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1.
Medicine (Baltimore) ; 103(17): e37900, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38669429

RESUMO

Anoikis is considered strongly associated with a biological procession of tumors. Herein, we utilized anoikis-related genes (ARGs) to predict the prognosis and immunotherapeutic efficacy for skin cutaneous melanoma (SKCM). RNA-seq data were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. After dividing patients into novel subtypes based on the expression of prognostic ARGs, K-M survival was conducted to compare the survival status. Subsequently, differentially expressed ARGs were identified and the predictive model was established. The predictive effects were validated using the areas under the curve about the receiver operating characteristic. Moreover, tumor mutation burden, the enriched functional pathway, immune cells and functions, and the immunotherapeutic response were also analyzed and compared. The distribution of model genes at cell level was visualized by the single-cell seq with tumor immune single-cell hub database. Patients of The Cancer Genome Atlas-SKCM cohort were divided into 2 clusters, the cluster 1 performed a better prognosis. Cluster 2 was more enriched in metabolism-related pathways whereas cluster 1 was more associated with immune pathways. A predictive risk model was established with 6 ARGs, showing the areas under the curves of 1-year, 3-year, and 5-year ROC were 0.715, 0,720, and 0.731, respectively. Moreover, risk score was negatively associated with tumor mutation burden and immune-related pathways enrichment. In addition, patients with high-risk scores performed immunosuppressive status but the decreasing scores enhanced immune cell infiltration, immune function activation, and immunotherapeutic response. In this study, we established a novel signature in predicting prognosis and immunotherapy. It can be considered reliable to formulate the complex treatment for SKCM patients.


Assuntos
Anoikis , Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/genética , Melanoma/imunologia , Melanoma/mortalidade , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Anoikis/genética , Prognóstico , Melanoma Maligno Cutâneo , Masculino , Feminino , Imunoterapia/métodos , Pessoa de Meia-Idade , Curva ROC , Regulação Neoplásica da Expressão Gênica
2.
Bioorg Med Chem Lett ; 105: 129752, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38631541

RESUMO

The misfolding and aggregation of α-Syn play a pivotal role in connecting diverse pathological pathways in Parkinson's disease (PD). Preserving α-Syn proteostasis and functionality by inhibiting its aggregation or disaggregating existing aggregates using suitable inhibitors represents a promising strategy for PD prevention and treatment. In this study, a series of benzothiazole-polyphenol hybrids was designed and synthesized. Three identified compounds exhibited notable inhibitory activities against α-Syn aggregation in vitro, with IC50 values in the low micromolar range. These inhibitors demonstrated sustained inhibitory effects throughout the entire aggregation process, stabilizing α-Syn proteostasis conformation. Moreover, the compounds effectively disintegrated preformed α-Syn oligomers and fibers, potentially by binding to specific domains within the fibers, inducing fibril instability, collapse, and ultimately resulting in smaller-sized aggregates and monomers. These findings offer valuable insights into the therapeutic potential of polyphenol hybrids with 2-conjugated benzothiazole targeting α-Syn aggregation in the treatment of PD.


Assuntos
Benzotiazóis , Polifenóis , Agregados Proteicos , alfa-Sinucleína , Benzotiazóis/química , Benzotiazóis/farmacologia , Benzotiazóis/síntese química , alfa-Sinucleína/antagonistas & inibidores , alfa-Sinucleína/metabolismo , Polifenóis/química , Polifenóis/farmacologia , Polifenóis/síntese química , Humanos , Agregados Proteicos/efeitos dos fármacos , Estrutura Molecular , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo
3.
Sensors (Basel) ; 24(1)2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38203142

RESUMO

Patterns entered into knitting CAD have thousands or tens of thousands of different colors, which need to be merged by color-separation algorithms. However, for degraded patterns, the current color-separation algorithms cannot achieve the desired results, and the clustering quantity parameter needs to be managed manually. In this paper, we propose a fast and automatic FCM color-separation algorithm based on superpixels, which first uses the Real-ESRGAN blind super-resolution network to clarify the degraded patterns and obtain high-resolution images with clear boundaries. Then, it uses the improved MMGR-WT superpixel algorithm to pre-separate the high-resolution images and obtain superpixel images with smooth and accurate edges. Subsequently, the number of superpixel clusters is automatically calculated by the improved density peak clustering (DPC) algorithm. Finally, the superpixels are clustered using fast fuzzy c-means (FCM) based on a color histogram. The experimental results show that not only is the algorithm able to automatically determine the number of colors in the pattern and achieve the accurate color separation of degraded patterns, but it also has lower running time. The color-separation results for 30 degraded patterns show that the segmentation accuracy of the color-separation algorithm proposed in this paper reaches 95.78%.

4.
Sensors (Basel) ; 23(8)2023 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-37112223

RESUMO

To be compatible with future wireless communication systems, it is very necessary to extend the bandwidth of the Doherty power amplifier (DPA). In this paper, a modified combiner integrated with a complex combining impedance is adopted to enable an ultra-wideband DPA. Meanwhile, a comprehensive analysis is performed on the proposed method. It is illustrated that the proposed design methodology can provide power amplifier (PA) designers with more freedom in implementing ultra-wideband DPAs. As a concept of proof, a DPA working over 1.2-2.8 GHz (a relative bandwidth of 80%) is designed, fabricated and measured in this work. Experimental results showed that the fabricated DPA delivers a saturation output power of 43.2-44.7 dBm with a gain of 5.2-8.6 dB. Meantime, the fabricated DPA achieves a saturation drain efficiency (DE) of 44.3-70.4% and a 6 dB back-off DE of 38.7-57.6%.

5.
J Cell Mol Med ; 27(7): 982-990, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36924030

RESUMO

Vitiligo is an autoimmune disease characterized by depigmentation. Kaempferol is a flavonoid compound with broad anti-inflammatory and antioxidant properties. The purpose of this study was to investigate the effect of kaempferol on melanogenesis in PIG1 normal human skin melanocytes and its response to oxidative stress. The effect of kaempferol on melanin synthesis in PIG1 normal human skin melanocytes was explored by measuring tyrosinase activity, melanin content, mRNA and protein expression of key enzymes and expression of related pathway proteins. The effects of kaempferol pretreatment on cell viability, apoptosis, ROS level and HO-1 protein level under H2 O2 stimulation were explored. When treated with kaempferol, the tyrosinase activity and melanin content of PIG1 cells increased, the mRNA and protein expressions of TYR, TRP1, TRP2 and MITF increased, and the phosphorylation level of ERK1/2 increased. Upon the stimulation of H2 O2 , kaempferol reduced the production of ROS, decreased apoptosis and increased the protein expression of HO-1 in PIG1 cells. In addition, kaempferol inhibited oxidative stress-induced melanin reduction and promoted melanin synthesis in PIG1 cells and protected against H2 O2 -induced oxidative stress damage.


Assuntos
Melaninas , Monofenol Mono-Oxigenase , Humanos , Espécies Reativas de Oxigênio/metabolismo , Monofenol Mono-Oxigenase/genética , Monofenol Mono-Oxigenase/metabolismo , Quempferóis/farmacologia , Melanócitos/metabolismo , Estresse Oxidativo , RNA Mensageiro/metabolismo
6.
Sensors (Basel) ; 23(4)2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36850588

RESUMO

Online detection of yarn roll's margin is one of the key issues in textile automation, which is related to the speed and scheduling of bobbin (empty yarn roll) replacement. The actual industrial site is characterized by uneven lighting, restricted shooting angles, diverse yarn colors and cylinder yarn types, and complex backgrounds. Due to the above characteristics, the neural network detection error is large, and the contour detection extraction edge accuracy is low. In this paper, an improved neural network algorithm is proposed, and the improved Yolo algorithm and the contour detection algorithm are integrated. First, the image is entered in the Yolo model to detect each yarn roll and its dimensions; second, the contour and dimensions of each yarn roll are accurately detected based on Yolo; third, the diameter of the yarn rolls detected by Yolo and the contour detection algorithm are fused, and then the length of the yarn rolls and the edges of the yarn rolls are calculated as measurements; finally, in order to completely eliminate the error detection, the yarn consumption speed is used to estimate the residual yarn volume and the measured and estimated values are fused using a Kalman filter. This method overcomes the effects of complex backgrounds and illumination while being applicable to different types of yarn rolls. It is experimentally verified that the average measurement error of the cylinder yarn diameter is less than 8.6 mm, and the measurement error of the cylinder yarn length does not exceed 3 cm.

7.
Org Lett ; 25(1): 267-271, 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36583596

RESUMO

A variety of 1,2,4-oxadiazoline derivatives were synthesized in moderate to good yields through a deoxygenative cyclization cascade reaction of N-vinyl-α,ß-unsaturated nitrones and hydroxamoyl chlorides. Mechanistic studies revealed that the reaction underwent double additions of nitrile oxides to N-vinyl-α,ß-unsaturated nitrones, sequential elimination, and intramolecular cyclization to afford 1,2,4-oxadiazolines. Alternatively, 1,2,5-oxadiazolines were also obtained as major products in i-PrOH solvent through [3 + 3] cycloaddition and selective [3,3]-rearrangement. Moreover, the prepared 1,2,4-oxadiazolines were easily converted to polysubstituted pyrroles under thermal conditions.

8.
Artigo em Inglês | MEDLINE | ID: mdl-36569347

RESUMO

Objective: This study aimed to explore the mechanisms of Baishi tablets (BSTs) in the treatment of vitiligo through network pharmacology-based identification and experimental validation. Methods: In brief, the compounds and related targets of BST were extracted from the TCMSP database, and disease information was obtained from the OMIM, GeneCards, PharmGkb, TTD, and DrugBank databases. A Venn diagram was generated to visualize the common targets of BST and vitiligo. GO and KEGG analyses were performed to explore the potential biological processes and signaling pathways. The PPI network and core gene subnetwork were constructed using STRING and Cytoscape software. In addition, the measurement of apoptosis in PIG1 cells and intracellular reactive oxygen species were measured using quercetin (QU), luteolin (LU), and kaempferol (KA) to protect melanocytes from oxidative stress. Results: A total of 55 compounds with 236 targets and 1205 vitiligo-related genes were obtained from the TCMSP database. GO and KEGG analyses were performed to explore the potential biological processes and signaling pathways, revealing that BST may cure vitiligo by influencing the biological processes of cellular oxidative stress and related signaling pathways. A critical subnetwork was obtained with 13 core genes by analyzing the PPI network, which includes HMOX1, CXCL8, CCL2, IL6, MAPK8, CASP3, PTGS2, AKT1, IL1B, MYC, TP53, IFNG, and IL2. Furthermore, a molecular docking analysis was conducted to simulate the combination of compounds and gene proteins, reflecting that QU, LU, and KA can strongly bind the core genes. Through a series of experimental validations, we found that QU, LU, and KA could attenuate H2O2-induced apoptosis in melanocytes. Further evidence revealed that QU, LU, and KA could enhance the scavenging of intracellular reactive oxygen species (ROS). Conclusion: Based on the results of network pharmacology analysis and experimental verification, QA, LU, and KA can be utilized to protect PIG1 cells by inhibiting oxidative stress and reducing the intracellular level of ROS. This may explain the underlying mechanism of BST therapy and provide a novel strategy for the treatment of vitiligo.

9.
Dis Markers ; 2022: 8232024, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36438905

RESUMO

The prognosis of skin cutaneous melanoma (SKCM) remains poor, and patients with SKCM show a poor response to immunotherapy. Thus, we aimed to identify necroptosis-related biomarkers, which can help predict the prognosis of SKCM and improve the effectiveness of precision medicine. Data of SKCM were obtained from The Cancer Genome Atlas (TCGA) and GEO databases. TCGA samples were classified into two clusters by consensus clustering of necroptosis-related genes. Univariate Cox and least absolute shrinkage and selection operator regression analyses led to the identification of 11 genes, which were used to construct a prognostic model. GSE65904 was used as the test set. Principal component, t-distributed stochastic neighbor embedding, and Kaplan-Meier survival analyses indicated that samples in the train and test sets could be divided into two groups, with the high-risk group showing a worse prognosis. Univariate and multivariate Cox regression analyses were performed, and a nomogram, calibration curve, and time-dependent receiver operating characteristic curve were constructed to verify the efficacy of our model. The 1-, 3-, and 5-year areas under the receiver operating characteristic curves for the train set were 0.702, 0.663, and 0.701 and for the test set were 0.613, 0.627, and 0.637, respectively. Moreover, we performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses between the high- and low-risk groups. Single sample gene set enrichment analysis, immune cell infiltration analysis, tumor microenvironment scores, immune checkpoint analysis, and half-maximal inhibitory concentration prediction indicated that the high-risk group showed weaker antitumor immunity; further, the response to immune checkpoint inhibitors was worse, and the high-risk group was sensitive to fewer antitumor drugs. Tumor mutational burden analysis, Kaplan-Meier survival analysis, and correlation analysis between risk score and RNA stemness score revealed that the high-risk group with low tumor mutational burden and high RNA stemness score was potentially associated with poor prognosis. To conclude, our model, which was based on 11 necroptosis-related genes, could predict the prognosis of SKCM; in addition, it has guiding significance for the selection of clinical treatment and provides new research directions to enhance necroptosis against SKCM.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/genética , Melanoma/patologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Necroptose/genética , Prognóstico , Biomarcadores Tumorais/genética , RNA , Microambiente Tumoral/genética , Melanoma Maligno Cutâneo
10.
Sensors (Basel) ; 22(17)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36081116

RESUMO

Automatic replacement of bobbins on the frame is one of the core problems that must be solved in the textile industry. In the process of changing the bobbin, it is faced with problems such as the position offset of the bobbin, the loosening and deformation of the bobbin, which will lead to the failure of replacing the bobbin. Therefore, it is necessary to initialize the creel coordinates regularly, also considering the labor intensity and poor reliability of manual positioning. This paper proposes an automatic creel positioning method based on monocular vision. Firstly, the industrial camera was installed on the drum changing manipulator controlled by the truss system, and each yarn frame in the yarn area was inspected. Secondly, the end face image of the creel was collected at a reasonable distance, and the collected images were transmitted to the computer in real time through the Ethernet bus. Thirdly, the center coordinates (x, y) and radius r of the creel were marked by the improved Hough circle detection algorithm. Finally, the coordinate deviation of the creel was calculated and transmitted to the system controller to realize deviation correction. Before the test, the creel positioning markers were specially designed and the camera was calibrated. Thus, the influence of image complex background, creel end roughness, reflection and other factors can be reduced, and the image processing speed and positioning accuracy can be improved. The results show that the positioning effect of this method is fine when the distance between the center of the camera lens and the center of the end face of the creel is 170~190 mm. Moreover, when the distance is 190 mm, the positioning effect is the best, with an average error of only 0.51 mm. In addition, the deviation between the center coordinate and the radius of the end face of the marker is also very small, which is better than the requirements of bobbin yarn changing accuracy.

11.
Regen Ther ; 21: 148-156, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35844295

RESUMO

Background: A large number of autologous melanocytes are required for surgical treatment of depigmentation diseases such as vitiligo. The purpose of this experiment is to explore the application of melanocytes induced by mesenchymal stem cells to clinical treatment. Therefore, we have induced mouse bone marrow mesenchymal stem cells (BMMSCs) into melanocytes (miMels) in the previous experiment. This experiment continues the previous experiment to further study the biological functions of miMels and their application in tissue engineering. Methods: We examined whether miMels can produce active tyrosinase, melanin, and response to α-MSH. The ability of miMels to produce melanin to keratinocytes was tested by co-culture. By applying miMels to tissue-engineered skin, the survival and function of miMels on the surface of nude mice were verified. Results: MiMels can produce active tyrosinase and melanin, and can pass melanin to the co-cultured keratinocytes. Under the stimulation of α-MSH, the active tyrosinase and melanin content of miMels increased. We tried to apply it to the establishment of tissue-engineered skin and obtained tissue-engineered skin containing miMels. Then we tried to transplant tissue-engineered skin on the back skin of nude mice and succeeded. The transplanted miMels survived in local tissues, synthesized active tyrosinase and melanin, and expressed the marker protein of melanocytes. Conclusion: In short, miMels can be used as a cell source for tissue engineering skin. MiMels not only have a typical melanocyte morphology but also have the same biological functions as normal melanocytes. What's more important is its successful application in mouse tissue-engineered experiments.

12.
J Cosmet Dermatol ; 21(10): 4510-4514, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35318791

RESUMO

BACKGROUND: Alopecia areata is a common non-scarring alopecia, mainly manifested as sudden localized patchy alopecia. It is currently believed to be related to autoimmune, genetic, emotional stress, and endocrine factors. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of the mixed preparation of piperine, capsaicin, and curcumin on alopecia areata treatment. METHODS: Sixty patients were enrolled in this study and divided into 2 groups randomly: topical treated with the mixed preparation (case) twice daily and 5%minoxidil (control) once daily for 3 months. The degree of hair loss was assessed by SALT and dermoscopy. RESULTS: On the completion of the study, compared with baseline, statistically significant regrowth occurred in both groups (p < 0.05). The mean SALT scores and hair follicle status under trichoscopy at baseline and at the end of 12 weeks in the mixed preparation group and in the minoxidil group were comparable, respectively. The effective rate of mixed preparation group was 63.33% and minoxidil group was 70%. Adverse symptoms were temporary and no serious adverse event occurred. CONCLUSION: Based on our findings, the mixed preparation of piperine, capsaicin, and curcumin is effective in treating alopecia areata, but it has not been shown to be superior to minoxidil in short-term therapy.


Assuntos
Alopecia em Áreas , Curcumina , Humanos , Alopecia em Áreas/diagnóstico , Minoxidil , Capsaicina/efeitos adversos , Curcumina/efeitos adversos , Administração Tópica , Alopecia/tratamento farmacológico , Alopecia/diagnóstico
13.
Front Genet ; 12: 758981, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804126

RESUMO

Ferroptosis is a non-apoptotic regulated cell death process, and much research has indicated that ferroptosis can induce the non-apoptotic death of tumor cells. Ferroptosis-related genes are expected to become a biological target for cancer treatment. However, the regulation of ferroptosis-related genes in skin cutaneous melanoma (SKCM) has not been well studied. In the present study, we conducted a systematic analysis of SKCM based on RNA sequencing data and clinical data obtained from The Cancer Genome Atlas (TCGA) database and the FerrD database. SKCM patients from the GSE78220 and MSKCC cohorts were used for external validation. Applying consensus clustering on RNA sequencing data from TCGA the generated ferroptosis subclasses of SKCM, which were analyzed based on the set of differentially expressed ferroptosis-related genes. Then, a least absolute shrinkage and selection operator (LASSO)-Cox regression was used to construct an eight gene survival-related linear signature. The median cut-off risk score was used to divide patients into high- and low-risk groups. The time-dependent receiver operating characteristic curve was used to examine the predictive power of the model. The areas under the curve of the signature at 1, 3, and 5 years were 0.673, 0.716, and 0.746, respectively. Kaplan-Meier survival analysis showed that the prognosis of high-risk patients was worse than that of low-risk patients. Univariate and multivariate Cox regression analyses showed that the risk signature was a robust independent prognostic indicator. By incorporating risk scores with tumor staging, a nomogram was constructed to predict prognostic outcomes for SKCM patients. In addition, the immunological analysis showed different immune cell infiltration patterns. Programmed-death-1 (PD-1) immunotherapy showed more significant benefits in the low-risk group than in the high-risk group. In summary, a model based on ferroptosis-related genes can predict the prognosis of SKCM and could have a potential role in guiding targeted therapy of SKCM.

14.
Sensors (Basel) ; 21(19)2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34640651

RESUMO

The automatic detection of the thread roll's margin is one of the kernel problems in the textile field. As the traditional detection method based on the thread's tension has the disadvantages of high cost and low reliability, this paper proposes a technology that installs a camera on a mobile robot and uses computer vision to detect the thread roll's margin. Before starting, we define a thread roll's margin as follows: The difference between the thread roll's radius and the bobbin's radius. Firstly, we capture images of the thread roll's end surface. Secondly, we obtain the bobbin's image coordinates by calculating the image's convolutions with a Circle Gradient Operator. Thirdly, we fit the thread roll and bobbin's contours into ellipses, and then delete false detections according to the bobbin's image coordinates. Finally, we restore every sub-image of the thread roll by a perspective transformation method, and establish the conversion relationship between the actual size and pixel size. The difference value of the two concentric circles' radii is the thread roll's margin. However, there are false detections and these errors may be more than 19.4 mm when the margin is small. In order to improve the precision and delete false detections, we use deep learning to detect thread roll and bobbin's radii and then can calculate the thread roll's margin. After that, we fuse the two results. However, the deep learning method also has some false detections. As such, in order to eliminate the false detections completely, we estimate the thread roll's margin according to thread consumption speed. Lastly, we use a Kalman Filter to fuse the measured value and estimated value; the average error is less than 5.7 mm.


Assuntos
Computadores , Visão Ocular , Reprodutibilidade dos Testes
15.
Mol Cancer ; 20(1): 121, 2021 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-34560891

RESUMO

N6-methyladenosine (m6A) is a prevalent internal modification in eukaryotic RNAs regulated by the so-called "writers", "erasers", and "readers". m6A has been demonstrated to exert critical molecular functions in modulating RNA maturation, localization, translation and metabolism, thus playing an essential role in cellular, developmental, and disease processes. Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently closed single-stranded structures generated by back-splicing. CircRNAs also participate in physiological and pathological processes through unique mechanisms. Despite their discovery several years ago, m6A and circRNAs has drawn increased research interest due to advances in molecular biology techniques these years. Recently, several scholars have investigated the crosstalk between m6A and circRNAs. In this review, we provide an overview of the current knowledge of m6A and circRNAs, as well as summarize the crosstalk between these molecules based on existing research. In addition, we present some suggestions for future research perspectives.


Assuntos
Adenosina/análogos & derivados , Regulação da Expressão Gênica , RNA Circular/genética , RNA Circular/metabolismo , Adenosina/metabolismo , Humanos , Metilação , Biossíntese de Proteínas , Splicing de RNA , Estabilidade de RNA , Transporte de RNA , Transcrição Gênica
16.
Org Lett ; 23(19): 7482-7486, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34533319

RESUMO

A variety of N-vinylindoles and N-vinylpyrroles were prepared in moderate to good yields through the nickel(II)-catalyzed [3 + 2] cycloaddition of α,ß-unsaturated nitrones with allenoates under mild reaction conditions. A rational mechanism for the formation of N-vinylindoles was proposed based on the 18O-labeled experiments and key intermediates detected by high-resolution mass spectrometry trace experiments. The present method highlights a nickel(II)-controlled cyclization, atom-economical reaction, broad substrate scope, good functional group tolerance, and high Z-stereoselectivity for the enamine bond.

17.
Rapid Commun Mass Spectrom ; 35(16): e9129, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34097785

RESUMO

RATIONALE: Tebipenem pivoxil (TBPM-PI) has been developed as the first oral carbapenem drug in the world to treat otolaryngological and respiratory infections in pediatric patients. Due to its structural properties and external factors, some related impurities, which may cause side effects in patients, might be formed during the synthesis and storage of TBPM-PI. It was vital to rapidly separate and identify the related impurities to guarantee the safe use of TBPM-PI. METHODS: A method using ultra-high-performance liquid chromatography (UHPLC) coupled with quadrupole time-of-flight tandem mass spectrometry (QTOF-MS/MS) was developed to separate and detect TBPM-PI and related impurities in an oral pharmaceutical formulation. LC/MS and MS/MS spectra of these compounds in the formulation were acquired to confirm their elemental compositions and propose their structures based on LC/MS data and fragmentation pathways of available reference substances. RESULTS: LC/MS parameters and MS/MS fragmentation pathways of reference substances of TBPM-PI and related impurities were summarized in detail. Based on this, a total of 23 related impurities were found and characterized in the oral pharmaceutical formulation. Eight of these were verified by comparison with reference substances and the structures of the other 15 were proposed for the first time. In addition, four of these compounds were produced by the reaction of excipients and pre-existing related impurities. CONCLUSIONS: A UHPLC/QTOF-MS method was established and used for the separation and identification of 23 related impurities in a TBPM-PI oral pharmaceutical formulation. Moreover, it was proved that new related impurities could be produced by the reaction of excipients in the pharmaceutical formulation and related impurities in the corresponding active pharmaceutical ingredient (API).


Assuntos
Carbapenêmicos/análise , Carbapenêmicos/química , Cromatografia Líquida de Alta Pressão/métodos , Contaminação de Medicamentos , Espectrometria de Massas por Ionização por Electrospray/métodos , Formas de Dosagem , Modelos Moleculares , Espectrometria de Massas em Tandem/métodos
18.
Rev Sci Instrum ; 92(2): 024712, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33648093

RESUMO

The influence of strong microwave electric field (SMEF) on the dielectric properties of materials is the result of the joint action of microwave thermal effect and microwave non-thermal effect. Generally, the thermal effect of SMEF is stronger than the non-thermal effect, which makes the non-thermal effect of SMEF difficult to detect. Moreover, it is difficult to distinguish the influence of these two factors from each other. Therefore, the formation mechanism and characteristics of the non-thermal effect of SMEF have not been elucidated so far. In this paper, a separation and extraction model of the non-thermal effect of SMEF on the dielectric property of material is proposed based on the time modulation method and cavity perturbation method. By adjusting the interaction time between SMEF and materials, reducing the influence of microwave thermal effect, and strengthening the proportion of microwave non-thermal effect, the separation and extraction of the non-thermal effect of SMEF is realized. Through the designed re-entrant coaxial cavity, the corresponding test system is constructed and the typical materials are tested. Experimental results show that the proposed research method is feasible. The research method proposed in this paper provides an effective way for the follow-up study on the formation mechanism and characteristics of the non-thermal effect of SMEF on the dielectric properties of materials.

19.
Mol Ther Nucleic Acids ; 24: 212-222, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-33767917

RESUMO

Circular RNAs (circRNAs) are a class of non-coding RNAs with covalently closed single-stranded structures lacking 5'-3' polarity and a polyadenine tail. Over recent years, a growing body of studies have been conducted to explore the roles of circRNAs in human diseases. Systemic lupus erythematosus (SLE) is a severe autoimmune disorder characterized by the presence of autoantibodies and excessive inflammation, which impact multiple organs. Recent advances have begun to shed light on the roles of circRNAs in SLE, providing fresh insights into the pathogenesis of SLE and the latent capacity for translation into clinical applications. Here, we briefly introduce these "star molecules" and summarize their roles in SLE. In addition, we outline the limitations of the current studies and raise prospects for future research.

20.
Exp Ther Med ; 21(2): 158, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33456525

RESUMO

Previous studies have shown the participation of the cytokines interleukin (IL) 17A and IL22 in the development of vitiligo. The aryl hydrocarbon receptor (AhR) functions in the pathogenesis of vitiligo and can modulate cytokine production. The aim of the present study was to determine the relationship between AhR activation and the secretion of IL17A and IL22 in CD4+ T cells in vitiligo. A total of 20 newly diagnosed patients with progressive, unstable vitiligo and 20 healthy controls were recruited. CD4+ T cells and skin samples were collected. Immunohistochemistry, ELISA, reverse transcription-quantitative PCR, western blotting and RNA interference experiments were performed. The expression of AhR was significantly lower in the CD4+ T cells and skin, both lesional and nonlesional, of patients with vitiligo compared with healthy subjects. AhR expression was markedly lower in nonlesional compared with lesional skin of patients with vitiligo. The expression levels of IL17A and IL22 were significantly higher in patients with vitiligo compared with healthy subjects. Knockdown of AhR significantly increased the production of IL17A and markedly decreased IL22 levels in the CD4+ T cells of patients with vitiligo. Ginkgo biloba extract EGb 761 activated AhR, inhibited IL17A secretion and enhanced IL22 release in the CD4+ T cells of patients with vitiligo. In conclusion, reduced AhR expression is associated with progressive, unstable vitiligo. Activation of AhR with G. biloba extract EGb 761 may have therapeutic potential for decreasing IL17A levels and increasing IL22 levels in patients with vitiligo.

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