Small Molecules Accelerate Skin Wound Healing: Shikonin Efficacy and Mechanism of Action in Mice / Las Moléculas Pequeñas Aceleran la Curación de Heridas en la Piel: Eficacia de Shikonin y Mecanismo de Acción en Ratones

SUMMARY: The objective of this study was to investigate the therapeutic wound healing potential and molecular mechanisms of shikonin as small molecules in vitro. A mouse burn model was used to explore the potential therapeutic effect of shikonin; we traced proliferating cells in vivo to locate the active area of skin cell proliferation. Through the results of conventional pathological staining, we found that shikonin has a good effect on the treatment of burned skin and promoted the normal distribution of skin keratin at the damaged site. At the same time, shikonin also promoted the proliferation of skin cells at the damaged site; importantly, we found a significant increase in the number of fibroblasts at the damaged site treated with shikonin. Most importantly, shikonin promotes fibroblasts to repair skin wounds by regulating the PI3K/AKT signaling pathway. This study shows that shikonin can effectively promote the proliferation of skin cell, and local injection of fibroblasts in burned skin can play a certain therapeutic role.

El objetivo de este trabajo fue investigar el potencial terapéutico de cicatrización de heridas y los mecanismos moleculares de la shikonina como moléculas pequeñas in vitro. Se utilizó un modelo de quemaduras en ratones para explorar el posible efecto terapéutico de la shikonina; Rastreamos las células en proliferación in vivo para localizar el área activa de proliferación de células de la piel. A través de los resultados de la tinción para patología convencional, encontramos que la shikonina tiene un buen efecto en el tratamiento de la piel quemada y promueve la distribución normal de la queratina de la piel en el sitio dañado. Al mismo tiempo, la shikonina también promovió la proliferación de células de la piel en el sitio dañado. Es importante destacar que encontramos un aumento significativo en la cantidad de fibroblastos en el sitio dañado tratado con shikonina. Lo más importante es que la shikonina promueve la función reparadora de fibroblastos en las heridas de la piel regulando la vía de señalización PI3K/ AKT. Este estudio muestra que la shikonina puede promover eficazmente la proliferación de células de la piel y que la inyección local de fibroblastos en la piel quemada puede desempeñar un cierto papel terapéutico.

Research progress on active ingredients from traditional Chinese medicine as inhibitors of PD-1/PD-L1 of cancer immune checkpoint / 药学实践杂志

Tumor immunotherapy has become a new cancer treatment which has been expected to eliminate tumors. Immune checkpoint inhibitors, especially programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) antibodies, have achieved significant clinical efficacy in the treatment of solid tumors. But biologics possess disadvantages such as strong immunogenicity and high cost. Therefore, the discovery of small molecule drugs as immune checkpoint inhibitors may overcome the shortcomings of biologics and become a new challenge for future tumor immunotherapy. The active small molecules from traditional Chinese medicine that inhibit the expression of PD-1/PD-L1 and their regulatory effects on the tumor immune microenvironment were reviewed in this paper.

Advances in in vitro induction of hepatocyte-like cells and the application of small-molecule compounds in inducing hepatocyte-like cells / 临床肝胆病杂志

The induction of hepatocyte-like cells (HLCs) in vitro is one of the effective ways to obtain a large number of useful hepatocyte, and these HLCs can be used in disease modeling, drug design, and toxicological evaluation. At present, the induction of HLCs in vitro is mainly achieved by introducing exogenous transcription factors, cytokines or small-molecule compounds. Since small-molecule compounds have the advantages of structural diversity, controllable time and dose, and convenient and safe operation, scientists are devoted to screening out the small-molecule compounds to replace exogenous transcription factors and cytokines, and such compounds have a promising application prospect in the field of regenerative medicine. This article reviews the studies on the in vitro induction of HLCs from pluripotent stem cells and other adult stem cells and summarizes the application of small-molecule compounds in the in vitro induction of HLCs, in order to provide ideas and references for the in vitro induction of HLCs.

Inibidores de JAK no tratamento da dermatite atópica / JAK inhibitors in the treatment of atopic dermatitis

A dermatite atópica é a doença inflamatória cutânea mais prevalente mundialmente. A via JAK/STAT tem papel importante no mecanismo da doença e as pequenas moléculas inibidores de JAK são fármacos com grande potencial de uso na dermatite atópica. Foi realizada uma revisão sistemática da literatura na base de dados PubMed, utilizando os termos "atopic dermatitis" e/ou "JAK inhibitors" e/ou "small molecules" entre 2017 e 2022. Foram incluídos os resultados disponíveis de estudos de fase 3, avaliando o uso de inibidores de JAK em apresentações tópicas e sistêmicas. Entre 646 estudos, foram selecionados 37 em humanos que avaliaram a eficácia e segurança dos inibidores de JAK. Os resultados do uso, quando bem indicados, mostraram-se positivos e em alguns casos superiores a outros tratamentos já preconizados para o controle da dermatite atópica, com um bom perfil de segurança.

Atopic dermatitis is the most common inflammatory skin disease worldwide. The JAK/STAT pathway plays an important role in the disease mechanism, and small-molecule JAK inhibitors are drugs with great potential for use in atopic dermatitis. We systematically reviewed PubMed using the search terms "atopic dermatitis" AND/OR "JAK inhibitors" AND/OR "small molecules" for studies published between 2017 and 2022. Results from phase III trials evaluating both topical and systemic application of JAK inhibitors were included. Of 646 studies retrieved, 37 evaluating the efficacy and safety of JAK inhibitors in humans were selected for analysis. When properly indicated, the use of JAK inhibitors yielded positive results, some of which were superior to those of recommended treatments for the control of atopic dermatitis, with a good safety profile.

Small-molecule targeted agents: new choices for the treatment of psoriasis / 中华皮肤科杂志

With the rapid development of immunology and molecular biology in recent years, great progress has been made in the research on psoriatic pathogenesis, as well as in therapeutic strategies targeting key molecules in the pathogenesis. In addition to biologics, small-molecule targeted agents for psoriasis have also received increasing attention, especially agents targeting phosphodiesterase 4, Janus kinase, and tyrosine kinase 2, etc. An increasing number of small-molecule drug candidates have shown favorable efficacy in clinical studies, and some of them have been approved for clinical application and play a unique role in the treatment of psoriasis.

Emerging immunological strategies: recent advances and future directions / 医学前沿

Immunotherapy plays a compelling role in cancer treatment and has already made remarkable progress. However, many patients receiving immune checkpoint inhibitors fail to achieve clinical benefits, and the response rates vary among tumor types. New approaches that promote anti-tumor immunity have recently been developed, such as small molecules, bispecific antibodies, chimeric antigen receptor T cell products, and cancer vaccines. Small molecule drugs include agonists and inhibitors that can reach the intracellular or extracellular targets of immune cells participating in innate or adaptive immune pathways. Bispecific antibodies, which bind two different antigens or one antigen with two different epitopes, are of great interest. Chimeric antigen receptor T cell products and cancer vaccines have also been investigated. This review explores the recent progress and challenges of different forms of immunotherapy agents and provides an insight into future immunotherapeutic strategies.

In silico approach of antiviral compounds potentials for SARS-CoV-2 and SARS-CoV and drug-like property predictions / Enfoque in silico de potenciales compuestos antivirales para SARS-CoV-2 Y SARS-CoV y predicción de propiedades drug-like

SUMMARY Introduction: SARS-CoV-2 (Coronavirus 2 of the severe acute respiratory syndrome; previously 2019-nCoV) and SARS-CoV (coronavirus of the severe acute respiratory syndrome) are closely related viruses, which have no treatment so far. Therefore, the search for new molecules is essential. Objectives: The objective of this study is to use in silico approach to propose antiviral compounds potential for SARS-CoV-2 and SARS-CoV and drug-like properties predictions. Materials and methods: Molecular docking were performed using AutoDock Vina with the molecules that had previously demonstrated drug-like properties. Subsequently, amino acids and the type of interaction involved in the protein-ligand complex were identified. Results: It was possible to identify six potential candidates available in the PubChem database capable of interacting with the 6U7 and 2GTB proteases, which bind to the same active site that lopinavir and remdesivir. Conclusion: Small molecules with drug-like properties could be used as antivirals, after experimental evaluations.

RESUMEN Introducción: Los coronavirus SARS-CoV-2 (coronavirus del síndrome respiratorio agudo grave de tipo 2; previamente identificado como 2019-nCoV) y SARS-CoV (coronavirus del síndrome respiratorio agudo grave) son virus estrechamente relacionados, que no tienen tratamiento hasta el momento. Por lo tanto, la búsqueda de nuevas moléculas es esencial. Objetivos: El objetivo de este estudio es utilizar un enfoque in silico para proponer potenciales compuestos antivirales para el SARS-CoV-2 y el SARS-CoV y predicciones de propiedades "drug-like". Materiales y métodos: El acoplamiento molecular se realizó utilizando "AutoDock Vina" con las moléculas que previamente habían demostrado propiedades similares a los fármacos. Posteriormente, se identificaron los aminoácidos y el tipo de interacción involucrada en el complejo proteína-ligando. Resultados: fue posible identificar seis candidatos potenciales disponibles en la base de datos PubChem capaces de interactuar con las proteasas 6U7 y 2GTB, que se unen al mismo sitio activo al que se unen lopinavir y remdesivir. Conclusiones: Moléculas pequeñas con propiedades similares a los fármacos podrían usarse como antivirales, después de evaluaciones experimentales.

Identification of potential molecular mechanisms and small molecule drugs in myocardial ischemia/reperfusion injury

Myocardial ischemia/reperfusion (MI/R) injury is a complex phenomenon that causes severe damage to the myocardium. However, the potential molecular mechanisms of MI/R injury have not been fully clarified. We identified potential molecular mechanisms and therapeutic targets in MI/R injury through analysis of Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were found between MI/R injury and normal samples, and overlapping DEGs were found between GSE61592 and GSE67308. Gene Ontology (GO) and pathway analysis were performed for overlapping DEGs by Database for Annotation, Visualization and Integration Discovery (DAVID). Then, a network of protein-protein interaction (PPI) was constructed through the Search Tool for the Retrieval of Interacting Genes (STRING) database. Potential microRNAs (miRNAs) and therapeutic small molecules were screened out using microRNA.org database and the Comparative Toxicogenomics database (CTD), respectively. Finally, we identified 21 overlapping DEGs related to MI/R injury. These DEGs were significantly enriched in IL-17 signaling pathway, cytosolic DNA-sensing pathway, chemokine signaling, and cytokine-cytokine receptor interaction pathway. According to the degree in the PPI network, CCL2, LCN2, HP, CCL7, HMOX1, CCL4, and S100A8 were found to be hub genes. Furthermore, we identified potential miRNAs (miR-24-3p, miR-26b-5p, miR-2861, miR-217, miR-4251, and miR-124-3p) and therapeutic small molecules like ozone, troglitazone, rosiglitazone, and n-3 polyunsaturated fatty acids for MI/R injury. These results identified hub genes and potential small molecule drugs, which could contribute to the understanding of molecular mechanisms and treatment for MI/R injury.

Identification of the molecular mechanisms associated with acute type A aortic dissection through bioinformatics methods

Aortic dissection is characterized by the redirection of blood flow, which flows through an intimal tear into the aortic media. The purpose of this study was to find potential acute type A aortic dissection (AAAD)-related genes and molecular mechanisms by bioinformatics. The gene expression profiles of GSE52093 were obtained from Gene Expression Omnibus (GEO) database, including 7 AAAD samples and 5 normal samples. The differentially expressed genes (DEGs) were detected between AAAD and normal samples. The functional annotation and pathway enrichment analysis were conducted through the Database for Annotation, Visualization and Integration Discovery (DAVID). A protein-protein interaction network was established by the Search Tool for the Retrieval of Interacting Genes (STRING) software. The microRNAs (miRNAs) of these differentially expressed genes were predicted using <microRNA.org> database. Moreover, DEGs were analyzed in the comparative toxicogenomics (CTD) database to screen out the potential therapeutic small molecules. As a result, there were 172 DEGs identified in patients with AAAD. These DEGs were significantly enriched in 6 pathways, including cell cycle, oocyte meiosis, DNA replication, extracellular matrix-receptor interaction, and mineral absorption pathway. Notably, CDC20, CDK1, CHEK1, KIF20A, MCM10, PBK, PTTG1, RACGAP, and TOP2A were crucial genes with a high degree in the protein-protein interaction network. Furthermore, potential miRNAs (miR-301, miR-302 family, and miR-130 family) were identified. In addition, small molecules like azathioprine and zoledronic acid were identified to be potential drugs for AAAD.

Effects of metal ions and small molecules on reduction of Cr (VI) resistant strain M52 / 吉林大学学报(医学版)

Objective: To investigate the growth of Sporosarcina saromensis M52 obtained from the sediment samples in Xiamen, to locate the Cr (VI) reduetase, and to study the effects of metal ions and small molecules on the reducing ability of Cr (VI) resisistant strain M52. Methods: The seed solution of M52 strain was inoculated into the LB medium containing different concentrations (0-600 mg · L-1) of Cr (VI). After cultivating for 0-48 h, the absorbance (A) value of M52 strain liquid at 600 nm was measured by UV spectrophotometry. The growth of M52 strain in LB medium containing 0, 50, 100, 200, 400, and 600 mg · L: Cr (VI) was observed. The intracellular and extracellular active substances obtained by centrifugation of M52 bacteria solution before and after sonication and the M52 in control group were cultured at 37°C and pH 7.5, respectively. Using diphenylcarbazide spectrophotometry, the concentrations of Cr (VI) in the solution at 0, 12, 24, and 48 h were measured, and the reduction rates of Cr (VI) in intracellular and extracellular active substances at each time point were calculated. 0. 2 mmol · L-1Mn21, Fe2 and Cu2, 1 mmol · L-1SDS and 1% Triton X-100, Tween 80 were added to the LB medium as treatment groups, and the untreated LB liquid medium was used as control group. The seed solution was inoculated in treatment groups and control group at 4% concentration. The reduction rates of Cr (VI) by M52 at 0, 6, 12, 24, 36, and 48 h were calculated. The changes of the reduction rates of Cr (VI) by M52 in metal ion and small molecule treatment groups were investigated. Results: When the concentration of Cr (VI) was lower than 100 mg · L-1, the growth of strain was promoted with the increase of concentration; when the concentration of Cr (VI) was higher than 100 mg · L-1, the growth of the strain was inhibited with the increase of concentration; when the concentration of Cr (VI) was higher than 600 mg · L-1, the M52 strain hardly grew. Compared with control group, the reduction rates of Cr (VI) by M52 occurred both inside and outside the cells were increased (P Fe21; the reduction rate was reduced in the presence of Mn21 (P Triton X-100 > Tween 80. Conclusion: Low concentration of Cr (VI) can promote the growth of the M52 strain, and high concentration of Cr (VI) can inhibit the growth of the strain. The reduction of Cr (VI) by M52 mainly occurs in the cells. Cu2 and Fe2 can promote the reduction of Cr (VI) by M52. Tween 80, Triton X-100, and SDS can inhibit the reduction of Cr (VI) by M52.

Screening of serum susceptibility biomarkers in patients with mild liver function abnormalities based on non-targeted metabolomics / 中国中药杂志

In the present study,non-targeted metabolomics technique was used to screen potentially susceptibility biomarkers in patients with mild liver function abnormalities during long-term use of Chinese herbal compound. According to the inclusion and exclusion criteria,we collected 7 cases of patients with abnormal liver function during the period of complete taking Chinese herbal medicine( 60 days),and 18 cases of patients with normal liver function in re-examination from the reproductive medicine center in our hospital. Ultra performance liquid chromatography coupled with time-of-flight mass spectrometry( UPLC-Q-TOF/MS~E) technique combined with Progenesis QI software was used to analyze the differential biomarkers in serum of patients with wild liver function abnormalities and normal liver function. 11 potential biomarkers such as bilirubin,pantothenic acid,hippuric acid,sphingomyelin,palmitic acid,and oleic acid were tentatively identified. Metabolic disorders in patients with herbal-induced mild liver abnormality were mainly related to two pathways: pantothenic acid and coenzyme A biosynthesis and linoleic acid metabolism. It could provide a reference for the early warning of mild liver function abnormalities of patients that may be caused by long-term use of Chinese medicine compound in clinical application,and will lay a foundation for further understanding the endogenous substance changes in different levels of liver injury.

Advancements in the preparation of high-performance liquid chromatographic organic polymer monoliths for the separation of small-molecule drugs / 药物分析学报

The various advantages of organic polymer monoliths, including relatively simple preparation processes, abundant monomer availability, and a wide application range of pH, have attracted the attention of chromatographers. Organic polymer monoliths prepared by traditional methods only have macropores and mesopores, and micropores of less than 50 nm are not commonly available. These typical monoliths are suitable for the separation of biological macromolecules such as proteins and nucleic acids, but their ability to separate small molecular compounds is poor. In recent years, researchers have successfully modified polymer monoliths to achieve uniform compact pore structures. In particular, microporous materials with pores of 50 nm or less that can provide a large enough surface area are the key to the separation of small molecules. In this review, preparation methods of polymer monoliths for high-per-formance liquid chromatography, including ultra-high cross-linking technology, post-surface modifica-tion, and the addition of nanomaterials, are discussed. Modified monolithic columns have been used successfully to separate small molecules with obvious improvements in column efficiency.

Reprogramming cell fates by small molecules

Reprogramming cell fates towards pluripotent stem cells and other cell types has revolutionized our understanding of cellular plasticity. During the last decade, transcription factors and microRNAs have become powerful reprogramming factors for modulating cell fates. Recently, many efforts are focused on reprogramming cell fates by non-viral and non-integrating chemical approaches. Small molecules not only are useful in generating desired cell types in vitro for various applications, such as disease modeling and cell-based transplantation, but also hold great promise to be further developed as drugs to stimulate patients' endogenous cells to repair and regenerate in vivo. Here we will focus on chemical approaches for generating induced pluripotent stem cells, neurons, cardiomyocytes, hepatocytes and pancreatic β cells. Significantly, the rapid and exciting advances in cellular reprogramming by small molecules will help us to achieve the long-term goal of curing devastating diseases, injuries, cancers and aging.

Analyzing gene expression profiles in dilated cardiomyopathy via bioinformatics methods

Dilated cardiomyopathy (DCM) is characterized by ventricular dilatation, and it is a common cause of heart failure and cardiac transplantation. This study aimed to explore potential DCM-related genes and their underlying regulatory mechanism using methods of bioinformatics. The gene expression profiles of GSE3586 were downloaded from Gene Expression Omnibus database, including 15 normal samples and 13 DCM samples. The differentially expressed genes (DEGs) were identified between normal and DCM samples using Limma package in R language. Pathway enrichment analysis of DEGs was then performed. Meanwhile, the potential transcription factors (TFs) and microRNAs (miRNAs) of these DEGs were predicted based on their binding sequences. In addition, DEGs were mapped to the cMap database to find the potential small molecule drugs. A total of 4777 genes were identified as DEGs by comparing gene expression profiles between DCM and control samples. DEGs were significantly enriched in 26 pathways, such as lymphocyte TarBase pathway and androgen receptor signaling pathway. Furthermore, potential TFs (SP1, LEF1, and NFAT) were identified, as well as potential miRNAs (miR-9, miR-200 family, and miR-30 family). Additionally, small molecules like isoflupredone and trihexyphenidyl were found to be potential therapeutic drugs for DCM. The identified DEGs (PRSS12 and FOXG1), potential TFs, as well as potential miRNAs, might be involved in DCM.

Exploration of the experimental conditions of drug affinity responsive target stability / 国际药学研究杂志

Objective To explore the optimal proteolysis condition for the new technology of target discovery, drug affinity responsive target stability (DARTS). Methods First, in order to determine the suitable pronase concentration range for DARTS, the extraction of human acute T lymphoblastic leukemia cells (Jurkat) were digested with a range of pronase concentrations (the mass ratio of pronase to protein was 1: 100 to 1: 10000) at room temperature and detected by SDS-PAGE and Coomassie brilliant blue staining. On this basis, in order to obtain the optimal proteolysis condition, we performed DARTS on α-ketoglutarate in combination with SDS-PAGE and gel staining, and observed the effect of different concentrations of pronase (1: 500-1: 5000) and different proteolysis time (5-30 min) on DARTS. The feasibility of the optimum condition was verified by using it on a target known small molecule, mycophenolic acid. Results When the protein extraction of Jurkat was hydrolyzed by a range of pronase concentrations, it was entirely hydrolysed by pronase 1: 100 while showing no significant effect under the condition of pronase 1: 10000. The effect of pronase 1: 500 to 1: 5000 on protein mixture was milder. And approximately 30%-60% of the protein was digested. The protein bands which were protected by α-ketoglutarate could be observed apparently under the conditon of pronase 1: 1000 when the proteolysis time was about 15 min. Then we performed DARTS on mycophenolic acid utilizing this condition (pronase 1: 1000, hydrolysed for 15 min) and obtained several visible protected protein bands between (4-7) ×104. Western blotting results showed that the target protein of mycophenolic acid, IMPDH1, was contained in the protected protein bands. Conclusion The optimal proteolysis condition for DARTS on protein mixture through α-ketoglutarate is obtained.

Exploration of the experimental conditions of drug affinity responsive target stability / 国际药学研究杂志

Objective To explore the optimal proteolysis condition for the new technology of target discovery ,drug affinity responsive target stability(DARTS). Methods First,in order to determine the suitable pronase concentration range for DARTS,the extraction of human acute T lymphoblastic leukemia cells(Jurkat)were digested with a range of pronase concentrations(the mass ratio of pronase to protein was 1∶100 to 1∶10000)at room temperature and detected by SDS-PAGE and Coomassie brilliant blue stain?ing. On this basis,in order to obtain the optimal proteolysis condition,we performed DARTS onα-ketoglutarate in combination with SDS-PAGE and gel staining,and observed the effect of different concentrations of pronase(1∶500-1∶5000)and different proteolysis time(5-30 min)on DARTS. The feasibility of the optimum condition was verified by using it on a target known small molecule ,myco?phenolic acid. Results When the protein extraction of Jurkat was hydrolyzed by a range of pronase concentrations,it was entirely hy?drolysed by pronase 1∶100 while showing no significant effect under the condition of pronase 1∶10000. The effect of pronase 1∶500 to 1∶5000 on protein mixture was milder. And approximately 30%-60%of the protein was digested. The protein bands which were protected byα-ketoglutarate could be observed apparently under the conditon of pronase 1∶1000 when the proteolysis time was about 15 min. Then we performed DARTS on mycophenolic acid utilizing this condition(pronase 1∶1000,hydrolysed for 15 min)and obtained sev?eral visible protected protein bands between(4-7)×104. Western blotting results showed that the target protein of mycophenolic acid , IMPDH1,was contained in the protected protein bands. Conclusion The optimal proteolysis condition for DARTS on protein mix?ture throughα-ketoglutarate is obtained.

Progress of methodology for identifying target protein of natural active small molecules / 中国中药杂志

Drug targets are special molecules that can interact with drugs and exert pharmacological functions in human body. The natural active small molecules are the bioactive basis of traditional Chinese medicine, and the mechanism study is a hot topic now, especially for the identification of their target proteins. However, little progress has been made in this field until now. Here, we summarized the recent technologies and methods for the identification of target proteins of natural bioactive small molecules, and introduced the main research methods, principles and successful cases in this field. We also explored the applicability and discussed the advantages and disadvantages among different methods. We hope this review can be used as a reference for the researchers who engaged in natural pharmaceutical chemistry, pharmacology and chemical biology.

A sting in the tail: The N-terminal domain of the androgen receptor as a drug target / 亚洲男科学杂志(英文版)

The role of androgen receptor (AR) in the initiation and progression of prostate cancer (PCA) is well established. Competitive inhibition of the AR ligand-binding domain (LBD) has been the staple of antiandrogen therapies employed to combat the disease in recent years. However, their efficacy has often been limited by the emergence of resistance, mediated through point mutations, and receptor truncations. As a result, the prognosis for patients with malignant castrate resistant disease remains poor. The amino-terminal domain (NTD) of the AR has been shown to be critical for AR function. Its modular activation function (AF-1) is important for both gene regulation and participation in protein-protein interactions. However, due to the intrinsically disordered structure of the domain, its potential as a candidate for therapeutic intervention has been dismissed in the past. The recent emergence of the small molecule EPI-001 has provided evidence that AR-NTD can be targeted therapeutically, independent of the LBD. Targeting of AR-NTD has the potential to disrupt multiple intermolecular interactions between AR and its coregulatory binding partners, in addition to intramolecular cross-talk between the domains of the AR. Therapeutics targeting these protein-protein interactions or NTD directly should also have efficacy against emerging AR splice variants which may play a role in PCA progression. This review will discuss the role of intrinsic disorder in AR function and illustrate how emerging therapies might target NTD in PCA.

Establishment of small molecular monoclonal antibody technology platform in Chinese materia medica / 中草药

Antibody is a tool of vital importance in modern bioscience research, small molecular antibody technology has a broad application prospect in the field of receptor binding analysis, enzyme assays, and quantitative and/or qualitative analytical techniques of Chinese materia medica (CMM) research. In this paper, combining with the research work carried out by our innovation team, we introduced the establishment background of the small molecular monoclonal antibody technology platform in CMM and technical difficulties in antibody preparation. In view of the technology products based on small molecular monoclonal antibody of CMM, such as ELISA test kit, immune affinity chromatography column, colloidal gold test paper, fluorescently labeled antibodies, and antibody microarrays, we explored and practised the various applications based on the small molecular monoclonal antibody technology looking forward to its scientific significances and application values in the field of CMM research.

Review of research on dual PI3K-mTOR small molecular inhibitors / 药学实践杂志

Objective The phosphoinositide 3-kinase (PI3K) constituted an important family of lipid kinase enzymes that control a range of cellular proliferation , differentiation and apoptosis through their regulation of a network of signal transduction path -ways, which had emerged as important therapeutic targets in the context of cancer and inflammation .Considerable progress had been made in the discovery and development of small molecular inhibitors targeting PI 3K.Progress in dual PI3K-mTOR inhibitors, a number of which had entered early phase clinical trials over recent years was summarized .