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1.
J Am Chem Soc ; 146(9): 5908-5915, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38391353

RESUMO

Unconventional superconductivity in bulk materials under ambient pressure is extremely rare among the 3d transition metal compounds outside the layered cuprates and iron-based family. It is predominantly linked to highly anisotropic electronic properties and quasi-two-dimensional (2D) Fermi surfaces. To date, the only known example of a Co-based exotic superconductor is the hydrated layered cobaltate, NaxCoO2·yH2O, and its superconductivity is realized in the vicinity of a spin-1/2 Mott state. However, the nature of the superconductivity in these materials is still a subject of intense debate, and therefore, finding a new class of superconductors will help unravel the mysteries of their unconventional superconductivity. Here, we report the discovery of superconductivity at ∼6.3 K in our newly synthesized layered compound Na2CoSe2O, in which the edge-shared CoSe6 octahedra form [CoSe2] layers with a perfect triangular lattice of Co ions. It is the first 3d transition metal oxychalcogenide superconductor with distinct structural and chemical characteristics. Despite its relatively low TC, this material exhibits very high superconducting upper critical fields, µ0HC2(0), which far exceeds the Pauli paramagnetic limit by a factor of 3-4. First-principles calculations show that Na2CoSe2O is a rare example of a negative charge transfer superconductor. This cobalt oxychalcogenide with a geometrical frustration among Co spins shows great potential as a highly appealing candidate for the realization of unconventional and/or high-TC superconductivity beyond the well-established Cu- and Fe-based superconductor families and opens a new field in the physics and chemistry of low-dimensional superconductors.

2.
Inorg Chem ; 62(37): 15226-15233, 2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37672326

RESUMO

The Mg/S battery has attracted enormous interest in recent years due to its high theoretical capacity, low cost, and high security. However, the understanding of many intermediate magnesium polysulfides in the Mg/S battery remains elusive. Combining extensive structural search and first-principles calculations, we investigate the phase stability, structural character, and electronic structure of magnesium polysulfides in a wide range from MgS to MgS8. The pyrite-type MgS2 (space group: Pa3̅) is predicted to be stable. Five magnesium polysulfides, MgSx (x = 3, 4, 5, 6, and 8), are found to be metastable, with formation enthalpies slightly above the convex hull. S2 dimer, "V"-like S3, and highly distorted Sx chains are found for the polysulfides with bond lengths close to or slightly longer than S8 and bond angles similar to S8. A wide range of band gaps (0.77-2.82 eV) are revealed for the polysulfides due to the contribution of the nonequivalent sp3 hybridization of the S atoms in Sx2-. Our results can help to further understand the electrochemical process in the Mg/S battery.

3.
Int J Med Sci ; 20(12): 1616-1630, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37859699

RESUMO

Purpose: Acute liver failure (ALF) is a clinically fatal disease that leads to the rapid loss of normal liver function. Acetaminophen (APAP) is a leading cause of drug-induced ALF. Ferroptosis, defined as iron-dependent cell death associated with lipid peroxide accumulation, has been shown to be strongly associated with APAP-induced liver injury. Growth arrest-specific 1 (GAS1) is a growth arrest-specific gene, which is closely related to the inhibition of cell growth and promotion of apoptosis. However, the functional role and underlying mechanism of GAS1 in APAP-induced ferroptosis remain unknown. Methods: We established liver-specific overexpression of GAS1 (GAS1AAV8-OE) mice and the control (GAS1AAV8-vector) mice by tail vein injection of male mice with adeno-associated virus. APAP at 500 mg/kg was intraperitoneally injected into these two groups of mice to induce acute liver failure. The shRNA packaged by the lentivirus inhibits GAS1 gene expression in human hepatoma cell line HepaRG (HepaRG-shNC and HepaRG-shGAS1-2) and primary hepatocytes of mice with liver-specific overexpression of GAS1 were isolated and induced by APAP in vitro to further investigate the regulatory role of GAS1 in APAP-induced acute liver failure. Results: APAP-induced upregulation of ferroptosis, levels of lipid peroxides and reactive oxygen species, and depletion of glutathione were effectively alleviated by the ferroptosis inhibitor, ferrostatin-1, and downregulation of GAS1 expression. GAS1 overexpression promoted ferroptosis-induced lipid peroxide accumulation via p53, inhibiting its downstream target, solute carrier family 7 member 11. Conclusion: Collectively, our findings suggest that GAS1 overexpression plays a key role in aggravating APAP-induced acute liver injury by promoting ferroptosis-induced accumulation of lipid peroxides.


Assuntos
Ferroptose , Falência Hepática Aguda , Animais , Humanos , Masculino , Camundongos , Acetaminofen/toxicidade , Proteínas de Ciclo Celular/metabolismo , Ferroptose/genética , Proteínas Ligadas por GPI/metabolismo , Hepatócitos/metabolismo , Peróxidos Lipídicos/metabolismo , Fígado , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/genética , Falência Hepática Aguda/metabolismo , Camundongos Endogâmicos C57BL
4.
BMC Gastroenterol ; 22(1): 544, 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36577952

RESUMO

BACKGROUND: Microvascular invasion (MVI) is important in early recurrence and leads to poor overall survival (OS) in hepatocellular carcinoma (HCC). A number of studies have reported independent risk factors for MVI. In this retrospective study, we designed to develop a preoperative model for predicting the presence of MVI in HCC patients to help surgeons in their surgical decision-making and improve patient management. PATIENTS AND METHODS: We developed a predictive model based on a nomogram in a training cohort of 225 HCC patients. We analyzed patients' clinical information, laboratory examinations, and imaging features from contrast-enhanced CT. Mann-Whitney U test and multiple logistic regression analysis were used to confirm independent risk factors and develop the predictive model. Internal and external validation was performed on 75 and 77 HCC patients, respectively. Moreover, the diagnostic performance of our model was evaluated using receiver operating characteristic (ROC) curves. RESULTS: In the training cohort, maximum tumor diameter (> 50 mm), tumor margin, direct bilirubin (> 2.7 µmol/L), and AFP (> 360.7 ng/mL) were confirmed as independent risk factors for MVI. In the internal and external validation cohort, the developed nomogram model demonstrated good diagnostic ability for MVI with an area under the curve (AUC) of 0.723 and 0.829, respectively. CONCLUSION: Based on routine clinical examinations, which may be helpful for clinical decision-making, we have developed a nomogram model that can successfully assess the risk of MVI in HCC patients preoperatively. When predicting HCC patients with a high risk of MVI, the surgeons may perform an anatomical or wide-margin hepatectomy on the patient.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Estudos Retrospectivos , Invasividade Neoplásica , Tomografia Computadorizada por Raios X/métodos
5.
Hepatology ; 71(6): 2033-2049, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31578733

RESUMO

BACKGROUND AND AIMS: Liver cancer stem cells (CSCs) exist in the tumor environment and are critically involved in the initiation and progression of hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms of self-renewal and maintenance of liver CSCs remain poorly understood. APPROACH AND RESULTS: We identified that xanthine oxidoreductase (XOR), which was expressed at low levels in human HCC samples and liver CSCs, restrained HCC formation and chemoresistance by attenuating liver CSC propagation. Mechanistically, XOR physically interacts with ubiquitin-specific peptidase 15 (USP15), thereby promoting deubiquitination of Kelch-like ECH associated protein 1 (KEAP1) to stabilize its expression, which leads to degradation of Nrf2 (nuclear factor erythroid 2-related factor 2) through ubiquitination and subsequently reactive oxygen species accumulation in liver CSCs. Finally, our data reveal that XOR promotes USP15-mediated Nrf2-KEAP1 signaling to block liver CSCs and tumor propagation. CONCLUSION: We identified that XOR may represent a potential therapeutic target for clinical intervention in HCC driven by liver CSCs.


Assuntos
Carcinoma Hepatocelular , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Neoplasias Hepáticas , Fator 2 Relacionado a NF-E2/metabolismo , Células-Tronco Neoplásicas/metabolismo , Proteases Específicas de Ubiquitina/metabolismo , Xantina Desidrogenase/metabolismo , Animais , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Autorrenovação Celular , Descoberta de Drogas , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Camundongos , Transdução de Sinais , Células Tumorais Cultivadas , Ubiquitinação
6.
BMC Gastroenterol ; 21(1): 138, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33771126

RESUMO

BACKGROUND: Laparoscopic anatomic hepatectomy (LAH) has gradually become a routine surgical procedure. However, how to expose the whole hepatic vein and avoid the hepatic vein laceration is still a challenge because of the caudate lobe, particularly in right hepatectomy. We adopted a dorsal approach combined with Glissionian appraoch to perform laparoscopic right anatomic hepatectomy (LRAH). METHODS: Twenty patients who underwent LRAH from January 2017 to November 2018 were retrospectively analysed. Of these patients, seven patients underwent laparoscopic right hemihepatectomy (LRH group), seven patients who underwent laparoscopic right posterior hepatectomy (LRPH group), and six patients who underwent laparoscopic hepatectomy for segment 7 (LS7 group). The paracaval portion of caudate lobe could be transected firstly through dorsal approach and the corresponding major hepatic vein could be exposed from its root to the peripheral branches safely. Due to exposure along the major hepatic vein trunk, the remaining liver parenchyma could be quickly transected from dorsal to cranial side. RESULTS: The mean age of the patients was 53.8 years and the male: female ratio was 8:12. The median operation time was 306.0 ± 58.2 min and the mean estimated volume of blood loss was 412.5 ± 255.4 mL. The mean duration of postoperative hospital stay was 10.2 days. The mean Pringle maneuver time was 64.8 ± 27.7 min. Five patients received transfusion of 2-4 U of red blood cells. Two patients suffered from transient hepatic dysfunction and one suffered from pleural effusion. None of the patients underwent conversion to an open procedure. The operative duration, volume of the blood loss, Pringle maneuver time, and postoperative hospital stay duration did not differ significantly among the LRH, LRPH, and LS7 groups (P > 0.05). CONCLUSIONS: Dorsal approach combined with Glissonian approach for right lobe is feasible and effective in laparoscopic right anatomic liver resections.


Assuntos
Laparoscopia , Neoplasias Hepáticas , Feminino , Hepatectomia/efeitos adversos , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Estudos Retrospectivos
7.
J Cell Mol Med ; 24(14): 7814-7828, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32445435

RESUMO

Hepatic ischaemia/reperfusion (I/R) injury is a major clinical problem during liver surgical procedures, which usually lead to early transplantation failure and higher organ rejection rate, and current effective therapeutic strategies are still limited. Therefore, in-depth exploring of the molecular mechanisms underlying liver I/R injury is key to the development of new therapeutic methods. ß-arrestins are multifunctional proteins serving as important signalling scaffolds in numerous physiopathological processes, including liver-specific diseases. However, the role and underlying mechanism of ß-arrestins in hepatic I/R injury remain largely unknown. Here, we showed that only ARRB1, but not ARRB2, was down-regulated during liver I/R injury. Hepatocyte-specific overexpression of ARRB1 significantly ameliorated liver damage, as demonstrated by decreases in serum aminotransferases, hepatocellular necrosis and apoptosis, infiltrating inflammatory cells and secretion of pro-inflammatory cytokines relative to control mice, whereas experiments with ARRB1 knockout mice gotten opposite effects. Mechanistically, ARRB1 directly interacts with ASK1 in hepatocytes and inhibits its TRAF6-mediated Lysine 6-linked polyubiquitination, which then prevents the activation of ASK1 and its downstream signalling pathway during hepatic I/R injury. In addition, inhibition of ASK1 remarkably abolished the disruptive effect result from ARRB1 deficiency in liver I/R injury in vivo, indicating that ASK1 was required for ARRB1 function in hepatic I/R injury. In conclusion, we proposed that ARRB1 is a novel protective regulator during liver I/R injury, and modulation of the regulatory axis between ARRB1 and ASK1 could be a novel therapeutic strategy to prevent this pathological process.


Assuntos
Hepatopatias/etiologia , Hepatopatias/metabolismo , MAP Quinase Quinase Quinase 5/metabolismo , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo , beta-Arrestina 1/genética , beta-Arrestina 1/metabolismo , Animais , Apoptose , Citocinas/metabolismo , Modelos Animais de Doenças , Hepatócitos/metabolismo , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Hepatopatias/patologia , Lisina/metabolismo , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Traumatismo por Reperfusão/patologia , Ubiquitinação
8.
FASEB J ; 33(6): 7049-7060, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30840837

RESUMO

Hepatic ischemia-reperfusion (I/R) injury is a major challenge in liver resection and transplantation surgeries. Previous studies have revealed that guanine nucleotide-binding protein G(i)α2 (GNAI2) was involved in the progression of myocardial and cerebral I/R injury, but the role and function of GNAI2 in hepatic I/R have not been elucidated. The hepatocyte-specific GNAI2 knockout (GNAI2hep-/-) mice were generated and subjected to hepatic I/R injury. Primary hepatocytes isolated from GNAI2hep-/- and GNAI2flox/flox mice were cultured and challenged to hypoxia-reoxygenation insult. The specific function of GNAI2 in I/R-triggered hepatic injury and the underlying molecular mechanism were explored by various phenotypic analyses and molecular biology methods. In this study, we demonstrated that hepatic GNAI2 expression was significantly increased in liver transplantation patients and wild-type mice after hepatic I/R. Interestingly, hepatocyte-specific GNAI2 deficiency attenuated I/R-induced liver damage, inflammation cytokine expression, macrophage/neutrophil infiltration, and hepatocyte apoptosis in vivo and in vitro. Mechanistically, up-regulation of GNAI2 phosphorylates mixed-lineage protein kinase 3 (MLK3) through direct binding, which exacerbated hepatic I/R damage via MAPK and NF-κB pathway activation. Furthermore, blocking MLK3 signaling reversed GNAI2-mediated hepatic I/R injury. Our study firstly identifies GNAI2 as a promising target for prevention of hepatic I/R-induced injury and related liver diseases.-Sun, Q., He, Q., Xu, J., Liu, Q., Lu, Y., Zhang, Z., Xu, X., Sun, B. Guanine nucleotide-binding protein G(i)α2 aggravates hepatic ischemia-reperfusion injury in mice by regulating MLK3 signaling.


Assuntos
Subunidade alfa Gi2 de Proteína de Ligação ao GTP/metabolismo , Hepatopatias/metabolismo , MAP Quinase Quinase Quinases/metabolismo , Traumatismo por Reperfusão/fisiopatologia , Animais , Apoptose , Células Cultivadas , Regulação para Baixo , Subunidade alfa Gi2 de Proteína de Ligação ao GTP/genética , Regulação da Expressão Gênica , Hepatócitos/metabolismo , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , MAP Quinase Quinase Quinases/genética , Sistema de Sinalização das MAP Quinases/fisiologia , Camundongos , Transdução de Sinais , MAP Quinase Quinase Quinase 11 Ativada por Mitógeno
9.
Med Sci Monit ; 24: 2259-2270, 2018 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-29656298

RESUMO

BACKGROUND Recent studies show that peroxiredoxin 1 (Prdx1) contributes to the progression and poor prognosis of carcinoma through multiple mechanisms. However, there is little information on its expression and prognostic value in gastric cancer. This study investigated the expression of Prdx1 in gastric cancer, along with evaluating its clinical-pathological and prognostic importance. MATERIAL AND METHODS A total of 189 pairs of gastric cancer and paracarcinomatous tissues were assessed for Prdx1 expression and its association with clinical characteristics. The molecular mechanism was further investigated through in vitro experimentation. RESULTS The mRNA and protein levels of Prdx1 in the GC tissues were higher than in the peri-tumor tissues. We also found that high Prdx1 expression was positively correlated with the lymph node invasion and poor prognosis. It also served as an autonomous prognostic factor for patients with gastric cancer. Moreover, Prdx1 regulates the invasion and metastasis of GC cell lines through inhibiting E-Ca expression. CONCLUSIONS Prdx1 can promote epithelial-mesenchymal transition and gastric cancer progression. Therefore, it might be a therapeutic target and prognostic indicator for gastric cancer patients.


Assuntos
Peroxirredoxinas/biossíntese , Neoplasias Gástricas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral/metabolismo , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Transição Epitelial-Mesenquimal/fisiologia , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Peroxirredoxinas/genética , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
10.
Cell Physiol Biochem ; 41(6): 2289-2306, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28456796

RESUMO

BACKGROUND & AIMS: To investigate the expression and prognostic value of α1-ACT (Alpha1-antichymotrypsin) in patients with HCC (hepatocellular carcinoma) and identify the mechanism by which α1-ACT inhibits proliferation and promotes apoptosis of HCC. METHODS: We first measured α1-ACT expression levels and determined their relationship with the clinicopathological characteristics and prognosis of patients with HCC.We then established stable HCC cell lines with both α1-ACT overexpression and knockdown and performed a functional analysis in vitro.We first examined the relationship between α1-ACT and the PTEN/PI3K/AKT/mTOR pathway using Western blotting. Then, we determined whether α1-ACT can directly bind to PTEN using co-immunoprecipitation. Finally, we measured α1-ACT expression to evaluate its correlation with the PI3K/AKT/mTOR pathway-related apoptosis proteins in a xenograft tumour mouse model using immunohistochemistry. RESULTS: The α1-ACT expression level was significantly lower in the HCC tissues than in the paratumour tissues and was negatively positively correlated with the level of Ki67, AFP, the AJCC stage, tumour size and tumour invasion. The overexpression of α1-ACT can inhibit cell proliferation and increase cell apoptosis by activating PI3K/AKT/mTOR-mediated apoptosis via binding to PTEN and activating it in vitro. Additionally, the overexpression of α1-ACT can also increase the proportion of cells in the G0/G1 stage by increasing cyclin p21 expression and inhibiting the migration and invasion abilities of HCC cells by regulating MMP2 and MMP9. The xenotransplantation studies with nude mice also showed that overexpression of α1-ACT inhibited tumourigenesis and knockdown of α1-ACT had the opposite effect. CONCLUSIONS: Our study demonstrates that α1-ACT suppresses liver cancer development and metastasis via targeting the PTEN/PI3K/AKT/mTOR signalling pathway, which may be a potential target for therapeutic intervention in HCC.


Assuntos
Carcinoma Hepatocelular/fisiopatologia , Neoplasias Hepáticas/fisiopatologia , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serpinas/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Adulto , Animais , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Prognóstico , Interferência de RNA , Serpinas/química , Serpinas/genética , Transdução de Sinais/fisiologia
11.
AAPS PharmSciTech ; 18(8): 3172-3181, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28536795

RESUMO

The objective of this study was to explore the feasibility of using alginate as a potential stabilizer of nanosuspension and elaborate the corresponding stabilization mechanism. Using lovastatin as a Biopharmaceutics Classification System (BCS) II drug model, alginate-stabilized nanosuspension was fabricated by the high-pressure homogenization method. The particle size, zeta potential, short-term stability, and dissolution behavior of the nanosuspension were characterized. Thereafter, the surface morphology, crystallinity, redispersability, and stability of the spray-dried nanosuspension were investigated. The spray-dried powder was further compressed into tablets via direct compression, and stressing test was carried out to investigate the stability of nanocrystal loaded tablets. It was demonstrated that alginate could stabilize nanocrystals by providing both electrostatic and steric stabilization, and the effective concentration was much lower than that of the commonly used stabilizers. Good redispersability was achieved after spray drying of the nanosuspension, and the existing state of lovastatin was not changed as indicated by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) studies. The stress test indicated that nanocrystal-loaded tablets possessed a favorable stability. In conclusion, alginate could be used as a potential stabilizer of nanosuspension with preferable stabilizing ability at a very low concentration either in liquid or in solid state.


Assuntos
Alginatos/química , Alginatos/metabolismo , Nanopartículas/química , Nanopartículas/metabolismo , Varredura Diferencial de Calorimetria/métodos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Tamanho da Partícula , Solubilidade , Suspensões/química , Suspensões/metabolismo , Comprimidos , Difração de Raios X/métodos
12.
Yao Xue Xue Bao ; 50(8): 1045-51, 2015 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-26669007

RESUMO

The objectives of this study are to prepare resveratrol loaded mixed micelles composed of poloxamer 403 and poloxamer 407, and optimize the formulation in order to achieve higher drug solubility and sustained drug release. Firstly, a thin-film hydration method was utilized to prepare the micelles. By using drug-loading, encapsulation yield and particle size of the micelles as criteria, influence of three variables, namely poloxamer 407 mass fraction, amount of water and feeding of resveratrol, on the quality of the micelles was optimized with a central composite design method. Steady fluorescence measurement was carried out to evaluate the critical micelle concentration of the carriers. Micelle stability upon dilution with simulated gastric fluid and simulated intestinal fluid was investigated. The in vitro release of resveratrol from the mixed micelles was monitored by dialysis method. It was observed that the particle size of the optimized micelle formulation was 24 nm, with drug-loading 11.78%, and encapsulation yield 82.51%. The mixed micelles increased the solubility of resveratrol for about 197 times. Moreover, the mixed micelles had a low critical micelle concentration of 0.05 mg · mL(-1) in water and no apparent changes in particle size and drug content were observed upon micelles dilution, indicating improved kinetic stability. Resveratrol was released from the micelles in a controlled manner for over 20 h, and the release process can be well described by Higuchi equation. Therefore, resveratrol-loaded poloxamer 403/407 mixed micelles could improve the solubility of resveratrol significantly and sustained drug release behavior can be achieved.


Assuntos
Portadores de Fármacos/química , Micelas , Poloxâmero/química , Estilbenos/química , Fluorescência , Cinética , Tamanho da Partícula , Resveratrol , Solubilidade , Água
13.
Heliyon ; 10(9): e30622, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38726103

RESUMO

Hepatocellular carcinoma (HCC) is the most common pathologic type of primary liver cancer. Liver transplantation (LT) is a radical strategy for treating patients with early-stage HCC, which may lead to a better prognosis compared to hepatectomy and ablation. However, survival of patients who develop HCC recurrence after LT is short, and early recurrence is the most common cause of death. Thus, efficient biomarkers are also needed in LT to guide precision therapy to improve patient prognosis and 5-year survival. Protein induced by vitamin K absence or antagonist II (PIVKA-II) is an abnormal prothrombin that cannot activate coagulation, and it is significantly increased in patients with HCC, obstructive jaundice, and those taking vitamin K antagonists. Over the past decades, substantial progress has been made in the study of PIVKA-II in diagnosing, surveilling, and treating HCC, but its role in LT still needs to be elaborated. In this review, we focused on the role of PIVKA-II as a biomarker in LT for HCC, especially its relationship with clinicopathologic features, early recurrence, long-term survival, and donor-recipient selection.

14.
Artigo em Inglês | MEDLINE | ID: mdl-38801182

RESUMO

INTRODUCTION: Liver fibrosis is a major cause of morbidity and mortality among in patients with chronic hepatitis. Radiomics, particularly of the spleen, may improve diagnostic accuracy and treatment strategies. External validations are necessary to ensure reliability and generalizability. METHODS: In this retrospective study, we developed 3 radiomics models using contrast-enhanced computed tomography scans from 167 patients with liver fibrosis (training group) between January 2020 and December 2021. Radiomic features were extracted from arterial venous, portal venous, and equilibrium phase images. Recursive feature selection random forest and the least absolute shrinkage and selection operator logistic regression were used for feature selection and dimensionality reduction. Performance was assessed by area under the curve, C-index, calibration plots, and decision curve analysis. External validation was performed on 114 patients from 2 institutions. RESULTS: Twenty-five radiomic features were significantly associated with fibrosis stage, with 80% of the top 10 features originating from portal venous phase spleen images. The radiomics models showed good performance in the validation cohort (C-indices 0.723-0.808) and excellent calibration. Decision curve analysis indicated clinical benefits, with machine learning-based radiomics models (Random Forest score and support vector machine based radiomics score) providing more significant advantages. DISCUSSION: Radiomic features offer significant benefits over existing serum indices for staging virus-driven liver fibrosis, underscoring the value of radiomics in enhancing diagnostic accuracy. Specifically, radiomics analysis of the spleen presents additional noninvasive options for assessing fibrosis, highlighting its potential in improving patient management and outcomes.

15.
Food Res Int ; 163: 112273, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36596184

RESUMO

Dry-cured mackerel is favored by consumers for its suitable salty flavor. Herein, the dynamic changes of volatile compounds and lipids in the mackerel, and the lipidomics based on UPLC-Orbitrap/MS technique during dry-cured processing were investigated. The results showed that endogenous lipases activities in dry-cured mackerel decreased. The dry-cured processing of mackerel had significant effects on its lipid classes and content. The contents of Arachidonic acid (C20:4n6), docosapentaenoic acid (C22:5n3), linoleic acid (LA, C18:2n6), alpha-linolenic acid (C18:3n3), eicosatrienoic acid (C20:3n3) and docosahexaenoic acid (DHA, C22:6n3) increased during dry-cured processing. A total of 38 kinds of volatile compounds were detected in the dry-cured mackerel, 12 of which were derived from fatty acid oxidation. Among 30 lipid metabolites (FC ≥ 2 and VIP > 2), phosphatidylethanolamine (PE, 19:0/22:6) accounted for the highest content, and its difference between three stages was the most obvious. Glycerophospholipid and sphingolipid metabolisms were the most important metabolic pathways involved in dry-cured processing.


Assuntos
Lipidômica , Perciformes , Animais , Ácido Linoleico , Ácido Araquidônico , Ácidos Docosa-Hexaenoicos
16.
Food Res Int ; 173(Pt 1): 113309, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37803620

RESUMO

The roles of enzymatic (Lipoxygenases, LOX) oxidation and autoxidation in the dry-cured processing of mackerel were investigated by adding exogenous substances in this study. Four groups, namely control, chlorogenic acid (inhibiting LOX activity), EDTA-2Na (inhibiting autoxidation), and exogenous LOX (adding eLOX), were assigned. The results showed that lipid oxidation of mackerel was reduced by inhibiting LOX activity and autoxidation, while adding eLOX promoted lipid oxidation. Inhibition of LOX activity and autoxidation suppressed fatty acid accumulation mainly in the air-drying and curing stage, respectively. The total contents of key flavors in the mackerel during dry-cured processing were decreased by inhibiting LOX activity and autoxidation, and the former inhibitory effect was stronger than autoxidation, while it was corresponding increased through adding eLOX, of particular in the later stage of air-drying. Collectively, LOX could promote the flavor formation of the mackerel in the dry-cured processing, which could be applied in the flavor adjustment of aquatic products or some similar fields.


Assuntos
Lipoxigenases , Perciformes , Animais , Oxirredução , Alimentos Marinhos , Ácidos Graxos
17.
Foods ; 12(13)2023 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-37444242

RESUMO

In this study, lipoxygenase (LOX) extracted from dry-cured mackerel was purified, resulting in a 4.1-fold purification factor with a specific activity of 493.60 U/min·g. LOX enzymatic properties were assessed, referring to its optimal storage time (1-2 days), temperature (30 °C), and pH value (7.0). The autoxidation and LOX-induced oxidation of palmitic acid (C16:0), stearic acid (C18:0), oleic acid (C18:2n9c), linoleic acid (C18:2n6c), arachidonic acid (C20:4), EPA (C20:5), and DHA (C22:6n3) were simulated to explore the main metabolic pathways of key flavors in dry-cured mackerel. The results showed that the highest LOX activity was observed when arachidonic acid was used as a substrate. Aldehydes obtained from LOX-treated C18:1n9c and C18:2n6c oxidation, which are important precursors of flavors, were the most abundant. The key flavors in dry-cured mackerel were found in the oxidative products of C16:0, C18:0, C18:1n9c, C18:2n6c, and C20:4. Heptanaldehyde could be produced from autoxidation or LOX-induced oxidation of C18:0 and C18:1n9c, while nonal could be produced from C18:1n9c and C18:2n6c oxidation. Metabolic pathway analysis revealed that C18:1n9c, C18:2n6c, EPA, and DHA made great contributions to the overall flavor of dry-cured mackerel. This study may provide a relevant theoretical basis for the scientific control of the overall taste and flavor of dry-cured mackerel and further standardize its production.

18.
Clin Case Rep ; 11(6): e7533, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37323266

RESUMO

Key Clinical Message: For potentially resectable HCC, a more aggressive conversion therapy strategy (high-intensity combined with multiple treatment modalities) can be used. Abstract: Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide. The best treatment for HCC is radical surgical resection, but 70%-80% of patients are ineligible for surgery. Although conversion therapy is an established treatment strategy for various solid tumors, there is no uniform protocol for treating HCC. In this case, we present a 69-year-old male patient diagnosed with massive HCC with Barcelona clinical liver cancer (BCLC) stage B. Because of the insufficient volume of the future liver remnant, we believed radical surgical resection was temporarily impossible. Therefore, the patient received conversion therapy, including four cycles of transcatheter arterial embolization (TAE) and hepatic arterial infusion chemotherapy (HAIC-Folfox), lenvatinib (8 mg orally once a day), and tislelizumab (an anti-PD-1 antibody, 200 mg intravenously once every 3 weeks). Fortunately, the patient achieved a good treatment response (smaller lesions and improved liver function) and underwent radical surgery finally. There was no clinical evidence of recurrence at 6 months of follow-up. For potentially resectable HCC, this case reveals that a more aggressive conversion therapy strategy (high-intensity combined with multiple treatment modalities) can be used.

19.
Methods Mol Biol ; 2695: 213-225, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37450121

RESUMO

Hepatocellular carcinoma (HCC) is one of the most deadly neoplasms with a poor prognosis. Due to the significant tumor heterogeneity of HCC, alpha-fetoprotein (AFP) or liver biopsy has not yet met the clinical needs in terms of early diagnosis or determining prognosis. In recent years, liquid biopsy techniques that analyze tumor by-products released into the circulation have shown great potential. Its ability to monitor tumors in real time and respond to their global characteristics is expected to improve the management of HCC patients clinically. This review discusses some of the findings of a liquid biopsy in terms of diagnosis and prognosis of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/patologia , alfa-Fetoproteínas/análise , Biópsia Líquida , Biomarcadores Tumorais
20.
Food Chem ; 421: 136174, 2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37086519

RESUMO

Effect of gamma irradiation on quality, flavor and sensory properties of smoked chicken breasts were investigated. Results indicated irradiation doses >3 kGy were effective for sterilization, while also produced a significant effect on overall quality of smoked chicken breast. Irradiation treatment could inhibit protein oxidation and accelerate lipid oxidation of smoked chicken breasts. High irradiation doses could increase the instability of free and bound water, as well as increase muscle fiber gap and juice loss significantly. Irradiation treatment also promoted free fatty acids and taste-presenting nucleotides degradation, effectively increased fresh-tasting amino acids contents and decreased bitter and sweet-tasting amino acids contents. The types and relative contents of volatiles, especially aldehydes, alcohols, aromatic hydrocarbons, and phenolic compounds, also changed after irradiation, while tartaric, pyruvic, and malic acids decreased. Results obtained can provide valuable reference data for improving the quality and flavor of smoked chicken breasts using gamma irradiation technology.


Assuntos
Galinhas , Fumaça , Animais , Paladar , Aminoácidos
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