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1.
Article in Chinese | WPRIM | ID: wpr-920596

ABSTRACT

@#All-ceramic restorations are widely used in oral restoration because of their beauty and high strength. Glass ceramics and zirconia all-ceramic materials are the two most widely used all-ceramic materials in the clinic. However, when all-ceramic restorations need to be removed due to marginal microleakage and secondary caries, its high strength and high bonding strength greatly increase the difficulty of removal. In recent years, clinicians have tried to use Er: YAG lasers to remove all-ceramic restorations. The Er: YAG laser can be safely and efficiently applied to the removal of glass restorations, and it can also play a role in thinner zirconia restorations. Various factors, such as the material and thickness of the all-ceramic restoration, the type of cement, and the laser power, can affect the speed of removal of the Er: YAG laser. However, the current research is limited to case reports and in vitro studies, lacking systematic clinical research. The specific mechanism of Er: YAG laser removal of all-ceramic restorations and the influence of laser frequency, adhesive type, and abutment on the removal speed need to be further demonstrated by follow-up research.

2.
Article in Chinese | WPRIM | ID: wpr-920528

ABSTRACT

Objective@#Oxygen-glucose deprivation (OGD) is used to mimic ischemia in vitro to observe whether endoplasmic reticulum (ER) stress is involved in human dental pulp cells (hDPCs) after OGD and to better understand the regulatory mechanism of hDPCs in ischemia.@*Methods@# hDPCs were cultured in glucose-free DMEM and hypoxia (volume fraction 2% O2) to establish an hDPCs OGD model in vitro, which mimics hDPCs ischemia in vitro. hDPCs were divided into a control group (normal culture) and an experimental group (OGD 0 h, 2 h, 4 h and 8 h groups). After pretreatment with OGD for 0, 2, 4 and 8 h, hDPC viability was measured by methylthiazol tetrazolium (MTT) assay. qRT-PCR was used to detect the mRNA expression of ER stress markers [splicing x-box binding protein1 (sXBP1), activating transcription Factor 4 (ATF4) and C/EBP homologous protein (chop)]. Western blot was used to detect the protein expression of ER stress markers [phosphorylated RNA-activated protein kinase-like ER-resident kinase (p-perk) and phosphorylated eukaryotic initiation factor-2α (p-eIF2α)]. @*Results@#Compared with OGD 0 h group, cell viability of hDPCs decreased when exposed to OGD treatment for 2 h, 4 h and 8 h. Compared with the control group, mRNA expressions of ER stress makers (sXBP1, ATF4 and chop) and the protein expressions of ER stress protein markers (p-perk andp-eIF2α) increased in OGD treatment cells after 4 h were higher in OGD cells. The differences were statistically significant (P<0.05).@*Conclusion@#The results indicate that ER stress response is involved in hDPCs in OGD treatment.

3.
Braz. dent. sci ; 25(1): 1-9, 2022. tab, ilus
Article in English | LILACS, BBO | ID: biblio-1354535

ABSTRACT

Objective: This study aimed to determine the push-out-bond-strength(PBS) of mineral trioxide aggregate (BIOMTA+) and calcium-enriched-mixture-cement (CEM) in retrograde cavities prepared using Er: YAG laser and stainless-steel bur. Material and Methods: The root canals of 60 extracted single-rooted human teeth were prepared, filled and their apical portion of 3-mm were resected using a diamond bur and randomly divided into four groups according to technique of retrograde preparation and filling material as follows(n=15): Group1: bur/ BIOMTA+ ,Group2: bur/ CEM, Group3: Er:YAG laser/ BIOMTA+, Group4: Er:YAG laser/ CEM. PBS test were performed to specimens and failure modes were evaluated. The data were statistically analyzed with ANOVA, Post-Hoc Tukey and t tests (p< 0.05). Results: CEM was exhibited higher than bond strength compared to BIOMTA+ in retrograde cavity prepared using laser (p= 0.021) and BIOMTA+ in retrograde cavity prepared using bur was exhibited higher than bond strength compared to in retrograde cavities prepared using laser (p= 0.024). Failure modes were dominantly cohesive in all groups tested and one representative specimen each failure mode was examined in SEM and the general characteristics of the failure modes were confirmed. Conclusion: With in the limitations of the present study, when used CEM, Er: YAG laser-assisted retrograde cavity preparation positively affected the bond strength values compared to BIO MTA+. Considering its optimal adhesion, the calcium-enriched-mixture-cement (CEM) might be a good option as a filling material in retrograde cavities in clinical use. (AU)


Objetivo: O objetivo deste estudo foi determinar a força de união (PBS) de cimento de agregado trióxido mineral (BIO MTA+) e cimento enriquecido com cálcio (CEM) em preparos cavitários retrógrados realizados com: Laser Er-YAG e brocas de aço inoxidável. Material e Métodos: Canais radiculares de 60 dentes unirradiculares extraídos foram preparados, preenchidos e 3 mm de suas porções apicais foram ressecadas usando uma broca diamantada e divididos randomicamente em quatro grupos de acordo com a técnica de preparação retrógrada e o material de preenchimento (n=15): Grupo 1: Broca/BIO MTA+, Grupo 2: Broca/CEM, Grupo 3: Laser Er-YAG/BIO MTA+, Grupo 4: Laser Er-YAG/CEM. O teste de PBS foi realizado para as amostras e os modelos de falha foram avaliados. Os dados foram analisados estatisticamente pelos testes de ANOVA, Post-Hoc Tukey e testes t (p< 0.05). Resultados: CEM apresentou maior força de união que BIO MTA+ em cavidades retrógradas preparadas com laser (p= 0.021) e BIO MTA+ em cavidades retrógradas preparadas com brocas apresentou maior força de união quando comparado à cavidades retrógradas preparadas com laser (p= 0.024). Os modelos de falha foram predominantemente coesos em todos os grupos testados e um espécime representativo de cada modelo de falha foi examinado em MEV e as características gerais dos modelos de falha foram confirmadas. Conclusão: Com as limitações do presente estudo, quando usou-se CEM, o preparo de cavidades retrógradas através de Laser Er-YAG afetou positivamente os valores da força de união quando comparados com BIO MTA+. Considerando sua ótima adesão, o cimento enriquecido com cálcio (CEM) pode ser uma boa opção como um material de preenchimento em cavidades retrógradas no uso clínico.


Subject(s)
Dental Cements , Dental Pulp Cavity , Lasers, Solid-State
4.
Braz. dent. sci ; 25(2): 1-13, 2022. tab
Article in English | LILACS, BBO | ID: biblio-1368754

ABSTRACT

Background: The debonding of crowns and ceramic veneers with laser is already a reality in the clinic. It presents benefits in comparison to traditional removal with the use of a rotating instrument; however, there is still no consolidated protocol and many professionals use it without the necessary scientific basis. Objective: The aim of this work was to perform a literature review on the debonding of indirect ceramic restorations using the Er:YAG and Er,Cr:YSGG lasers to provide clinical professionals and the scientific community a careful analysis, and also to guiding the use of irradiation at laser for such procedures. Methods: Bibliographic searches were performed in the following databases: Pubmed, Web of Science and Google Scholar. According to the inclusion criteria adopted, twenty-seven clinical and in vitro studies were selected in the period from 2007 to 2021. In the present work, the composition of the crowns and facets, as well as the types of cement and the laser irradiation protocols adopted in the selected studies is detailed. Conclusions: It was concluded that the use of erbium lasers for debonding of indirect ceramic restorations proved to be more selective and conservative when compared to removal with a rotary diamond instrument. Furthermore, it was shown to be in more efficient in debonding different types of ceramics. However, there are great variations in the "debonding" protocols, which emphasizes the need for further studies that seek to standardize the irradiation protocols considering the different clinical situations (AU)


Antecedentes: A remoção de coroas e facetas cerâmicas com laser já é uma realidade clínica e apresenta benefícios em relação à remoção tradicional com uso de instrumento rotatório diamantado; entretanto, ainda não existe um protocolo consolidado e muitos profissionais o utilizam sem o embasamento científico necessário. Objetivos: O objetivo deste trabalho foi realizar uma revisão da literatura sobre a remoção de restaurações cerâmicas indiretas utilizando os lasers Er:YAG e Er,Cr:YSGG para fornecer uma análise cuidadosa aos profissionais clínicos e à comunidade científica, além de orientar o uso da irradiação a laser para tal aplicação. Métodos: As buscas bibliográficas foram realizadas, nas seguintes bases de dados: Pubmed, Web of Science e Google Scholar. De acordo com os critérios de inclusão adotados, foram selecionados vinte e sete estudos clínicos e in vitro no período de 2007 a 2021. No presente trabalho, a composição das coroas e facetas, bem como os tipos de cimento e os protocolos de irradiação laser adotados nos estudos selecionados foram detalhados. Conclusão: Concluiu-se que o uso dos lasers de érbio para remoção de restaurações cerâmicas indiretas mostrou-se mais seletivo e conservador quando comparado à remoção com instrumento rotatório diamantado, além de ser eficiente na remoção de diferentes tipos de cerâmicas. No entanto, existem grandes variações nos protocolos de "debonding", o que enfatiza a necessidade de novos estudos que busquem uma padronização dos protocolos de irradiação considerando as diferentes situações clínicas.(AU)


Subject(s)
Lifting , Crowns , Dental Veneers , Lasers, Solid-State
5.
Multimed (Granma) ; 25(1): e1406, ene.-feb. 2021. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1154953

ABSTRACT

RESUMEN Un modelo matemático es una descripción matemática (a menudo por medio de una función o una ecuación) de un fenómeno del mundo real, como el tamaño de una población, la expectativa de vida de una persona al nacer o la propagación de una epidemia. Para ver la importancia de estos en las Ciencias de la Salud, específicamente en la especialidad de Higiene y Epidemiología mostramos dos de ellos para predecir el comportamiento de epidemias. El primero lo exponemos mediante una ecuación diferencial de 1er orden y el segundo mediante un sistema de ecuaciones diferenciales.


ABSTRACT A mathematical model is a mathematical description (often by means of a function or an equation) of a real-world phenomenon, such as the size of a population, the life expectancy of a person at birth, or the spread of an epidemic. To see the importance of these in Health Sciences, specifically in the specialty of Hygiene and Epidemiology, we show two of them to predict the behavior of epidemics. We expose the first through a 1st order differential equation and the second through a system of differential equations.


RESUMO Um modelo matemático é uma descrição matemática (frequentemente por meio de uma função ouequação) de um fenômeno do mundo real, como o tamanho de uma população, a expectativa de vida de uma pessoaao nascer ou a propagação de uma epidemia. Para perceber a importância destesnas Ciências da Saúde, especificamente na especialidade Higiene e Epidemiologia, mostramos dois deles para prever o comportamento de epidemias. Expomos o primeiro por meio de uma equação diferencial de 1ª ordem e o segundo por meio de um sistema de equaçõ es diferenciais.

6.
Braz. dent. sci ; 24(2): 1-7, 2021. tab, ilus
Article in English | LILACS, BBO | ID: biblio-1178409

ABSTRACT

Background: To present the benefits of high power lasers (Er: YAG and Nd: YAG) over the use of the high speed turbine for the extraction of ceramics restorations, without damaging the surfaces of the teeth; being a relatively easier and faster procedure without the use of anesthetic agents, and the preparation of the ceramic restorations and cementing in the single session; with a follow-up of 1 year. Objective: The benefits of lasers over high-speed turbine mechanical instrumentation for crown removal encompass efficient restoration recovery without damage to tooth surfaces; and a relatively easier and faster procedure without the use of anesthetic agents. Methods: The Er: YAG laser (no contact; 3.2-4.0 W, 20 Hz) was used to extract the porcelain prosthesis, followed by a gingivectomy with the Nd: YAG laser on tooth 12 to improve the gingival contour. The dental surfaces where the ceramic prosthesis will be cemented were scanned. Then, CAD / CAM technology was used to make the ceramic veneers that were cemented in the same session. Results: The efficacy the Er:YAG laser energy was observed by the decreased of the time to remove all-ceramic materials through ablation of bonding cements, reducing working time by 75% compared to a high-speed turbine. Conclusions: An Er: YAG laser can safely remove lithium disilicate crowns with the settings used in this study. Laser-assisted removal of all ceramic PDFs is a promising treatment protocol. The use of the Nd: YAG (2.0 W power, short 20Hz, 320 µm optical fiber, in contact) laser allowed gingivoplasty to be performed, automatically cauterizing avoiding post-operative bleeding, and facilitating the preparation of ceramic restorations the same day. The use of high-power lasers and the use of accompanying CAD / CAM technology allowed this clinical case to be completed in a single visit without the use of temporary restorations, achieving absolute patient satisfaction. (AU)


Antecedentes: Apresentar os benefícios dos lasers de alta potência (Er: YAG e Nd:YAG) sobre o uso da turbina de alta velocidade para a remoção de restaurações cerâmicas, sem danificar as superfícies dos dentes; sendo um procedimento relativamente mais fácil e rápido evitando o uso de agentes anestésicos, conseguindo fazer o preparo das restaurações de cerâmica e cimentação em uma única sessão; com seguimento de 1 ano. Objetivo: Os benefícios dos lasers sobre a instrumentação mecânica com turbina de alta velocidade para a remoção da coroa abrangem a recuperação eficiente da restauração sem danos às superfícies dos dentes; e um procedimento relativamente mais fácil e rápido sem o uso de agentes anestésicos. Métodos: O laser Er: YAG (sem contato; 3,2-4,0 W, 20 Hz) foi utilizado para remover a prótese de porcelana, seguido de gengivectomia com o laser Nd: YAG no dente 12 para melhorar o contorno gengival. As superfícies dentais onde a prótese de cerâmica será cimentada foram escaneadas. Em seguida, a tecnologia CAD / CAM foi utilizada para confeccionar as facetas de cerâmicas que foram cimentadas na mesma sessão. Resultados: A eficácia da energia do laser Er: YAG foi observada pela diminuição do tempo na remoção dos materiais cerâmicos por meio da ablação dos cimentos de ligação, reduzindo o tempo de trabalho em 75% em relação a uma turbina de alta velocidade. Conclusão: Um laser Er: YAG pode remover com segurança as coroas de dissilicato de lítio com as configurações usadas neste estudo. A remoção assistida por laser de todos os PDFs de cerâmica é um protocolo de tratamento promissor. O uso do laser Nd: YAG (2,0 W potência, curta 20Hz, 320 µm fibra ótica, em contato) permitiu a realização da gengivoplastia, cauterizando automaticamente evitando sangramento pós-operatório e facilitando o preparo das restaurações cerâmicas no mesmo dia. O uso de lasers de alta potência e o uso da tecnologia CAD / CAM que o acompanha permitiram que este caso clínico fosse concluído em uma única visita, sem o uso de restaurações temporárias, alcançando a satisfação absoluta do paciente (AU)


Subject(s)
Humans , Female , Middle Aged , Computer-Aided Design , Dental Materials , Lasers, Solid-State
7.
Article in Chinese | WPRIM | ID: wpr-873685

ABSTRACT

@#Er: YAG laser bleaching is a new tooth bleaching method compared with traditional bleaching technology. The Er: YAG laser significantly improves the bleaching efficiency, has the advantages of high safety, short treatment time and excellent bleaching effect and is widely used in clinical operations. This paper summarizes the working principle and bleaching characteristics of Er: YAG laser bleaching technology and its effect on tooth structure. The existing literature suggests that the high absorption of water and hydroxyapatite by the Er: YAG laser makes it work well on water-bearing tissues and dental tissues. When it is absorbed by the bleaching agent on the tooth surface, it accelerates the catalytic oxidation-reduction reaction and selectively acts on the pigment particles deposited on the tooth, thereby achieving the effect of tooth bleaching. Er: YAG laser bleaching can be applied to most discolored teeth. The bleaching process is rapid and effective. During the bleaching process, for the dental pulp tissue, the temperature of the pulp cavity is lower than the critical value of 5.6 ℃, causing no pathological damage to the dental pulp tissue. For the hard tissues of the teeth, laser irradiation will cause changes in the chemical composition of calcium and phosphorus. The enamel presents a unique lava-like shape, and the bonding strength of the tooth increases after bleaching. Compared with other lasers, the Er: YAG laser has a wavelength close to the peak of water, and adding other ingredients to the bleaching agent is not required. Almost all the energy is used for the bleaching agent, with no damage to the surrounding tissues.

8.
Article in Chinese | WPRIM | ID: wpr-907666

ABSTRACT

Objective:To explore the targets and signal pathways of Maxing-Ersan Decoction in the treatment of COPD by using network pharmacology, and to reveal the mechanism of intervention of multiple targets and multiple pathways of Maxing-Ersan Decoction in the treatment of COPD. Methods:The active ingredients and corresponding targets of Maxing-Ersan Decoction were screened with the help of TCMSP database, and the targets related to COPD disease were screened with GeneCards database. The STRING database was used for protein-protein interaction (PPI) network analysis. By using Cytoscape to build compound target network and PPI network; by using Draw Venn Diagram website to draw a Venn diagram, and using R software to perform gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG). Results:A total of 101 active ingredients were obtained, with 250 corresponding targets, including 214 targets related to COPD. Through GO and KEGG enrichment analysis, all together 48 signal pathways related to the main components of Maxing-Ersan Decoction were screened out. Conclusion:Based on the network pharmacological analysis, the effective chemical components of Maxing-Ersan Decoction were found, and it was found that Maxing-Ersan Decoction may act on COPD through multiple targets and multiple pathways such as inflammation and immune regulation.

9.
Article in Chinese | WPRIM | ID: wpr-907632

ABSTRACT

Objective:To explore the molecular targets and therapeutic mechanism of Er Miao San in the treatment of atopic dermatitis (AD), analyzing its active ingredients, moleculartargets and network analysis. Methods:The active ingredients and targets of Er Miao San were obtained from Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) and Drugbank databases. The differential expression genes of AD were obtained by Intergovernmental Group on Earth Observations (GEO) database. The target genes of Er Miao San in the treatment of AD were obtained by using Cytoscape plugin Bisogenet and CytoNCA. Enrichment analysis was obtained from the DAVID database. Results:In total, 12 active ingredients and 107 targets of Er Miao San were screened out by TCMSP and Drugbank databases; 274 differential expression genes (with an adjust P value < 0.005 and |log2 (fold change)|>1.5) were identified between AD patient and control groups using the intergovernmental Group on Earth Observations (GEO) database. 187 target genes of Er Miao San against AD were finally identified by using Cytoscape plugin Bisogenet and CytoNCA. The functional annotations of target genes were related to telomere organization, protein heterotetramerization, regulation of gene expression and so on. Twenty pathways including PI3K-Akt, MAPK and HIF-1 signaling pathway were significantly enriched. Several genes including MAPK1, AKT, RELA and TP53 were the key genes in the gene-pathway network of Er Miao San treating AD. Conclusion:This study suggested that quercetin, tetrahydroberberine, stigmastol and other core ingredientss in Er Miao San may treat AD by participating in PI3K-Akt, MAPK, HIF-1 and other signaling pathways, and regulating the core gene targets of MAPK1, Akt, Rela and TP53.

10.
Article in Chinese | WPRIM | ID: wpr-907613

ABSTRACT

Objective:To establish an UHPLC-PDA method for determinating the content of 7 iridoid glycosides and 4 flavonoids constitutents simultaneously in Xiaoer-Ganyan granules. Methods:To take Agilent Ecilipse C18 (2.1 mm × 100 mm, 1.6 μm), and the colunm temperature was at 30 ℃. The mobile phase consists of acetonitrile (A) and 0.05% phosphoric acid (B) in gradient elution at a flow rate of 0.3 ml/min. The detection wavelength was set at 240 and 278 nm.Results:The linear ranges of swertiamain, gentiopicrin, sweroside, shanzhiside methy ester, gardenoside, genipin-1-β-D-gentiobioside, geniposide, baicalin, wogonoside, baicalein and wogonin were 19.16-306.56 μg ( r=0.999 4), 3.34-53.28 μg ( r=0.999 1), 5.30-84.64 μg ( r=0.999 5), 0.80-12.80 μg ( r=0.999 4), 0.46-7.20 μg ( r=0.999 2), 2.78-44.48 μg ( r=0.999 6), 6.02-96.16 μg ( r=0.999 9), 33.22-531.36 μg ( r=0.999 9), 3.92-62.72 μg ( r=0.999 2), 2.38-37.92 μg ( r=0.999 7), 1.32-20.96 μg ( r=0.999 9), respectively. The average recoveries ( n=9) varied from 94.62%-107.53% with RSDs no more than 3.0%. Conclusion:Method validation suggested that the developed method was suitable for simultaneous determination of 11 major constitutents in Xiaoer-Ganyan granules, thus providing reference for the improvement of quality standard of the drug.

11.
Article in Chinese | WPRIM | ID: wpr-906109

ABSTRACT

Objective:To explore the possible mechanism of Yanghe Huayantang in reversing the drug resistance of breast cancer by observing the effect of Yanghe Huayantang on the transplant tumor of tamoxifen (TAM)-resistant breast cancer and its influences on the interaction pathway of estrogen receptor (ER)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian rapamycin target protein (mTOR). Method:Fifty mice were randomly divided into 5 groups: blank group, model group, Yanghe Huayantang group, everolimus group, and Yanghe Huayantang+everolimus group. The model of kidney deficiency was established by bilateral ovariectomy, and the blank group was treated with sham operation. Three days after the establishment of the model, all the five groups of mice were inoculated with breast cancer TAM drug-resistant cells (MCF-7/TAM<sup>-</sup>) to establish breast cancer TAM -resistant transplanted tumor model. After successful modeling, Yanghe Huayantang group received intragastric administration of Yanghe Huayantang (traditional Chinese medicine preparation 20 mL·kg<sup>-1</sup>), everolimus group received intraperitoneal injection of everolimus (10 mg·kg<sup>-1</sup>). Yanghe Huayantang + everolimus group received Yanghe Huayantang by intragastric administration and everolimus by intraperitoneal injection. The blank group and model group received intragastric administration and intraperitoneal injection of phosphate buffer (PBS). Drug administration was lasted for 28 days in all groups, once a day. After administration, the tumor tissue was separated and weighed, and the tumor inhibition rate was calculated. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of tumor tissue. Immunofluorescence and Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) were used to detect the expression of PI3K, Akt, mTOR, ER protein and mRNA in tumor tissue. Result:Compared with the model group, the tumor volume and tumor weight of Yanghe Huayantang group decreased significantly on the 12th, 20th and 28th days (<italic>P</italic><0.01), and the tumor inhibition rate increased significantly (<italic>P</italic><0.01).Yanghe Huayantang group significantly reduced the density of tumor cells and caused tumor cell necrosis. Compared with the model group, Yanghe Huayantang group, everolimus group and Yanghe Huayantang+everolimus group inhibited the expression of PI3K, Akt, mTOR protein and mRNA (<italic>P</italic><0.05, <italic>P</italic><0.01). Compared with the blank group, Yanghe Huayantang group, everolimus group and Yanghe Huayantang+everolimus group all inhibited the protein and mRNA expression of ER, and mRNA expression of ER in Yanghe Huayantang+everolimus group was significantly lower than that in the model group (<italic>P</italic><0.01). Conclusion:Yanghe Huayantang can inhibit the growth of TAM-resistant breast cancer. The mechanism may be that Yanghe Huayantang can reverse the TAM resistance of breast cancer by down-regulating the expression of key molecules of ER/PI3K/Akt/mTOR cross-signal pathway.

12.
Acta Pharmaceutica Sinica B ; (6): 3433-3446, 2021.
Article in English | WPRIM | ID: wpr-922806

ABSTRACT

RAS, a member of the small GTPase family, functions as a binary switch by shifting between inactive GDP-loaded and active GTP-loaded state. RAS gain-of-function mutations are one of the leading causes in human oncogenesis, accounting for ∼19% of the global cancer burden. As a well-recognized target in malignancy, RAS has been intensively studied in the past decades. Despite the sustained efforts, many failures occurred in the earlier exploration and resulted in an 'undruggable' feature of RAS proteins. Phosphorylation at several residues has been recently determined as regulators for wild-type and mutated RAS proteins. Therefore, the development of RAS inhibitors directly targeting the RAS mutants or towards upstream regulatory kinases supplies a novel direction for tackling the anti-RAS difficulties. A better understanding of RAS phosphorylation can contribute to future therapeutic strategies. In this review, we comprehensively summarized the current advances in RAS phosphorylation and provided mechanistic insights into the signaling transduction of associated pathways. Importantly, the preclinical and clinical success in developing anti-RAS drugs targeting the upstream kinases and potential directions of harnessing allostery to target RAS phosphorylation sites were also discussed.

13.
Acta Pharmaceutica Sinica B ; (6): 3015-3034, 2021.
Article in English | WPRIM | ID: wpr-922781

ABSTRACT

Parkinson's disease (PD), known as one of the most universal neurodegenerative diseases, is a serious threat to the health of the elderly. The current treatment has been demonstrated to relieve symptoms, and the discovery of new small-molecule compounds has been regarded as a promising strategy. Of note, the homeostasis of the autolysosome pathway (ALP) is closely associated with PD, and impaired autophagy may cause the death of neurons and thereby accelerating the progress of PD. Thus, pharmacological targeting autophagy with small-molecule compounds has been drawn a rising attention so far. In this review, we focus on summarizing several autophagy-associated targets, such as AMPK, mTORC1, ULK1, IMPase, LRRK2, beclin-1, TFEB, GCase, ERR

14.
Acta Pharmaceutica Sinica B ; (6): 3983-3993, 2021.
Article in English | WPRIM | ID: wpr-922454

ABSTRACT

Unfolded protein response (UPR) is a stress response that is specific to the endoplasmic reticulum (ER). UPR is activated upon accumulation of unfolded (or misfolded) proteins in the ER's lumen to restore protein folding capacity by increasing the synthesis of chaperones. In addition, UPR also enhances degradation of unfolded proteins and reduces global protein synthesis to alleviate additional accumulation of unfolded proteins in the ER. Herein, we describe a cell-based ultra-high throughput screening (uHTS) campaign that identifies a small molecule that can modulate UPR and ER stress in cellular and

15.
Acta Pharmaceutica Sinica B ; (6): 3567-3584, 2021.
Article in English | WPRIM | ID: wpr-922425

ABSTRACT

Protein neddylation is catalyzed by a three-enzyme cascade, namely an E1 NEDD8-activating enzyme (NAE), one of two E2 NEDD8 conjugation enzymes and one of several E3 NEDD8 ligases. The physiological substrates of neddylation are the family members of cullin, the scaffold component of cullin RING ligases (CRLs). Currently, a potent E1 inhibitor, MLN4924, also known as pevonedistat, is in several clinical trials for anti-cancer therapy. Here we report the discovery, through virtual screening and structural modifications, of a small molecule compound HA-1141 that directly binds to NAE in both

16.
Article in Chinese | WPRIM | ID: wpr-921714

ABSTRACT

This study intended to explore the effect and mechanism of total flavonoids of Drynariae Rhizoma in improving scopola-mine-induced learning and memory impairments in model mice. Ninety four-month-old Kunming(KM) mice were randomly divided into six groups. The ones in the model group and blank group were treated with intragastric administration of normal saline, while those in the medication groups separately received the total flavonoids of Drynariae Rhizoma, Kangnaoshuai Capsules, donepezil, as well as total flavonoids of Rhizoma Drynariae plus estrogen receptor(ER) blocker by gavage. The mouse model of learning and memory impairments was established via intraperitoneal injection of scopolamine. Following the measurement of mouse learning and memory abilities in Morris water maze test, the hippocampal ERβ expression was detected by immunohistochemistry, and the expression levels of ERβ and phosphorylated p38(p-p38) in the hippocampus and B-cell lymphoma 2(Bcl-2), Bcl-2-associated death promoter(Bad), and cysteinyl aspartate-specific protease-3(caspase-3) in the apoptotic system were assayed by Western blot. The contents of malondia-ldehyde(MDA), superoxide dismutase(SOD), and nitric oxide(NO) in the hippocampus were then determined using corresponding kits. Compared with the control group, the model group exhibited significantly prolonged incubation period, reduced frequency of cros-sing the platform, shortened residence time in the target quadrant, lowered ERβ, Bcl-2 and SOD activity in the hippocampus, and increased p-p38/p38, Bad, caspase-3, MDA, and NO. Compared with the model group, the total flavonoids of Rhizoma Drynariae increased the expression of ERβ and SOD in the hippocampus, down-regulated the expression of neuronal pro-apoptotic proteins, up-re-gulated the expression of anti-apoptotic proteins, and reduced p-p38/p38, MDA, and NO. The effects of total flavonoids of Drynariae Rhizoma on the above indexes were reversed by ER blocker. It has been proved that the total flavonoids of Drynariae Rhizoma obviously alleviate scopolamine-induced learning and memory impairments in mice, which may be achieved by regulating the neuronal apoptotic system and oxidative stress via the ER-p38 mitogen-activated protein kinase(ER-p38 MAPK) signaling pathway.


Subject(s)
Animals , Flavonoids , Hippocampus , Maze Learning , Mice , Polypodiaceae , Receptors, Estrogen , Scopolamine/toxicity , Signal Transduction , p38 Mitogen-Activated Protein Kinases/genetics
17.
Acta Pharmaceutica Sinica B ; (6): 1853-1866, 2021.
Article in English | WPRIM | ID: wpr-888838

ABSTRACT

Mitochondrial shape rapidly changes by dynamic balance of fusion and fission to adjust to constantly changing energy demands of cancer cells. Mitochondrial dynamics balance is exactly regulated by molecular motor consisted of myosin and actin cytoskeleton proteins. Thus, targeting myosin-actin molecular motor is considered as a promising strategy for anti-cancer. In this study, we performed a proof-of-concept study with a natural-derived small-molecule J13 to test the feasibility of anti-cancer therapeutics

18.
Acta Pharmaceutica Sinica B ; (6): 1708-1720, 2021.
Article in English | WPRIM | ID: wpr-888831

ABSTRACT

Stroke is considered a leading cause of mortality and neurological disability, which puts a huge burden on individuals and the community. To date, effective therapy for stroke has been limited by its complex pathological mechanisms. Autophagy refers to an intracellular degrading process with the involvement of lysosomes. Autophagy plays a critical role in maintaining the homeostasis and survival of cells by eliminating damaged or non-essential cellular constituents. Increasing evidence support that autophagy protects neuronal cells from ischemic injury. However, under certain circumstances, autophagy activation induces cell death and aggravates ischemic brain injury. Diverse naturally derived compounds have been found to modulate autophagy and exert neuroprotection against stroke. In the present work, we have reviewed recent advances in naturally derived compounds that regulate autophagy and discussed their potential application in stroke treatment.

20.
Acta Pharmaceutica Sinica B ; (6): 1412-1433, 2021.
Article in English | WPRIM | ID: wpr-888812
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