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1.
Colloids Surf B Biointerfaces ; 244: 114192, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39226847

RESUMO

Medin amyloid, prevalent in the vessel walls of 97 % of individuals over 50, contributes to arterial stiffening and cerebrovascular dysfunction, yet our understanding of its aggregation mechanism remains limited. Dividing the full-length 50-amino-acid medin peptide into five 10-residue segments, we conducted individual investigations on each segment's self-assembly dynamics via microsecond-timescale atomistic discrete molecular dynamics (DMD) simulations. Our findings showed that medin1-10 and medin11-20 segments predominantly existed as isolated unstructured monomers, unable to form stable oligomers. Medin31-40 exhibited moderate aggregation, forming dynamic ß-sheet oligomers with frequent association and dissociation. Conversely, medin21-30 and medin41-50 segments demonstrated significant self-assembly capability, readily forming stable ß-sheet-rich oligomers. Residue pairwise contact frequency analysis highlighted the critical roles of residues 22-26 and 43-49 in driving the self-assembly of medin21-30 and medin41-50, acting as the ß-sheet core and facilitating ß-strand formation in other regions within medin monomers, expecting to extend to oligomers and fibrils. Regions containing residues 22-26 and 43-49, with substantial self-assembly abilities and assistance in ß-sheet formation, represent crucial targets for amyloid inhibitor drug design against aortic medial amyloidosis (AMA). In summary, our study not only offers deep insights into the mechanism of medin amyloid formation but also provides crucial theoretical and practical guidance for future treatments of AMA.


Assuntos
Amiloide , Simulação de Dinâmica Molecular , Humanos , Amiloide/química , Amiloide/metabolismo , Aorta/metabolismo , Agregados Proteicos , Peptídeos/química , Peptídeos/metabolismo , Conformação Proteica em Folha beta , Antígenos de Superfície/metabolismo , Antígenos de Superfície/química , Sequência de Aminoácidos , Proteínas do Leite
2.
Int J Mol Sci ; 25(17)2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39273591

RESUMO

GRK2 and arrestin3, key players in the functional regulation of G protein-coupled receptors (GPCRs), are ubiquitinated by Mdm2, a nuclear protein. The agonist-induced increase in arrestin3 ubiquitination occurs in the nucleus, underscoring the crucial role of its nuclear translocation in this process. The ubiquitination of arrestin3 occurs in the nucleus, highlighting the pivotal role of its nuclear translocation in this process. In contrast, GRK2 cannot translocate into the nucleus; thus, facilitation of the cytosolic translocation of nuclear Mdm2 is required to ubiquitinate GRK2 in the cytosol. Among the explored cellular components and processes, arrestin, Gßγ, clathrin, and receptor phosphorylation were found to be required for the nuclear import of arrestin3, the ubiquitination of arrestin3 in the nucleus, nuclear export of Mdm2, and the ubiquitination of GRK2 in the cytosol. In conclusion, our findings demonstrate that agonist-induced ubiquitination of arrestin3 in the nucleus is interconnected with cytosolic GRK2 ubiquitination.


Assuntos
Transporte Ativo do Núcleo Celular , Núcleo Celular , Citosol , Quinase 2 de Receptor Acoplado a Proteína G , Proteínas Proto-Oncogênicas c-mdm2 , Ubiquitinação , Proteínas Proto-Oncogênicas c-mdm2/metabolismo , Humanos , Citosol/metabolismo , Quinase 2 de Receptor Acoplado a Proteína G/metabolismo , Núcleo Celular/metabolismo , Fosforilação , Arrestinas/metabolismo , Células HEK293 , Animais
3.
J Hazard Mater ; 477: 135327, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39111180

RESUMO

The widespread occurrence of Microplastics (MPs) has aroused increasing concerns. However, the fate of MPs in remote areas remains poorly understood. Here, the spatial distribution, potential sources, and environmental risks of MPs were analyzed in the headstream of the Yellow River on the eastern Tibetan Plateau. The average MP abundances are (464.3 ± 200.9) items /m3 and (63.6 ± 34.7) items /kg in the water and sediment, respectively, with both majority polymer is polypropylene (PP) (water: 28.7 %; sediment: 25.2 %). The structural equation modeling and conditional fragmentation model were used in this study to analyze the source and impact factors of riverine MPs. According to the models, MPs were influenced by water quality parameters and anthropogenic activities. Furthermore, the source analysis through MP characteristics and statistical analysis showed that the main sources of MPs include domestic sewage, plastic waste disposal, and the use of agricultural plastic film. Moreover, the differences in MP sources along the river were distinguished by the conditional fragmentation model. The potential ecological risks of MPs were evaluated, resulting in relatively medium-to-low levels. Our findings will serve as important references for improving the understanding of the plateau environmental impacts of MP distribution in the headwaters of large rivers.

4.
Transplant Proc ; 56(6): 1436-1445, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38972762

RESUMO

BACKGROUND: Liver injury post allogeneic hematopoietic stem cell transplantation (Allo-HSCT), particularly first-time occurrences, is a prevalent and severe complication. METHODS: Clinical data from 262 patients treated at 3 medical centers in Shenzhen, China, between January 2018 and December 2021 were retrospectively collected. Risk factors and outcomes of initial liver injury post allo-HSCT were analyzed. RESULTS: Liver injury occurred in 70.8% of patients, with drug-induced liver injury (DILI) being the most common cause. Other causes included graft-versus-host disease (GVHD) and veno-occlusive disease (VOD). Pre-transplant HBsAg positivity was a significant risk factor. Differences in the timing and survival outcomes were observed among patients with different causes and types of liver injury. Patients with VOD or hepatic aGVHD had lower overall survival compared to those with DILI or hepatic cGVHD. Patients with isolated enzyme elevation had a more favorable prognosis than those with isolated bilirubin elevation or simultaneous enzyme and bilirubin elevation. CONCLUSION: Findings of our study serve as a crucial resource for clinicians, assisting in the challenging task of diagnosing and managing liver injuries after allo-HSCT, especially when it occurs for the first time, which may ultimately help to reduce early treatment-related mortality and enhance the long-term survival of transplant recipients.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos , Masculino , Feminino , Adulto , Doença Enxerto-Hospedeiro/etiologia , Pessoa de Meia-Idade , Prognóstico , Incidência , Fatores de Risco , China/epidemiologia , Adolescente , Adulto Jovem , Transplante Homólogo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Hepatopatia Veno-Oclusiva/etiologia , Criança
5.
Expert Rev Gastroenterol Hepatol ; 18(7): 339-349, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39031456

RESUMO

INTRODUCTION: Ulcerative colitis (UC) is a chronic, nonspecific inflammatory disease of the intestine. The intestinal microbiota is essential in the occurrence and development of UC. Gut gases are produced via bacterial fermentation or chemical interactions, which can reveal altered intestinal microbiota, abnormal cellular metabolism, and inflammation responses. Recent studies have demonstrated that UC patients have an altered gut gas metabolism. AREAS COVERED: In this review, we integrate gut gas metabolism advances in UC and discuss intestinal gases' clinical values as new biomarkers or therapeutic targets for UC, providing the foundation for further research. Literature regarding gut gas metabolism and its significance in UC from inception to October 2023 was searched on the MEDLINE database and references from relevant articles were investigated. EXPERT OPINION: Depending on their type, concentration, and volume, gut gases can induce or alleviate clinical symptoms and regulate intestinal motility, inflammatory responses, immune function, and oxidative stress, significantly impacting UC. Gut gases may function as new biomarkers and provide potential diagnostic or therapeutic targets for UC.


Assuntos
Biomarcadores , Colite Ulcerativa , Microbioma Gastrointestinal , Humanos , Colite Ulcerativa/metabolismo , Colite Ulcerativa/microbiologia , Colite Ulcerativa/fisiopatologia , Microbioma Gastrointestinal/fisiologia , Biomarcadores/metabolismo , Gases/metabolismo , Animais , Estresse Oxidativo , Fermentação
6.
Biochem Pharmacol ; 226: 116362, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38871335

RESUMO

AKT, also known as protein kinase B (PKB), serves as a crucial regulator of numerous biological functions, including cell growth, metabolism, and tumorigenesis. Increasing evidence suggests that the kinase activity of AKT is regulated via ubiquitination by various E3 ligase enzymes in response to different stimuli. However, the molecular mechanisms underlying insulin-induced AKT ubiquitination are not yet fully understood. Here, we show that activation of the insulin receptor (IR) leads to enhanced ubiquitination of AKT1 at K8 and K14 residues, facilitated by the cytosolic E3 ubiquitin ligase enzyme, TRAF6. Further investigation using AKT1 mutants with modified nucleocytoplasmic shuttling properties reveals that TRAF6-mediated AKT1 ubiquitination occurs within the nucleus in a ß-Arr2-dependent manner. The nuclear entry of TRAF6 depends on importin ß1, while ß-Arr2 regulates this process by facilitating the interaction between TRAF6 and importin ß1. Additionally, the ubiquitination of AKT1 is essential for its translocation to the activated IR on the plasma membrane, where it plays a functional role in recruiting Glut4 and facilitating glucose uptake. This study uncovers the cellular components and processes involved in insulin-induced ubiquitination and activation of AKT1, providing insights and detailed strategies for manipulating AKT1.


Assuntos
Núcleo Celular , Insulina , Proteínas Proto-Oncogênicas c-akt , Fator 6 Associado a Receptor de TNF , Ubiquitinação , beta-Arrestina 2 , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ubiquitinação/fisiologia , Ubiquitinação/efeitos dos fármacos , Insulina/metabolismo , Insulina/farmacologia , Animais , Fator 6 Associado a Receptor de TNF/metabolismo , Núcleo Celular/metabolismo , Camundongos , Humanos , beta-Arrestina 2/metabolismo , beta-Arrestina 2/genética , Células HEK293
7.
J Med Chem ; 67(11): 9194-9213, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38829718

RESUMO

The epigenetic target CREB (cyclic-AMP responsive element binding protein) binding protein (CBP) and its homologue p300 were promising therapeutic targets for the treatment of acute myeloid leukemia (AML). Herein, we report the design, synthesis, and evaluation of a class of CBP/p300 PROTAC degraders based on our previously reported highly potent and selective CBP/p300 inhibitor 5. Among the compounds synthesized, 11c (XYD129) demonstrated high potency and formed a ternary complex between CBP/p300 and CRBN (AlphaScreen). The compound effectively degraded CBP/p300 proteins and exhibited greater inhibition of growth in acute leukemia cell lines compared to its parent compound 5. Furthermore, 11c demonstrated significant inhibition of tumor growth in a MOLM-16 xenograft model (TGI = 60%) at tolerated dose schedules. Our findings suggest that 11c is a promising lead compound for the treatment of AML.


Assuntos
Antineoplásicos , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Camundongos , Proteína p300 Associada a E1A/antagonistas & inibidores , Proteína p300 Associada a E1A/metabolismo , Relação Estrutura-Atividade , Descoberta de Drogas , Proteína de Ligação a CREB/antagonistas & inibidores , Proteína de Ligação a CREB/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Fatores de Transcrição de p300-CBP/antagonistas & inibidores , Fatores de Transcrição de p300-CBP/metabolismo , Proteólise/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos
8.
Pestic Biochem Physiol ; 202: 105970, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38879314

RESUMO

This study aimed to develop a relatively natural and safe botanical insecticide for controlling the storage pest Tribolium castaneum in the egg and pupal stages. It examined how Elsholtzia densa Benth. essential oil (EO) and its primary components, ß-caryophyllene and limonene, affected T. castaneum eggs and pupae through contact and fumigation. Among th, the contact activities of ß-caryophyllene against T. castaneum eggs and pupae are LD50 (median lethal dose, 50%) = 0.156 mg/cm2 and ED50 (median effective dose, 50%) = 16.35 mg/pupa respectively. The study also investigated the effect of ß-caryophyllene and limonene on T. castaneum eggs and pupae through synergistic contact and fumigation. When the mixing ratio of ß-caryophyllene and limonene was 7:1, the LD50 value of contact activity against T. castaneum eggs was reduced to 0.100 mg/cm2, displaying an obvious synergistic effect. Experiments were conducted to investigate the antitoxic effect of ß-caryophyllene on T. castaneum eggs and pupae, as well as its effects on the enzymatic activity of acetylcholinesterase, succinate dehydrogenase, glutathione S-transferase and carboxylesterase in T. castaneum pupae. Finally, the molecular docking techniques were employed to confirm the aforementioned effects on enzyme function. The findings of this study might help improve storage pest control with T. castaneum and create eco-friendly insecticides using E. densa EO, ß-caryophyllene, and limonene.


Assuntos
Inseticidas , Lamiaceae , Óleos Voláteis , Pupa , Tribolium , Animais , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Tribolium/efeitos dos fármacos , Lamiaceae/química , Inseticidas/farmacologia , Inseticidas/química , Pupa/efeitos dos fármacos , Óvulo/efeitos dos fármacos , Limoneno/farmacologia , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos Policíclicos/química
9.
J Environ Manage ; 365: 121623, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38943743

RESUMO

Microplastics (MPs) have been found in remote high-altitude areas, but the main source and migration process remained unclear. This work explored the characteristics and potential sources of MPs in the Yarlung Tsangpo River Basin. The average abundances of MPs in water, sediment, and soil samples were 728.26 ± 100.53 items/m3, 43.16 ± 5.82 items/kg, and 61.92 ± 4.29 items/kg, respectively, with polypropylene and polyethylene as the main polymers. The conditional fragmentation model revealed that the major source of MPs lower than 4000 m was human activities, while that of higher than 4500 m was atmospheric deposition. Community analysis was further conducted to explore the migration process and key points of MPs among different compartments in the basin. It was found that Lhasa (3600 m) and Shigatse (4100 m) were vital sources of MPs inputs in the midstream and downstream, respectively. This work would provide new insights into the fate of MPs in high-altitude areas.


Assuntos
Altitude , Monitoramento Ambiental , Microplásticos , Rios , Rios/química , Microplásticos/análise , Poluentes Químicos da Água/análise , Sedimentos Geológicos/química , Sedimentos Geológicos/análise
10.
J Chem Inf Model ; 64(13): 5303-5316, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38921060

RESUMO

The coexistence of amyloid-ß (Aß) and human islet amyloid polypeptide (hIAPP) in the brain and pancreas is associated with an increased risk of Alzheimer's disease (AD) and type 2 diabetes (T2D) due to their coaggregation and cross-seeding. Despite this, the molecular mechanisms underlying their interaction remain elusive. Here, we systematically investigated the cross-talk between Aß and hIAPP using atomistic discrete molecular dynamics (DMD) simulations. Our results revealed that the amyloidogenic core regions of both Aß (Aß10-21 and Aß30-41) and hIAPP (hIAPP8-20 and hIAPP22-29), driving their self-aggregation, also exhibited a strong tendency for cross-interaction. This propensity led to the formation of ß-sheet-rich heterocomplexes, including potentially toxic ß-barrel oligomers. The formation of Aß and hIAPP heteroaggregates did not impede the recruitment of additional peptides to grow into larger aggregates. Our cross-seeding simulations demonstrated that both Aß and hIAPP fibrils could mutually act as seeds, assisting each other's monomers in converting into ß-sheets at the exposed fibril elongation ends. The amyloidogenic core regions of Aß and hIAPP, in both oligomeric and fibrillar states, exhibited the ability to recruit isolated peptides, thereby extending the ß-sheet edges, with limited sensitivity to the amino acid sequence. These findings suggest that targeting these regions by capping them with amyloid-resistant peptide drugs may hold potential as a therapeutic approach for addressing AD, T2D, and their copathologies.


Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Diabetes Mellitus Tipo 2 , Polipeptídeo Amiloide das Ilhotas Pancreáticas , Simulação de Dinâmica Molecular , Doença de Alzheimer/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Polipeptídeo Amiloide das Ilhotas Pancreáticas/química , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Humanos , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/química , Agregados Proteicos
11.
Molecules ; 29(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38731415

RESUMO

Investigations have shown that storage bugs seriously harm grains during storage. In the interim, essential oils (EOs) have been proven to be a good botanical pesticide. The anti-Lasioderma serricorne properties of Elsholtzia ciliata essential oil, which was obtained by steam distillation, were evaluated using DL-limonene, carvone, and their two optical isomer components using contact, repelling, and fumigation techniques. Simultaneously, the fumigation, contact, and repellent activities of carvone and its two optical isomers mixed with DL-limonene against L. serruricorne were evaluated. The results showed that E. ciliata, its main components (R-carvone, DL-limonene), and S-carvone exhibited both fumigations (LC50 = 14.47, 4.42, 20.9 and 3.78 mg/L) and contact (LD50 = 7.31, 4.03, 28.62 and 5.63 µg/adult) activity against L.serricorne. A binary mixture (1:1) of R-carvone and DL-limonene displayed an obvious synergistic effect. A binary mixture (1:1) of carvone and its two optical isomers exhibited an obvious synergistic effect, too. Furthermore, the repellent activity of the EO, carvone, and its two optical isomers, DL-limonene, and a combination of them varied. To stop insect damage during storage, E. ciliata and its components can be utilized as bio-insecticides.


Assuntos
Inseticidas , Lamiaceae , Óleos Voláteis , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Lamiaceae/química , Animais , Inseticidas/química , Inseticidas/farmacologia , Limoneno/química , Limoneno/farmacologia , Repelentes de Insetos/química , Repelentes de Insetos/farmacologia , Monoterpenos Cicloexânicos/química , Monoterpenos Cicloexânicos/farmacologia , Sinergismo Farmacológico , Fumigação
12.
Cell Commun Signal ; 22(1): 213, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566235

RESUMO

BACKGROUND: Desensitization of G protein-coupled receptors (GPCRs) refers to the attenuation of receptor responsiveness by prolonged or intermittent exposure to agonists. The binding of ß-arrestin to the cytoplasmic cavity of the phosphorylated receptor, which competes with the G protein, has been widely accepted as an extensive model for explaining GPCRs desensitization. However, studies on various GPCRs, including dopamine D2-like receptors (D2R, D3R, D4R), have suggested the existence of other desensitization mechanisms. The present study employed D2R/D3R variants with different desensitization properties and utilized loss-of-function approaches to uncover the mechanisms underlying GPCRs homologous desensitization, focusing on the signaling cascade that regulates the ubiquitination of AKT. RESULTS: AKT undergoes K8/14 ubiquitination by TRAF6, which occurs in the nucleus and promotes its membrane recruitment, phosphorylation and activation under receptor desensitization conditions. The nuclear entry of TRAF6 relies on the presence of the importin complex. Src regulates the nuclear entry of TRAF6 by mediating the interaction between TRAF6 and importin ß1. Ubiquitinated AKT translocates to the plasma membrane where it associates with Mdm2 to phosphorylate it at the S166 and S186 residues. Thereafter, phosphorylated Mdm2 is recruited to the nucleus, resulting in the deubiquitination of ß-Arr2. The deubiquitinated ß-Arr2 then forms a complex with Gßγ, which serves as a biomarker for GPCRs desensitization. Like in D3R, ubiquitination of AKT is also involved in the desensitization of ß2 adrenoceptors. CONCLUSION: Our study proposed that the property of a receptor that causes a change in the subcellular localization of TRAF6 from the cytoplasm to the nucleus to mediate AKT ubiquitination could initiate the desensitization of GPCRs.


Assuntos
Proteínas Proto-Oncogênicas c-akt , Fator 6 Associado a Receptor de TNF , Fator 6 Associado a Receptor de TNF/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Ubiquitinação , Fosforilação , Carioferinas
14.
Mol Ther ; 32(5): 1387-1406, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38414247

RESUMO

Cisplatin-induced hearing loss is a common side effect of cancer chemotherapy in clinics; however, the mechanism of cisplatin-induced ototoxicity is still not completely clarified. Cisplatin-induced ototoxicity is mainly associated with the production of reactive oxygen species, activation of apoptosis, and accumulation of intracellular lipid peroxidation, which also is involved in ferroptosis induction. In this study, the expression of TfR1, a ferroptosis biomarker, was upregulated in the outer hair cells of cisplatin-treated mice. Moreover, several key ferroptosis regulator genes were altered in cisplatin-damaged cochlear explants based on RNA sequencing, implying the induction of ferroptosis. Ferroptosis-related Gpx4 and Fsp1 knockout mice were established to investigate the specific mechanisms associated with ferroptosis in cochleae. Severe outer hair cell loss and progressive damage of synapses in inner hair cells were observed in Atoh1-Gpx4-/- mice. However, Fsp1-/- mice showed no significant hearing phenotype, demonstrating that Gpx4, but not Fsp1, may play an important role in the functional maintenance of HCs. Moreover, findings showed that FDA-approved luteolin could specifically inhibit ferroptosis and alleviate cisplatin-induced ototoxicity through decreased expression of transferrin and intracellular concentration of ferrous ions. This study indicated that ferroptosis inhibition through the reduction of intracellular ferrous ions might be a potential strategy to prevent cisplatin-induced hearing loss.


Assuntos
Cisplatino , Ferroptose , Perda Auditiva , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Animais , Cisplatino/efeitos adversos , Ferroptose/efeitos dos fármacos , Ferroptose/genética , Camundongos , Perda Auditiva/induzido quimicamente , Perda Auditiva/genética , Perda Auditiva/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Modelos Animais de Doenças , Receptores da Transferrina/metabolismo , Receptores da Transferrina/genética , Espécies Reativas de Oxigênio/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Células Ciliadas Auditivas Externas/metabolismo , Células Ciliadas Auditivas Externas/efeitos dos fármacos , Células Ciliadas Auditivas Externas/patologia , Ototoxicidade/etiologia , Ototoxicidade/metabolismo , Antineoplásicos/efeitos adversos , Apoptose/efeitos dos fármacos
15.
Chin Med J (Engl) ; 137(9): 1115-1117, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38310445
16.
Curr Med Imaging ; 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38178675

RESUMO

Dual-energy computed tomography (DECT) applies two energy spectra distributions to collect raw data based on traditional CT imaging. The application of hepatobiliary imaging, has the advantages of optimizing the scanning scheme, improving the imaging quality, highlighting the disease characterization, and increasing the detection rate of lesions. In order to summarize the clinical application value of DECT in hepatobiliary diseases, we searched the technical principles of DECT and its existing studies, case reports, and clinical guidelines in hepatobiliary imaging from 2010 to 2023 (especially in the past 5 years) through PubMed and CNKI, focusing on the clinical application of DECT in hepatobiliary diseases, including liver tumors, diffuse liver lesions, and biliary system lesions. The first part of this article briefly describes the basic concept and technical advantages of DECT. The following will be reviewed:the detection of lesions, diagnosis and differential diagnosis of lesions, hepatic steatosis, quantitative analysis of liver iron, and analyze the advantages and disadvantages of DECT in hepatobiliary imaging. Finally, the contents of this paper are summarized and the development prospect of DECT in hepatobiliary imaging is prospected.

17.
Thromb Haemost ; 124(2): 108-121, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37657484

RESUMO

BACKGROUND: Classical anticoagulants and antiplatelets are associated with high frequencies of bleeding complications or treatment failure when used as single agents. Thrombin plays an important role in the blood coagulation system. GP IIb/IIIa is the central receptor of platelets, which can recognize the Arg-Gly-Asp (RGD) sequence and activate platelets. MATERIAL AND METHODS: Molecular simulation and homology modeling were performed to design a novel dual-target anticoagulant short peptide (PTIP ). The activities of PTIP on coagulation and platelet in vitro were analyzed. The antithrombotic activity of PTIP was determined by pulmonary thromboembolism model, ferric chloride injury model and arteriovenous bypass thrombosis model. Bleeding effect and toxicity of PTIP were evaluated. RESULTS: We have constructed a novel dual-target peptide (PTIP) based on the direct thrombin inhibitor peptide (DTIP). PTIP was expressed at high levels in Pichia pastoris. PTIP interfered with thrombin-mediated coagulation and ADP-induced platelet aggregation in vitro. When injected intravenously or subcutaneously, PTIP showed potent and dose-dependent extension of aPTT and PT which were similar to DTIP; but only PTIP was capable of inhibiting platelet aggregation. PTIP (1.0 mg/kg) decelerated thrombosis formation in venous and arterial vessels induced by FeCl3 injury. PTIP (1.0 mg/kg) also prevented deep venous thrombosis and increased the survival rate associated with pulmonary thromboembolism. And PTIP effectively reduced thrombus length in arteriovenous bypass thrombosis model. Moreover, the antithrombotic dose of PTIP could not induce bleeding. CONCLUSION: These data establish that PTIP represents a novel antithrombotic agent whose effects involve both inhibition of platelet activation and reduction of fibrin generation. And PTIP not only can be used in venous thrombosis and arterial thrombosis, it can also replace the combined treatment of antiplatelet and anticoagulant drugs in thrombotic diseases.


Assuntos
Embolia Pulmonar , Trombose , Humanos , Agregação Plaquetária , Trombina , Fibrinolíticos/farmacologia , Fibrinolíticos/uso terapêutico , Hemorragia/tratamento farmacológico , Anticoagulantes/uso terapêutico , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/uso terapêutico , Inibidores da Agregação Plaquetária/química , Trombose/tratamento farmacológico , Trombose/prevenção & controle , Antitrombinas/uso terapêutico , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Embolia Pulmonar/tratamento farmacológico
18.
Arq. bras. oftalmol ; 87(4): e2022, 2024.
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1520239

RESUMO

ABSTRACT Purpose: Opsoclonus-myoclonus syndrome is extremely uncommon in adults with an autoimmune pathophysiology. Because of the rarity of the syndrome, international recognition of opsoclonus-myoclonus-ataxia syndrome needs to be improved urgently. Therefore, the goal of this study was to raise the awareness of the opsoclonus-myoclonus-ataxia syndrome and help doctors in better diagnosing and using immunotherapy. Methods: We present a case study of an adult-onset case of idiopathic opsoclonus-myoclonus syndrome characterized by spontaneous arrhythmic multidirectional conjugate eye movements, myoclonus, ataxia, sleep disorders, and intense fear. Additionally, we conduct a literature search and summarize the pathophysiology, clinical presentation, diagnosis, and treatment of opsoclonus-myoclonus-ataxia syndrome. Results: Immunotherapies successfully treated the patient's opsoclonus, myoclonus, and ataxia. Further, the article also includes an update summary of the opsoclonus-myoclonus-ataxia syndrome. Conclusion: The prevalence of residual sequela in adults with opsoclonus-myoclonus-ataxia syndrome is low. Early diagnosis and treatment may result in a better prognosis. Furthermore, combined immunotherapy is expected to reduce the incidence of refractory and reoccurring opsoclonus-myoclonus-ataxia syndrome.


RESUMO Objetivo: A síndrome de opsoclonia-mioclonia é extremamente rara em adultos e tem uma fisiopatologia autoimune. Devido à raridade dessa síndrome, o reconhecimento da síndrome de opsoclonia-mioclonia-ataxia precisa melhorar urgentemente em todo o mundo. Assim sendo, este estudo visou aumentar a conscientização sobre a síndrome de opsoclonia-mioclonia-ataxia e ajudar os médicos para um melhor diagnóstico e o uso correto da imunoterapia. Métodos: Este é o relato de um caso adulto de síndrome de opsoclonia-mioclonia idiopática com movimentos oculares conjugados, multidirecionais, arrítmicos e espontâneos, mioclonia, ataxia, distúrbios do sono e medo intenso. Além disso, foram pesquisadas as publicações recentes relevantes e resumiu-se a fisiopatologia, a apresentação clínica, o diagnóstico e o tratamento da síndrome de opsoclonia-mioclonia-ataxia. Resultados: A paciente recuperou-se totalmente da opsoclonia, da mioclonia e da ataxia através de imunoterapia. O artigo também fornece um resumo atualizado sobre a síndrome de opsoclonia-mioclonia-ataxia. Conclusão: Adultos com síndrome de opsoclonia-mioclonia-ataxia têm uma baixa frequência de sequelas residuais. O diagnóstico e o tratamento precoces podem levar a melhores prognósticos. Espera-se que a imunoterapia combinada reduza a incidência da síndrome de opsoclonia-mioclonia-ataxia refratária e recorrente.

19.
Medicine (Baltimore) ; 102(47): e36196, 2023 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-38013345

RESUMO

Bone and soft tissue tumors are diverse, accompanying by complex histological components and significantly divergent biological behaviors. It is a challenge to address the demand for qualitative imaging as traditional imaging is restricted to the detection of anatomical structures and aberrant signals. With the improvement of digitalization in hospitals and medical centers, the introduction of electronic medical records and easier access to large amounts of information coupled with the improved computational power, traditional medicine has evolved into the combination of human brain, minimal data, and artificial intelligence. Scholars are committed to mining deeper levels of imaging data, and radiomics is worthy of promotion. Radiomics extracts subvisual quantitative features, analyzes them based on medical images, and quantifies tumor heterogeneity by outlining the region of interest and modeling. Two observers separately examined PubMed, Web of Science and CNKI to find existing studies, case reports, and clinical guidelines about research status and progress of radiomics in bone and soft tissue tumors from January 2010 to February 2023. When evaluating the literature, factors such as patient age, medical history, and severity of the condition will be considered. This narrative review summarizes the application and progress of radiomics in bone and soft tissue tumors.


Assuntos
Inteligência Artificial , Neoplasias de Tecidos Moles , Humanos , Diagnóstico por Imagem , Neoplasias de Tecidos Moles/diagnóstico por imagem
20.
J Dent Sci ; 18(4): 1517-1526, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37799880

RESUMO

Background: /purpose: Bone ring technique (BRT) is an effective method to reconstruct alveolar bone defects with simultaneous implant placement. This study aimed to evaluate the efficacy of the BRT in single maxillary anterior tooth implantation and its esthetic outcomes over 2-3 years of follow-up. Materials and methods: Fifteen patients with single maxillary incisor loss received autogenous BRT with simultaneous implant placement. The vertical/horizontal bone gain, remaining vertical bone height (RVBH), remaining buccal bone width (RBBW), and vertical/horizontal bone resorption around implant over 2-3 years of follow-up were measured by using cone-beam computed tomography. Esthetic results including white esthetic score (WES), pink esthetic score (PES), and papilla index (PI) were evaluated by clinical recorded photographs. Results: All implants showed evidence of osseointegration, and the mean vertical and horizontal bone gain of 14 sites was 5.55 ± 0.87 mm and 4.73 ± 0.70 mm, respectively. During 2-3 years of follow-up, all mean values of RBBW were more than 2 mm. Main vertical bone loss appeared within 4 months after surgery and the RVBH value decreased as the follow-up duration continued. Maximum buccal bone thickness resorption mostly appeared in the middle level of the implant during the primary two follow-up periods (P < 0.05). Esthetic results showed that the mean WES/PES was higher than 17, and more than half cases demonstrated relatively high PI (3 points) throughout the follow-up. Conclusion: BRT could achieve excellent bone augmentation effect and can offer predictable esthetic outcomes for single tooth implant restoration in the esthetic zone.

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