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1.
iScience ; 27(9): 110836, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39310774

RESUMO

Histological grading is the key factors affecting the prognosis and instructive in guiding treatment and assessing recurrence in non-functional pancreatic neuroendocrine tumor (NF-Pan-NET). Approximately one-third of patients without copy number variation (CNV) alteration and the prognosis of these patients are better than that of patients with CNV alteration. However, the difference between CNV and histological grading is unclear. Here, we analyzed the heterogeneity of tumor cells according to two classification criteria, genomic instability (including CNV alteration and tumor mutation burden) and histological grading. We revealed that the activated core pathways of tumor cells were significantly different under different histological grading's and genomic instability patterns. We also found that tip cells, lymphatic endothelial cells, macrophages, CD1A + dendritic cell, Treg, MAIT, ILC, and CAFs might participate in the process of hepatic metastases, which will facilitate the understanding of the patterns to decode the malignant potential and of NF-Pan-NET.

2.
Heliyon ; 10(17): e36898, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39296051

RESUMO

Background: Ovarian cancer (OV) is regarded as one of the most lethal malignancies affecting the female reproductive system, with individuals diagnosed with OV often facing a dismal prognosis due to resistance to chemotherapy and the presence of an immunosuppressive environment. T cells serve as a crucial mediator for immune surveillance and cancer elimination. This study aims to analyze the mechanism of T cell-associated markers in OV and create a prognostic model for clinical use in enhancing outcomes for OV patients. Methods: Based on the single-cell dataset GSE184880, this study used single-cell data analysis to identify characteristic T cell subsets. Analysis of high dimensional weighted gene co-expression network analysis (hdWGCNA) is utilized to identify crucial gene modules along with their corresponding hub genes. A grand total of 113 predictive models were formed utilizing ten distinct machine learning algorithms along with the combination of the cancer genome atlas (TCGA)-OV dataset and the GSE140082 dataset. The most dependable clinical prognostic model was created utilizing the leave one out cross validation (LOOCV) framework. The validation process for the models was achieved by conducting survival curve analysis and receiver operating characteristic (ROC) analysis. The relationship between risk scores and immune cells was explored through the utilization of the Cibersort algorithm. Additionally, an analysis of drug sensitivity was carried out to anticipate chemotherapy responses across various risk groups. The genes implicated in the model were authenticated utilizing qRT-PCR, cell viability experiments, and EdU assay. Results: This study developed a clinical prognostic model that includes ten risk genes. The results obtained from the training set of the study indicate that patients classified in the low-risk group experience a significant survival advantage compared to those in the high-risk group. The ROC analysis demonstrates that the model holds significant clinical utility. These results were verified using an independent dataset, strengthening the model's precision and dependability. The risk assessment provided by the model also serves as an independent prognostic factor for OV patients. The study also unveiled a noteworthy relationship between the risk scores calculated by the model and various immune cells, suggesting that the model may potentially serve as a valuable tool in forecasting responses to both immune therapy and chemotherapy in ovarian cancer patients. Notably, experimental evidence suggests that PFN1, one of the genes included in the model, is upregulated in human OV cell lines and has the capacity to promote cancer progression in in vitro models. Conclusion: We have created an accurate and dependable clinical prognostic model for OV capable of predicting clinical outcomes and categorizing patients. This model effectively forecasts responses to both immune therapy and chemotherapy. By regulating the immune microenvironment and targeting the key gene PFN1, it may improve the prognosis for high-risk patients.

3.
Eur J Med Chem ; 276: 116674, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39004017

RESUMO

Crocetin (CCT), a natural bioactive compound extracted and purified from the traditional Chinese medicinal herb saffron, has been shown to play a role in neurodegenerative diseases, particularly depression. However, due to challenges with solubility, targeting, and bioavailability, formulation development and clinical use of CCT are severely limited. In this study, we used the emulsification-reverse volatilization method to prepare CCT-loaded nanoliposomes (CN). We further developed a borneol (Bor) and lactoferrin (Lf) dual-modified CCT-loaded nanoliposome (BLCN) for brain-targeted delivery of CCT. The results of transmission electron microscope (TEM) and particle size analysis indicated that the size of BLCN (∼140 nm) was suitable for transcellular transport across olfactory axons (∼200 nm), potentially paving a direct path to the brain. Studies on lipid solubility, micropolarity, and hydrophobicity showed that BLCN had a relatively high Lf grafting rate (81.11 ± 1.33 %) and CCT entrapment efficiency (83.60 ± 1.04 %) compared to other liposomes, likely due to Bor improving the lipid solubility of Lf, and the combination promoting the orderly arrangement of liposome membrane molecules. Microplate reader and fluorescence microscopy analysis showed that BLCN efficiently promoted the endocytosis of fluorescent coumarin 6 into HT22 cells with a maximal fluorescence intensity of (13.48 ± 0.80 %), which was significantly higher than that of CCT (5.73 ± 1.17 %) and CN (12.13 ± 1.01 %). BLCN also exhibited sustained function, remaining effective for more than 12 h after reaching a peak at 1 h in cells, while CN showed a significant decrease after 4 h. The uptake mechanisms of BLCN in HT22 cells mainly involve energy-dependent, caveolae-mediated, and microtubule-mediated endocytosis, as well as micropinocytosis. Furthermore, BLCN displayed a significant neuroprotective effect on HT22 cells in glutamate-, corticosterone-, and H2O2-induced models. Tissue fluorescence image analysis of mice showed that BLCN exhibited substantial retention of fluorescent DiR in the brain after nasal administration for 12 h. These findings suggest that CCT has the potential for cellular uptake, neuroprotection, and targeted delivery to the brain following intranasal administration when encapsulated in Bor and Lf dual-modified nanoliposomes.


Assuntos
Encéfalo , Canfanos , Carotenoides , Lactoferrina , Lipossomos , Nanopartículas , Fármacos Neuroprotetores , Vitamina A , Animais , Vitamina A/química , Vitamina A/administração & dosagem , Vitamina A/análogos & derivados , Lipossomos/química , Carotenoides/química , Carotenoides/farmacologia , Camundongos , Encéfalo/metabolismo , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/administração & dosagem , Canfanos/química , Canfanos/farmacologia , Lactoferrina/química , Lactoferrina/farmacologia , Lactoferrina/administração & dosagem , Nanopartículas/química , Linhagem Celular , Tamanho da Partícula , Masculino , Estrutura Molecular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Relação Estrutura-Atividade , Neuroproteção/efeitos dos fármacos
4.
J Ethnopharmacol ; 333: 118404, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-38824977

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sepsis presents complex pathophysiological challenges. Taohe Chengqi Decoction (THCQ), a traditional Chinese medicine, offers potential in managing sepsis-related complications, though its exact mechanisms are not fully understood. AIM OF THE STUDY: This research aimed to assess the therapeutic efficacy and underlying mechanisms of THCQ on sepsis-induced lung injury. MATERIALS AND METHODS: The study began with validating THCQ's anti-inflammatory effects through in vitro and in vivo experiments. Network pharmacology was employed for mechanistic exploration, incorporating GO, KEGG, and PPI analyses of targets. Hub gene-immune cell correlations were assessed using CIBERSORT, with further scrutiny at clinical and single-cell levels. Molecular docking explored THCQ's drug-gene interactions, culminating in qPCR and WB validations of hub gene expressions in sepsis and post-THCQ treatment scenarios. RESULTS: THCQ demonstrated efficacy in modulating inflammatory responses in sepsis, identified through network pharmacology. Key genes like MAPK14, MAPK3, MMP9, STAT3, LYN, AKT1, PTPN11, and HSP90AA1 emerged as central targets. Molecular docking revealed interactions between these genes and THCQ components. qPCR results showed significant modulation of these genes, indicating THCQ's potential in reducing inflammation and regulating immune responses in sepsis. CONCLUSION: This study sheds light on THCQ's anti-inflammatory and immune regulatory mechanisms in sepsis, providing a foundation for further research and potential clinical application.


Assuntos
Anti-Inflamatórios , Medicamentos de Ervas Chinesas , Simulação de Acoplamento Molecular , Sepse , Sepse/tratamento farmacológico , Sepse/complicações , Sepse/imunologia , Animais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Humanos , Lesão Pulmonar/tratamento farmacológico , Farmacologia em Rede , Modelos Animais de Doenças
5.
Langenbecks Arch Surg ; 409(1): 164, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775920

RESUMO

PURPOSE: To explore the risk factors for incisional hernia (IH) recurrence following open prepertioneal repair. METHODS: Patients diagnosed with primary IH who underwent open preperitoneal repair at our hospital were enrolled. Patients were assessed, and perioperative factors were collected. Recurrence surveys were performed at regular intervals throughout the long-term postoperative follow-up. The risk factors for IH recurrence were identified using univariate and multivariate analyses. RESULTS: This study included 145 patients. Significant differences were found between recurrence and non-recurrence patients regarding pulmonary ventilation function (PVT), age, body mass index (BMI), mesh materials, type of surgery (clean, clean-contaminated, or contaminated), surgical site infections (SSIs), maximum width of the hernia defect (MWHD), and site of incisional hernia (P < 0.01). The univariate survival analysis revealed that PVT abnormalities, age > 70 years, BMI > 27 kg/m2, porcine small intestine submucosal (PSIS) mesh, non-clean surgery, SSIs, MWHD > 10 cm, and location in the lateral zones were significant factors for IH recurrence after open preperitoneal repair. The multivariate survival analysis showed that PVT abnormalities, age > 70 years, BMI > 27 kg/m2, and PSIS mesh were independent risk factors for IH recurrence after open preperitoneal repair. CONCLUSIONS: We identified PVT abnormalities, age > 70 years, BMI > 27 kg/m2, and PSIS mesh as novel risk factors for IH recurrence after open preperitoneal repair.


Assuntos
Herniorrafia , Hérnia Incisional , Recidiva , Telas Cirúrgicas , Humanos , Masculino , Feminino , Hérnia Incisional/cirurgia , Hérnia Incisional/etiologia , Estudos Retrospectivos , Fatores de Risco , Idoso , Pessoa de Meia-Idade , Herniorrafia/efeitos adversos , Herniorrafia/métodos , Adulto , Estudos de Coortes , Idoso de 80 Anos ou mais
6.
Heliyon ; 10(9): e29914, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38737285

RESUMO

This study was based on the use of whole-genome DNA methylation sequencing technology to identify DNA methylation biomarkers in tumor tissue that can predict the prognosis of patients with pancreatic cancer (PCa). TCGA database was used to download PCa-related DNA methylation and transcriptome atlas data. Methylation driver genes (MDGs) were obtained using the MethylMix package. Candidate genes in the MDGs were screened for prognostic relevance to PCa patients by univariate Cox analysis, and a prognostic risk score model was constructed based on the key MDGs. ROC curve analysis was performed to assess the accuracy of the prognostic risk score model. The effects of PIK3C2B knockdown on malignant phenotypes of PCa cells were investigated in vitro. A total of 2737 differentially expressed genes were identified, with 649 upregulated and 2088 downregulated, using 178 PCa samples and 171 normal samples. MethylMix was employed to identify 71 methylation-driven genes (47 hypermethylated and 24 hypomethylated) from 185 TCGA PCa samples. Cox regression analyses identified eight key MDGs (LEF1, ZIC3, VAV3, TBC1D4, FABP4, MAP3K5, PIK3C2B, IGF1R) associated with prognosis in PCa. Seven of them were hypermethylated, while PIK3C2B was hypomethylated. A prognostic risk prediction model was constructed based on the eight key MDGs, which was found to accurately predict the prognosis of PCa patients. In addition, the malignant phenotypes of PANC-1 cells were decreased after the knockdown of PIK3C2B. Therefore, the prognostic risk prediction model based on the eight key MDGs could accurately predict the prognosis of PCa patients.

7.
Int J Surg ; 110(6): 3591-3605, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38498399

RESUMO

Pancreatic adenocarcinoma characterized by a mere 10% 5-year survival rate, poses a formidable challenge due to its specific anatomical location, making tumor tissue acquisition difficult. This limitation underscores the critical need for novel biomarkers to stratify this patient population. Accordingly, this study aimed to construct a prognosis prediction model centered on S100 family members. Leveraging six S100 genes and their corresponding coefficients, an S100 score was calculated to predict survival outcomes. The present study provided comprehensive internal and external validation along with power evaluation results, substantiating the efficacy of the proposed model. Additionally, the study explored the S100-driven potential mechanisms underlying malignant progression. By comparing immune cell infiltration proportions in distinct patient groups with varying prognoses, the research identified differences driven by S100 expression. Furthermore, the analysis explored significant ligand-receptor pairs between malignant cells and immune cells influenced by S100 genes, uncovering crucial insights. Notably, the study identified a novel biomarker capable of predicting the sensitivity of neoadjuvant chemotherapy, offering promising avenues for further research and clinical application.


Assuntos
Adenocarcinoma , Biomarcadores Tumorais , Neoplasias Pancreáticas , Proteínas S100 , Microambiente Tumoral , Humanos , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/genética , Microambiente Tumoral/imunologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Prognóstico , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Adenocarcinoma/mortalidade , Adenocarcinoma/genética , Masculino , Feminino , Pessoa de Meia-Idade , Idoso
8.
Acta Biochim Biophys Sin (Shanghai) ; 56(4): 576-585, 2024 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-38433576

RESUMO

Poly ADP-ribose polymerase (PARP) inhibitor monotherapies are selectively effective in patients with pancreatic, breast, prostate, and ovarian cancers with BRCA1 mutations. Cancer patients with more frequent wild-type BRCA show poor responses to PARP inhibitors. Moreover, patients who are initially sensitive to these inhibitors eventually respond poorly to drugs. In the present study, we discover that abrogation of Kruppel-like factor 5 (KLF5) significantly inhibits homologous recombination, which is the main mechanism for DNA double-stranded repair. Furthermore, the downregulation of KLF5 expression promotes the DNA damage induced by olaparib and significantly reduces the IC 50 of the RARP inhibitor in pancreatic cancer cells. Overexpression of BRCA1 reverses the above effects caused by silencing of KLF5. Olaparib combined with a KLF5 inhibitor has an enhanced cytotoxic effect. Mechanistically, we identify BRCA1 as a KLF5 target gene. BRCA1 is positively correlated with KLF5 in PDAC tissue. Our results indicate that inhibition of KLF5 may induce BRCAness in a larger pancreatic cancer subset with proficient BRCA. The combination of KLF5 inhibitors and PARP inhibitors provides a novel treatment strategy to enhance the sensitivity of BRCA1-proficient pancreatic cancer to PARP inhibitors.


Assuntos
Antineoplásicos , Fatores de Transcrição Kruppel-Like , Neoplasias Pancreáticas , Humanos , Antineoplásicos/uso terapêutico , Proteína BRCA1/genética , Linhagem Celular Tumoral , Reparo do DNA , Fatores de Transcrição Kruppel-Like/genética , Neoplasias Ovarianas/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico
9.
J Gastrointest Oncol ; 15(1): 22-32, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38482225

RESUMO

Background: Gastric cancer (GC) is a common tumors in the digestive tract, and effective treatment methods are still lacking. Bone morphogenetic protein 6 (BMP6) is closely related to the occurrence and development of various tumors, but its relevance to GC is still unclear. The aim of the study was to explore the relationship between BMP6 and the occurrence and development of GC. Methods: In this study, we investigated the relationship between BMP6 and the prognosis of GC patients using bioinformatics technology and clinical tissue samples. We also explored the connection between BMP6 and the biological behavior of GC cells through molecular biology experiments and relevant in vivo animal experiments. Finally, we examined the mechanisms by which BMP6 inhibits the onset and progression of GC. Results: Through analysis of The Cancer Genomics Atlas (TCGA) database, we observed that BMP6 is expressed at low levels in GC, and its low expression is associated with a poor prognosis in GC patients. Cell experiments demonstrated that BMP6 expression can influence the proliferation of GC cells both in vitro and in vivo. Furthermore, we discovered that BMP6 is linked to the nuclear factor-κB (NF-κB) pathway, and subsequent experiments confirmed that BMP6 can inhibit the biological activity of GC cells by activating the NF-κB pathway. Conclusions: Our findings suggest that BMP6 is a potential prognostic biomarker in GC and can regulate the biological activity of GC cells through the NF-κB pathway. BMP6 may serve as a promising therapeutic target for GC, and our study introduces novel ideas for the prevention and treatment of this disease.

11.
J Biomed Mater Res A ; 112(5): 721-732, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38093473

RESUMO

Injectable hyaluronic acid (HA) hydrogel plays an important role in dermal filling. However, conventional HA dermal fillers mostly lack bio-functional diversity and frequently cause adverse reactions because of the chemical stiffness of highly modified degree and crosslinker residues. In this study, polylactic acid (PLA) was embedded into HA hydrogel as a bioactive substance and 1,4-butanediol diglycidyl ether was used as a crosslinker to prepare the HA/PLA composite hydrogel with enhanced biocompatibility and biological performance. We aimed to investigate the properties of HA/PLA composite hydrogels as dermal fillers by assessing the rheological properties, surface microstructure, enzymolysis stability, swelling ratio, degradation rate, cytotoxicity, and anti-wrinkle effect on photo-aged skin. The results showed that the stability and stiffness of the composite hydrogel decreased with an increasing amount of PLA, while the in vivo safety of the HA/PLA hydrogel was enhanced, showing no adverse reactions such as edema, redness, or swelling. Moreover, the composite hydrogel with 2 wt% PLA exhibited excellent anti-wrinkle effects, showing the highest collagen production. Thus, the PLA-embedded HA composite hydrogel showed potential as a dermal filler with high safety, easy injectability, and excellent anti-wrinkle effects.


Assuntos
Preenchedores Dérmicos , Preenchedores Dérmicos/farmacologia , Preenchedores Dérmicos/química , Ácido Hialurônico/química , Hidrogéis/farmacologia , Hidrogéis/química , Poliésteres
12.
Neurochem Res ; 49(2): 477-491, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37935859

RESUMO

The current first-line antidepressants have the drawback of slow onset, which greatly affects the treatment of depression. Crocetin, one of the main active ingredients in saffron (Crocus sativus L.), has been demonstrated to have antidepressant activities, but whether it has a rapid antidepressant effect remains unclear. This study aimed to investigate the onset, duration, and mechanisms of the rapid antidepressant activity of crocetin (20, 40 and 80 mg/kg, intraperitoneal injection) in male mice subjected to chronic restraint stress (CRS). The results of behavioral tests showed that crocetin exerted rapid antidepressant-like effect in mice with depression-like phenotypes, including rapid normalization of depressive-like behaviors within 3 h, and the effects could be maintained for 2 days. Hematoxylin-eosin (HE) and Nissl staining showed that crocetin ameliorated hippocampal neuroinflammation and nerve injuries in mice with depression-like phenotypes. The levels of inflammatory factors, corticosterone and pro brain-derived neurotrophic factor in crocetin-administrated mice serum were significantly reduced compared with those in the CRS group, as well as the levels of inflammatory factors in hippocampus. What's more, Western blot analyses showed that, compared to CRS-induced mice, the relative levels of mitogen-activated kinase phosphatase 1 and toll-like receptor 4 were significantly reduced after the administration of crocetin, and the relative expressions of extracellular signal-regulated kinase 1/2 (ERK1/2), cAMP-response element binding protein, phosphorylated phosphoinositide 3 kinase (p-PI3K)/PI3K, phosphorylated protein kinase B (p-AKT)/AKT, phosphorylated glycogen synthase kinase 3ß (p-GSK3ß)/GSK3ß, phosphorylated mammalian target of rapamycin (p-mTOR)/mTOR were markedly upregulated. In conclusion, crocetin exerted rapid antidepressant effects via suppressing the expression of inflammatory cytokines and the apoptosis of neuronal cells through PI3K/AKT signaling pathways. The rapid antidepressant effect of crocetin (40 mg/kg) could be maintained for at least 2 days after single treatment.


Assuntos
Carotenoides , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Vitamina A/análogos & derivados , Camundongos , Masculino , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Depressão/tratamento farmacológico , Depressão/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Hipocampo/metabolismo , Mamíferos/metabolismo
13.
Drug Deliv Transl Res ; 14(7): 1923-1939, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38117406

RESUMO

The most promising active ingredient of Crocus sativus L., crocetin (CCT), has been demonstrated to possess many biological activities. However, only a few studies have been conducted on CCT formulation, especially in oral formulation, mainly due to its insolubility in water, which limits its application for oral administration. This article reports an equilibrium saturation solubility and single-pass intestinal perfusion studies conducted to classify the biopharmaceutics classification system (BCS) of CCT. To enhance in vitro dissolution and in vivo oral bioavailability, ternary solid dispersions of CCT (CCT-SDs) with soluplus (SOL) as hydrophilic carrier and meglumine (MEG) as alkalizer were optimized using response surface methodology (RSM) with central composite design (CCD) experiments. Four different preparation methods were evaluated using the optimal formulation, including solvent evaporation, ball milling, spray drying, and freeze-drying. Prepared formulations were characterized by TG-DSC, FTIR, X-RPD, and SEM; the pharmacokinetic studies were performed in rats after oral administration. The cumulative dissolution rate of CCT-SDs containing SOL and MEG prepared by the ball milling method was 97.1% at 15 min and remained at 95.6% at 480 min, which was significantly higher than that of untreated CCT. The lower crystallinity, smaller particle size, and higher microenvironment pH (pHM) were observed in CCT-SDs prepared by the ball milling method. In vivo absorption of CCT-SDs (Cmax = 52.789 ± 12.441 µg/mL and AUC0-12 = 191.748 ± 35.043 µg/mL·h) was greater than untreated CCT (Cmax = 5.918 ± 1.388 µg/mL and AUC0-12 = 44.309 ± 7.264 µg/mL·h). In conclusion, the current study provides ternary solid dispersion formulation of CCT to increase the in vitro dissolution and in vivo bioavailability, which will benefit the commercial production and future clinical applications of CCT.


Assuntos
Disponibilidade Biológica , Carotenoides , Ratos Sprague-Dawley , Solubilidade , Vitamina A , Animais , Carotenoides/farmacocinética , Carotenoides/química , Carotenoides/administração & dosagem , Administração Oral , Vitamina A/farmacocinética , Vitamina A/análogos & derivados , Vitamina A/administração & dosagem , Vitamina A/química , Concentração de Íons de Hidrogênio , Masculino , Ratos , Liberação Controlada de Fármacos , Polietilenoglicóis/química , Polietilenoglicóis/farmacocinética , Polietilenoglicóis/administração & dosagem
14.
Inorg Chem ; 62(46): 19052-19059, 2023 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-37922206

RESUMO

Spinel oxides have attracted increasing interest due to their excellent activity in the oxygen evolution reaction (OER). However, despite the high intrinsic OER activity, their poor electrical conductivity and weak structural stability prevented their application for a long time. These shortcomings can be solved by effectively adjusting the electronic structures of spinel oxides through a high-entropy strategy. Herein, a rapid two-step method was developed to prepare self-supported high-entropy spinel-type oxides on a carbon cloth (CC) to yield (Fe0.2Co0.2Ni0.2Mn0.2Cr0.2)3O4@CC (abbreviated as FeCoNiMnCr@CC). The unique electronic structure and stable crystal configuration of the resulting FeCoNiMnCr@CC materials required only an overpotential of 287 mV for the OER at a current density of 10 mA cm-2 coupled with excellent cyclic stability. In summary, the proposed high-entropy strategy looks promising for improving the catalytic performance of spinel oxides.

15.
In Vivo ; 37(6): 2533-2542, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37905651

RESUMO

BACKGROUND/AIM: Acute exogenous lipoid pneumonia (AELP) is a rare disorder caused by intake of lipid formulations and is often underdiagnosed. Meanwhile, the mechanism of AELP is still underlying. MCC950, was previously found to significantly suppress the release of inflammatory cytokines IL-18 and IL-1ß. However, the effect of MCC950 on AELP induced by sewing machine oil has not been reported. MATERIALS AND METHODS: The NLRP3, NF-[Formula: see text]B p65, caspase-1 and IL-1ß expression in lung tissues were compared between a rat model of AELP and control rats using western blotting and real-time quantitative assay. Moreover, haematoxylin and eosin (H&E) staining was performed to elucidate the mechanisms by which MCC950 ameliorates sewing machine oil-induced AELP in vivo. RESULTS: MCC950 reduced the expression of NF-[Formula: see text]B p65 in the lung samples of the treatment group and further down-regulated the NLRP3 and caspase-1 levels while inhibited the production of IL-1ß. Besides, decreases in inflammatory cell infiltration in the lung were shown using H&E staining. CONCLUSION: MCC950 ameliorates sewing machine oil-induced acute exogenous lipoid pneumonia in rats through inhibition of the NF-[Formula: see text]B/NLRP3 inflammasome pathway.


Assuntos
Inflamassomos , Pneumonia Lipoide , Ratos , Animais , Inflamassomos/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Sulfonamidas/farmacologia , Caspases
16.
Mater Horiz ; 10(12): 5343-5353, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-37768106

RESUMO

The continuous development of different kinds of materials plays a significant role in social productivity. However, the lack of a complete synthesis kinetic theory has resulted in the absence of scientific guidance for the emergence of advanced manufacturing technologies, limiting the research and production of new types of materials. The present work aims at obtaining the basic form of the diffusion flux-driving force equation through the concept of ion diffusion so as to establish a synthesis kinetic theory. Using this theory, the scientific principles of existing synthesis technologies are summarized, and the key directions that future manufacturing technologies need to break through are proposed as well. Based on a comprehensive analysis of this theory, the feasible directions are discussed, providing strong support for the early realization of targeted design and manufacturing of new materials with specific functions.

17.
Front Endocrinol (Lausanne) ; 14: 1188284, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37547307

RESUMO

Objective: Although previous studies have reported an association between thyroid function and anti-Müllerian hormone (AMH) levels, which is considered a reliable marker of ovarian reserve, the causal relationship between them remains uncertain. This study aims to investigate whether thyrotropin (TSH), free thyroxine (fT4), hypo- and hyperthyroidism are causally linked to AMH levels. Methods: We obtained summary statistics from three sources: the ThyroidOmics Consortium (N = 54,288), HUNT + MGI + ThyroidOmics meta-analysis (N = 119,715), and the most recent AMH genome-wide association meta-analysis (N = 7,049). Two-sample MR analyses were conducted using instrumental variables representing TSH and fT4 levels within the normal range. Additionally, we conducted secondary analyses to explore the effects of hypo- and hyperthyroidism. Subgroup analyses for TSH were also performed. Results: MR analyses did not show any causality relationship between thyroid function and AMH levels, using normal range TSH, normal range fT4, subclinical hypothyroidism, subclinical hyperthyroidism and overt hypothyroidism as exposure, respectively. In addition, neither full range TSH nor TSH with individuals <50 years old was causally associated with AMH levels. MR sensitivity analyses guaranteed the robustness of all MR results, except for the association between fT4 and AMH in the no-DIO1+DIO2 group. Conclusion: Our findings suggest that there was no causal association between genetically predicted thyroid function and AMH levels in the European population.


Assuntos
Hipertireoidismo , Hipotireoidismo , Humanos , Pessoa de Meia-Idade , Tiroxina , Hormônio Antimülleriano , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Hipotireoidismo/epidemiologia , Hipotireoidismo/genética , Tireotropina , Hipertireoidismo/genética , Hipertireoidismo/epidemiologia
18.
Mater Horiz ; 10(9): 3293-3303, 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37365968

RESUMO

High-entropy materials (HEMs) have attracted increasing research interests owing to their structural diversity and great potential for regulation. Numerous HEMs synthesis criteria have so far been reported but most are based on thermodynamics while a guiding basis for the synthesis of HEMs is lacking, resulting in many synthesis problems. Based on the overall thermodynamic formation criterion of HEMs, this study has explored the principles of the synthesis dynamics required based on this criterion and the influence of different synthesis kinetic rates on the final products of the reaction, filling the gap suggesting that thermodynamic criteria cannot guide the specific process changes. This will effectively provide more specific guidelines for the top-level design of material synthesis. By considering various aspects of HEMs synthesis criteria, new technologies suitable for high-performance HEMs catalysts were extracted. Also, the physical and chemical characteristics of the HEMs obtained from actual synthesis can be predicted in a better way, playing an important role in the personalized customization of HEMs with specific performance. Future development directions of HEMs synthesis were prospected for possible prediction and customization of HEMs catalysts with high performance.

19.
J Colloid Interface Sci ; 644: 64-72, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37094473

RESUMO

Cobalt hydroxylfluoride (CoOHF) is an emerging supercapacitor material. However, it remains highly challenging to effectively enhance the performance of CoOHF, which is limited by its poor electron and ion transport ability. In this study, the intrinsic structure of CoOHF was optimized through Fe doping (CoOHF-xFe, where x represents the Fe/Co feeding ratio). As indicated by the experimental and theoretical calculation results, the incorporation of Fe effectively enhances the intrinsic conductivity of CoOHF and optimizes its surface ion adsorption capacity. Moreover, since the radius of Fe is slightly larger than that of Co, the space between the crystal planes of CoOHF increases to a certain extent, and the ability to store ions is consequently enhanced. The optimized CoOHF-0.06Fe sample exhibits the maximum specific capacitance (385.8 F g-1). The asymmetric supercapacitor with activated carbon achieves a high energy density of 37.2 Wh kg-1 at a power density of 1600 W kg-1, and a full hydrolysis pool is successfully driven by the device, indicating great application potential. This study lays a solid basis for the application of hydroxylfluoride to a novel generation of supercapacitors.

20.
Reprod Sci ; 30(7): 2188-2197, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36650372

RESUMO

Endometriosis (EMS) is an estrogen-dependent disease. However, little is known about the regulation of estrogen, a potential therapeutic target, in EMS, which remains very poorly managed in the clinic. We hypothesized that microRNAs (miRNAs) can be exploited therapeutically to regulate transcription factor 21 (TCF21) and steroidogenic factor-1 (SF-1) gene expression. In our study, paired eutopic and ectopic endometrial samples were obtained from women with EMS and processed by a standard protocol to obtain human endometrial stromal cells (EMs) for in vitro studies. We found that miR-92a-3p levels were decreased in ectopic endometrium and ectopic stromal cells (ESCs) compared with paired eutopic lesions. miR-92a-3p overexpression significantly suppressed the proliferation and migration of ESCs, whereas a decreased level of miR-92a-3p generated the opposite results. Next, we identified TCF21 as a candidate target gene of miR-92a-3p. In vitro cell experiments showed that miR-92a-3p negatively regulated the expression of TCF21 and its downstream target gene SF-1. Moreover, cell proliferation and invasion ability decreased after the silencing of SF-1 and increased after SF-1 overexpression. We also observed that silencing SF-1 while inhibiting miR-92a-3p partially blocked the increase in cell proliferation and invasion ability caused by miR-92a-3p knockdown while overexpressing both SF-1 and miR-92a-3p mitigated the impairment in cell proliferation and invasion ability caused by miR-92a-3p overexpression. Our results may provide a novel potential therapeutic target for the treatment of EMS.


Assuntos
Endometriose , MicroRNAs , Humanos , Feminino , MicroRNAs/genética , MicroRNAs/metabolismo , Endometriose/metabolismo , Fator Esteroidogênico 1/genética , Fator Esteroidogênico 1/metabolismo , Proliferação de Células/genética , Estrogênios , Fatores de Transcrição Hélice-Alça-Hélice Básicos
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