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1.
Mol Carcinog ; 63(5): 926-937, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38380957

RESUMO

Early treatment of retinoblastoma (RB) has significantly improved clinical outcomes. N6-methyladenosine (m6A) methylation is crucial for cancer progression. Thus, we investigated the role of FTO-dependent demethylation in RB and its underlying mechanisms. The biological behavior of RB cells was analyzed using cell counting kit-8, colony formation analysis, transwell assay, flow cytometry, and western blot analysis. m6A modification was evaluated using methylated RNA immunoprecipitation and dual-luciferase reporter assays, and E2F3 stability was assessed using Actinomycin D. The roles of FTO and E2F3 were also elucidated in vivo. These results indicated that FTO was highly expressed in RB cells with low m6A levels. FTO knockdown inhibited RB cell growth, migration, invasion, and epithelial-mesenchymal transition and arrested the cell cycle at the G0/G1 phase. Mechanistically, FTO interference promoted m6A methylation of E2F3, which was recognized by YTHDF2, thereby reducing mRNA stability. E2F3 overexpression partially rescued the effects of FTO knockdown on biological behavior. Moreover, FTO knockdown reduced tumor weight, tumor volume, ki67 expression, and tumor cell infiltration by mediating E2F3. Taken together, FTO silencing inhibited the malignant processes of RB by suppressing E2F3 in an m6A-YTHD2-dependent manner. These findings suggest that FTO is a novel therapeutic target for RB.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato , Fator de Transcrição E2F3 , Neoplasias da Retina , Retinoblastoma , Humanos , Adenosina , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Ciclo Celular , Fator de Transcrição E2F3/genética , Fator de Transcrição E2F3/metabolismo , Retinoblastoma/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
2.
J Am Chem Soc ; 146(9): 5964-5976, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38381843

RESUMO

Fluorinated ethers have become promising electrolyte solvent candidates for lithium metal batteries (LMBs) because they are endowed with high oxidative stability and high Coulombic efficiencies of lithium metal stripping/plating. Up to now, most reported fluorinated ether electrolytes are -CF3-based, and the influence of ion solvation in modifying degree of fluorination has not been well-elucidated. In this work, we synthesize a hexacyclic coordinated ether (1-methoxy-3-ethoxypropane, EMP) and its fluorinated ether counterparts with -CH2F (F1EMP), -CHF2 (F2EMP), or -CF3 (F3EMP) as terminal group. With lithium bis(fluorosulfonyl)imide as single salt, the solvation structure, Li-ion transport behavior, lithium deposition kinetics, and high-voltage stability of the electrolytes were systematically studied. Theoretical calculations and spectra reveal the gradually reduced solvating power from nonfluorinated EMP to fully fluorinated F3EMP, which leads to decreased ionic conductivity. In contrast, the weakly solvating fluorinated ethers possess higher Li+ transference number and exchange current density. Overall, partially fluorinated -CHF2 is demonstrated as the desired group. Further full cell testing using high-voltage (4.4 V) and high-loading (3.885 mAh cm-2) LiNi0.8Co0.1Mn0.1O2 cathode demonstrates that F2EMP electrolyte enables 80% capacity retention after 168 cycles under limited Li (50 µm) and lean electrolyte (5 mL Ah-1) conditions and 129 cycles under extremely lean electrolyte (1.8 mL Ah-1) and the anode-free conditions. This work deepens the fundamental understanding on the ion transport and interphase dynamics under various degrees of fluorination and provides a feasible approach toward the design of fluorinated ether electrolytes for practical high-voltage LMBs.

3.
J Am Chem Soc ; 146(8): 5597-5604, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38366992

RESUMO

Rechargeable aqueous batteries are potential systems for large-scale energy storage due to their high safety and low cost. However, developing aqueous batteries with high sustainability, affordability, and reversibility is urgent and challenging. Here we report an amphoteric aluminum hydroxyacetate (AlAc(OH)2) electrolyte with the ability of bipolar ionization of H+ and OH-, which facilitates the redox reactions at both the anthraquinone (AQ) anode and nickel hydroxide (Ni(OH)2) cathode. The bipolar ionization ability of the AlAc(OH)2(H2O)3 solvation structure results from the strong polarization ability of Al3+ and OH-. The H+/OH- dissociation ability with a dissociation constant of 5.0/3.0 is stronger than that of water (14.0), which boosts the simultaneous stable redox reactions of electrodes. Specifically, H+ uptake prevents the AQ anode from the formation of an ionic bond, suppressing the electrode dissolution, whereas OH- provides the local alkaline environment for the stable conversion reaction of the Ni(OH)2 cathode. The AQ anode in the designed AQ||Ni(OH)2 battery delivers a discharge capacity of 243.9 mAh g-1 and a capacity retention of 78.2% after 300 cycles with high reversibility. Moreover, a pouch cell with a discharge capacity of 0.90 Ah was assembled, exhibiting an energy density of 44.7 Wh kg-1 based on the total mass of the battery. This work significantly widens the types of aqueous batteries and represents a design philosophy of bipolar electrolytes and distinct electrochemical reactions with H+ and OH-.

4.
J Neurochem ; 168(2): 142-160, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38169121

RESUMO

White matter injury (WMI) is one of the most serious complications associated with preterm births. Damage to oligodendrocytes, which are the key cells involved in WMI pathogenesis, can directly lead to myelin abnormalities. L-ascorbyl-2-phosphate (AS-2P) is a stable form of vitamin C. This study aimed to explore the protective effects of AS-2P against chronic hypoxia-induced WMI, and elucidate the underlying mechanisms. An in vivo chronic hypoxia model and in vitro oxygen-glucose deprivation (OGD) model were established to explore the effects of AS-2P on WMI using immunofluorescence, immunohistochemistry, western blotting, real-time quantitative polymerase chain reaction, Morris water maze test, novel object recognition test, beaming-walking test, electron microscopy, and flow cytometry. The results showed that AS-2P resulted in the increased expression of MBP, Olig2, PDGFRα and CC1, improved thickness and density of the myelin sheath, and reduced TNF-α expression and microglial cell infiltration to alleviate inflammation in the brain after chronic hypoxia. Moreover, AS-2P improved the memory, learning and motor abilities of the mice with WMI. These protective effects of AS-2P may involve the upregulation of protein arginine methyltransferase 5 (PRMT5) and downregulation of P53 and NF-κB. In conclusion, our study demonstrated that AS-2P attenuated chronic hypoxia-induced WMI in vivo and OGD-induced oligodendrocyte injury in vitro possibly by regulating the PRMT5/P53/NF-κB pathway, suggesting that AS-2P may be a potential therapeutic option for WMI.


Assuntos
Lesões Encefálicas , Substância Branca , Animais , Camundongos , NF-kappa B/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais Recém-Nascidos , Substância Branca/patologia , Hipóxia/metabolismo , Lesões Encefálicas/patologia , Ácido Ascórbico/metabolismo , Oxigênio/metabolismo
5.
Inorg Chem ; 63(3): 1543-1549, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38189236

RESUMO

We synthesize four novel quasi-one-dimensional organic-inorganic hybrid iron chloride compounds (CH3NH3FeCl3, CH(NH2)2FeCl3, C(NH2)3FeCl3, and C3H5N2FeCl3) and characterize their structural and magnetic properties. These materials crystallize in a hexagonal perovskite-type structure, constituting a triangular array of face-sharing iron chloride octahedra chains running along the c-axis, isolated from one another by the organic cation. Through magnetization and heat capacity measurements, we find that the intrachain coupling is weakly ferromagnetic for each variant. Importantly, this work underscores the utility of solid-state chemistry approaches in synthesizing new organic-inorganic hybrid materials.

6.
Asian J Surg ; 47(1): 471-476, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37142503

RESUMO

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) plays a major role in the diagnosis of malignant biliary strictures. ERCP fluoroscopy-guided biliary biopsy is more sensitive than brushing, but it is more difficult to perform and less successful. Therefore, a new technique of biliary biopsy using a new biliary biopsy cannula via the ERCP route was developed in our center with the aim of improving the diagnosis rate of malignant biliary strictures. METHODS: This is a retrospective study that included 42 patients who underwent ERCP-guided biliary brushing and biliary biopsy for biliary strictures using a new biliary biopsy cannula in our department from January 2019 to May 2022. The final diagnosis was determined after brushing, biliary biopsy under the new biliary biopsy cannula or adequate follow-up. Diagnostic rates were calculated and analyzed for relevant factors. RESULTS: The satisfactory rates of pathological specimens of 42 patients who underwent bile duct biopsy with bile duct brush and new bile duct biopsy cannula were 57.14% and 95.24% respectively. Cholangiocarcinoma was diagnosed in 45.23% and 83.30% of the samples by biliary brush examination and biliary biopsy using the new biliary biopsy cannula, respectively (p < 0.001). CONCLUSIONS: The ERCP route using a new biliary biopsy cannula for biliary biopsy technique can improve pathology positivity and benefit ratio. It provides a new approach in the diagnosis of malignant stenosis in the bile duct.


Assuntos
Neoplasias dos Ductos Biliares , Colestase , Humanos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Cânula , Constrição Patológica/diagnóstico , Constrição Patológica/etiologia , Estudos Retrospectivos , Sensibilidade e Especificidade , Biópsia , Colestase/diagnóstico , Colestase/etiologia , Ductos Biliares , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos
7.
Angew Chem Int Ed Engl ; 62(43): e202310761, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37668230

RESUMO

Despite carbonate electrolytes exhibiting good stability to sulfurized polyacrylonitrile (SPAN), their chemical incompatibility with lithium (Li) metal anode leads to poor electrochemical performance of Li||SPAN full cells. While the SPAN employs conventional ether electrolytes that suffer from the shuttle effect, leading to rapid capacity fading. Here, we tailor a dilute electrolyte based on a low solvating power ether solvent that is both compatible with SPAN and Li metal. Unlike conventional ether electrolytes, the weakly solvating ether electrolyte enables SPAN to undergo reversibly "solid-solid" conversion. It features an anion-rich solvation structure that allows for the formation of a robust cathode electrolyte interphase on the SPAN, effectively blocking the dissolution of polysulfides into the bulk electrolyte and avoiding the shuttle effect. What's more, the unique electrolyte chemistry endowed Li ions with fast electroplating kinetics and induced high reversibility Li deposition/stripping process from 25 °C to -40 °C. Based on tailored electrolyte, Li||SPAN full cells matched with high loading SPAN cathodes (≈3.6 mAh cm-2 ) and 50 µm Li foil can operate stably over a wide range of temperatures. Additionally, Li||SPAN pouch cell under lean electrolyte and 5 % excess Li conditions can continuously operate stably for over a month.

8.
Am J Cancer Res ; 13(4): 1571-1581, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37168343

RESUMO

Renal impairment (RI) is a very common complication of multiple myeloma (MM) with a negative impact on survival. Herein we retrospectively analyzed 334 MM patients with renal impairment at diagnosis from three hospitals in China. All 334 patients were divided into three groups, including dialysis dependence (n=43), dialysis independence (n=42), and without dialysis (n=249). Compared with dialysis independence and without dialysis groups, dialysis dependence group had the lowest overall hematologic response (48.8% vs. 97.6% vs. 77.1%, P<0.001) and overall renal response (0.0% vs. 97.6% vs. 72.7%, P<0.001), as well as the highest early mortality within 24 months (50.0% vs. 24.4% vs. 26.3%, P=0.006). Dialysis dependence group had similar progression-free survival (24 vs. 26 vs. 27 months, P=0.231) and significantly shorter overall survival (25 vs. 69 vs. 45 months, P=0.001). Dialysis dependence was independently associated with high mortality within 24 months and shorter overall survival. In conclusion, MM patients with dialysis dependence still tend to suffer a dismal disease course, including a high probability to suffer early mortality, worse hematological and renal response, as well as shorter survival. Dialysis independence could be very promising for survival improvement.

9.
Front Biosci (Landmark Ed) ; 28(5): 101, 2023 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-37258465

RESUMO

BACKGROUND: Rapid progression and early metastasis remain the main cause of high mortality in epithelial ovarian cancer (EOC) patients. The objective of this study was to explore the mechanisms of EOC progression and detect the function of leucine-rich alpha-2-glycoprotein 1 (LRG1) in modulating the pathologic process. METHODS: Ultracentrifugation was initially performed to extract exosomes from the urine samples of EOC patients and healthy female subjects. Mass spectrometry (MS) was employed to analyze differentially expressed proteins. Survival analysis was performed to examine the association between LRG1 levels and the prognosis of EOC patients. LRG1 silencing ovarian cancer cell lines were built and cell migration was further evaluated via wound healing and transwell assays. Immunoblot, immunofluorescence and immunohistochemistry analyses were performed. A subcutaneous tumor model was established to study the function of LRG1 in vivo. RESULTS: Exosomal LRG1 was specifically expressed in urine samples of EOC patients and high LRG1 levels were significantly associated with poor prognosis. Function analyses showed that LRG1 was associated with ovarian cancer migration and progression. Mechanistically, LRG1 was significantly related to the focal adhesion kinase/protein kinase B (FAK/AKT) signaling pathway. CONCLUSIONS: LRG1 participated in progression and metastasis of ovarian cancer via activation of the FAK/AKT pathway probably.


Assuntos
Neoplasias Ovarianas , Proteínas Proto-Oncogênicas c-akt , Humanos , Feminino , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Carcinoma Epitelial do Ovário/metabolismo , Carcinoma Epitelial do Ovário/patologia , Transdução de Sinais , Linhagem Celular Tumoral , Proliferação de Células , Glicoproteínas/metabolismo
10.
Int J Hematol ; 118(2): 231-241, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37247070

RESUMO

Light chain amyloidosis is a plasma cell dyscrasia characterized by deposition of misfolded amyloid fibrils in tissues, leading to multi-organ dysfunction. We retrospectively analyzed 335 patients (median age, 60 years) with systemic light chain amyloidosis in the First Hospital of Peking University from 2011 to 2021. Involved organs were the kidney (92.8%), heart (57.9%), liver (12.8%) and peripheral nervous system (6.3%). Chemotherapy was administered to 55.8% (187/335) of patients, among whom 94.7% received novel agent-based regimens. Hematologic response (≥ very good partial response) was achieved in 63.4% of patients who received chemotherapy. Only 18.2% of patients received autologous hematopoietic stem cell transplant (ASCT). Among transplant-eligible patients, the overall survival of ASCT recipients was better than those who received chemotherapy only. The median overall survival of the patients with light chain amyloidosis was 77.5 months. Estimated glomerular filtration rate and Mayo 2012 stage were independent prognostic factors for overall survival in multivariate analysis. Although the younger age and high ratio of renal involvement might contribute to the favorable prognosis of this cohort, the role of novel agents and ASCT is also discernible. This study will provide a comprehensive perspective on progress in treatment of light chain amyloidosis in China.


Assuntos
Amiloidose , Transplante de Células-Tronco Hematopoéticas , Amiloidose de Cadeia Leve de Imunoglobulina , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , População do Leste Asiático , Resultado do Tratamento , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Prognóstico , Transplante Autólogo
12.
J Transl Med ; 21(1): 334, 2023 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-37210575

RESUMO

BACKGROUND: Ovarian cancer (OC) has high mortality and poor prognosis for lacking of specific biomarkers and typical clinical symptoms in the early stage. CEBPG is an important regulator in tumor development, yet it is unclear exactly how it contributes to the progression of OC. METHODS: TCGA and tissue microarrays with immunohistochemical staining (IHC) were used to examine CEBPG expression in OC. A variety of in vitro assays were conducted, including colony formation, proliferation, migration, and invasion. The orthotopic OC mouse model was established for in vivo studies. Ferroptosis was detected by observing mitochondrial changes with electron microscopy, detecting ROS expression, and detecting cell sensitivity to drugs by CCK8 assay. The interaction between CEBPG and SLC7A11 was confirmed by CUT&Tag and dual luciferase reporter assays. RESULTS: A significantly higher expression level of CEBPG in OC when compared with benign tissues of ovary, and that high CEBPG expression level was also tightly associated with poor prognosis of patients diagnosed with OC, as determined by analysis of datasets and patient samples. Conversely, knockdown of CEBPG inhibited OC progression using experiments of OC cell lines and in vivo orthotopic OC-bearing mouse model. Importantly, CEBPG was identified as a new participator mediating ferroptosis evasion in OC cells using RNA-sequencing, which could contribute to OC progression. The CUT&Tag and dua luciferase reporter assays further revealed the inner mechanism that CEBPG regulated OC cell ferroptosis through transcriptional control of SLC7A11. CONCLUSIONS: Our findings established CEBPG as a novel transcriptional regulator of OC ferroptosis, with potential value in predicting clinical outcomes and as a therapeutic candidate.


Assuntos
Sistema y+ de Transporte de Aminoácidos , Proteínas Estimuladoras de Ligação a CCAAT , Ferroptose , Neoplasias Ovarianas , Animais , Feminino , Humanos , Camundongos , Sistema y+ de Transporte de Aminoácidos/genética , Bioensaio , Linhagem Celular Tumoral , Ferroptose/genética , Regulação da Expressão Gênica , Neoplasias Ovarianas/genética , Proteínas Estimuladoras de Ligação a CCAAT/genética
13.
Scand J Gastroenterol ; 58(5): 542-548, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36369879

RESUMO

OBJECTIVES: Contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) has been used in the differential diagnosis of benign and malignant tumors by visualization of tumor microcirculation and perfusion. However, its diagnostic role in submucosal tumors (SMTs), especially leiomyomas and gastric submucosal tumors (GISTs) was rarely studied. The aim of this study was to analyze the diagnostic role of CEH-EUS for SMTs (<50 mm) and the value of assessing the malignant potential of GISTs. MATERIALS AND METHODS: We retrospectively included patients with tumors <50 mm in diameter who underwent preoperative EUS and CEH-EUS examination and had pathologically confirmed as leiomyomas and GISTs. To analyze the imaging features of CEH-EUS with pathological diagnosis as the gold standard and evaluate its diagnostic value. RESULTS: This study included 10 cases of leiomyomas and 38 cases of GISTs. Under CEH-EUS detection, 86.9% of GISTs showed hyper-enhancement, 89.5% showed diffuse enhancement, 39.5% showed non-enhancing spots, and 97.4% showed obvious capsule enhancement. In contrast, the leiomyoma cases mostly showed hypo-enhancement (50.0%) or non-enhancement (30.0%) (p < 0.05). Then, the value of CEH-EUS in the differential diagnosis of benign and malignant tumors based on blood flow is significantly higher than that of B-EUS. Signal appearance time was significantly faster in the intermediate-high risk GISTs than in the very low-low risk group (5.1 s versus 15.5 s, p < 0.05), and the AUROC values predicted the risk at this time to be 0.903 (0.763-0.975). Heterogeneous perfusion and non-enhancing spots were also more common in the intermediate-high risk group. Univariate and multivariate analysis revealed that intratumoral irregularitie was an independent predictor of moderate to high risk (OR 3.99, 95%CI 1.04-90.95), with sensitivity, specificity and accuracy of 73.33%, 91.30% and 84.21%, respectively. CONCLUSIONS: Through this study, CEH-EUS has a good differential diagnostic ability for leiomyomas and GISTs, and has a high value in predicting the risk of GISTs.


Assuntos
Tumores do Estroma Gastrointestinal , Leiomioma , Neoplasias Gástricas , Humanos , Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/patologia , Diagnóstico Diferencial , Estudos Retrospectivos , Meios de Contraste , Endossonografia/métodos , Neoplasias Gástricas/diagnóstico por imagem , Leiomioma/diagnóstico por imagem
14.
Technol Cancer Res Treat ; 21: 15330338221132370, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36254566

RESUMO

Objectives: Myelomatous pleural effusion is a rare presentation of extramedullary disease in multiple myeloma, which has been reported with dismal prognosis. We aimed to explore whether it has distinctive clinical characteristics and outcomes compared to other anatomic locations of extramedullary involvements. Methods: Multiple myeloma patients diagnosed at our institution from 2010 to 2020 were retrieved retrospectively. In total, 42 pairs of patients with and without extramedullary disease were enrolled, including 13 with myelomatous pleural effusion. The clinical and laboratory parameters were collected and compared between different groups. Prognostic effect of myelomatous pleural effusion was assessed in cox regression model and Kaplan-Meier curves. Results: Myelomatous pleural effusion patients presented a higher level of ß2-microglobulin (P = .041), greater prevalence of multisites extramedullary lesions (69.2% vs 38.0%, P = .036) and International Staging System stage III (76.9% vs 44.8%, P = .016). Median overall survival was 60.6 months in patients without extramedullary disease versus 35.0 months in patients with extramedullary disease (P = .045). Notably, median overall survival was 13.0 months in myelomatous pleural effusion patients versus 37.0 months in other extramedullary disease patients with a significant difference (P = .029). Furtherly, multivariate analysis recognized myelomatous pleural effusion as an independent prognostic indicator (Hazard ratio: 2.669, 95% CI [1.132-6.293], P = .025). Conclusion: Myelomatous pleural effusion patients presented heavier tumor burden and worse outcomes than other extramedullary diseases.


Assuntos
Mieloma Múltiplo , Derrame Pleural Maligno , Derrame Pleural , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/patologia , Derrame Pleural/diagnóstico , Derrame Pleural/etiologia , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/etiologia , Prognóstico , Estudos Retrospectivos
15.
Front Oncol ; 12: 876257, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36033461

RESUMO

Background: Octamer-binding transcription factor 4 (OCT4) is a key stem cell transcription factor involved in the development of various cancers. The role of OCT4 in ovarian cancer (OC) progression and its molecular mechanism are not fully understood. Methods: First, immunohistochemistry (IHC) assays of ovarian benign cyst tissues, OC tissues, and omental metastatic tissues were performed to reveal OCT4 expression profiles. We knocked down OCT4 in two OC cell lines (SKOV3 and A2780) using a lentiviral vector and performed in vitro and in vivo experiments. OCT4 was knocked down to assess the proliferation, migration, and invasion of OC cells using CCK-8, colony formation, wound healing, and Transwell assays. In addition, the nude tumor mouse model was used for in vivo study. Mechanistically, we demonstrated that OCT4 influenced protein expression in the phosphoinositol 3-kinase (PI3K)/AKT/mTOR pathway and epithelial-mesenchymal transition (EMT)-related proteins by Western blotting and immunofluorescence (IF) assays. The interaction between OCT4 and p-AKT was further confirmed by coimmunoprecipitation (CoIP) assays. Importantly, AKT activation by its activator SC79 reversed the biological functions of OCT4 knockdown. Results: OCT4 expression was significantly upregulated in OC samples and metastatic tissues. OCT4 knockdown notably inhibited the proliferation, migration, and invasion of OC cells in vitro and in vivo. Moreover, the expression of p-PI3K, p-AKT, and p-mTOR was downregulated after OCT4 knockdown. An AKT agonist reversed the effect of OCT4 knockdown on OC cells. EMT in OC samples was enhanced by OCT4. Conclusions: Our study shows that OCT4 promotes the proliferation, migration, and invasion of OC cells by participating in the PI3K/AKT/mTOR signaling axis, suggesting that it could serve as a potential therapeutic target for OC patients.

16.
Bioengineered ; 13(6): 14357-14367, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35758265

RESUMO

Epithelial-melancholy transition (EMT) is the main cause of organ fibrosis and a common pathogenetic mechanism in most cataracts. This study aimed to explore the molecular mechanism of Toll-like receptor (TLR)-3 in the occurrence and development of post-cataract EMT and to provide new ideas for the prevention and treatment of posterior capsule opacification (PCO). In the presence or absence of TLR3, the human lens epithelial cell (LEC) line, SRA01/04, was treated with the transforming growth factor (TGF)-ß2. Cell counting kit-8 (CCK-8) and Transwell assays were used to analyze the cell proliferation, migration, and invasion. The expression levels of proteins and RNAs were detected by western blotting and quantitative polymerase chain reaction (qPCR) experiments. Functional gain and loss studies showed that TLR3 regulates the proliferation, migration, and invasion of LECs and EMT induced by TGF-ß2. Moreover, TLR3 regulates the expression of Jagged-1, Notch-1, and Notch-3 These findings indicate that TLR3 prevents the progression of lens fibrosis by targeting the Jagged-1/Notch signaling pathway to regulate the proliferation, migration, and invasion of LECs, and TGF-ß2-induced EMT. Therefore, the TLR3-Jagged-1/Notch signaling axis may be a potential therapeutic target for the treatment of fibrotic cataracts.


Assuntos
Opacificação da Cápsula , Receptores Notch , Receptor 3 Toll-Like , Opacificação da Cápsula/genética , Opacificação da Cápsula/metabolismo , Opacificação da Cápsula/patologia , Movimento Celular/genética , Proliferação de Células/genética , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Transição Epitelial-Mesenquimal , Fibrose , Humanos , Proteína Jagged-1/genética , Proteína Jagged-1/metabolismo , Receptores Notch/genética , Receptores Notch/metabolismo , Transdução de Sinais/genética , Receptor 3 Toll-Like/genética , Receptor 3 Toll-Like/metabolismo , Fator de Crescimento Transformador beta2/farmacologia
17.
Inorg Chem ; 61(27): 10486-10492, 2022 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-35766995

RESUMO

We synthesize and characterize the magnetic and thermodynamic properties of the quasi one-dimensional organic-inorganic hybrid ANiCl3 compounds [A = N(CH3)4+, CH3NH3+, (CH3)2NH2+, C(NH2)3+, and CH(NH2)2+]. Additionally, the crystal structure of (CH3)2NH2NiCl3 is reported. These materials possess chains of face-sharing NiCl6 octahedra in a triangular array. The chains run in one direction and are separated from one another by organic cations of different sizes and geometries. In accordance with the 90° superexchange model, we find that the nature of the magnetic coupling within chains can be predicted by the value of the Ni-Cl-Ni angle. As the Ni-Cl-Ni angle decreases from 90°, the magnetic interactions become increasingly antiferromagnetic. These findings provide a foundation for predicting the magnetic properties of quasi one-dimensional organic-inorganic hybrid ANiCl3 compounds.

18.
NPJ Digit Med ; 5(1): 23, 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35236921

RESUMO

Malignant eyelid tumors can invade adjacent structures and pose a threat to vision and even life. Early identification of malignant eyelid tumors is crucial to avoiding substantial morbidity and mortality. However, differentiating malignant eyelid tumors from benign ones can be challenging for primary care physicians and even some ophthalmologists. Here, based on 1,417 photographic images from 851 patients across three hospitals, we developed an artificial intelligence system using a faster region-based convolutional neural network and deep learning classification networks to automatically locate eyelid tumors and then distinguish between malignant and benign eyelid tumors. The system performed well in both internal and external test sets (AUCs ranged from 0.899 to 0.955). The performance of the system is comparable to that of a senior ophthalmologist, indicating that this system has the potential to be used at the screening stage for promoting the early detection and treatment of malignant eyelid tumors.

19.
Phytochem Anal ; 33(4): 517-532, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35144310

RESUMO

INTRODUCTION: The diterpenoids are the most important active constituents that contribute to the pharmacological efficacy of Isodon serra (Maxim.) Hara. Clinical studies have revealed that diterpenoids possess multiple features, e.g. antitumour, antitubercular and anti-ischemic activities. Therefore, the identification and detection of diterpenoids may be equally important for understanding the pharmacological basis of diterpenoids and enhancing the product quality control of I. serra. OBJECTIVES: The purpose of this study was to develop a practical analysis approach of rapid characterisation using ultrahigh-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) for the structure characterisation of the ent-kaurane diterpenoids from I. serra. METHODOLOGY: The analytical strategy was as follows: first, ent-kaurane diterpenoids were detected by a novel on-line data acquisition approach, i.e. sequential window acquisition of all theoretical fragment-ion spectra (SWATH). Second, the MS of eight ent-kaurane diterpenoids was explored, and their mass spectrum cleavage pathways were summarised and determined. Finally, the methanol extract of I. serra was studied using SWATH and identified by extracted ion chromatography (XIC). RESULTS: Compared to the traditional information-dependent acquisition (IDA) method, SWATH significantly improved the hit rate of ent-kaurane diterpenoids. With support from UHPLC separation and specific detection by tandem mass spectrometry (MS/MS), 48 ent-kaurane diterpenoids were successfully characterised and classified as ent-kaurane diterpenoids from a complex matrix. CONCLUSIONS: These combined qualitative methods were used to provide a potential approach for the characterisation of traditional Chinese medicine (TCM) and its preparations. Meanwhile, the SWATH provided a novel and reliable method for the structural characterisation of ent-kaurane diterpenoids from other complicated TCMs.


Assuntos
Diterpenos do Tipo Caurano , Diterpenos , Isodon , Cromatografia Líquida de Alta Pressão , Diterpenos/análise , Diterpenos do Tipo Caurano/análise , Isodon/química , Espectrometria de Massas em Tandem/métodos
20.
Int Wound J ; 19(6): 1319-1328, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34854236

RESUMO

We performed a meta-analysis to evaluate the effect of negative pressure wound therapy compared with conventional wound dressings on closed incisions in orthopaedic trauma surgery. A systematic literature search up to October 2021 was done and 12 studies included 3555 subjects with closed incisions in orthopaedic trauma surgery at the start of the study: 1833 of them were provided with negative pressure wound therapy and 1722 were conventional wound dressings. They were reporting relationships about the effect of negative pressure wound therapy compared with conventional wound dressings on closed incisions in orthopaedic trauma surgery. We calculated the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) to assess the effect of negative pressure wound therapy compared with conventional wound dressings on closed incisions in orthopaedic trauma surgery using the dichotomous and continuous methods with a random or fixed-effect model. Negative pressure wound therapy had significantly lower deep surgical site infection (OR, 0.65; 95% CI, 0.48-0.88, P = .005), superficial surgical site infection (OR, 0.23; 95% CI, 0.11-0.49, P = .31), and wound dehiscence (OR, 0.41; 95% CI, 0.21-0.80, P = .009) compared with conventional wound dressings in subjects with closed incisions in orthopaedic trauma surgery. However, negative pressure wound therapy had no significant effect on the length of hospital stay (MD, 0.29; 95% CI, -2.00- 2.58, P = .80) compared with conventional wound dressings in subjects with closed incisions in orthopaedic trauma surgery. Negative pressure wound therapy had significantly lower deep surgical site infection, superficial surgical site infection, and wound dehiscence; however, negative pressure wound therapy had no beneficial effect on the length of hospital stay compared with conventional wound dressings in subjects with closed incisions in orthopaedic trauma surgery. Further studies are required to validate these findings.


Assuntos
Tratamento de Ferimentos com Pressão Negativa , Ortopedia , Bandagens , Humanos , Tratamento de Ferimentos com Pressão Negativa/métodos , Deiscência da Ferida Operatória/terapia , Infecção da Ferida Cirúrgica/prevenção & controle , Cicatrização
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