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1.
Artigo em Inglês | MEDLINE | ID: mdl-36600159

RESUMO

Complexes formed by organic matter and clay minerals, which are active components of soil systems, play an important role in the migration and transformation of pollutants in nature. In this study, humic-acid-montmorillonite (HA-MT) and humic-acid-kaolin (HA-KL) complexes were prepared, and their structures before and after the adsorption of aniline were analyzed. The aniline adsorption-desorption characteristics of complexes with different clay minerals and varying HA contents were explored using the static adsorption-desorption equilibrium method. Compared with the pristine clay minerals, the flaky and porous structure of the complexes and the aromaticity were enhanced. The adsorption of aniline on the different clay mineral complexes was nonlinear, and the adsorption capacity increased with increasing HA content. Additionally, the adsorption capacity of HA-MT was higher than that of HA-KL. After adsorption, the specific surface area of the complexes decreased, the surfaces became more complicated, and the aromaticity decreased because aniline is primarily adsorption onto the complexes via aromatic rings. Aniline was adsorbed onto the complexes via spontaneous exothermic physical adsorption. The amount of aniline desorbed from the complexes increased with increasing HA content, and a lag in desorption was observed, with a greater lag for HA-KL than for HA-MT.

2.
Acta Pharm ; 73(1): 75-90, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36692465

RESUMO

Breast cancer is one of the most common malignant tumors in women and it is the most frequently diagnosed cancer in the world. Ampelopsin (AMP) is a purified component from the root of Ampelopsis grossedentata. It is reported that AMP could significantly inhibit the proliferation of breast cancer cells. However, the antitumor mechanism against breast cancer has not yet been fully elucidated. The purpose of this work was to study the role of AMP against breast cancer MDA-MB-231 cells and to further investigate the underlying mechanism. PI3K/AKT/mTOR plays a very important role in tumor cell growth and proliferation and we hypothesize that AMP may inhibit this pathway. In the present work, the results showed that AMP could significantly inhibit the growth of breast cancer MDA-MB-231 cells in vitro and in vivo. In addition, treatment with AMP decreased the levels of PI3K, AKT and mTOR, as well as cyclin B1 expression, followed by p53/p21 pathway activation to arrest the cell cycle at G2/M. Moreover, it demonstrated a positive association between cyclin B1 and PI3K/AKT/mTOR levels. Importantly, this pathway was found to be regulated by cyclin B1 in MDA-MB-231 cells treated with AMP. Also, it was observed that cyclin B1 overexpression attenuated cell apoptosis and weakened the inhibitory effects of AMP on cell proliferation. Together, AMP could inhibit breast cancer MDA-MB-231 cell proliferation in vitro and in vivo, due to cell cycle arrest at G2/M by inactivating PI3K/AKT/mTOR pathway regulated by cyclin B1.


Assuntos
Neoplasias da Mama , Proteínas Proto-Oncogênicas c-akt , Feminino , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/farmacologia , Ciclina B1/metabolismo , Ciclina B1/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Apoptose , Proliferação de Células , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral
3.
Eur J Pharm Sci ; 182: 106376, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36626944

RESUMO

INTRODUCTION: Drug-drug interaction (DDI) is one of the major concerns for the clinical use of NOACs in the older adults considering that coexistence of multiple diseases and comorbidity were common. Current guidelines on the DDI management were established based on clinical studies conducted in healthy adults and mainly focus on the Caucasians, whereas systemic and ethnic differences may lead to distinct management in the Chinese older adults. OBJECTIVES: To investigate the impact of aging on the DDI magnitude between P-gp and/or CYP3A4 inhibitors with dabigatran etexilate and rivaroxaban in older adults, providing additional information for the use in clinical practice. RESULTS: Compared with the simulated adult, the AUC of the simulated older adults increased by 42-88% (DABE) and 21-60% (rivaroxaban), respectively, during NOACs monotherapy. Simulation on DDIs predicted that verapamil and clarithromycin further increase the exposure of dabigatran by 29-72% and 40-47%, whereas clarithromycin, fluconazole, and ketoconazole increase the exposure of rivaroxaban by 21-30%, 16-24%, and 194-247% in the older adults. Overall, our simulation result demonstrated that aging and DDIs both increased the exposure of NOACs. However, aging does not have a drastic impact on the extent of DDIs. The DDI ratios of young and old older adults were similar to the adults and were also similar between Caucasians and Chinese. DISCUSSION: We further simulated the interactions under steady-state based on the EHRA guideline (2021). Our simulation results revealed that recommended reduced dosing regimen of dabigatran etexilate during comedication with verapamil and clarithromycin (110 and 75 mg BID for Chinese young and old older adults) will result in exposure (trough concentration) that was either slightly higher or similar to the trough concentration of patients with any bleeding events. Routine monitoring of bleeding risk is encouraged. Further studies on the use of rivaroxaban in Chinese older adults are warranted. CONCLUSION: Aging and DDI increases exposure of drug in Chinese older adults. However, aging does not have a drastic impact on the extent of DDIs. Clinical management of DDIs in Chinese older adults in the absence of complex polypharmacy can a priori be similar to the EHRA guideline but routine monitoring of bleeding risk is encouraged when dabigatran etexilate given with verapamil and clarithromycin.


Assuntos
Dabigatrana , Rivaroxabana , Humanos , Idoso , Dabigatrana/farmacocinética , Rivaroxabana/uso terapêutico , Rivaroxabana/farmacocinética , Claritromicina/farmacologia , Administração Oral , Anticoagulantes , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Verapamil/farmacocinética , Interações Medicamentosas
4.
Bioengineering (Basel) ; 9(12)2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36550935

RESUMO

Meat quality and meat composition are not separated from the influences of animal genetic improvement systems; the growth and development of skeletal muscle are the primary factors in agricultural meat production and meat quality. Though the muscle-type cofilin (CFL2) gene has a crucial influence on skeletal muscle fibers and other related functions, the epigenetic modification mechanism of the CFL2 gene regulating meat quality remains elusive. After exploring the spatiotemporal expression data of CFL2 gene in a group of samples from fetal bovine, calf, and adult cattle, we found that the level of CFL2 gene in muscle tissues increased obviously with cattle age, whereas DNA methylation levels of CFL2 gene in muscle tissues decreased significantly along with cattle age by BSP and COBRA, although DNA methylation levels and mRNA expression levels basically showed an opposite trend. In cell experiments, we found that bta-miR-183 could suppress primary bovine myoblast differentiation by negatively regulated CFL2. In addition, we packaged recombinant adenovirus vectors for CFL2 gene knockout and overexpression and found that the CFL2 gene could promote the differentiation of primary bovine myoblasts by regulating marker genes MYOD, MYOG and MYH3. Therefore, CFL2 is an essential mediator for promoting myogenic differentiation by regulating myogenic marker genes in cattle myoblasts.

5.
Front Pediatr ; 10: 1045070, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36389359

RESUMO

Background: Physical activity can increase joint stability and reduce the risk of injury in hemophilia patients. There is limited clinical data on target trough FVIII levels during physical activity in hemophilia A patients. Hence, this study aimed to explore the target trough FVIII level required to avoid bleeding during different physical activities in hemophilia A patients. Methods: Patients with severe or moderate hemophilia A, who underwent pharmacokinetics (PK) tests at our center were enrolled in this study. Physical activities and clinical information such as bleeding were recorded. The FVIII level during physical activity was calculated by the WAPPS-Hemo. Results: A total of 105 patients were enrolled in this study. A total of 373 physical activities were recorded, of which 57.6% (215/373) was low-risk activities and the remaining 42.4% (158/373) was medium-risk activities. Most common physical activities were bicycling (59.0%), swimming (43.8%), running (48.6%), and jumping rope (41.0%). The FVIII trough level of low-risk physical activity was 3.8 IU/dl (AUC = 0.781, p = 0.002) and moderate-risk physical activity was 7.7 IU/dl (AUC = 0.809, p < 0.001). FVIII trough levels [low-risk activities: 6.1 (3.1, 13.2) IU/dl vs. 7.7 (2.3, 10.5) IU/dl, moderate-risk activities: 9.6 (5.8, 16.9) IU/dl vs. 10.2 (5.5, 11.0) IU/dl] were not statistically different between the mild arthropathy group and the moderate-severe arthropathy group. Multiple bleeding risk tended to increase with physical activities classified as moderate-risk (OR [95% CI]: 3.815 [1.766-8.238], p = 0.001). Conclusion: The minimum necessary FVIII level increased with higher risk physical activity, irrespective of arthropathy.

6.
Int Immunopharmacol ; 113(Pt B): 109431, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36384076

RESUMO

Artemisinins are well-known antimalarial drugs with clinical safety. In addition to antimalarial effects, their anti-inflammatory and immunoregulatory properties have recently attracted much attention in the treatment of inflammatory diseases. However, these artemisinins only have sub-millimolar anti-inflammatory activity in vitro, which may pose a high risk of toxicity in vivo with high doses of artemisinins. Here, we identified another derivative, artemisitene, which can increase the activity of inhibiting the NLRP3 pathway by more than 200-fold through introducing a covalent binding group while retaining the peroxide bridge structure. Mechanistically, artemisitene inhibits the production of ROS (especially mtROS) and prevents the assembly and activation of NLRP3 inflammasome, thereby inhibiting IL-1ß production. In addition, it can also block IL-1ß secretion mediated by NLRC4 and AIM2 inflammasome and IL-6 production. Furthermore, treatment with artemisitene significantly attenuated inflammatory response in DSS-induced ulcerative colitis. Our work provides a potential artemisinin derivative, which is worthy of further structural optimization based on pharmacokinetic properties as a drug candidate for inflammatory disorders.


Assuntos
Antimaláricos , Artemisininas , Colite Ulcerativa , Humanos , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Espécies Reativas de Oxigênio , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico
7.
RSC Adv ; 12(49): 32020-32026, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36380947

RESUMO

Recently, effective and rapid deep-learning methods for predicting chemical reactions have significantly aided the research and development of organic chemistry and drug discovery. Owing to the insufficiency of related chemical reaction data, computer-assisted predictions based on low-resource chemical datasets generally have low accuracy despite the exceptional ability of deep learning in retrosynthesis and synthesis. To address this issue, we introduce two types of multitask models: retro-forward reaction prediction transformer (RFRPT) and multiforward reaction prediction transformer (MFRPT). These models integrate multitask learning with the transformer model to predict low-resource reactions in forward reaction prediction and retrosynthesis. Our results demonstrate that introducing multitask learning significantly improves the average top-1 accuracy, and the RFRPT (76.9%) and MFRPT (79.8%) outperform the transformer baseline model (69.9%). These results also demonstrate that a multitask framework can capture sufficient chemical knowledge and effectively mitigate the impact of the deficiency of low-resource data in processing reaction prediction tasks. Both RFRPT and MFRPT methods significantly improve the predictive performance of transformer models, which are powerful methods for eliminating the restriction of limited training data.

8.
Heliyon ; 8(11): e11511, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36411881

RESUMO

An 80-year-old woman presented to our Ophthalmology Clinic for sudden pain and loss of vision in her right eye for seven days. She had a medical history of atrial fibrillation and cardiac valvular disease and received prophylactic antiplatelet therapy for more than ten years. Spontaneous suprachoroidal and orbital hemorrhage and secondary angle-closure glaucoma was diagnosed according to clinical manifestation and confirmed with B-scan ultrasound and Magnetic Resonance Imaging. The patient was given transscleral cyclophotocoagulation (TSCPC) combined with medical therapy to lower intraocular pressure (IOP). At a follow-up visit of 4 weeks after treatment, the patient's IOP was normal and symptoms such as eye pain and headache disappeared completely. In this case, we found that TSCPC was beneficial for lowering IOP and relieving pain.

9.
Front Pharmacol ; 13: 996635, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339559

RESUMO

Transdifferentiation of keratocytes into fibroblasts or further into myofibroblasts, which produced denser and more disorganized extracellular matrix, is the major cause of corneal fibrosis and scarring, leading to corneal blindness. TGF-ß1 is the critical cytokine for the myofibroblast's transdifferentiation and survival. Hypoxia Inducible Factor (HIF) was found to play an important role in promoting fibrosis in lung, kidney, and dermal tissues recently. Our preliminary study demonstrated that topical administration of the acriflavine (ACF), a drug inhibiting HIF dimerization, delayed corneal opacity and neovascularization after the alkali burn. To know whether ACF could prevent corneal fibrosis and improve corneal transparency, we created a mouse mechanical corneal injury model and found that topical administration of ACF significantly inhibited corneal fibrosis at day 14 post-injury. The reduction of myofibroblast marker α-SMA, and fibronectin, one of the disorganized extracellular matrix molecules, in the corneal stroma were confirmed by the examination of immunohistochemistry and real-time PCR. Furthermore, the ACF inhibited the expression of α-SMA and fibronectin in both TGF-ß1 stimulated or unstimulated fibroblasts in vitro. This effect was based on the inhibition of HIF signal pathways since the levels of the HIF-1α downstream genes including Slc2a1, Bnip3 and VEGFA were downregulated. To our knowledge, this is the first time to implicate that HIFs might be a new treatment target for controlling corneal fibrosis in mechanical corneal injuries.

10.
Foods ; 11(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36360114

RESUMO

Foods of animal origin, as nutritional supplements, are usually consumed after cooking, but residues of amphenicols in fresh raw meat threaten human health. Therefore, this study was designed to evaluate the effects of boiling, deep-frying and microwave processing under different time conditions on the residue levels of amphenicols and metabolites in livestock and poultry meat. Antibiotic-free pork, beef, lamb and chicken samples were spiked with chloramphenicol (CAP), thiamphenicol (TAP), florfenicol (FF) and florfenicol amine (FFA) standard solutions and made into homogeneous meat blocks. These positive mock meat blocks were processed using three different cooking methods, and the analyses were performed by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The results showed that cooking methods, time and food matrices were the main factors influencing the changes in amphenicols and metabolites residues in livestock and poultry meat. With the increase in cooking time, boiling processing was the most effective in reducing the four drug residues in livestock and poultry meat matrices, followed by deep-frying, while microwaving caused an increase in drug residue concentrations. Although boiling and frying processes are effective strategies to reduce amphenicols and metabolites residues in meat, it cannot be assumed that these residues can always decrease to levels that are safe for consumer health, especially when the drug residue concentrations in raw meat are above the maximum residue limits (MRLs). Therefore, it is not reliable to remove residues of amphenicols and metabolites from food by cooking. The solution to the food safety problem of veterinary drug residues must start from the breeding source and accelerate the implementation of antibiotic reduction, antibiotic substitution and antibiotic-free farming.

11.
Pharmacol Res ; 186: 106548, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36336216

RESUMO

Ras-GAP SH3 domain binding proteins (G3BPs) are a family of RNA-binding proteins that include G3BP1 and G3BP2 in mammals. The protein structure of G3BP2 allows it to bind with RNA or protein and regulate the nucleoplasmic shuttle, therefore participating in a variety of biological functions such as cell growth, differentiation and migration, and RNA and protein metabolism. G3BP2 is abnormally expressed in many tumors and diseases, such as breast cancer, lung cancer, prostate cancer, cardiac hypertrophy, and atherosclerosis. Many researchers have found that G3BP2 may be a potential therapeutic target. In this review, we examine the structure and expression regulation of G3BP2, and further summarize the function of G3BP2 from three aspects: RNA stabilization, protein subcellular localization, and stress granules assembling to provide a broader understanding of the role of G3BP2.


Assuntos
Neoplasias da Mama , DNA Helicases , Masculino , Animais , Humanos , Proteínas com Motivo de Reconhecimento de RNA/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/genética , DNA Helicases/genética , DNA Helicases/metabolismo , RNA Helicases/metabolismo , Proteínas de Transporte/metabolismo , Neoplasias da Mama/metabolismo , RNA , Mamíferos/genética , Mamíferos/metabolismo , Proteínas de Ligação a RNA , Proteínas Adaptadoras de Transdução de Sinal/metabolismo
12.
Front Plant Sci ; 13: 995609, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36325550

RESUMO

Rice, which supports more than half the population worldwide, is one of the most important food crops. Thus, potential yield-related quantitative trait nucleotides (QTNs) and QTN-by-environment interactions (QEIs) have been used to develop efficient rice breeding strategies. In this study, a compressed variance component mixed model, 3VmrMLM, in genome-wide association studies was used to detect QTNs for eight yield-related traits of 413 rice accessions with 44,000 single nucleotide polymorphisms. These traits include florets per panicle, panicle fertility, panicle length, panicle number per plant, plant height, primary panicle branch number, seed number per panicle, and flowering time. Meanwhile, QTNs and QEIs were identified for flowering times in three different environments and five subpopulations. In the detections, a total of 7~23 QTNs were detected for each trait, including the three single-environment flowering time traits. In the detection of QEIs for flowering time in the three environments, 21 QTNs and 13 QEIs were identified. In the five subpopulation analyses, 3~9 QTNs and 2~4 QEIs were detected for each subpopulation. Based on previous studies, we identified 87 known genes around the significant/suggested QTNs and QEIs, such as LOC_Os06g06750 (OsMADS5) and LOC_Os07g47330 (FZP). Further differential expression analysis and functional enrichment analysis identified 30 candidate genes. Of these candidate genes, 27 genes had high expression in specific tissues, and 19 of these 27 genes were homologous to known genes in Arabidopsis. Haplotype difference analysis revealed that LOC_Os04g53210 and LOC_Os07g42440 are possibly associated with yield, and LOC_Os04g53210 may be useful around a QEI for flowering time. These results provide insights for future breeding for high quality and yield in rice.

13.
Genes (Basel) ; 13(11)2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36421768

RESUMO

Dendrobium catenatum (Dendrobium officinale) is a valuable genuine herb. The source of this species is difficult to be identified by traditional methods including morphology, spectroscopy, and chromatography. We used the restriction site-associated DNA sequencing (RAD-seq) approach to perform the high-throughput sequencing of 24 D. catenatum provenances. In this study, 371.18 Gb clean data were obtained, and 655,057 high-quality SNPs were selected after their filtration. We used phylogenetic tree, genetic structure, and principal component analyses to examine the genetic diversities and genetic relationships of the 109 accessions. We found that D. catenatum could be divided into two groups, and each group was closely related to the distribution of the sampling sites. At the population level, the average nucleotide diversity (π) of the D. catenatum population mutation parameters was 0.1584 and the expected heterozygosity (HE) was 0.1575. The GXLPTP07 accessions showed the highest genetic diversity in terms of the private allele number, observed heterozygosity, and nucleotide diversity. The Mantel test showed a significant positive correlation between the genetic and geographic distances among the overall distribution. A genetic information database of D. catenatum was established, which confirmed that RAD-seq technology has the potential to be applied in the identification of medicinal Dendrobium of different origins.


Assuntos
Dendrobium , Filogenia , Dendrobium/genética , Nucleotídeos , Análise de Sequência de DNA
14.
Int Immunopharmacol ; 113(Pt A): 109279, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36272359

RESUMO

Fungal keratitis (FK) is a serious corneal infection caused by pathogenic fungi. Monocyte chemoattractant protein-induced protein 1 (MCPIP1) plays an important role in restricting the inflammatory response in various immune disorders. However, the function of MCPIP1 in Aspergillus fumigatus (A. fumigatus) keratitis is unclear. In the present study, we found that A. fumigatus infection promotes the expression of MCPIP1 in human corneal epithelial cells (HCECs) and in mouse corneas. Overexpression of MCPIP1 decreased the production of inflammatory cytokines, including TNF-α, IL-6, and IL-1ß, while knockdown of MCPIP1 increased the expression of these cytokines. MCPIP1 enhanced autophagy flux by inhibiting the mTOR signaling in HCECs with A. fumigatus infection. Further study showed that inhibition of autophagy using chloroquine reverses the anti-inflammatory effect of MCPIP1 in HCECs infected with A. fumigatus. Moreover, MCPIP1 alleviated the severity of keratitis and inhibited the expression of inflammatory cytokines by activating autophagy in an FK mouse model. In conclusion, our study demonstrated that MCPIP1 alleviates the severity of A. fumigatus keratitis by inducing mTOR-mediated autophagy in HCECs and in a mouse model. Exogenous use of MCPIP1 protein may have potential applications in FK clinical therapy.


Assuntos
Aspergilose , Epitélio Corneano , Infecções Oculares Fúngicas , Ceratite , Ribonucleases , Fatores de Transcrição , Animais , Humanos , Camundongos , Aspergilose/metabolismo , Aspergillus fumigatus , Autofagia , Citocinas/metabolismo , Modelos Animais de Doenças , Epitélio Corneano/metabolismo , Infecções Oculares Fúngicas/tratamento farmacológico , Ceratite/microbiologia , Camundongos Endogâmicos C57BL , Serina-Treonina Quinases TOR/metabolismo , Ribonucleases/genética , Fatores de Transcrição/genética
15.
Plants (Basel) ; 11(19)2022 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-36235370

RESUMO

Rice (Oryza sativa) is one of the most important cereal crops in the world, and yield-related agronomic traits, including plant height (PH), panicle length (PL), and protein content (PC), are prerequisites for attaining the desired yield and quality in breeding programs. Meanwhile, the main effects and epistatic effects of quantitative trait nucleotides (QTNs) are all important genetic components for yield-related quantitative traits. In this study, we conducted genome-wide association studies (GWAS) for 413 rice germplasm resources, with 36,901 single nucleotide polymorphisms (SNPs), to identify QTNs, QTN-by-QTN interaction (QQI), and their candidate genes, using a multi-locus compressed variance component mixed model, 3VmrMLM. As a result, two significant QTNs and 56 paired QQIs were detected, amongst 5219 genes of these QTNs, and 26 genes were identified as the yield-related confirmed genes, such as LCRN1, OsSPL3, and OsVOZ1 for PH, and LOG and QsBZR1 for PL. To reveal the substantial contributions related to the variation of yield-related agronomic traits in rice, we further implemented an enrichment analysis and expression analysis. As the results showed, 114 genes, nearly all significant QQIs, were involved in 37 GO terms; for example, the macromolecule metabolic process (GO:0043170), intracellular part (GO:0044424), and binding (GO:0005488). It was revealed that most of the QQIs and the candidate genes were significantly involved in the biological process, molecular function, and cellular component of the target traits. The demonstrated genetic interactions play a critical role in yield-related agronomic traits of rice, and such epistatic interactions contributed to large portions of the missing heritability in GWAS. These results help us to understand the genetic basis underlying the inheritance of the three yield-related agronomic traits and provide implications for rice improvement.

16.
Sci Rep ; 12(1): 17098, 2022 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-36224331

RESUMO

To improve the performance of data-driven reaction prediction models, we propose an intelligent strategy for predicting reaction products using available data and increasing the sample size using fake data augmentation. In this research, fake data sets were created and augmented with raw data for constructing virtual training models. Fake reaction datasets were created by replacing some functional groups, i.e., in the data analysis strategy, the fake data as compounds with modified functional groups to increase the amount of data for reaction prediction. This approach was tested on five different reactions, and the results show improvements over other relevant techniques with increased model predictivity. Furthermore, we evaluated this method in different models, confirming the generality of virtual data augmentation. In summary, virtual data augmentation can be used as an effective measure to solve the problem of insufficient data and significantly improve the performance of reaction prediction.


Assuntos
Projetos de Pesquisa
17.
Drug Des Devel Ther ; 16: 3297-3314, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36193286

RESUMO

Objective: The mechanism of Wendan Decoction (WDD) against Generalized Anxiety Disorder (GAD) was predicted by network pharmacology and validated by in vivo and in vitro experiments. Methods: The targets of WDD for the treatment of GAD were obtained by a search of online databases. Further, PPI network and KEGG enrichment were used to identify the key targets and pathways. Ultimately, these key targets and pathways were validated by in vivo experiments on GAD mice modeled by repeated restraint stress (RRS) and in vitro experiments on inflammatory factor stimulated BV-2 cells. Results: Through searching the databases, the 137 ingredients of WDD that correspond to 938 targets and 4794 targets related to GAD were identified. Among them, 569 overlapping targets were considered as the therapeutic targets of WDD for GAD. PPI analysis showed that the inflammation-related proteins IL-6, TNF, SRC and AKT1 were the key targets, and KEGG enrichment suggested that PI3K/AKT and MAPK signaling pathways were key pathways of WDD in the treatment of GAD. In vivo experiments, RRS mice exhibited abnormality in behavioristics in open field test (OFT) and elevated plus maze (EPM) and increases in serum corticosterone and the percentage of lymphocytes positive for IL-6 in peripheral blood. These abnormal changes can be reversed by WDD and the positive control drug paroxetine. In vitro experiments, WDD can inhibit IL-6 induced activation of PI3K/AKT and MAPK signaling pathways in BV2 cells, and suppress the ensuing release of inflammatory factors TNF-α, IL-1ß and PGE2, and showed a dose-dependent effect. Conclusion: WDD is able to resist GAD by relieving inflammatory response in peripheral and central system.


Assuntos
Medicamentos de Ervas Chinesas , Fosfatidilinositol 3-Quinases , Animais , Transtornos de Ansiedade/tratamento farmacológico , Corticosterona , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Interleucina-6 , Camundongos , Simulação de Acoplamento Molecular , Paroxetina , Prostaglandinas E , Proteínas Proto-Oncogênicas c-akt , Fator de Necrose Tumoral alfa
18.
Nanoscale Adv ; 4(5): 1246-1262, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36133685

RESUMO

With the fast development of industry, large amounts of organic and inorganic pollutants are inevitably released into the natural environment, which results in the pollution of the environment and are thereby dangerous to human health. The efficient elimination of these pollutants is crucial to environment protection and human health. The high sorption capacity of carbon-based materials and high photocatalytic ability of carbon-based composites result in the application of carbon-based materials in environmental pollution cleanup. In this review article, we summarized recent studies on the synthesis of carbon-based materials, and their application in the sorption of organic and inorganic pollutants, the photocatalytic degradation of organic pollutants, and the in situ photocatalytic reduction-solidification of heavy metal ions. The sorption method is useful to remove pollutants from aqueous solutions. The sorption-photocatalytic degradation of organic pollutants is applicable, especially at low concentrations, whereas the catalytic reduction of metal ions is the best method for the in situ immobilization of high valent metal ions under complicated conditions. The interaction mechanism is discussed using advanced spectroscopy analysis and theoretical calculations, and at the end the challenges in the future are described.

19.
J Med Chem ; 65(18): 11985-12001, 2022 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-36063115

RESUMO

NLRP3 inflammasome activation plays a critical role in inflammation-related disorders. More small-molecule entities are needed to study the mechanism of NLRP3 inflammasome activation and to validate the efficacy and safety of the NLRP3 pathway. Herein, we report the discovery of an orally bioavailable proteasome inhibitor NIC-0102 (27) that specifically prevents NLRP3 inflammasome activation but has no effect on NLRC4 or AIM2 inflammasomes. In vitro studies revealed that NIC-0102 induced the polyubiquitination of NLRP3, interfered with the NLRP3-ASC interaction, and blocked ASC oligomerization, thereby resulting in the inhibition of NLRP3 inflammasome activation. In addition, NIC-0102 also inhibited the production of pro-IL-1ß. Importantly, NIC-0102 showed potent anti-inflammatory effects on DSS-induced ulcerative colitis model in vivo. As a result of these studies, a potential small molecule is identified to demonstrate the possible link between the proteasome and NLRP3 pathway, which supports further exploration of potentially druggable nodes to modulate NLRP3 inflammasome activation.


Assuntos
Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Interleucina-1beta/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Complexo de Endopeptidases do Proteassoma , Inibidores de Proteassoma/farmacologia
20.
Front Endocrinol (Lausanne) ; 13: 947085, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36060980

RESUMO

Purpose: We aimed to perform a retrospective analysis of a rare subtype of corticotroph adenoma, Crooke's cell adenoma, to better understand its clinical features. Methods: We collected T-PIT-positive pituitary adenomas and screened Crooke's cell adenomas from January 2020 to December 2021 in our center. Case reports of such tumors were also collected through a literature search. Clinical data such as biochemical tests, imaging examinations, and pathological data of the above cases were analyzed. Results: A total of 101 T-PIT-positive patients were treated in our center in the last 2 years, and 4 were finally pathologically diagnosed with Crooke's cell adenomas. All of these patients were male with elevated adrenocorticotropic hormone levels, and 50.0% presented with hypercortisolemia, Cushing's syndrome, visual impairment, and headache. The tumor diameter was significantly larger in these 4 patients (37.0 mm) than in the other patients (26.0 mm), and their tumor invasive behavior was more pronounced. Cases reported in the literature were mainly female (72.8%), and the clinical presentation was also dominated by Cushing's syndrome (65.1%) and hormonal dysfunction. Tumors were more common as macroadenomas (33.2 mm) and suprasellar growths (63.8%). The tumor recurrence rate was as high as 55.6%, with 6 cases progressing to pituitary carcinomas and 7.7% of tumor-related deaths. Our further integrated analysis of our center and reported cases revealed that gender, Cushing's syndrome, visual dysfunction, hormonal disorders, and tumor growth characteristics were statistically different in different tumor categories. Conclusion: Crooke's cell adenoma is a tumor subtype with obvious clinical aggressive behavior, and an in-depth analysis of its clinical characteristics may assist in developing a comprehensive treatment plan.


Assuntos
Adenoma , Síndrome de Cushing , Neoplasias Hipofisárias , Adenoma/patologia , Síndrome de Cushing/patologia , Feminino , Humanos , Masculino , Recidiva Local de Neoplasia , Neoplasias Hipofisárias/patologia , Prevalência , Estudos Retrospectivos
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