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1.
Microsc Microanal ; 30(1): 66-76, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38180779

RESUMO

In this study, a conjugate radiation/conduction multimode heat transfer analysis of cryogenic focused ion beam (FIB) milling steps necessary for producing ex situ lift out specimens under cryogenic conditions (cryo-EXLO) is performed. Using finite volume for transient heat conduction and enclosure theory for radiation heat transfer, the analysis shows that as long as the specimen is attached or touching the FIB side wall trenches, the specimen will remain vitreous indefinitely, while actively cooled at liquid nitrogen (LN2) temperatures. To simulate the time needed to perform a transfer step to move the bulk sample containing the FIB-thinned specimen from the cryo-FIB to the cryo-EXLO cryostat, the LN2 temperature active cooling is turned off after steady-state conditions are reached and the specimen is monitored over time until the critical devitrification temperature is reached. Under these conditions, the sample will remain vitreous for >3 min, which is more than enough time needed to perform the cryo-transfer step from the FIB to the cryostat, which takes only ∼10 s. Cryo-transmission electron microscopy images of a manipulated cryo-EXLO yeast specimen prepared with cryo-FIB corroborates the heat transfer analysis.

2.
J Immunoassay Immunochem ; 44(4): 326-337, 2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-36949573

RESUMO

Studying the expression of hematopoietic stem cell markers from different sources might be useful in understanding stem cell biology in different niche conditions. The study aimed to assess the difference in cell surface markers (CD44, CD90, CD96) on hematopoietic stem cells in three different niche conditions; umbilical cord blood (UCB), normal bone marrow (NBM) and bone marrow samples from idiopathic (immune) thrombocytopenic purpura (IBM). This study was conducted on 300 cases divided into three study groups; 100 umbilical cord blood units collected from mothers undergoing cesarian section in gynecology and obstetrics department, 100 bone marrow samples from idiopathic (immune) thrombocytopenic purpura patients collected from university children hospital and 100 normal bone marrow samples with no evidence of disease in bone marrow tissue. CD44 was significantly elevated in UCB and NBM groups compared to IBM group (<0.001). There was also a significant elevation of CD90 and CD96 in IBM group compared to NBM group and UCB (<0.001). CD90 and CD96 play a role in the pathogenesis of ITP disorder and could be applied as a targeted therapy to improve the outcome of this disease.


Assuntos
Púrpura Trombocitopênica Idiopática , Humanos , Antígenos CD , Receptores de Hialuronatos , Púrpura Trombocitopênica Idiopática/patologia , Antígenos Thy-1/genética
3.
Int J Mol Sci ; 24(6)2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36982733

RESUMO

Parthenocarpy and stenospermocarpy are the two mechanisms underlying the seedless fruit set program. Seedless fruit occurs naturally and can be produced using hormone application, crossbreeding, or ploidy breeding. However, the two types of breeding are time-consuming and sometimes ineffective due to interspecies hybridization barriers or the absence of appropriate parental genotypes to use in the breeding process. The genetic engineering approach provides a better prospect, which can be explored based on an understanding of the genetic causes underlying the seedlessness trait. For instance, CRISPR/Cas is a comprehensive and precise technology. The prerequisite for using the strategy to induce seedlessness is identifying the crucial master gene or transcription factor liable for seed formation/development. In this review, we primarily explored the seedlessness mechanisms and identified the potential candidate genes underlying seed development. We also discussed the CRISPR/Cas-mediated genome editing approaches and their improvements.


Assuntos
Edição de Genes , Vitis , Vitis/genética , Melhoramento Vegetal , Sementes/genética , Frutas/genética , Sistemas CRISPR-Cas/genética
4.
Saudi Pharm J ; 31(5): 706-726, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37181141

RESUMO

Chorisia (syn. Ceiba) species are important ornamental, economic, and medicinal plants that are endowed with a diversity of secondary metabolites; however, their volatile organic compounds (VOCs) have been scarcely studied. Therefore, this work explores and compares the headspace floral volatiles of three common Chorisia species, namely Chorisia chodatii Hassl., Chorisia speciosa A. St.-Hil, and Chorisia insignis H.B.K. for the first time. A total of 112 VOCs of varied biosynthetic origins were identified at different qualitative and quantitative ratios, encompassing isoprenoids, fatty acid derivatives, phenylpropanoids, and others. Flowers of the investigated species showed perceptibly differentiated volatile profiles, with those emitted by C. insignis being dominated by non-oxygenated compounds (56.69 %), whereas oxygenated derivatives prevailed among the volatiles of C. chodatii (66.04 %) and C. speciosa (71.53 %). The variable importance in the projection (VIP) in the partial least-squares-discriminant (PLS-DA) analysis described 25 key compounds among the studied species, of which linalool was verified as the most important aroma compound based on VIP values and significance analysis, and it could represent the most typical VOC among these Chorisia species. Furthermore, molecular docking and dynamics analyses of both the major and the key VOCs displayed their moderate to promising binding interactions with four main proteins of SARS-CoV-2, including Mpro, PLpro, RdRp, and spike S1 subunit RBD. The current results collectively cast new light on the chemical diversity of the VOCs of Chorisia plants as well as their chemotaxonomic and biological relevance.

5.
Inflammopharmacology ; 30(6): 2097-2106, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36085399

RESUMO

Piroxicam is used to treat the pain, swelling, and stiffness associated with osteoarthritis and rheumatoid arthritis, but it has many side effects, such as hypertension, elevation of liver enzymes, and hepatitis. This study used selenium-enriched probiotics to reduce the side effects of piroxicam on the liver and kidney tissues and functions. Forty-eight male albino mice were randomly assigned to control, piroxicam (P), piroxicam plus selenium-enriched Lactobacillus plantarum PSe40/60/1 (P + SP), piroxicam plus selenium-enriched Bifidobacterium longum BSe50/20/1 (P + SB), selenium-enriched L. plantarum PSe40/60/1 (SP), and selenium-enriched B. longum BSe50/20/1 (SB) groups. In this study, the function of the liver and kidney was biochemically determined; the histopathology of the liver and kidney tissues was microscopically examined and the expression of inflammatory and anti-inflammatory genes in liver and kidney tissues was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Liver and kidney functions were significantly reduced in the piroxicam group compared with control. Liver and kidney tissues were damaged in the piroxicam group while they appeared more or less normal in the SB group. The expression of inflammatory genes was significantly up-regulated in the liver and kidney tissues of the piroxicam group compared to the control group. The expression of anti-inflammatory genes was significantly down-regulated in the liver and kidney of the piroxicam group and up-regulated in the liver and kidney of the SB group compared to the control group. Therefore, these mutated strains of probiotics were useful in reducing the side effects of the piroxicam drug on the liver and kidney.


Assuntos
Probióticos , Selênio , Animais , Camundongos , Masculino , Selênio/farmacologia , Piroxicam/farmacologia , Probióticos/farmacologia , Fígado , Rim/metabolismo
6.
J Exp Bot ; 72(2): 371-384, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-32945838

RESUMO

Fruit development is orchestrated by a complex network of interactions between hormone signaling pathways. The phytohormone gibberellin (GA) is known to regulate a diverse range of developmental processes; however, the mechanisms of GA action in perennial fruit species are yet to be elucidated. In the current study, a GA signaling gene PslSLY1, encoding a putative F-box protein that belongs to the SLY1 (SLEEPY1)/GID2 (gibberellin-insensitive dwarf2) gene family, was isolated from Japanese plum (Prunus salicina). PslSLY1 transcript abundance declined as fruit development progressed, along with potential negative feedback regulation of PslSLY1 by GA. Subcellular localization and protein-protein interaction assays suggested that PslSLY1 functions as an active GA signaling component that interacts with the ASK1 (Arabidopsis SKP1) subunit of an SCF-ubiquitin ligase complex and with PslDELLA repressors, in a GA-independent manner. By using a domain omission strategy, we illustrated that the F-box and C-terminal domains of PslSLY1 are essential for its interactions with the downstream GA signaling components. PslSLY1 overexpression in wild-type and Arabidopsissly1.10 mutant backgrounds resulted in a dramatic enhancement in overall plant growth, presumably due to triggered GA signaling. This includes germination characteristics, stem elongation, flower structure, and fertility. Overall, our findings shed new light on the GA strategy and signaling network in commercially important perennial crops.


Assuntos
Proteínas de Arabidopsis , Proteínas F-Box , Prunus domestica , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas F-Box/genética , Proteínas F-Box/metabolismo , Frutas/genética , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Giberelinas , Mutação , Prunus domestica/metabolismo
7.
Arch Virol ; 166(4): 1071-1081, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33533976

RESUMO

Elimination of hepatitis C virus (HCV) may fail, leading to a non-response outcome because of inappropriate testing for viral RNA in peripheral blood mononuclear cells (PBMCs). Sequelae of HCV genotype 4 therapy with sofosbuvir and daclatasvir ± ribavirin were assessed in our study at the 12th week after end of treatment (EOT) by screening for viral genomic RNA in serum and PBMCs with correlation to hepatic parenchymal changes. We recruited 102 out of 2165 patients who had received sofosbuvir/daclatasvir, either alone (n = 1573) or together with ribavirin (n = 592). Subjects were classified into three groups based on testing by single-step reverse transcription PCR: group I, HCV negative in both serum and PBMCs (n = 25); group II, HCV positive in PBMCs only (n = 52); and group III, HCV positive in both serum and PBMCs (n = 25). Groups I and II (n = 77) were selected out of 2102 (every 27th subject), while group III (n = 25) were selected from every second or third serologic relapse (n = 63). The pre-sampling population (n = 2165) showed sustained virologic response (SVR) in 33.21%; serologic relapse in 2.91%; HCV RNA only in PBMCs (66.79%) compared to serologic relapses and potential cure (P < 0.0001); higher serologic (38 out of 63, P = 0.03210) and cellular (36 out of 52, P = 0.0002) relapses in dual therapy than in triple therapy. The post-sampling population (n = 102) showed more HCV relapses in dual (50 out of 60) than in triple (27 out of 42) therapy (P = 0.0351); increased HCV antisense RNA strand in relapses compared to positive-sense strands alone (P < 0.001); and significant SVR events in undetectable (15 out of 31) compared to early (10 out of 55, P = 0.0058) and cirrhotic liver tissue changes (0 out of 16, P = 0.0006). In summary, HCV treatment with sofosbuvir/daclatasvir is followed by higher rates of serologic and intracellular viral RNA relapse than treatment with sofosbuvir/daclatasvir plus ribavirin. Cellular and serum viral RNA relapses are accompanied by HCV-induced hepatic pathology. An increased SVR with no detectable liver tissue changes was observed after triple therapy due to elimination of HCV RNA from PBMCs.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , RNA Viral/efeitos dos fármacos , Ribavirina/uso terapêutico , Adulto , Carbamatos/uso terapêutico , Quimioterapia Combinada , Feminino , Hepacivirus/genética , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Humanos , Imidazóis/uso terapêutico , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/virologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Tecido Parenquimatoso/efeitos dos fármacos , Tecido Parenquimatoso/patologia , Pirrolidinas/uso terapêutico , RNA Viral/análise , Prevenção Secundária , Sofosbuvir/uso terapêutico , Resultado do Tratamento , Valina/análogos & derivados , Valina/uso terapêutico
8.
Mol Biol Rep ; 48(5): 4333-4340, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34080097

RESUMO

Diabetes is a metabolic disorder described as insufficient secretion of insulin in the pancreas or the inability of the existing insulin to function properly. It poses a greater risk on human health as it is considered the base of several diseases. Thus, this study was designed to evaluate two novel strains of Lactobacillus in handling pancreas disorders. 50 BALB/c male mice were divided into five groups; (a) feeding on normal diet only as control group, (b) given 21% fructose in drinking water as diabetes group, (c) feeding on Lactobacillus rhamnosus strain Pro2 (MT505335.1) plus 21% fructose as LR group, (d) feeding on Lactobacillus plantarum strain Pro1 (MT505334.1) plus 21% fructose as LP group and (e) mixture of two strains plus 21% fructose as Mix group. The serum content of glucose, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) was determined. Pancreases histopathology was examined. Expression of GH, IGF1, and GLP-1 genes was measured in the liver and pancreas by RT-qPCR. Serum content of glucose, ALT, and AST significantly increased in diabetes group, and significantly reduced in (LP) and (Mix) groups compared with control. Pathological changes occurred in the exocrine and endocrine components of the diabetes group pancreas. Besides, islet cells are almost entirely disturbed and acinar cells degenerated. However, in (LP) and (Mix) groups, the pathological changes significantly decreased and became related to the control group. Expression of GH, IGF1, and GLP-1 genes was significantly downregulated in the liver and pancreas of mice given fructose compared with control. Expression of these genes was either significantly upregulated in groups (LP and Mix) or identical to the control group. This study shows that the strain Pro1 (MT505334.1) or a combination of two strains is useful in reducing diabetic risk.


Assuntos
Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/dietoterapia , Frutose/efeitos adversos , Lacticaseibacillus rhamnosus , Lactobacillus plantarum , Probióticos/administração & dosagem , Substâncias Protetoras/administração & dosagem , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Glicemia/análise , Diabetes Mellitus/sangue , Diabetes Mellitus/genética , Dieta da Carga de Carboidratos/efeitos adversos , Expressão Gênica , Peptídeo 1 Semelhante ao Glucagon/genética , Hormônio do Crescimento/genética , Fator de Crescimento Insulin-Like I/genética , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pâncreas/metabolismo , Resultado do Tratamento
9.
Pediatr Surg Int ; 37(7): 937-944, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33839906

RESUMO

BACKGROUND: Swallowing multiple magnets or a magnet and second metallic object can carry risks of intestinal obstruction, fistula and perforation because they can attach to each other with loop of bowel in between. An updated management plan and reviewing our experience are warranted because of increased incidence of magnets ingestion among children. METHODS: All the patients who had a history of single, multiple magnet or single magnet and second metallic object ingestion in Bristol Royal Hospital for children during the period from January 2014 till November 2020 were included in our study. RESULTS: A total of 46 patients were referred to our hospital with a history of magnet ingestion. The number of magnets ingested ranged between one and twenty one magnets. All patients had abdominal x-ray undertaken either Antero-posterior alone (AP) (n = 32) or both AP and lateral (n = 14). Surgical intervention was performed in 18 patients; Oesophago-gastro-duodenoscopy (n = 8), laparotomy/laparoscpy (n = 10) to retrieve the magnets or deal with the complications. CONCLUSIONS: Magnets ingestion in children can be tricky when it comes to management. Complications can happen quite often and carry severe risks on children. An updated structured algorithm is proposed to manage children with magnet ingestion.


Assuntos
Algoritmos , Corpos Estranhos/complicações , Obstrução Intestinal/etiologia , Laparotomia/métodos , Imãs , Centros de Atenção Terciária , Criança , Pré-Escolar , Ingestão de Alimentos , Feminino , Corpos Estranhos/cirurgia , Humanos , Incidência , Obstrução Intestinal/cirurgia , Masculino
10.
Artif Organs ; 43(10): E249-E263, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31066923

RESUMO

Mechanical heart valve replacement is the preferred alternative in younger patients with severe symptomatic aortic valve disease. However, thrombus and pannus formations are common complications associated with bileaflet mechanical heart valves. This leads to risks of valve leaflet dysfunction, a life-threatening event. In this experimental study, we investigate, using time-resolved planar particle image velocimetry, the flow characteristics in the ascending aorta in the presence of a dysfunctional bileaflet mechanical heart valve. Several configurations of leaflet dysfunction are investigated and the induced flow disturbances in terms of velocity fields, viscous energy dissipation, wall shear stress, and accumulation of viscous shear stresses are evaluated. We also explore the ability of a new set of parameters, solely based on the analysis of the normalized axial velocity profiles in the ascending aorta, to detect bileaflet mechanical heart valve dysfunction and differentiate between the different configurations tested in this study. Our results show that a bileaflet mechanical heart valve dysfunction leads to a complex spectrum of flow disturbances with each flow characteristic evaluated having its own worst case scenario in terms of dysfunction configuration. We also show that the suggested approach based on the analysis of the normalized axial velocity profiles in the ascending aorta has the potential to clearly discriminate not only between normal and dysfunctional bilealfet heart valves but also between the different leaflet dysfunction configurations. This approach could be easily implemented using phase-contrast MRI to follow up patients with bileaflet mechanical heart valves.


Assuntos
Velocidade do Fluxo Sanguíneo , Doenças das Valvas Cardíacas/terapia , Próteses Valvulares Cardíacas , Aorta/fisiologia , Próteses Valvulares Cardíacas/efeitos adversos , Humanos , Desenho de Prótese , Estresse Mecânico , Trombose/etiologia
11.
Arch Virol ; 163(10): 2765-2774, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29971486

RESUMO

The disappearance of hepatitis C virus (HCV) from serum and tissues for 12 weeks after the end of treatment (EOT) with direct-acting antivirals (DAAs) is known as a "sustained virologic response" (SVR) and occurs more frequently in non-cirrhotic patients than in cirrhotic patients. In this study, we evaluated the outcome of HCV treatment with sofosbuvir (SOF) plus ledipasvir (LDV) at both EOT and 12 weeks after EOT in patients with and without hepatic cirrhosis to address the relationship of serologic relapse to persistent infection of PBMCs and the frequency of hepatic encephalopathy and hepatocellular carcinoma (HCC) after treatment. Seventy-five patients with post-HCV liver cirrhosis were assigned to one of three groups (A, B, and C), each of which included 25 patients and corresponded to the patients' Child-Turcotte-Pugh (CTP) classification. All of the patients received a daily dose of SOF (400 mg) plus LDV (90 mg) for 24 weeks and were tested using HCV single-strand reverse transcription (SRT) and PCR analysis of PBMCs at both EOT and 12 weeks after EOT. Fourteen (18.7%) out of 75 patients (all study populations) had intra-PBMC HCV RNA, but only nine of them (64.3%) developed HCV RNA serum relapse (seroconversion) 12 weeks after EOT (P < 0.001). Encephalopathy was significantly higher in group C at EOT and 12 weeks after EOT (P < 0.05). Development of HCC was observed in decompensated patients of group C (2 out of 5 = 40.0%) 12 weeks post-EOT (P = 0.03). In conclusion, detection of HCV RNA within PBMCs at the EOT provides an indication of potential relapse after 12 weeks. Moreover, development of encephalopathy and HCC after HCV eradication by SOF plus LDV therapy is perhaps a future warning for post-treatment hepatic decompensation in cirrhotic patients.


Assuntos
Antivirais/administração & dosagem , Benzimidazóis/administração & dosagem , Fluorenos/administração & dosagem , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Leucócitos Mononucleares/virologia , Cirrose Hepática/patologia , RNA Viral/sangue , Uridina Monofosfato/análogos & derivados , Adulto , Idoso , Feminino , Seguimentos , Genótipo , Hepacivirus/genética , Hepacivirus/imunologia , Hepatite C/sangue , Hepatite C/complicações , Hepatite C/virologia , Humanos , Cirrose Hepática/etiologia , Masculino , Pessoa de Meia-Idade , RNA Viral/genética , Recidiva , Sofosbuvir , Resposta Viral Sustentada , Uridina Monofosfato/administração & dosagem , Adulto Jovem
14.
Chem Pharm Bull (Tokyo) ; 64(4): 360-5, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27039833

RESUMO

Phytochemical investigation of the n-BuOH fraction of the mangrove plant Lumnitzera racemosa WILLD. (Combretaceae) led to the isolation of one new flavonoid glycoside; myrcetin 3-O-methyl glucuronate (1), one new phenolic glycoside; lumniracemoside (2) and one new aliphatic alcohol glycoside; n-hexanol 1-O-rutinoside (3), in addition to seven known compounds (4-10). The structures of these compounds were determined by spectroscopic analyses (UV, IR, high resolution-electrospray ionization (HR-ESI)-MS, one- and two-dimensional (1D- and 2D)-NMR). Compound 7 showed the highest hepatoprotective activity against acetaminophen-induced hepatotoxicity using human HepG2 cells at protection % value of 34.2±3.1%, while compounds 1, 2, 3, 6, and 9 showed weak to moderate hepatoprotective activity (11.6-18.9%). Almost all of these compounds showed stronger 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity compared with the standard Trolox. These results suggest the usefulness of this plant extract and the isolated compounds as promising hepatoprotective agents.


Assuntos
Acetaminofen/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Combretaceae/química , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Folhas de Planta/química , Células Hep G2 , Humanos , Técnicas In Vitro , Espectroscopia de Ressonância Magnética , Extratos Vegetais/isolamento & purificação , Espectroscopia de Infravermelho com Transformada de Fourier
15.
Cardiovasc Eng Technol ; 15(3): 374-381, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38228812

RESUMO

In vitro modeling of the left heart relies on accurately replicating the physiological conditions of the native heart. The targeted physiological conditions include the complex fluid dynamics coming along with the opening and closing of the aortic and mitral valves. As the mitral valve possess a highly sophisticated apparatus, thence, accurately modeling it remained a missing piece in the perfect heart duplicator puzzle. In this study, we explore using a hydrogel-based mitral valve that offers a full representation of the mitral valve apparatus. The valve is tested using a custom-made mock circulatory loop to replicate the left heart. The flow analysis includes performing particle image velocimetry measurements in both left atrium and ventricle. The results showed the ability of the new mitral valve to replicate the real interventricular and atrial flow patterns during the whole cardiac cycle. Moreover, the investigated valve has a ventricular vortex formation time of 5.2, while the peak e- and a-wave ventricular velocities was 0.9 m/s and 0.4 m/s respectively.


Assuntos
Hemodinâmica , Valva Mitral , Modelos Cardiovasculares , Valva Mitral/fisiopatologia , Valva Mitral/diagnóstico por imagem , Humanos , Função Ventricular Esquerda , Velocidade do Fluxo Sanguíneo , Hidrogéis , Função do Átrio Esquerdo , Desenho de Prótese , Reologia
16.
Artigo em Inglês | MEDLINE | ID: mdl-38652281

RESUMO

Notch pathway is a widely observed signaling system that holds pivotal functions in regulating various developmental cellular functions and operations. The Notch signaling mechanism is crucial for lung homeostasis, damage, and restoration. Based on increasing evidence, the Notch pathway has been identified, as critical for fibrosis and subsequently, the development of chronic fibroproliferative conditions in various organs and tissues. Recent research indicates that deregulation of Notch signaling correlates with the pathogenesis of significant pulmonary conditions, particularly chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, asthma, pulmonary arterial hypertension (PAH), lung carcinoma, and pulmonary abnormalities in some hereditary disorders. In various cellular and tissue environments, and across both physiological and pathological conditions, multiple consequences of Notch activation have been observed. Studies have ascertained that the Notch signaling cascade exhibits close associations with various other signaling systems. This study provides an updated overview of Notch signaling's role, especially its link to fibrosis and its potential therapeutic implications. This study sheds light on the latest findings regarding the mechanisms and outcomes of irregular or lacking Notch activity in the onset and development of pulmonary diseases. As our insight into this signaling mechanism suggests that modulating Notch signaling might hold potential as a valuable additional therapeutic approach in upcoming research.

17.
Plants (Basel) ; 13(11)2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38891319

RESUMO

This study was conducted for the comparative analysis of antioxidant activity and untargeted metabolomics of dark- and light-colored sour cherry cultivars grown in Canada. Based on our previous study, we selected four cultivars-'Heimann R', 'Gorsemska', V70142, and 'Montmorency'-to determine the untargeted metabolites and their role in antioxidant activities. A total of 473 metabolites were identified from four sour cherry genotypes using UPLC-ToF-MS. Untargeted metabolomics revealed the dominant chemical groups present in sour cherries. PCA showed that the diversity in sour cherry metabolites was due to the genotype differences indicating iditol, malic acid, chlorobenzene, 2-mercaptobenzothiazole, and pyroglutamic acid as the predominant contributors. The variable importance in the projection (VIP > 1.0) in partial least-squares-discriminant analysis described 20 biomarker metabolites representing the cherry metabolome profiles. A heatmap of Pearson's correlation analysis between the 20 biomarker metabolites and antioxidant activities identified seven antioxidant determinants that displayed the highest correlations with different types of antioxidant activities. TPC and TAC were evaluated using the Folin-Ciocalteu method. The total antioxidant activity was performed using three different assays (ABTS, FRAP, and DPPH). This study of correlating metabolomics and antioxidant activities elucidated that the higher nutritional value and biological functions of sour cherry genotypes can be useful for the development of nutraceutical and functional foods.

18.
Eur J Surg Oncol ; 50(7): 108447, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38843661

RESUMO

INTRODUCTION: Vulval cancer is a rare gynaecological malignancy. In this study, we present a tertiary centre case analysis to examine the recurrence patterns and survival outcomes of vulval squamous cell carcinoma (SCC). METHODS: This is a retrospective cohort study of women who received treatment at Oxford University Hospitals between February 2010 and July 2022 for primary vulval SCC. RESULTS: We included 98 cases. The median age at diagnosis was 68 years. Human Papillomavirus (HPV) infection and lichen sclerosis were observed in 21 and 50 cases, respectively. Surgical excision was the primary treatment. Recurrence within 2 years was more common with advanced stage (p = 0.047, RR = 2.26) and extracapsular lymph node spread (p = 0.013, RR = 2.88). Local recurrence was not associated with a specific cut-off value for tumour-free margin. Poor survival outcomes were observed with higher grade (p = 0.01), advanced FIGO stage (p < 0.001), HPV-independent cancer (p = 0.048), lymph node involvement (p < 0.001, HR = 7.14), extracapsular spread (p < 0.001, HR = 7.93), lymphovascular space invasion (p = 0.002, HR = 3.17), tumour diameter wider than 23 mm (p = 0.029, HR = 2.53) and depth of invasion more than 6 mm (p = 0.006, HR = 3.62). Perineural invasion is associated with shorter disease-free survival. Five-year cancer-specific survival rates for stages I, III, and IV were 90.2%, 40.8%, and 14.3%, respectively.


Assuntos
Carcinoma de Células Escamosas , Metástase Linfática , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Centros de Atenção Terciária , Neoplasias Vulvares , Humanos , Feminino , Neoplasias Vulvares/patologia , Neoplasias Vulvares/cirurgia , Neoplasias Vulvares/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Infecções por Papillomavirus/complicações , Idoso de 80 Anos ou mais , Adulto , Gradação de Tumores , Margens de Excisão , Invasividade Neoplásica
19.
Indian J Otolaryngol Head Neck Surg ; 76(1): 865-870, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38440643

RESUMO

Aim: to assess radiologically the prevalence of SSCD with its clinical presentations and its relationship with age. Methods: a prospective cohort study carried out on 200 consecutive patients (400 temporal bones). Radiological evaluation was performed using High Resolution Computed Tomography (HRCT) with measurement of thickness of bone covering superior semicircular canal (SCC), height and diameter of SSC. Results: Two hundred patients (400 temporal bones) were involved. The mean thickness ± SD, the mean diameter ± SD and the mean height ± SD were 1.38 ± 0.80 mm, 0.94 ± 0.26 mm and 10.91 ± 2.39 mm respectively. The prevalence of SSCD and predehiscence were 1% and 14% respectively. The commonest symptom encountered was autophony (48.3%). When the SSC thickness, diameter and height were compared with the age of patients, statistically significant differences were detected. The highest diameter, lowest height and lowest thickness were found in patients aged from 54 to 72 years. Thickness of bony layer covering SSC was found to be the most validated measurement for differentiation between cases with positive and negative symptoms with the highest sensitivity and specificity. Conclusion: The prevalence of SSCD and predehiscence varied among the studies. Autophony is the commonest symptom usually encountered. The condition is acquired rather than congenital. The thickness of bone covering SCC is the most validated measurement in differentiation between cases with positive and negative symptoms.

20.
Biol Trace Elem Res ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38321304

RESUMO

Increasing fertility rates have become one of the factors that concern all people in the world. Therefore, the study aims to use two mutated strains of probiotics enriched with selenium (PSe40/60/1 and BSe50/20/1) to improve fertility. Thirty Swiss albino male mice were divided into three groups; control, LP + S was given Lactobacillus plantarum PSe40/60/1 plus selenium, and BL + S was given Bifidobacterium longum BSe50/20/1 plus selenium. Free testosterone, LH, and FSH were measured in serum by biochemical analysis. Testicular tissues were examined by histopathological analysis. The count and motility of sperm, and sperm abnormalities were determined by microscopic examination. The method of qRT-PCR was used to detect gene expression of Tspyl1, Hsd3b6, and Star genes. The biochemical results showed that serum content of free testosterone (FT) hormone had significantly increase in the BL + S and LP + S groups compared with control. Levels of LH and FSH hormones were the highest in the BL + S group. The treated groups showed all developmental stages of spermatogenesis, including spermatogenesis, spermatocytes, and seminiferous tubule spermatids, as well as intact Sertoli cells and Leydig cells without changes. When compared to the control group, sperm count and motility increased in the BL + S group, while sperm abnormalities decreased. The expression of Tspyl1 gene in testicular tissues decreased in the LP + S and BL + S groups, while the expression of Star and Hsd3b6 genes was higher in the BL + S group and lower in the LP + S group compared with the control group. Therefore, Bifidobacterium longum BSe50/20/1 enriched with selenium could be useful in enhancing male fertility.

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