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1.
BMC Med Educ ; 21(1): 553, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34717612

RESUMO

BACKGROUND: In view of the teaching characteristics of the motion system injury course and the actual clinical teaching. The orthopedic teaching team of the Affiliated Hospital of Inner Mongolia Medical University took the lead in proposing the "Hand as Foot teaching method" and applied it in clinical teaching. Through this teaching method, students' understanding and memorization of key and difficult issues in motion system injuries are strengthened, teacher-student interaction is increased, and teaching effect is improved.  METHODS: The "Hand as Foot teaching method" was used to teach the key and difficult problems to the clinical undergraduate medical students of Inner Mongolia Medical University, and the teaching process was complemented by PPT + model teaching aids. RESULTS: The "Hand as Foot teaching method" is generally welcomed by medical students and has achieved good teacher-student interaction, and is effective in understanding and remembering difficult knowledge points. CONCLUSION: The "Hand as Foot teaching method" is a novel teaching method that can be applied in clinical teaching. This image teaching method improves the teaching effect, enlivens the classroom atmosphere, and enhances the interaction between teachers and students, which makes students' learning process from abstract to intuitive, from simple rote memorization to comprehension and memory, and achieves satisfactory results. It can complement each other with the traditional teaching method of pure PPT + teaching aids model, and to some extent it is worth promoting in the motion system injury courses.


Assuntos
Educação de Graduação em Medicina , Estudantes de Medicina , China , Humanos , Ensino
2.
Org Lett ; 23(21): 8429-8433, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34652930

RESUMO

The construction of chemical libraries containing polysubstituted pyrazoline scaffolds is highly desirable for the discovery of novel chemical ligands for biological targets. Herein, we report a sequential DNA-encoded synthesis strategy for polysubstituted pyrazoline heterocycles, which fuses a broad panel of aldehydes, aryl amines, and alkenes as building blocks. Furthermore, mock library synthesis and selection demonstrated the ability of the method to produce DNA-encoded focused libraries with highly functionalized pyrazoline cores.

3.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638947

RESUMO

Perilipin5 (Plin5) is a scaffold protein that plays an important role in lipid droplets (LD) formation, but the regulatory effect of leptin on it is unclear. Our study aimed to explore the underlying mechanisms by which leptin reduces the N6-methyladenosine (m6A) methylation of Plin5 through fat mass and obesity associated genes (FTO) and regulates the lipolysis. To this end, 24 Landrace male piglets (7.73 ± 0.38 kg) were randomly sorted into two groups, either a control group (Control, n = 12) or a 1 mg/kg leptin recombinant protein treatment group (Leptin, n = 12). After 4 weeks of treatment, the results showed that leptin treatment group had lower body weight, body fat percentage and blood lipid levels, but the levels of Plin5 mRNA and protein increased significantly in adipose tissue (p < 0.05). Leptin promotes the up-regulation of FTO expression level in vitro, which in turn leads to the decrease of Plin5 M6A methylation (p < 0.05). In in vitro porcine adipocytes, overexpression of FTO aggravated the decrease of M6A methylation and increased the expression of Plin5 protein, while the interference fragment of FTO reversed the decrease of m6A methylation (p < 0.05). Finally, the overexpression in vitro of Plin5 significantly reduces the size of LD, promotes the metabolism of triglycerides and the operation of the mitochondrial respiratory chain, and increases thermogenesis. This study clarified that leptin can regulate Plin5 M6A methylation by promoting FTO to affect the lipid metabolism and energy consumption, providing a theoretical basis for treating diseases related to obesity.


Assuntos
Adenosina/análogos & derivados , Dioxigenase FTO Dependente de alfa-Cetoglutarato/metabolismo , Leptina/administração & dosagem , Lipólise/efeitos dos fármacos , Perilipina-5/metabolismo , Adenosina/metabolismo , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Animais , Peso Corporal/efeitos dos fármacos , Células Cultivadas , Expressão Gênica/efeitos dos fármacos , Lipólise/genética , Masculino , Metilação/efeitos dos fármacos , Perilipina-5/genética , Interferência de RNA , RNA Mensageiro/genética , Proteínas Recombinantes/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Suínos , Transfecção , Triglicerídeos/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética
4.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(4): 590-594, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34494531

RESUMO

Objective To investigate the oral health status and awareness of urban children in Lhasa,aiming to provide a data basis for the prevention and treatment of children's caries and the promotion of oral health education. Methods A total of 504 Tibetan students were selected by cluster sampling from 2 primary schools in Chengguan District of Lhasa.All the participants were required to take oral health examination and complete a questionnaire about oral health awareness and behavior. Results The caries prevalence rate and mean decayed-missing-filled tooth(DMFT)of permanent teeth were 75.00% and 2.18±1.91,respectively.The rates of pit and fissure sealant and filling of permanent teeth were 3.77% and 6.81%,respectively.The caries prevalence rate of first permanent molars was 47.62%.The mean DMFT of permanent teeth and caries prevalence rate of first permanent molar were significantly higher in female group(P=0.001 and P=0.007,respectively).The prevalence rate of dental fluorosis was 61.51%,and the detection rate of dental calculus was 71.83%.Multivariate logistic regression analysis showed that prevalence of caries was influenced by many independent factors including gender,oral health awareness,intention of dental intervention,and dental experience. Conclusion High caries prevalence rate,low filling rate,and poor oral hygiene and health awareness were found among the primary school students in Lhasa,which require continuous dentistry investment and oral health education for the local students and their parents.


Assuntos
Cárie Dentária , Saúde Bucal , Criança , Índice CPO , Cárie Dentária/epidemiologia , Feminino , Humanos , Higiene Bucal , Prevalência , Instituições Acadêmicas , Estudantes , Inquéritos e Questionários
5.
Int J Mol Sci ; 22(18)2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34576160

RESUMO

Collagen XV (Col XV), a basement membrane (BM) component, is highly expressed in adipose tissue, and studies have found that Col XV is related to extracellular matrix (ECM) remodeling involving in adipose tissue fibrosis and inflammation. Furthermore, the ECM is essential for maintaining normal development and tissue function. In this study, we found that Col XV is related to the endoplasmic reticulum stress (ERS) and inflammation of adipose tissue. Moreover, we found that overexpression of Col XV in mice could cause macrophages to infiltrate white adipose tissue (iWAT). At the same time, the expression of the ERS sensor IRE1α (Inositol-Requiring Enzyme-1α) was significantly up-regulated, which intensified the inflammation of adipose tissue and the polarization of M1 macrophages after the overexpression of Col XV in mice. In addition, after overexpression of Col XV, the intracellular Ca2+ concentration was significantly increased. Using focal adhesion kinase (FAK) inhibitor PF573228, we found that PF-573228 inhibited the phosphorylation of FAK and reversed the upward trend of Col XV-induced protein expression levels of IRE1α, C/EBP-homologous protein (CHOP), and 78 kDa glucose-regulated protein (GRP78). After treatment with IRE1α inhibitor STF-083010, the results showed that the expression of adipocyte inflammation-related genes interleukin 6 (IL-6) and tumor necrosis factor α (TNFα) significantly were decreased. Our results demonstrate that Col XV induces ER-stress in adipocytes by activating the Integrinß1/FAK pathway and disrupting the intracellular Ca2+ balance. At the same time, Col XV regulates the inflammation induced by ER stress in adipocytes by promoting IRE1α/XBP1 (X-Box binding protein 1) signaling. Our study provides new ideas for solving the problems of adipose tissue metabolism disorders caused by abnormal accumulation of ECM.


Assuntos
Tecido Adiposo/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Inflamação/metabolismo , Células 3T3-L1 , Animais , Cálcio/metabolismo , Estresse do Retículo Endoplasmático/genética , Ensaio de Imunoadsorção Enzimática , Imunofluorescência , Imuno-Histoquímica , Inflamação/genética , Integrina beta1/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Quinolonas/farmacologia , RNA-Seq , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Sulfonas/farmacologia
6.
Expert Opin Drug Discov ; : 1-15, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34455870

RESUMO

INTRODUCTION: Undruggable targets refer to clinically meaningful therapeutic targets that are 'difficult to drug' or 'yet to be drugged' via traditional approaches. Featuring characteristics of lacking defined ligand-binding pockets, non-catalytic protein-protein interaction functional modes and less-investigated 3D structures, these undruggable targets have been targeted with novel therapeutic entities developed with the progress of unconventional drug discovery approaches, such as targeted degradation molecules and display technologies. AREA COVERED: This review first presents the concept of 'undruggable' exemplified by RAS and other targets. Next, detailed strategies are illustrated in two aspects: innovation of therapeutic entities and development of unconventional drug discovery technologies. Finally, case studies covering typical undruggable targets (Bcl-2, p53, and RAS) are depicted to further demonstrate the feasibility of the strategies and entities above. EXPERT OPINION: Targeting the undruggable expands the scope of therapeutically reachable targets. Consequently, it represents the drug discovery frontier. Biomedical studies are capable of dissecting disease mechanisms, thus broadening the list of undruggable targets. Encouraged by the recent approval of the KRAS inhibitor Sotorasib, we believe that merging multiple discovery approaches and exploiting various novel therapeutic entities would pave the way for dealing with more 'undruggable' targets in the future.

7.
Apoptosis ; 26(7-8): 474-487, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34212271

RESUMO

As a nucleic acid demethylase, Fat and obesity associated gene (FTO) plays a vital role in modulating adipose metabolism. However, it is still unknown how FTO affects apoptosis in adipocytes. In this study, we found that overexpression of FTO inhibited the expression of pro-apoptosis factors Caspase-3, Caspase-9 and Bax and mitochondrial unfolded protein response (UPRmt) markers HSP60 and ClpP in vivo and in vitro. Particularly, overexpression of FTO inhibited mitochondria-dependent apoptosis in adipocytes. Further studies revealed that FTO suppressed UPRmt by reducing HSP60 mRNA N6-methyladenosine (m6A) modification. Moreover, FTO inhibited the activation of Caspase-3 via JAK2/STAT3 signaling pathway in adipocytes. Further experiments showed that pro-apoptosis gene Bax was upregulated by UPRmt-activated PKR/eIF2α/ATF5 axis in adipocytes. In summary, this study confirms that FTO reduces adipocytes apoptosis by activiting JAK2/STAT3 signaling pathway and inhibiting UPRmt, revealing a novel mechanism of FTO on adipocytes apoptosis, which provides some new potential therapy for treating obesity and related metabolic syndromes.

8.
J Mol Med (Berl) ; 99(9): 1221-1235, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34061242

RESUMO

Obesity is a chronic epidemic disease worldwide which has become one of the important public health issues. It is a process that excessive accumulation of adipose tissue caused by long-term energy intake exceeding energy expenditure. So far, the prevention and treatment strategies of obesity on individuals and population have not been successful in the long term. Acetylation is one of the most common ways of protein post-translational modification (PTM). It exists on thousands of non-histone proteins in almost every cell chamber. It has many influences on protein levels and metabolome levels, which is involved in a variety of metabolic reactions, including sugar metabolism, tricarboxylic acid cycle, and fatty acid metabolism, which are closely related to biological activities. Studies have shown that protein acetylation levels are dynamically regulated by lysine acetyltransferases (KATs) and lysine deacetylases (KDACs). Protein acetylation modifies protein-protein and protein-DNA interactions and regulates the activity of enzymes or cytokines which is related to obesity in order to participate in the occurrence and treatment of obesity-related metabolic diseases. Therefore, we speculated that acetylation was likely to become effective means of controlling obesity in the future. In consequence, this review focuses on the mechanisms of protein acetylation controlled obesity, to provide theoretical basis for controlling obesity and curing obesity-related diseases, which is a significance for regulating obesity in the future. This review will focus on the role of protein acetylation in controlling obesity.

9.
Interdiscip Sci ; 13(4): 638-651, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34160760

RESUMO

The development of Hi-C technology has generated terabytes of chromatin interaction data, which bring possibilities for insight study of chromatin structure. Several studies revealed that mammalian chromosomes are folded into topological associated domains (TADs), which are conserved across cell types. Accurate detection of topological associated domains is now a vital process for revealing the relationship between the structure and function of genome organization. Unfortunately, the current TAD detection methods require massive computing resources, careful parameter adjustment and/or encounter inconsistent results. In this paper, we propose a novel method, Spectral-Based TAD Detector (SBTD), and evaluate its performance with a set of widely accepted statistical methods. We treat the chromatin interaction matrix as a graph and first introduce cosine similarity as a measure of the interaction patterns between bins. The results show that SBTD identifies higher quality TADs than the popular methods (DomainCaller, TopDom and SpectralTAD) and the internal bins of TADs identified by SBTD have higher correlation. Besides, The TADs identified by SBTD show a highly similar histone modification signal enrichment pattern at the boundary as reported in the previous literature. Finally, the motif enrichment analysis shows that compared with the background region, the DNA motifs of known insulator proteins are significantly enriched in the TAD boundary region identified by our method, which proves the high performance of our proposed method. Overall, SBTD is much more effective than existing methods with only one easy-to-adjust parameter, cluster number, for which we provide optimization guidelines.


Assuntos
Cromatina , Cromossomos , Animais
10.
Hum Mutat ; 42(6): 667-684, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33822436

RESUMO

One of the greatest challenges in human genetics is deciphering the link between functional variants in noncoding sequences and the pathophysiology of complex diseases. To address this issue, many methods have been developed to sort functional single-nucleotide variants (SNVs) for neutral SNVs in noncoding regions. In this study, we integrated well-established features and commonly used datasets and merged them into large-scale datasets based on a random forest model, which yielded promising performance and outperformed some cutting-edge approaches. Our analyses of feature importance and data coverage also provide certain clues for future research in enhancing the prediction of functional noncoding SNVs.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33719966

RESUMO

BACKGROUND: The prediction of drug-protein interaction (DPI) plays an important role in drug discovery and re-positioning. Unfortunately, traditional experimental validation of DPIs is expensive and time-consuming. Therefore, it is necessary to develop in silico methods for the identification of potential DPIs. METHOD: In this work, the identification of DPIs was performed by the generated recommendation of the unexplored interaction of the drug-protein bipartite graph. Three kinds of recommenders were proposed to predict the potential DPIs. RESULTS: The simulation results showed that the proposed models obtained good performance in cross validation and independent test. CONCLUSION: Our recommendation strategy based on collaborative filtering can effectively improve the DPI identification performance, especially for certain DPIs lacking chemical structure similarity or genomic sequence similarity.

13.
Front Microbiol ; 12: 605782, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33552038

RESUMO

Gram-negative bacteria can deliver secreted proteins (also known as secreted effectors) directly into host cells through type III secretion system (T3SS), type IV secretion system (T4SS), and type VI secretion system (T6SS) and cause various diseases. These secreted effectors are heavily involved in the interactions between bacteria and host cells, so their identification is crucial for the discovery and development of novel anti-bacterial drugs. It is currently challenging to accurately distinguish type III secreted effectors (T3SEs) and type IV secreted effectors (T4SEs) because neither T3SEs nor T4SEs contain N-terminal signal peptides, and some of these effectors have similar evolutionary conserved profiles and sequence motifs. To address this challenge, we develop a deep learning (DL) approach called DeepT3_4 to correctly classify T3SEs and T4SEs. We generate amino-acid character dictionary and sequence-based features extracted from effector proteins and subsequently implement these features into a hybrid model that integrates recurrent neural networks (RNNs) and deep neural networks (DNNs). After training the model, the hybrid neural network classifies secreted effectors into two different classes with an accuracy, F-value, and recall of over 80.0%. Our approach stands for the first DL approach for the classification of T3SEs and T4SEs, providing a promising supplementary tool for further secretome studies.

19.
Nat Chem ; 13(1): 77-88, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33349694

RESUMO

Membrane proteins on the cell surface perform a myriad of biological functions; however, ligand discovery for membrane proteins is highly challenging, because a natural cellular environment is often necessary to maintain protein structure and function. DNA-encoded chemical libraries (DELs) have emerged as a powerful technology for ligand discovery, but they are mainly limited to purified proteins. Here we report a method that can specifically label membrane proteins with a DNA tag, and thereby enable target-specific DEL selections against endogenous membrane proteins on live cells without overexpression or any other genetic manipulation. We demonstrate the generality and performance of this method by screening a 30.42-million-compound DEL against the folate receptor, carbonic anhydrase 12 and the epidermal growth factor receptor on live cells, and identify and validate a series of novel ligands for these targets. Given the high therapeutic significance of membrane proteins and their intractability to traditional high-throughput screening approaches, this method has the potential to facilitate membrane-protein-based drug discovery by harnessing the power of DEL.


Assuntos
Anidrases Carbônicas/química , DNA/química , Receptores ErbB/química , Receptores de Folato com Âncoras de GPI/química , Bibliotecas de Moléculas Pequenas/química , Anticorpos Imobilizados/química , Anticorpos Imobilizados/imunologia , Anidrases Carbônicas/metabolismo , Receptores ErbB/imunologia , Receptores ErbB/metabolismo , Fluoresceína-5-Isotiocianato/química , Receptores de Folato com Âncoras de GPI/metabolismo , Células HeLa , Humanos , Ligantes , Microscopia de Fluorescência , Bibliotecas de Moléculas Pequenas/metabolismo
20.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(6): 687-691, 2020 Dec 01.
Artigo em Chinês | MEDLINE | ID: mdl-33377348

RESUMO

The application of artificial intelligence in medicine has gradually received attention along with its development. Many studies have shown that machine learning has a wide range of applications in stomatology, especially in the clinical diagnosis and treatment of maxillofacial cysts and tumors. This article reviews the application of machine learning in maxillofacial cyst and tumor to provide a new method for the diagnosis of oral and maxillofacial diseases.


Assuntos
Cistos , Medicina Bucal , Inteligência Artificial , Cistos/diagnóstico , Humanos , Aprendizado de Máquina
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