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1.
Int J Cancer ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38738971

RESUMO

Peroxiredoxin 1 (PRDX1) is an important member of the peroxiredoxin family (PRDX) and is upregulated in a variety of tumors. Previous studies have found that high PRDX1 expression is closely related to the metastasis of oral squamous cell carcinoma (OSCC), but the specific molecular mechanism is elusive. To elucidate the role of PRDX1 in the metastasis process of OSCC, we evaluated the expression of PRDX1 in OSCC clinical specimens and its impact on the prognosis of OSCC patients. Then, the effect of PRDX1 on OSCC metastasis and cytoskeletal reconstruction was explored in vitro and in nude mouse tongue cancer models, and the molecular mechanisms were also investigated. PRDX1 can directly interact with the actin-binding protein Cofilin, inhibiting the phosphorylation of its Ser3 site, accelerating the depolymerization and turnover of actin, promoting OSCC cell movement, and aggravating the invasion and metastasis of OSCC. In clinical samples and mouse tongue cancer models, PRDX1 also increased lymph node metastasis of OSCC and was negatively correlated with the phosphorylation of Cofilin; PRDX1 also reduced the overall survival rate of OSCC patients. In summary, our study identified that PRDX1 may be a potential therapeutic target to inhibit OSCC metastasis.

2.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(2): 279-283, 2024 Apr 18.
Artigo em Zh | MEDLINE | ID: mdl-38595245

RESUMO

OBJECTIVE: To investigate the incidence and risk factors of deep vein thrombosis (DVT) in patients with rheumatoid arthritis (RA). METHODS: The clinical data of RA patients who were hospi-talized in the Department of Rheumatology and Immunology of Aerospace Center Hospital from May 2015 to September 2021 was retrospectively analyzed, including demographic characteristics, concomitant diseases, laboratory examinations (blood routine, biochemistry, coagulation, inflammatory markers, rheumatoid factor, antiphospholipid antibodies and lupus anticoagulant, etc.) and treatment regimens. The patients were compared according to the presence or absence of DVT, and the t test, Mann-Whitney U test or Chi-square test were applied to screen for relevant factors for DVT, followed by Logistic regression analysis to determine risk factors for DVT in patients with RA. RESULTS: The incidence of DVT in the RA patients was 9.6% (31/322); the median age of RA in DVT group was significantly older than that in non-DVT group [64 (54, 71) years vs. 50 (25, 75) years, P < 0.001]; the level of disease activity score using 28 joints (DAS28)-erythrocyte sedimentation rate (ESR) in DVT group was higher than that in non-DVT group [5.2 (4.5, 6.7) vs. 4.5(4.5, 5.0), P < 0.001]; the incidence of hypertension, chronic kidney disease, fracture or surgery history within 3 months, and varicose veins of the lower extremities in DVT group was higher than that in non-DVT group (P < 0.001). The levels of hemoglobin and albumin in DVT group were significantly lower than that in non-DVT group (P=0.009, P=0.004), while the D-dimer level and rheumatoid factor positive rate in DVT group were significantly higher than that in non-DVT group (P < 0.001). The use rate of glucocorticoid in DVT group was higher than that in non-DVT group (P=0.009). Logistic regression analysis showed that the age (OR=1.093, P < 0.001), chronic kidney disease (OR=7.955, P=0.005), fracture or surgery history within 3 months (OR=34.658, P=0.002), DAS28-ESR (OR=1.475, P=0.009), and the use of glucocorticoid (OR=5.916, P=0.003) were independent risk factors for DVT in RA patients. CONCLUSION: The incidence of DVT in hospitalized RA patients was significantly increased, in addition to traditional factors, such as age and chronic kidney disease, increased DAS28-ESR level and the use of glucocorticoid were also independent risk factors for DVT.


Assuntos
Artrite Reumatoide , Fraturas Ósseas , Insuficiência Renal Crônica , Trombose Venosa , Humanos , Fator Reumatoide , Estudos Retrospectivos , Incidência , Glucocorticoides , Trombose Venosa/etiologia , Trombose Venosa/complicações , Artrite Reumatoide/complicações , Artrite Reumatoide/cirurgia , Fatores de Risco
3.
Mol Breed ; 43(6): 43, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37313220

RESUMO

Seed oil content is one of the most important quantitative traits in soybean (Glycine max) breeding. Here, we constructed a high-density single nucleotide polymorphism linkage map using two genetically similar parents, Heinong 84 and Kenfeng 17, that differ dramatically in their seed oil contents, and performed quantitative trait loci (QTL) mapping of seed oil content in a recombinant inbred line (RIL) population derived from their cross. We detected five QTL related to seed oil content distributed on five chromosomes. The QTL for seed oil content explained over 10% of the phenotypic variation over two years. This QTL was mapped to an interval containing 20 candidate genes, including a previously reported gene, soybean RING Finger 1a (RNF1a) encoding an E3 ubiquitin ligase. Notably, two short sequences were inserted in the GmRNF1a coding region of KF 17 compared to that of HN 84, resulting in a longer protein variant in KF 17. Our results thus provide information for uncovering the genetic mechanisms determining seed oil content in soybean, as well as identifying an additional QTL and highlighting GmRNF1a as candidate gene for modulating seed oil content in soybean. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01384-2.

4.
AAPS PharmSciTech ; 24(6): 145, 2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37353673

RESUMO

Dissolving microneedle (DMN) has been researched as a drug delivery technology that improves drug molecule transportation through the skin with little discomfort. However, the sluggish drug absorption, poor skin dissolution, and lengthy time lags of DMN have limited its potential uses. The aim of this study was to design a novel DMN system for the administration of the poorly water-soluble drug, estradiol (E2), with fast skin penetration and a stable release rate for a long time. DMN containing E2 emulsion (E2-EM-DMN) and traditional DMN (T-DMN) were prepared. Rat skin was used for penetration test and guinea pig skin was used for skin irritation experiment. The drug release profiles and stability properties of these two kinds of DMNs were also investigated. High performance liquid chromatography was employed to determine the E2 content in DMN. The E2 concentration in rat plasma was achieved by a newly developed liquid chromatography-mass spectrometry method that was fast, reproducible, and specific. The height of E2-EM-DMN and T-DMN was 600 µm. The drug loading of the E2-EM-DMN and T-DMN was 667.30 ± 7.21 µg/patch and 672.56 ± 6.98 µg/patch. E2-EM-DMN possessed enough mechanical strength to penetrate the skin and caused no irritation to the skin. E2-EM-DMN could release the drug more rapidly and more continuously than T-DMN. E2-EM-DMN had good pharmaceutical stability. In summary, the E2-EM-DMN showed reliable quality and superior release performance. Emulsion-embedded DMN is an ideal transdermal delivery system for drugs.


Assuntos
Estradiol , Pele , Ratos , Animais , Estradiol/farmacologia , Preparações de Ação Retardada/farmacologia , Emulsões/farmacologia , Administração Cutânea , Sistemas de Liberação de Medicamentos/métodos , Inflamação , Agulhas
5.
Chem Biodivers ; 19(8): e202200039, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35794072

RESUMO

A series of novel pathalide-1,2,4-oxadiazole analogs were synthesized for discovering novel anti-inflammatory agents. After the assessment of their cytotoxicity in vitro, all compounds had been screened for their anti-inflammatory activity by evaluating their inhibitory effect on LPS-induced NO production in RAW 264.7 macrophages. SARs had been concluded, and finally compound E13 was found to be the most potent compound. This compound could also significantly decrease the production of iNOS and COX-2. Preliminary mechanism studies indicated that compound E13 could inhibit the TLR4/NF-κB and ERK/p38 signaling pathways. These findings indicate that E13 holds great potential to be a lead compound for discovering novel anti-inflammatory drugs.


Assuntos
Benzofuranos , Oxidiazóis , Animais , Anti-Inflamatórios/farmacologia , Lipopolissacarídeos/farmacologia , Camundongos , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Oxidiazóis/farmacologia , Células RAW 264.7
6.
Int J Mol Sci ; 23(19)2022 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-36232577

RESUMO

Soybeans are essential crops that supply protein and oil. The composition and contents of soybean fatty acids are relevant to human health and have a significant relationship with soybean oil processing and applications. Identifying quantitative trait locus (QTL) genes related to palmitic acid could facilitate the development of a range of nutritive soybean cultivars using molecular marker-assisted selection. In this study, we used a cultivar with higher palmitic acid content, 'Dongnong42', and a lower palmitic acid content cultivar, 'Hobbit', to establish F2:6 recombinant inbred lines. A high-density genetic map containing 9980 SLAF markers was constructed and distributed across 20 soybean chromosomes. The genetic map contained a total genetic distance of 2602.58 cM and an average genetic distance of 0.39 cM between adjacent markers. Two QTLs related to palmitic acid content were mapped using inclusive composite interval mapping, explaining 4.2-10.1% of the phenotypic variance in three different years and environments, including the QTL included in seed palmitic 7-3, which was validated by developing SSR markers. Based on the SNP/Indel and significant differential expression analyses of Dongnong42 and Hobbit, two genes, Glyma.15g119700 and Glyma.15g119800, were selected as candidate genes. The high-density genetic map, QTLs, and molecular markers will be helpful for the map-based cloning of palmitic acid content genes. These could be used to accelerate breeding for high nutritive value cultivars via molecular marker-assisted breeding.


Assuntos
Glycine max , Óleo de Soja , Ácidos Graxos , Genótipo , Humanos , Ácido Palmítico , Fenótipo , Melhoramento Vegetal , Polimorfismo de Nucleotídeo Único , Óleo de Soja/genética , Glycine max/genética
7.
Mol Pharm ; 18(12): 4531-4542, 2021 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-34739255

RESUMO

Having benefited from the combination of different therapeutic modalities, functionalized nanoplatforms with synergistic strategies have aroused great interest in anticancer treatment. Herein, an engineered, a biodegradable hollow mesoporous organosilica nanoparticle (HMON)-based nanoplatform was fabricated for photothermal-enhanced chemotherapy of tumor. For the first time, we demonstrated that HMONs could serve as nanocarriers for co-delivering of both the paclitaxel and photothermal agent new indocyanine green (IR820), denoted as Paclitaxel/IR820@ HMONs-PEG. The as-prepared nanosystem exhibited a high paclitaxel-loading capacity of 28.4%, much higher than most paclitaxel-loaded nanoformulations. Furthermore, incorporating thioether bonds (S-S) into the HMONs' framework endowed them with GSH-responsive biodegradation behavior, leading to the controllable release of drugs under a tumor reducing microenvironment, and hindered the premature release of paclitaxel. Upon being irradiated with an NIR laser, the obtained co-delivery nanosystem exhibited great photothermal properties generated from IR820. The fabricated nanocomposites could significantly suppress tumor growth under NIR laser irradiation, as validated by in vitro and in vivo assessments. Combined with outstanding biocompatibility, the constructed nanosystem holds great potential in combinational antitumor therapy.


Assuntos
Sistemas de Liberação de Medicamentos , Nanopartículas/química , Neoplasias Experimentais/tratamento farmacológico , Compostos de Organossilício/química , Paclitaxel/química , Fototerapia/métodos , Animais , Liberação Controlada de Fármacos , Feminino , Glutationa/metabolismo , Hipertermia Induzida , Camundongos , Camundongos Endogâmicos BALB C , Paclitaxel/farmacocinética , Paclitaxel/uso terapêutico , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
8.
Biochem Cell Biol ; 97(4): 406-414, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30475650

RESUMO

Compound K [C-K; 20-O-(ß-d-glucopyranosyl)-20(S)-protopanaxadiol], as a metabolite of ginsenoside, has been verified to have antitumor effects in various cancers, including non-small cell lung cancer (NSCLC). However, the detailed mechanisms of C-K in NSCLC remain largely unknown. In this study, we aimed to evaluate the effect of C-K on apoptosis and autophagy in NSCLC cells as well as its related mechanisms. According to the results, C-K suppressed the proliferation, and led to G1 phase arrest and apoptosis in A549 and H1975 cells. Subsequently, C-K promoted autophagy, as confirmed by the enhanced rate of cells staining positive with acridine orange, increased levels of LC3II and Beclin-1, and with decreased levels of p62 in A549 and H1975 cells. Moreover, 3-methyladenine (3-MA; an inhibitor of autophagy) effectively suppressed the inhibition of proliferation and apoptosis that was induced with C-K. Finally, C-K treatment promoted the activation of the AMPK-mTOR and c-Jun N-terminal kinase (JNK) signaling pathways. Treatment with compound C (AMPK inhibitor) or SP600125 (JNK inhibitor) significantly restrained the inhibition of proliferation, apoptosis, and autophagy induced with C-K in A549 and H1975 cells. In conclusion, this study demonstrates that C-K promotes autophagy-mediated apoptosis in NSCLC via AMPK-mTOR and JNK signaling pathways.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Ginsenosídeos/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Serina-Treonina Quinases TOR/metabolismo , Células A549 , Antineoplásicos/química , Antineoplásicos/metabolismo , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Ginsenosídeos/química , Ginsenosídeos/metabolismo , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Conformação Molecular , Relação Estrutura-Atividade
9.
Org Biomol Chem ; 17(3): 573-584, 2019 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-30574975

RESUMO

Without employing any transition metal, a highly enantioselective α-alkylation of cyclic ß-keto esters and ß-keto amides has been realized by phase-transfer catalysis. This improved procedure is applicable to different kinds of halides with cinchona derivatives and gives the corresponding products in excellent enantiopurities (up to 98% ee) and good yields (up to 98%). Moreover, the reaction was scalable and the phase-transfer catalyst was recyclable. This provided an alternative and competitive method to the asymmetric α-alkylation of ß-dicarbonyl compounds.

10.
Org Biomol Chem ; 17(34): 7938-7942, 2019 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-31417995

RESUMO

A series of C-2' modified cinchonine-derived phase-transfer catalysts were synthesized and used in the enantioselective photo-organocatalytic aerobic oxidation of ß-dicarbonyl compounds with excellent yields (up to 97%) and high enantioselectivities (up to 90% ee). Furthermore, the reaction was carried out in a flow photomicroreactor, in which the heterogeneous gas-liquid-liquid asymmetric photocatalytic oxidation reaction was performed affording good yields (up to 97%) and enantioselectivities (up to 86% ee) within 0.89 min.

11.
BMC Nephrol ; 20(1): 277, 2019 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-31337345

RESUMO

BACKGROUND: Alport syndrome is a rare genetic kidney disease, and rheumatoid arthritis as a common autoimmune disease also causes renal lesions in addition to arthritis. The overlap of them has rarely been reported. CASE PRESENTATION: A 44-year-old man had a history of multi-joint swelling and pain for more than half a year. His laboratory data with double positive for rheumatoid factor and anticitrullinated protein antibodies further supported the diagnosis of early rheumatoid arthritis. His previous medical history including progressive hearing loss for several years and microhematuria for one year attracted our attention. Renal biopsy showed thin basement membrane nephropathy and lymphocytes infiltration of interstitium. To make a precise diagnosis, targeted Next Generation Sequencing (NGS) of an inherited renal disease panel including Alport syndrome genes was performed, which revealed the missense mutation in COL4A5 (c.1351 T > C, p.Cys451Arg). Further in silico analyses predicted that the p. Cys451Arg mutation is functionally "damaging", so the diagnosis of Alport syndrome was finally proved. The patient has been receiving the treatment of total glucosides of paeony and leflunomide for rheumatoid arthritis, and Cozaar 50 mg for the protection of kidney so far. During the 10-months follow-up, swelling and tenderness of the joints in this patient had been generally relieved, with no obvious improvement in microhematuria and a slight increase in proteinuria. CONCLUSION: we reported an adult man with the coexistence of rheumatoid arthritis and Alport syndrome with the missense mutation in COL4A5 (c.1351 T > C, p.Cys451Arg). Whether the overlap of them is occasional or has a common pathophysiological mechanism is still unclear.


Assuntos
Artrite Reumatoide/complicações , Nefrite Hereditária/complicações , Adulto , Humanos , Masculino , Nefrite Hereditária/diagnóstico
12.
Extremophiles ; 22(3): 525-535, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29476252

RESUMO

Fungal communities represent an indispensable part of the geothermal spring ecosystem; however, studies on fungal community within hot springs are still scant. Here, we used Illumina HiSeq 2500 sequencing to detect fungal community diversity in extremely acidic hot springs (pH < 4) and neutral and alkaline springs (pH > 6) of Tengchong-indicated by the presence of over 0.75 million valid reads. These sequences were phylogenetically assigned to 5 fungal phyla, 67 order, and 375 genera, indicating unexpected fungal diversity in the hot springs. The genera such as Penicillium, Entyloma, and Cladosporium dominated the fungal community in the acidic geothermal springs, while the groups such as Penicillium, Engyodontium, and Schizophyllum controlled the fungal assemblages in the alkaline hot springs. The alpha-diversity indices and the abundant fungal taxa were significantly correlated with physicochemical factors of the hot springs particularly pH, temperature, and concentrations of Fe2+, NH4+, NO 2-, and S2-, suggesting that the diversity and distribution of fungal assemblages can be influenced by the complex environmental factors of hot springs.


Assuntos
Fungos/isolamento & purificação , Fontes Termais/microbiologia , Microbiota , Ácidos/análise , Álcalis/análise , Amônia/análise , Amônia/metabolismo , Fungos/classificação , Fungos/metabolismo , Fontes Termais/química , Ferro/análise , Ferro/metabolismo , Enxofre/análise , Enxofre/metabolismo
13.
J Org Chem ; 83(4): 2263-2273, 2018 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-29360355

RESUMO

An efficient and enantioselective α-benzoyloxylation of ß-keto esters has been achieved by phase-transfer catalysis. This simple catalytic procedure is applicable to a range of ß-keto esters with cinchona-derived N-oxide asymmetric phase-transfer catalysts and gives the corresponding products in good enantiopurity (up to 95% ee) and yield (up to 99%). This simple and effective oxyfunctionalization is a useful synthetic strategy for introducing an oxygen-containing functional group at the α position of ß-dicarbonyl compounds.

14.
J Org Chem ; 83(21): 13051-13062, 2018 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-30285439

RESUMO

An aerobic photoepoxidation of α,ß-unsaturated ketones driven by visible light in the presence of tetramethylguanidine (3b), tetraphenylporphine (H2TPP), and molecular oxygen under mild conditions was revealed. The corresponding α,ß-epoxy ketones were obtained in yields of up to 94% in 96 h. The reaction time was shortened to 4.6 h by flow synthesis. The mechanism related to singlet oxygen was supported by experiments and density functional theory (DFT) calculations.

15.
J Exp Bot ; 68(3): 469-482, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28204559

RESUMO

Cell wall invertase (CWI) and vacuolar invertase (VI) play multiple functions in plant growth. As well as depending on transcriptional and post-transcriptional regulation, there is growing evidence that CWI and VI are also subject to post-translational control by small inhibitory proteins. Despite the significance of this, genes encoding inhibitors, their molecular and biochemical properties, and their potential roles in regulating seed production have not been well documented in soybean (Glycine max). In this study, two invertase inhibitor isoforms, GmCIF1 and GmC/VIF2, were characterized to possess inhibitory activities in vitro via heterologous expression. Transcript analyses showed that they were predominantly expressed in developing seeds and in response to ABA. In accordance with this, surveys of primary targets showed subcellular localizations to the apoplast in tobacco epidermis after expressing YFP-fusion constructs. Investigations using RNAi transgenic plants demonstrated marked elevations of CWI activities and improvements in seed weight in conjunction with higher accumulations of hexoses, starch, and protein in mature seeds. Further co-expression analyses of GmCIF1 with several putative CWI genes corroborated the notion that GmCIF1 modulation of CWI that affects seed weight is mainly contingent on post-translational mechanisms. Overall, the results suggest that post-translational elevation of CWI by silencing of GmCIF1 expression orchestrates the process of seed maturation through fine-tuning sucrose metabolism and sink strength.


Assuntos
Regulação da Expressão Gênica de Plantas , Glycine max/fisiologia , Proteínas de Plantas/genética , Sementes/fisiologia , beta-Frutofuranosidase/genética , Sequência de Aminoácidos , Proteínas de Plantas/química , Proteínas de Plantas/metabolismo , Alinhamento de Sequência , Glycine max/genética , beta-Frutofuranosidase/química , beta-Frutofuranosidase/metabolismo
16.
J Org Chem ; 81(16): 7042-50, 2016 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-27336753

RESUMO

A series of cinchona-derived N-oxide asymmetric phase-transfer catalysts were synthesized and applied in the enantioselective photo-organocatalytic α-hydroxylation of ß-keto esters and ß-keto amides (23 examples) using molecular oxygen in excellent yields (up to 98%) and high enantioselectivities (up to 83% ee). These new catalysts could be recycled and reused six times for such a reaction with almost the original reactivity and enantioselectivity.

17.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 40(11): 1246-52, 2015 Nov.
Artigo em Zh | MEDLINE | ID: mdl-26643430

RESUMO

OBJECTIVE: To explore the clinical value of virtual touch tissue quantification (VTQ) technique and the PGA index [prothrombin time (P), γ-glutamyl transpeptadase (GG) and apolipoprotein A1 (ApoAl)] in evaluating the degree of liver fibrosis in alcoholic patients.
 METHODS: A total of 64 patients with long-term alcohol history were enrolled for this study. The liver ultrasonography elasticity was examined by VTQ techniques, the VTQ value was assessed in the liver target region, and then the PGA index was calculated. According the liver biopsy biological results, a golden standard, the patients were divided into a non-fibrosis group (n=11), a fibrosis group (n=10), a significant fibrosis group (n=14) and a cirrhosis group (n=29). The diagnostic value of VTQ and PGA index were compared in alcoholic patients following the classification of liver fibrosis.
 RESULTS: The elastography VTQ values were (1.38±0.33), (1.49±0.30), (1.76±0.22) and (2.28±0.53) m/s; while the PGA indexes were 2.09±0.94, 2.30±1.06, 3.57±1.09, and 2.21±1.99 in the non-fibrosis group, the fibrosis group, the significant fibrosis group and the cirrhosis group, respectively. The VTQ value and PGA index were positively correlated with the classification of liver fibrosis (VTG: r=0.719, PGA: r=0.683; both P<0.01).
 CONCLUSION: The alcoholic liver fibrosis can be assessed by noninvasive VTQ technology and PGA index. As a real-time ultrasound elastography technique, VTQ is more accurate than the PGA index. Combination of the two methods is helpful for early diagnosis and treatment in the patients with alcoholic liver fibrosis.


Assuntos
Técnicas de Imagem por Elasticidade , Cirrose Hepática Alcoólica/diagnóstico por imagem , Apolipoproteína A-I/metabolismo , Biópsia , Humanos , Cirrose Hepática Alcoólica/classificação , Valor Preditivo dos Testes , Tempo de Protrombina , Reprodutibilidade dos Testes , gama-Glutamiltransferase/metabolismo
18.
Heliyon ; 10(5): e26415, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38449650

RESUMO

Skin cancer is a prevalent form of cancer that necessitates prompt and precise detection. However, current diagnostic methods for skin cancer are either invasive, time-consuming, or unreliable. Consequently, there is a demand for an innovative and efficient approach to diagnose skin cancer that utilizes non-invasive and automated techniques. In this study, a unique method has been proposed for diagnosing skin cancer by employing an Xception neural network that has been optimized using Boosted Dipper Throated Optimization (BDTO) algorithm. The Xception neural network is a deep learning model capable of extracting high-level features from skin dermoscopy images, while the BDTO algorithm is a bio-inspired optimization technique that can determine the optimal parameters and weights for the Xception neural network. To enhance the quality and diversity of the images, the ISIC dataset is utilized, a widely accepted benchmark system for skin cancer diagnosis, and various image preprocessing and data augmentation techniques were implemented. By comparing the method with several contemporary approaches, it has been demonstrated that the method outperforms others in detecting skin cancer. The method achieves an average precision of 94.936%, an average accuracy of 94.206%, and an average recall of 97.092% for skin cancer diagnosis, surpassing the performance of alternative methods. Additionally, the 5-fold ROC curve and error curve have been presented for the data validation to showcase the superiority and robustness of the method.

19.
J Mol Histol ; 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38758520

RESUMO

Hypoxia is a key trigger in the transformation of oral leukoplakia into oral cancer. However, it is still too early to determine the role of hypoxia in the development of oral leukoplakia. Prx1, an antioxidant protein, upregulated by hypoxia, regulates cellular autophagy in leukoplakia. This study aimed to understand the mechanisms by which hypoxia induces Prx1 expression during autophagy in oral leukoplakia. We used an experimental model of tongue epithelial hyperplasia induced by 4-nitroquinoline-1-oxide (4NQO) and dysplastic oral keratinocytes. Prx1 knockdown DOK cells, Leuk-1 cells and control cells were harvested, and cell proliferation was assayed using the Cell Counting Kit-8. Several hypoxia and autophagy-related proteins were examined using quantitative real-time polymerase chain reaction, immunohistochemistry, immunofluorescence, and western blotting in cells and mouse tongue tissues. In addition, the ultrastructure of the cells was observed by transmission electron microscopy. Hypoxia induces cell proliferation, autophagic vesicles and the expression of Prx1, BNIP3, LC3II/I and Beclin-1 in DOK and Leuk-1 cells. However, these effects were all attenuated by Prx1 knockdown. Histologically, 4NQO induced epithelial hyperplasia in the tongue mucosa. The expression of proliferation marker PCNA, autophagy-related proteins LC3B and Beclin-1, as well as HIF-1α/BNIP3 was significantly lower in the tongue tissues of Prx1flox/flox:Cre+ mice compared with Prx1flox/flox mice. In Prx1flox/flox:Cre+ mice, an increased expression of HIF-1α/BNIP3, LC3B and Beclin-1 was detected in epithelial hyperplasia tongue tissues compared to normal tissues. The current study suggests that Prx1 may promotes cell proliferation and autophagy in oral leukoplakia cells via the HIF-1α/BNIP3 pathway.

20.
Pathol Res Pract ; 260: 155411, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38936092

RESUMO

BACKGROUND: Oral leukoplakia (OLK) is the most common oral potentially malignant disorder (OPMD), which can be malignantly transformed into oral squamous cell carcinoma (OSCC). Peroxiredoxin1(Prx1) has been predicted to bind to Prohibitin2 (PHB2), which confers to affect OLK progression; however, the mechanism of Prx1/PHB2 mediated mitophagy involved in OLK remains unclear. METHODS: This study aimed to explore the mechanism of the Prx1/PHB2 axis on senescence in OLK through mediating mitophagy. The positive rate of Ki67 and the expression of p21, p16, PHB2, and LC3 in human normal, OLK, and OSCC tissues were detected by immunohistochemical staining. The mitophagy and mitochondrial function changes were then analyzed in Prx1 knockdown and Prx1C52S mutations in dysplastic oral keratinocyte (DOK) cells treated with H2O2. In situ Proximity Ligation Assay combined with co-immunoprecipitation was used to detect the interaction between Prx1 and PHB2. RESULTS: Clinically, the positive rate of Ki67 progressively increased from normal to OLK, OLK with dysplasia, and OSCC. Higher p21, p16, PHB2, and LC3 expression levels were observed in OLK with dysplasia than in normal and OSCC tissues. In vitro, PHB2 and LC3II expression gradually increased with the degree of DOK cell senescence. Prx1/PHB2 regulated mitophagy and affected senescence in H2O2-induced DOK cells. Furthermore, Prx1C52S mutation specifically reduced interaction between Prx1 and PHB2. Prx1Cys52 is associated with mitochondrial reactive oxygen species (ROS) accumulated and cell cycle arrest. CONCLUSION: Prx1Cys52 functions as a redox sensor that binds to PHB2 and regulates mitophagy in the senescence of OLK, suggesting its potential as a clinical target.

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