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1.
J Adv Res ; 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36243399

RESUMO

INTRODUCTION: Serum amyloid P component (SAP) regulates the innate immune system and microbial diseases. Periodontitis is an inflammatory oral disease developed by the host immune system's interaction with the dysbiotic oral microbiome, thereby SAP could play a role in periodontitis pathogenicity. OBJECTIVES: To investigate the role of SAP in oral microbiome modulation and peridontitis pathogenicity. METHODS: In this study, wildtype and SAP-knockout (KO) mice were used. Ligature-based periodontitis was developed in mice. Oral microbiome diversity was analyzed by 16 s rRNA sequencing. Macrophages and Porphyromonas gingivalis (P. gingivalis) co-culture system analyzed the effect of SAP in macrophage phagocytosis of P. gingivalis. RESULTS: The level of SAP was upregulated in the periodontitis-affected periodontium of humans and mice but not in the liver and blood circulation. Periodontal macrophages were the key source of upregulated SAP in periodontitis. SAP-KO aggravated periodontal inflammation, periodontitis, and a higher number of M1-type inflammatory macrophage infiltration in the periodontium. The oral microbiome of SAP-KO periodontitis mice was altered with a higher abundance of Porphyromonas at the genus level. SAP-KO macrophages showed compromised phagocytosis of P. gingivalis in the co-culture system. Co-culture of SAP-KO macrophages and P. gingivalis induced the C5a expression and exogenous SAP treatment nullified this effect. Exogenous recombinant SAP treatment did not affect P. gingivalis growth and opsonization. PMX205, an antagonist of C5a, treatment robustly enhanced P. gingivalis phagocytosis by SAP-KO macrophages, indicating the involvement of the C5a-C5aR signaling in the compromised P. gingivalis phagocytosis by SAP-KO macrophages. CONCLUSION: SAP deficiency aggravates periodontitis possibly via C5a-C5aR signaling-mediated defective macrophage phagocytosis of P. gingivalis. A higher abundance of P. gingivalis during SAP deficiency could promote M1 macrophage polarization and periodontitis. This finding suggests the possible protecting role of elevated levels of periodontal SAP against periodontitis progression.

2.
J Orthop Translat ; 34: 91-101, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35847603

RESUMO

Objective: Meniscus tear is a common problem in sports trauma, and its imaging diagnosis mainly relies on MRI. To improve the diagnostic accuracy and efficiency, a deep learning model was employed in this study and the identification efficiency was evaluated. Methods: Standard knee MRI images from 924 individual patients were used to complete the training, validation and testing processes. Mask regional convolutional neural network (R-CNN) was used to build the deep learning network structure, and ResNet50 was adopted to develop the backbone network. The deep learning model was trained and validated with a dataset containing 504 and 220 patients, respectively. Internal testing was performed based on a dataset of 200 patients, and 180 patients from 8 hospitals were regarded as an external dataset for model validation. Additionally, 40 patients who were diagnosed by the arthroscopic surgery were enrolled as the final test dataset. Results: After training and validation, the deep learning model effectively recognized healthy and injured menisci. Average precision for the three types of menisci (healthy, torn and degenerated menisci) ranged from 68% to 80%. Diagnostic accuracy for healthy, torn and degenerated menisci was 87.50%, 86.96%, and 84.78%, respectively. Validation results from external dataset demonstrated that the accuracy of diagnosing torn and intact meniscus tear through 3.0T MRI images was higher than 80%, while the accuracy verified by arthroscopic surgery was 87.50%. Conclusion: Mask R-CNN effectively identified and diagnosed meniscal injuries, especially for tears that occurred in different parts of the meniscus. The recognition ability was admirable, and the diagnostic accuracy could be further improved with increased training sample size. Therefore, this deep learning model showed great potential in diagnosing meniscus injuries. Translational potential of this article: Deep learning model exerted unique effect in terms of reducing doctors' workload and improving diagnostic accuracy. Injured and healthy menisci could be more accurately identified and classified based on training and learning datasets. This model could also distinguish torn from degenerated menisci, making it an effective tool for MRI-assisted diagnosis of meniscus injuries in clinical practice.

3.
4.
J Hazard Mater ; 435: 129054, 2022 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-35650743

RESUMO

Dissolved black carbon (DBC), the water-soluble component of black carbon, which is formed by incomplete combustion of fossil fuels or biochar, takes up about 10% of dissolved organic matter (DOM) in river water. However, the distribution of DBC in water environment especially in source water is not clear and as an important component of DOM, whether DBC can produce disinfection byproducts (DBPs) like other DOM during disinfection remains unknown. In this study, the DBC concentrations in seventeen source water samples from East China were measured. The concentrations of DBC in the source water samples ranged from 60 to 270 µg/L, which were positively correlated with UV254 absorbance and chemical oxygen demand. The levels of DBC in wet season were higher than that in dry season. The average concentrations of DBC in different types of source water samples followed the order of reservoir > canal > lake > river. DBC could only be removed by 20% during the simulated coagulation, and further generate different categories of DBPs during chlorination, among which the concentrations of haloacetic acids (HAA) were the highest. The results indicated that DBC widely distributes in source water and is an important precursor of HAAs and THMs during chlorination.


Assuntos
Desinfetantes , Poluentes Químicos da Água , Purificação da Água , 2,5-Dimetoxi-4-Metilanfetamina , Desinfetantes/análise , Desinfecção/métodos , Halogenação , Lagos , Fuligem , Água , Poluentes Químicos da Água/análise , Purificação da Água/métodos
5.
Pharm Res ; 39(8): 1907-1920, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35650450

RESUMO

PURPOSE: The generalizability of numerous tacrolimus population pharmacokinetic (popPK) models constructed to promote optimal tacrolimus dosing in patients with primary nephrotic syndrome (PNS) is unclear. This study aimed to evaluate the predictive performance of published tacrolimus popPK models for PNS patients with an external data set. METHODS: We prospectively collected 223 concentrations from 50 Chinese adult patients with PNS who were undergoing tacrolimus treatment. Data on published tacrolimus popPK models for adults and children with PNS were extracted from the literature. Model predictability was evaluated with prediction-based and simulation-based diagnostics and Bayesian forecasting. RESULTS: In prediction-based evaluation, none of the 11 identified published popPK models of tacrolimus had met a predefined criteria of a mean prediction error ≤ ± 20%, and the prediction error within ± 30% of the identified models didn't exceed 50%. Simulation-based diagnostics also indicated unsatisfactory predictability. Bayesian forecasting demonstrated amelioration in the model predictability with the inclusion of 2-3 prior observations. Moreover, the predictive performance of nonlinear models was not better than that of one-compartment models. CONCLUSIONS: The prediction of tacrolimus concentrations for patients with PNS remains challenging; published models are not applicable for extrapolation to other hospitals. Bayesian forecasting significantly improved model predictability and thereby helped to individualize tacrolimus dosing.


Assuntos
Síndrome Nefrótica , Tacrolimo , Adulto , Teorema de Bayes , Criança , China , Humanos , Imunossupressores , Modelos Biológicos , Síndrome Nefrótica/tratamento farmacológico
6.
Front Oncol ; 12: 897751, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35619921

RESUMO

Background: Dysregulated non-coding RNAs exhibit critical functions in various cancers. Nonetheless, the levels and corresponding functions of cirCSNX14 in esophageal squamous cell carcinoma (ESCC) yet remain to be elucidated. Methods: Initially, the aberrant low levels of lncRNA-LET within ESCC tissues are validated via qRT-PCR observations. Moreover, the effects of lncRNA-LET upregulation on cell proliferation in vitro are determined. In addition, a series of assays determining the mechanistic views related to metabolism is conducted. Furthermore, the effects of lncRNA-LET in affecting tumor growth are investigated in vivo in a mouse model. Moreover, the interactions between lncRNA-LET and its networks are predicted and determined by RNA immunoprecipitation-assisted qRT-PCR as well as luciferase reporter assays. Results: The downregulation of lncRNA-LET is correlated to the poor prognosis of ESCC patients. Moreover, the upregulated expression of lncRNA-LET could have reduced the cell viability. In vivo tumor inhibition efficacy assays showed that an increase of lncRNA-LET presented excellent inhibitory effects on cancer proliferation as reflected by tumor weight and volume in mice. Finally, the mechanistic views regarding the effects of miR-106b-5p or miR-93-5p and SOCS4 on ESCC are related to the feedback of lncRNA-LET. Conclusion: Collectively, this study suggested that lncRNA-LET miR-93-5p or the miR-106b-5p-SOCS4 axis may provide great potential in establishing ESCC therapy.

7.
J Ethnopharmacol ; 294: 115341, 2022 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-35551978

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: QiruiWeishu capsule is an herbal preparation from a herbal formula prescribed by an experienced doctor at Guang'anmen Hospital of China Academy of Chinese Medical Sciences. It has been used clinically for more than 30 years. Abdominal pain, distension, and nausea are common symptoms of chronic non-atrophic gastritis with erosion dampness and heat stasis syndrome, and this herbal medicine has been used to treat them. AIM OF THE STUDY: To verify the clinical efficacy and safety of QiruiWeishu capsule in the treatment of chronic non-atrophic gastritis with damp-heat stasis syndrome. MATERIALS AND METHODS: This study was a multicenter randomized double-blind clinical trial with positive herbal drug SanjiuWeitai capsule as control and superiority test of main efficacy. A total of 477 subjects with chronic non-atrophic gastritis with erosion diagnosed by gastroscopy and pathological biopsy were randomly divided into QiruiWeishu capsule and SanjiuWeitai groups respectively in a ratio of 3:1. During the trial, subjects were required to complete medication for 28 days. The primary outcome was the disappearance rate of epigastric pain from baseline to 4weeks. At baseline, treatment at 1, 2, and 4 weeks, and follow-up at 8 and 16 weeks, the epigastric pain and traditional Chinese medicine (TCM) symptom scores were evaluated; gastroscopy, histopathology, and the helicobacter pylori test were evaluated at baseline and after 4 weeks of treatment. The safety assessment included blood routine, liver and kidney function, coagulation of laboratory tests, and electrocardiogram (ECG). RESULTS: Both groups of subjects had a high level of medication adherence (defined as treatment completion for over 80%) (346/357, 96.9% in Qirui Weishu group vs 118/120, 98.3% in Sanjiu Weitai group; p > 0.05). The QiruiWeishu capsule was significantly better than SanjiuWeitai capsule in disappearance rate of epigastric pain (64.2%, 229/357vs 46.7%, 56/120; p < 0.001),especially subgroupsubjects with moderate epigastric pain (65.0%, 89/137 vs 30.4%, 14/46; p < 0.001), grade1 erythema (67.7%, 149/220 vs 51.9%, 42/81; p = 0.011) and grade 2 erythema (57.6%, 70/121 vs37.1%, 13/35; p = 0.050) of gastroscopy, grade 2 erosion (66.7%, 118/177 vs43.9%, 25/57; p = 0.002) of gastroscopy and Helicobacter pylori negative (65.4%, 155/237 vs 42.7%, 35/82; p < 0.001) at baseline. For the scores of TCM symptoms in QiruiWeishu group were significantly lower than those in SanjiuWeitai group after 28 days of treatment (p = 0.002). The number and incidence of adverse events related to the trial drug were 14/355 (3.9%) in QiruiWeishu group, 6/118 (5.1%) in SanjiuWeitai group (p > 0.05). No serious adverse reactions occurred in the two groups. According to laboratory tests and ECG, there was no discernible effect on heart, liver, kidney, or blood coagulation function. CONCLUSION: Qirui Weishu capsule appears to be more effective in terms of symptoms than the SanjiuWeitai capsule, and its use is both safe and effective for the treatment of chronic non-atrophic gastritis. A further randomized, double-blind, placebo-control trial is warranted to verify its benefit.


Assuntos
Medicamentos de Ervas Chinesas , Gastrite Atrófica , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Gastrite Atrófica/tratamento farmacológico , Humanos , Medicina Tradicional Chinesa , Dor/tratamento farmacológico , Resultado do Tratamento
8.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 47(2): 174-182, 2022 Feb 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-35545407

RESUMO

OBJECTIVES: Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of ligand activated transcription factors and belongs to bile acid receptor. Studies have shown that the expression of FXR in renal tissue can reduce renal injury via regulation of glucose and lipid metabolism, inhibition of inflammatory response, reduction of oxidative stress and renal fibrosis. However, it is unclear whether FXR is involved in autophagy in renal diseases. This study aims to investigate the role of FXR in cisplatin-induced acute renal injury and whether its mechanism is related to autophagy regulation. METHODS: Twelve male WT or FXR-KO mice at 12 weeks were randomly divided into a WT group, a WT+cisplatin group, a FXR-KO group, and a FXR-KO+cisplatin group, with 6 mice in each group. The WT+cisplatin group and the FXR-KO+cisplatin group were intraperitoneally injected with cisplatin (20 mg/kg), and the WT group and the FXR-KO group were intraperitoneally injected with equal volume of cisplatin solvent. Seventy-two hours later, the mice were killed and blood and renal tissue samples were collected. The levels of SCr and BUN were detected by immunoturbidimetry. After the staining, the pathological changes of renal tissue were observed under optical microscope. The protein levels of LC3 and p62 were detected by Western blotting and immunohistochemistry. The clearance of damaged mitochondria and the accumulation of lysosomal substrate were observed under electron microscope. The apoptosis of renal tubular epithelial cells was detected by TUNEL. RESULTS: Compared with the WT group or the FXR-KO group, both SCr and BUN levels in the WT+cisplatin group or the FXR-KO+cisplatin group were significantly increased (P<0.01 or P<0.001), and SCr and BUN levels in the FXR-KO+cisplatin group were significantly higher than those in the WT+cisplatin group (both P<0.05). Under the light microscope, there were no obvious pathological changes in the renal tissue of mice in the WT group and the FXR-KO group. Both the WT+cisplatin group and the FXR-KO+cisplatin group had vacuolar or granular degeneration of renal tubular epithelial cells, flat cells, lumen expansion, brush edge falling off, and even exposed basement membrane and tubular formation. The scores of renal tubular injury in the WT+cisplatin group and the FXR-KO+cisplatin group were significantly higher than those in the WT group and the FXR-KO group, respectively (both P<0.001), and the score in the FXR-KO+cisplatin group was significantly higher than that in the WT+cisplatin group (P<0.05). Under the transmission electron microscope, the mitochondria of mouse tubular epithelial cell in the WT+cisplatin group and the FXR-KO+cisplatin group was swollen, round, vacuolated, cristae broken or disappeared; the lysosome was uneven and high-density clumps, and the change was more obvious in the FXR-KO+cisplatin group. Western blotting showed that the ratio of LC3-II to LC3-I was decreased and the expression of p62 was increased in the WT+cisplatin group compared with the WT group and the FXR-KO+cisplatin group compared with FXR-KO group (P<0.05 or P<0.01); compared with the FXR-KO group, the ratio of LC3-II to LC3-I was decreased and the expression of p62 was increased significantly in the FXR-KO+cisplatin group (both P<0.05). Immunohistochemistry results showed that the expression of total LC3 and p62 in renal cortex of the WT+cisplatin group and the FXR-KO+cisplatin group was increased significantly, especially in the FXR-KO+cisplatin group. TUNEL results showed that the mice in the WT group and the FXR-KO group had negative staining or only a few apoptotic tubular epithelial cells, and the number of apoptotic cells in the WT+cisplatin group and the FXR-KO+cisplatin group were increased. The apoptosis rates of renal tubular epithelial cells in the WT+cisplatin group and the FXR-KO+cisplatin group were significantly higher than those in the WT group and the FXR-KO group, respectively (both P<0.001), and the apoptosis rate in the FXR-KO+cisplatin group was significantly higher than that in the WT+cisplatin group (P<0.05). CONCLUSIONS: Knockout of FXR gene aggravates cisplatin induced acute renal injury, and its mechanism may be related to inhibiting autophagy and promoting apoptosis.


Assuntos
Injúria Renal Aguda , Cisplatino , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/patologia , Animais , Apoptose/fisiologia , Cisplatino/efeitos adversos , Feminino , Humanos , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
9.
Adv Mater ; 34(32): e2202609, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35610760

RESUMO

Palladium nanosheets (Pd NSs) are well-investigated photothermal therapy agents, but their catalytic potential for tumor therapy has been underexplored owing to the inactive dominant (111) facets. Herein, lattice tensile strain is introduced by surface reconstruction to activate the inert surface, endowing the strained Pd NSs (SPd NSs) with photodynamic, catalase-like, and peroxidase-like properties. Tensile strain promoting the photodynamic and enzyme-like activities is revealed by density functional theory calculations. Compared with Pd NSs, SPd NSs exhibit lower photothermal effect, but approximately five times higher tumor inhibition rate. This work calls for further study to activate nanomaterials by strain engineering and surface reconstruction for catalytic therapy of tumors.


Assuntos
Nanoestruturas , Neoplasias , Catálise , Humanos , Nanoestruturas/uso terapêutico , Neoplasias/terapia , Paládio , Fototerapia
10.
Int J Mol Sci ; 23(10)2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35628470

RESUMO

The tricarboxylic acid (TCA) metabolite, succinate, is a competitive inhibitor of dioxygenase enzymes that require alpha ketoglutarate as a cofactor. One family of dioxygenases are the ten-eleven translocation (TET) proteins, which oxidize 5-methylcytosine to promote DNA demethylation. Inhibition of DNA demethylation is expected to lead to DNA hypermethylation, at least at genomic regions at which TET proteins are engaged. We treated human bronchial epithelial cells with succinate for five days and confirmed its effect on TET protein function by observing diminished formation of 5-hydroxymethylcytosine, the first oxidation product of the TET enzymatic reaction. We then analyzed global DNA methylation patterns by performing whole-genome bisulfite sequencing. Unexpectedly, we did not observe differentially methylated regions (DMRs) that reached genome-wide statistical significance. We observed a few regions of clustered DNA hypomethylation, which was also not expected based on the proposed mechanisms. We discuss potential explanations for our observations and the implications of these findings for tumorigenesis.


Assuntos
Metilação de DNA , Dioxigenases , DNA/metabolismo , Dioxigenases/genética , Células Epiteliais/metabolismo , Humanos , Succinatos , Ácido Succínico/farmacologia
11.
Front Psychol ; 13: 847882, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35478764

RESUMO

This study examines whether psychological capital (PsyCap) indirectly predicts occupational well-being among Chinese special education teachers through work engagement. In total, 615 Chinese special education teachers (female = 567) completed the Psychological Capital Questionnaire, the Special Education Teachers' Occupational Well-Being Questionnaire, and the Utrecht Work Engagement Scale. The results indicated that PsyCap was positively correlated with occupational well-being and work engagement. Furthermore, work engagement mediated the influence of PsyCap on occupational well-being. Notably, the multiple mediation model indicated that the indirect effects of PsyCap on occupational well-being were mainly due to dedication and absorption. The study's results illustrate the association between PsyCap, work engagement, and occupational well-being, which may help educational administrators and social workers assist with special education and special education teachers develop and maintain good working conditions.

12.
RSC Adv ; 12(16): 9524-9533, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35424939

RESUMO

The incidence of articular cartilage defects is increasing year by year. In order to repair the cartilage tissue at the defect, scaffolds with nanofiber structure and biocompatibility have become a research hotspot. In this study, we designed and fabricated a bi-layer scaffold prepared from an upper layer of drug-dispersed gelatin methacrylate (GELMA) hydrogel and a lower layer of a drug-encapsulated coaxial fiber scaffold prepared from silk fiber (SF) and polylactic acid (PLA). These bi-layer scaffolds have porosity (91.26 ± 3.94%) sufficient to support material exchange and pore size suitable for cell culture and infiltration, as well as mechanical properties (2.65 ± 0.31 MPa) that meet the requirements of cartilage tissue engineering. The coaxial fiber structure exhibited excellent drug release properties, maintaining drug release for 14 days in PBS. In vitro experiments indicated that the scaffolds were not toxic to cells and were amenable to chondrocyte migration. Notably, the growth of cells in a bi-layer scaffold presented two states. In the hydrogel layer, cells grow through interconnected pores and take on a connective tissue-like shape. In the coaxial fiber layer, cells grow on the surface of the coaxial fiber mats and appeared tablet-like. This is similar to the structure of the functional partitions of natural cartilage tissue. Together, the bi-layer scaffold can play a positive role in cartilage regeneration, which could be a potential therapeutic choice to solve the current problems of clinical cartilage repair.

13.
PeerJ ; 10: e12974, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35256918

RESUMO

Background: Lymphangio vascular invasion (LVI) and perineural invasion (PNI) are associated with survival following resection for gastrointestinal cancer. But the relationship between LVI/PNI and survival of esophageal squamous cell carcinoma (ESCC) is still unclear. We aim to demonstrate the prognostic significance of LVI/PNI in ESCC. Methods: A total of 195 ESCC patients underwent curative surgery from 2012 to 2018 was collected in the 2nd Affiliated Hospital of Fujian Medical University. All the patients were divided into four groups based on the status of the neurovascular invasion: (1) neither LVI nor PNI (V0N0); (2) LVI alone (V1N0); (3) PNI alone (V0N1); (4) combined LVI and PNI (V1N1). First, the analysis included the Kaplan-Meier survival estimates with the Log rank test were performed to determine median overall survival (OS) in different groups divided according to the clinical factor, respectively. And the association between OS with multi clinical factors was examined using Cox regression analysis. Next, the risk factors for recurrence in patients with V1N1 were analyzed with univariate and multivariate logistic regression analyses, respectively. Results: The cases in V0N0, V1N0, V0N1, and V1N1 groups were 91 (46.7%), 62 (31.8%), 9 (4.6%) and 33 (16.9%), respectively. The OS in the four groups was different (P < 0.001). The 1-, 3- and 5-year OS in V0N0 group was higher than that in V1N1 group, respectively (1-year OS: 93.4% vs 75.8%, 3-year OS: 53.8 % vs 24.2%, 5-year OS: 48.1% vs 10.5%). The OS in stage I-II for patients with V1N1 was significantly lower than that in the other groups (V0N0, V1N0, V0N1) (P < 0.001). The postoperative adjuvant chemotherapy was a significant impact factor of OS for ESCC patients with V1N1 (P = 0.004). Lymphatic invasion and LVI were significantly prognosis factors associated (P = 0.036, P = 0.030, respectively). The ulcerative type is a risk factor for V1N1 occurance (P = 0.040). Conclusions: The LVI and PNI are important prognosis factors for ESCC patients. ESCC patients with simultaneous lymphangio vascular and perineural invasion (V1N1) showed worse OS than patients with either lymphangio vascular or perineural invasion alone (V1N0 or V0N1) or none (V0N0). In addition, adjuvant chemotherapy may prolong the OS for ESCC patients with V1N1.

14.
Front Pharmacol ; 13: 841954, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35250587

RESUMO

This study aimed to determine the effect of vitamin D (VD) deficiency on the efficacy and pharmacokinetics of pravastatin and clarify whether the effects are mediated by Organic anion-transporting polypeptides (OATPs). Experiments were conducted in rats to explore the effect of VD deficiency on the pharmacodynamics and pharmacokinetics of pravastatin. In the pharmacodynamic study, rats were fed a VD-free or VD-supplement high-fat diet for 25-30 days, and plasma 25(OH)VD was dynamically monitored. The response of pravastatin (changes in blood lipids) on rats were then examined after 15 days of pravastatin treatment. In the pharmacokinetic study, rats were fed a VD-free or VD-supplement diet for 25-30 days. The pharmacokinetics of single oral dose pravastatin was then studied, and intestinal and hepatic Oatp1a1 and Oatp2b1 expression was determined using quantitative polymerase chain reaction (qPCR) and western blot. Furthermore, OATP1B1 and OATP2B1 expression in Huh7 cells with or without 1.25(OH)2D were assessed via qPCR and western blot. For the pharmacodynamic study, the decrease of total cholesterol and increase of high-density lipoprotein cholesterol in VD-deficient rats were smaller than in VD-sufficient rats, indicating that VD deficiency reduced the response of pravastatin in rats. For the pharmacokinetic study, the plasma exposure slightly increased, and liver exposure decreased in VD-deficient rats, but not significantly. VD deficiency decreased the Oatp1a1 and Oatp2b1 expression in the liver, but not in the small intestine. Similarly, OATP1B1 and OATP2B1 protein levels in Huh7 cells were reduced when 1.25(OH)2D was absent. In conclusion, VD deficiency can decrease the response of pravastatin in rats by reducing the liver pravastatin exposure and expression of hepatic OATPs, consistent with the extended hepatic clearance model theory.

15.
Clin Res Hepatol Gastroenterol ; 46(6): 101886, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35183792

RESUMO

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Casein kinase 2 (CK2) has been reported to be involved in several cellular processes in multiple cancers. However, the role of CK2 in GIST remains unclear. AIM: We aimed to investigate the combinatorial treatment of imatinib (IM) and CK2 inhibition on the progression of GISTs. METHODS: GIST biopsies and adjacent normal tissues were collected from patients. GIST882 and GIST48 cell lines were subjected to investigate the effect of IM and CK2 inhibition in GIST cells. CCK-8 assay, Caspase-3 activity assay, western blotting, and flow cytometry analysis were employed in the present investigation. RESULTS: Our results showed that CK2 was highly expressed in GIST biopsies, and inhibition of CK2 resulted in decrease in cell viability and increase in apoptosis of GIST cells. Moreover, the combination treatment with CX-4945 (CX) and IM resulted in a more significant decrease in cell viability and increase in cell apoptosis compared with mono-treatment. Mechanistically, the combination treatment influenced the activation of the PI3K/AKT pathway. The activation of the PI3K/AKT pathway reversed the synergistic impacts of the combined treatment on cell viability and apoptosis. CONCLUSION: Our results demonstrated that inhibition of CK2 combined with IM exhibited a synergistic anti-cancer effect on GIST cells through inactivation of the PI3K/AKT pathway.


Assuntos
Antineoplásicos , Neoplasias Gastrointestinais , Tumores do Estroma Gastrointestinal , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Caseína Quinase II/farmacologia , Linhagem Celular Tumoral , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/patologia , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/patologia , Humanos , Mesilato de Imatinib/farmacologia , Mesilato de Imatinib/uso terapêutico , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-akt
16.
Ecol Evol ; 12(1): e8539, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35127042

RESUMO

The natural regeneration of native broadleaved species underneath forest monoculture plantations is important to recover ecosystem functions and to mitigate adverse environmental effects. To understand how seed rain and soil seed bank facilitate natural regeneration, we surveyed their density and composition in a monoculture Chinese fir plantation, a mixed Chinese fir-broadleaf plantation, and an adjacent natural broadleaved forest for two years in southern China. Twenty-eight species (16 families) were in seed rain, and 45 species (27 families) were in soil seed bank. Seed rain density did not differ significantly across stands; however, the number of taxa in seed rain was highest in the mixed plantation and lowest in the natural forest. Seed bank density was significantly higher in the mixed plantation than in the other stands (p < .05). The Sørensen similarity index of species composition between seed sources and aboveground vegetation were relatively low (<.50). The seeds of various native tree species were common in the seed bank of the plantations, indicating that seed rain and seed bank played an important role in native forest regeneration. We recommend that managers interested in sustainable forestry should take into consideration the presence of existing soil seed bank when developing their management strategies. In addition, with regard to forest regeneration process, we also recommend supplementation of the species composition by direct seeding or planting of desired species.

17.
Sci Total Environ ; 826: 154062, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35217036

RESUMO

Exposure to single metals have been linked to childhood behavior problems, But little is known about the effects of metals mixtures on children. We aimed to evaluate associations of multiple metals exposures in urine with childhood behavior in China. For this population-based study, the children eligible for inclusion provided urine samples and their parents agreed to take in-person interview. A total of 831 children were remained from three cities for the final analysis. Urinary metals concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS). The childhood behavior scores was calculated by the Conners' Parent Rating Scale (CPRS). Variable selection was achieved by the least absolute shrinkage and selection operator (LASSO) regularization and stepwise regression to for all metals in the study. Linear regression models and Bayesian kernel machine regression (BKMR) were applied to estimate the associations of urinary metals concentrations with children's behavior. In BKMR models, the overall effect of mixture was significantly associated with conduct problems, learning problems and hyperactive index when urinary metals concentrations were all above the 50th percentile compared to all of them at their medians. The models also suggested marginally significant interaction effects of Se and Fe as well as Se and Sb (PSe∗Fe = 0.063; PSe∗Sb = 0.061), with a decline in estimate of Se on learning problems when Sb/Fe levels were relatively high. The concentrations of 22 metals in boys were higher than girls. In summary, multiple metals are associated with an increased risk of childhood behavioral problems in China. Potential interaction effects of Se and Fe as well as Se and Sb on childhood behavior should be taken into consideration.


Assuntos
Comportamento Problema , Teorema de Bayes , Criança , China/epidemiologia , Feminino , Humanos , Modelos Lineares , Masculino , Metais
18.
Adv Mater ; 34(15): e2107088, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35102632

RESUMO

Single-atom nanozymes (SAzymes) represent a new research frontier in the biomedical fields. The rational design and controllable synthesis of SAzymes with well-defined electronic and geometric structures are essential for maximizing their enzyme-like catalytic activity and therapeutic efficacy but remain challenging. Here, a melamine-mediated pyrolysis activation strategy is reported for the controllable fabrication of iron-based SAzyme containing five-coordinated structure (FeN5 ), identified by transmission electron microscopy imaging and X-ray absorption fine structure analyses. The FeN5 SAzyme exhibits superior peroxidase-like activity owing to the optimized coordination structure, and the corresponding catalytic efficiency of Fe-species in the FeN5 SAzyme is 7.64 and 3.45 × 105 times higher than those in traditional FeN4 SAzyme and Fe3 O4 nanozyme, respectively, demonstrated by steady-state kinetic assay. In addition, the catalytic mechanism is jointly disclosed by experimental results and density functional theory studies. The as-synthesized FeN5 SAzyme demonstrates significantly enhanced antitumor effect in vitro and in vivo due to the excellent peroxidase-like activity under tumor microenvironment.


Assuntos
Ferro , Neoplasias , Catálise , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Peroxidase , Microambiente Tumoral
19.
J Appl Toxicol ; 42(7): 1146-1158, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34989008

RESUMO

Quantum dots (QDs), with unique and tunable optical properties, have been widely used in many fields closely related to our daily lives, such as biomedical application and electronic products. Therefore, the potential toxicity of QDs on the human health should be understood. Autophagy plays an important role in cell survival and death. Endoplasmic reticulum autophagy (ER-phagy), a selective autophagy that degrades ER, responds to the accumulation of misfolded proteins and ER stress. Although many reports have revealed that autophagy can be disturbed by cadmium telluride (CdTe)-QDs and other nanomaterials, there are still lack more detailed researches to illustrate the function of autophagy in CdTe-QDs-treated cells, and the function of ER-phagy in CdTe-QDs-treated cells remains to be illustrated. On the basis of transcriptome analysis, we explored the effect of CdTe-QDs on Saccharomyces cerevisiae and first illustrated that both of autophagy and ER-phagy were protective mechanisms in CdTe-QDs-treated cells. It was found that CdTe-QDs inhibited the proliferation of yeast cells, disrupted homeostasis of cells, membrane integrity, and metabolism process. All of these can be reasons of the reduction of cell viability. The abolishment of autophagy and ER-phagy reduce the cell survival, indicating both of them are cell protective mechanisms against CdTe-QDs toxicity in yeast cells. Therefore, our data are significant for the application of CdTe-QDs and provide precious information for understanding of nanomaterials-related ER-phagy.


Assuntos
Compostos de Cádmio , Pontos Quânticos , Autofagia , Compostos de Cádmio/toxicidade , Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Humanos , Pontos Quânticos/toxicidade , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Telúrio/toxicidade
20.
Front Nutr ; 8: 754663, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34938758

RESUMO

Objective: The effect of processed foods on atopic dermatitis (AD) in adults is unclear. This study was to evaluate the association between processed foods and AD in the Chinese adult population. Design: This study included three population-based cross-sectional studies using cluster sampling by villages, institutions, or factories. Participants underwent dermatological examinations by certificated dermatologists and a food frequency questionnaire survey. A spot urine sample was collected to estimate the daily sodium intake. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were presented as the effect size. Setting: Shiyan city of Hubei province, and Huayuan, Shimen, Hengyang, Zhuzhou, and Changsha of Hunan province. Participants: Automobile manufacture workers from Shiyan of Hubei province, and rural residents and civil servants from Hunan. Results: A total of 15,062 participants, including 3,781 rural residents, 5,111 civil servants, and 6,170 workers, completed all evaluations. Compared to those hardly consumed pickles, consumption of pickles 1-3 times per week was significantly associated with AD (aOR: 1.35; 95% CI: 1.06-1.70). The intake of processed meats 1-3 times per month (aOR: 1.29; 95% CI: 1.05-1.58) and 1-3 times per week (aOR: 1.44; 95% CI: 1.11-1.87) were associated with AD dose-dependently when compared with those who rarely ate processed meats. Compared with non-consumers, the consumption of any processed foods 1-3 times per week (aOR: 1.39; 95% CI: 1.08-1.80) and ≥4 times per week (aOR: 1.41; 95% CI: 1.05-1.89) showed increased risks of AD. A positive association of estimated sodium intake with AD was also observed. Conclusion: Intake of processed foods is associated with AD in Chinese adults.

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