treatment of these cases is a safe, fast and an effective option.

14.
Acta Radiol ; 55(1): 39-44, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23926236

RESUMO

BACKGROUND: Preoperative lymphoscintigraphy is without doubt a valid method for the detection of the sentinel lymph node (SLN). There has been considerable debate regarding the optimal site for the introduction of the tracer; various sites include peritumoral (PT), periareolar (PA), subdermal, and intradermal injection. PURPOSE: To evaluate retrospectively the lymphoscintigraphic identification rate of peritumoral (PT) injection versus subdermal periareolar (PA) injection in the detection of SLNs in breast cancer. MATERIAL AND METHODS: Between October 2002 and December 2011, a cohort of 906 consecutive patients with biopsy proven breast cancer underwent 914 SLN biopsy procedures. A total of 339 procedures (Group A) were performed using a PT deep injection of radiotracer while 575 procedures (Group B) adopted a subdermal PA injection of radiotracer towards the upper outer quadrant, regardless of the site of the carcinoma. All the patients underwent synchronous excision of the breast cancer and SLN biopsy. RESULTS: SLNs were identified in the lymphoscintigram in 308/339 cases (90.85%) of Group A (PT injection) and in 537/575 cases (93.39%) of Group B (PA injection). Furthermore, in 2/339 patients (0.58%) of Group A, internal mammary lymph nodes were found at lymphoscintigraphy, whereas no internal mammary sentinel nodes were found in the Group B patients. The intraoperative identification rate of axillary SLNs was 99.41% (337 of 339) in the Group A patients and 99.65% (573 of 575) in the Group B patients. There was no significant difference in the two groups between the incidence of the number of SLNs detected and the incidence of identification of positive SLNs. CONCLUSION: PT versus PA injection of radiotracer showed comparable success rates for axillary SLN identification, and can be considered a rapid and reliable method.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Linfocintigrafia/métodos , Biópsia de Linfonodo Sentinela , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Aumento da Imagem/métodos , Injeções Intralesionais , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Agregado de Albumina Marcado com Tecnécio Tc 99m
15.
BMC Sports Sci Med Rehabil ; 16(1): 196, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39300545

RESUMO

BACKGROUND: CrossFit® combines different types of activities (weightlifting, gymnastics, and cardiovascular training) that challenge aerobic and anaerobic pathways. Over the last few years, the scientific interest in CrossFit® has increased considerably. However, there have been no published reviews characterizing the physical demands and physiological responses to CrossFit®. The present study synthesizes current evidence on the physical demands and physiological responses to CrossFit®. METHODS: The search was performed in three electronic databases (PubMed, Scopus, and Web of Science). Manuscripts related to the physical and physiological performance of adult CrossFit® participants written in English, Portuguese, and Spanish were retrieved for the analysis. RESULTS: In addition, a meta-correlation was conducted to examine the predictors of CrossFit® performance. A total of 68 papers were included in the review. Physical and physiological markers differed between the different workouts analyzed. In addition, 48 to 72 h are needed to recover from a CrossFit® challenge. Specific tests that involve CrossFit® movements were more related to CrossFit® performance than non-specific. CONCLUSION: Although the characterization of CrossFit® is dependent on the workout examined, the benefits of muscle hypertrophy are aligned with the recent findings of concurrent training. The characterization of CrossFit® entire sessions and appropriate recovery strategies should be considered in future studies to help coaches manipulate and adjust the training load.

16.
Sci Total Environ ; 918: 170387, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38280604

RESUMO

Glyphosate hormesis, identified as a potential means to enhance crop yields, encounters practical constraints because it is typically assessed through foliar applications. The expression and extend of hormesis in this approach are influenced by unpredictable environmental conditions, highlighting the need to explore alternative glyphosate application methods, such as seed treatment. This study aimed to assess glyphosate hormesis on growth rates and biomass accumulation in seedlings soybean cultivars. Two dose-response experiments [doses from 0 to 2880 g acid equivalent (ae) ha-1], one via foliar and one via seed, were conducted on three soybean cultivars [one non-glyphosate-resistant (NGR) and two glyphosate-resistant (GR, one RR and one RR2)]. In a subsequent experiment, three safe glyphosate doses (0, 90 and 180 g ae ha-1) applied via seed were evaluated on four soybean cultivars (two RR and two RR2). For foliar applications, the range of glyphosate doses increasing growth rates and dry biomass by 12-28 % were 5.6-45 g ae ha-1 for the NGR cultivar, of 45-720 g ae ha-1 for RR and of 11.25-180 g ae ha-1 for RR2. In the seed treatment, biomass increases of 16-60 % occurred at 45-180 g ae ha-1 for the NGR and RR cultivars, and 90-360 g ae ha-1 for RR2. Glyphosate doses of 90 and 180 g ae ha-1, applied via seeds, provided greater growth and biomass accumulation for the RR and RR2 soybean cultivars. Both foliar and seed applications of glyphosate increased growth and biomass accumulation in soybean cultivars, with seed treatments showing greater and more consistent enhancements. These findings propose practical and viable alternative for harnessing glyphosate hormesis to facilitate the early development of soybeans and potentially enhance crop yield.


Assuntos
Glifosato , Herbicidas , Glycine max , Plântula , Glicina/toxicidade , Hormese , Herbicidas/toxicidade , Biomassa , Sementes
17.
Front Chem ; 12: 1394126, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39139919

RESUMO

The oil of Carapa guianensis showed leishmanicidal activity, with its activity being related to limonoids, but fatty acids are the major constituents of this oil. The present study evaluated the physicochemical, pharmacokinetic, and toxicity profiles of limonoids and fatty acids already identified in the species. Based on these results, 2 limonoids (methyl angosinlate, 6-OH-methyl angosinlate) and 2 fatty acids (arachidic acid; myristic acid) were selected for the prediction of possible targets and molecular docking. Included in this study were: Gedunin, 6α-acetoxygedunin, Methyl angosenlato, 7-deacetoxy-7-oxogedunin, Andirobin, 6-hydroxy-angolensate methyl, 17ß-hydroxyazadiradione, 1,2-dihydro-3ß-hydroxy-7-deacetoxy-7-oxogedunin, xyllocensin k, 11beta-Hydroxygedunin, 6α,11-11ß-diacetoxygedunin, Oleic Acid, Palmitic Acid, Stearic Acid, Arachidic Acid, Myristic Acid, Palmitoleic Acid, Linoleic Acid, Linolenic Acid, and Beenic Acid. Regarding physicochemical aspects, fatty acids violated LogP, and only limonoid 11 violated Lipinski's rule. A common pharmacokinetic aspect was that all molecules were well absorbed in the intestine and inhibited CYP. All compounds showed toxicity in some model, with fatty acids being mutagenic and carcinogenic, and limonoids not being mutagenic and carcinogenic at least for rats. In in vivo models, fatty acids were less toxic. Molecular dockings were performed on COX-2 steroids (15 and 16) and hypoxia-inducible factor 1 alpha for limonoids (3,6), with this target being essential for the intracellular development of leishmania. Limonoids 3 and 6 appear to be promising as leishmanicidal agents, and fatty acids are promising as wound healers.

18.
PLoS One ; 19(8): e0308785, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39146271

RESUMO

The genus Rhinella corresponds to a group of anurans characterized by numerous taxonomic and systemic challenges, leading to their organization into species complexes. Cytogenetic data for this genus thus far are limited to the diploid number and chromosome morphology, which remain highly conserved among the species. In this study, we analyse the karyotypes of three species of the genus Rhinella (Rhinella granulosa, Rhinella margaritifera, and Rhinella marina) using both classical (conventional staining and C-banding) and molecular (FISH-fluorescence in situ hybridization with 18S rDNA, telomeric sequences, and microsatellite probes) cytogenetic approaches. The aim of this study is to provide data that can reveal variations in the distribution of repetitive sequences that can contribute to understanding karyotypic diversification in these species. The results revealed a conserved karyotype across the species, with 2n = 22 and FN = 44, with metacentric and submetacentric chromosomes. C-banding revealed heterochromatic blocks in the pericentromeric region for all species, with a proximal block on the long arms of pairs 3 and 6 in R. marina and on the short arms of pairs 4 and 6 in R. margaritifera. Additionally, 18S rDNA probes hybridized to pair 5 in R. granulosa, to pair 7 in R. marina, and to pair 10 in R. margaritifera. Telomeric sequence probes displayed signals exclusively in the distal region of the chromosomes, while microsatellite DNA probes showed species-specific patterns. These findings indicate that despite a conserved karyotypical macrostructure, chromosomal differences exist among the species due to the accumulation of repetitive sequences. This variation may be attributed to chromosome rearrangements or differential accumulation of these sequences, highlighting the dynamic role of repetitive sequences in the chromosomal evolution of Rhinella species. Ultimately, this study emphasizes the importance of the role of repetitive DNAs in chromosomal rearrangements to elucidate the evolutionary mechanisms leading to independent diversification in the distinct phylogenetic groups of Rhinella.


Assuntos
Análise Citogenética , Hibridização in Situ Fluorescente , Cariótipo , Repetições de Microssatélites , Animais , Repetições de Microssatélites/genética , Bufonidae/genética , Bufonidae/classificação , Feminino , RNA Ribossômico 18S/genética , Telômero/genética , Especificidade da Espécie , Bandeamento Cromossômico , Cariotipagem , Masculino , DNA Ribossômico/genética
19.
Front Chem ; 12: 1336001, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38456183

RESUMO

SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is the etiological agent responsible for the global outbreak of COVID-19 (Coronavirus Disease 2019). The main protease of SARS-CoV-2, Mpro, is a key enzyme that plays a vital role in mediating viral replication and transcription. In this study, a comprehensive computational approach was employed to investigate the binding affinity, selectivity, and stability of natural product candidates as potential new antivirals acting on the viral polyprotein processing mediated by SARS-CoV-2 Mpro. A library of 288 flavonoids extracted from Brazilian biodiversity was screened to select potential Mpro inhibitors. An initial filter based on Lipinski's rule of five was applied, and 204 compounds that did not violate any of the Lipinski rules were selected. The compounds were then docked into the active site of Mpro using the GOLD program, and the poses were subsequently re-scored using MM-GBSA (Molecular Mechanics Generalized Born Surface Area) binding free energy calculations performed by AmberTools23. The top five flavonoids with the best MM-GBSA binding free energy values were selected for analysis of their interactions with the active site residues of the protein. Next, we conducted a toxicity and drug-likeness analysis, and non-toxic compounds were subjected to molecular dynamics simulation and free energy calculation using the MM-PBSA (Molecular Mechanics Poisson-Boltzmann Surface Area) method. It was observed that the five selected flavonoids had lower MM-GBSA binding free energy with Mpro than the co-crystal ligand. Furthermore, these compounds also formed hydrogen bonds with two important residues, Cys145 and Glu166, in the active site of Mpro. Two compounds that passed the drug-likeness filter showed stable conformations during the molecular dynamics simulations. Among these, NuBBE_867 exhibited the best MM-PBSA binding free energy value compared to the crystallographic inhibitor. Therefore, this study suggests that NuBBE_867 could be a potential inhibitor against the main protease of SARS-CoV-2 and may be further examined to confirm our results.

20.
JSLS ; 17(1): 121-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23743383

RESUMO

OBJECTIVES: To examine the feasibility of early laparoscopic ureteroneocystostomy for ureteral obstruction due to hysterectomy injury. METHODS: We retrospectively reviewed a 10-y experience from 2 institutions in patients who underwent early (<30 d) or late (>30 d) laparoscopic ureteroneocystostomy for ureteral injury after hysterectomy. Evaluation of the surgery included the cause of the stricture and intraoperative and postoperative outcomes. RESULTS: A total of 9 patients with distal ureteral injury after hysterectomy were identified. All injuries were identified and treated as early as 21 d after hysterectomy. Seven of 9 patients underwent open hysterectomy, and the remaining patients had vaginal and laparoscopic radical hysterectomy. All ureteroneocystostomy cases were managed laparoscopically without conversion to open surgery and without any intraoperative complications. The Lich-Gregoir reimplantation technique was applied in all patients, and 2 patients required a psoas hitch. The mean operative time was 206.6 min (range, 120-280 min), the mean estimated blood loss was 122.2 cc (range, 25-350 cc), and the mean admission time was 3.3 d (range, 1-7 d). Cystography showed no urine leak when the ureteral stent was removed at 4 to 6 wk after the procedure. Ureteroneocystostomy patency was followed up with cystography at 6 mo and at least 10 y after ureteroneocystostomy. CONCLUSION: Early laparoscopic ureteral reimplantation may offer an alternative surgical approach to open surgery for the management of distal ureteral injuries, with favorable cosmetic results and recovery time from ureteral obstruction due to hysterectomy injury.


Assuntos
Cistostomia/métodos , Histerectomia/efeitos adversos , Complicações Intraoperatórias/cirurgia , Laparoscopia , Ureter/lesões , Ureterostomia/métodos , Adulto , Idoso , Perda Sanguínea Cirúrgica , Constrição Patológica , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Ureter/patologia
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