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Integration of network pharmacology and bone marrow mesenchymal stem cells experimental research to reveal the molecular mechanisms for Hai Honghua medicinal liquor against osteoporosis

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Integrative Medicine Discovery

Integrative Medicine Discovery 2024年第3期8卷 1-11页

作者： Die Qian Chi Xu Cheng-Xun He Mei-Yan Li juan guo Hong Zhang School of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu 611137China Department of Orthopedics Longquan Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610017China Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese MedicineShanghai 201203China

Background:Hai Honghua medicinal liquor(HHML)formula has been used in clinical practice for a long time,mainly for the treatment of freshly closed fractures,to promote osteogenesis,to increase bone mass,and thus to promote fracture healing.However,the underlying mechanisms of HHML in the treatment of osteoporosis(OP)are still unclear.Methods:Firstly,Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform and The Encyclopedia of Traditional Chinese Medicine were used to screen the targets of the active compounds of HHML.At the same time,OP targets were identified through GeneCards,Online Mendelian Inheritance in Man,DisGeNET,Therapeutic Target Database,Comparative Toxicogenomics Database and Human Phenotype Ontology databases.Next,protein-protein interaction and pathway networks were constructed for compound-disease common targets,and core targets and compounds were screened for molecular docking.Furthermore,rat bone marrow mesenchymal stem cells were extracted as model cells,and the osteogenic effects of HHML were verified via in vitro experiments.Results:Total of 343 common targets of HHML-OP and the top 10 target proteins in the protein-protein interaction network are TP53,AKT1,STAT3,HSP90AA1,ESR1,TNF,IL6,MAPK1,MAPK3 and MAPK8.Enrichment analysis yielded that the key molecular pathway was the PI3K/Akt signaling pathway.Molecular docking analysis showed that baicalein,erysodienone and naringenin docked with the target proteins AKT1,STAT3 and TP53,respectively,with low binding energy and high affinity.In addition,In vitro experiments demonstrated that HHML promoted the proliferation of bone marrow mesenchymal stem cells;compared with the control group,HHML-treated cells showed enhanced alkaline phosphatase staining,promoted the expression of OCN,RUNX2,BSP,and COL1 mRNAs as well as the expression of PI3K and AKT phosphorylated proteins.Secondly,the expression of target proteins revealed that HHML promoted the phosphorylation of STAT3 protein and inhibited the expression of P53.Conclusions

关键词： Hai Honghua medicinal liquor osteoporosis network pharmacology molecular docking PI3K/AKT signal pathway

Selective laser trabeculoplasty as adjunctive treatment for open-angle glaucoma vs following incisional glaucoma surgery in Chinese eyes

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World Journal of Clinical Cases 2023年第4期11卷 780-787页

作者： Jing Zhu juan guo Department of Ophthalmology The Third People's Hospital of ChengduAffiliated Hospital of Southwest Jiao Tong UniversityAffiliated Chengdu Second Clinical College of Chongqing Medical UniversityChengdu 610031Sichuan ProvinceChina

BACKGROUND Selective laser trabeculoplasty(SLT)is a relatively safe and effective therapy in lowering intraocular pressures(IOP)for glaucoma.AIM To study the long-term effects of SLT on IOP and number of glaucoma medications used in Chinese eyes.METHODS This is a retrospective study in which 75 eyes of 70 patients with open-angle glaucoma(OAG,n=36)and eyes with prior glaucoma surgery(PGS,n=39)were included.Changes in mean IOP and number of glaucoma medications used evaluated at 1 d,1 wk,1 mo,3 mo,6 mo,12 mo,and 36 mo after laser treatment.RESULTS All patients(33 male,37 female)were Chinese.The mean age was 44.34±16.14years.Mean pre-SLT IOP was 22.75±2.08 mmHg in OAG and 22.52±2.62 mmHg in PGS.Mean IOP was significantly reduced 1 d,1 wk,1 mo and 3 mo after laser treatment(P0.05)and in PGS(P=0.309,P>0.05).Six months after SLT treatment,some patients received retreatment of SLT or were given more topical IOP-lowering medication to control the IOP.By the end of our study,the average IOP decreased to 20.73±1.82 mmHg in OAG and 20.49±1.53 mmHg in PGS groups.The number of glaucoma medications used was significantly reduced until the end of 3 years compared to baseline.CONCLUSION SLT could reduce IOP as adjunctive treatment both in OAG and PGS groups.SLT significantly reduced the number of glaucoma medications used 3-years following treatment in glaucoma patients.

关键词： Selective laser trabeculoplasty Open-angle glaucoma Intraocular pressure Prior glaucoma surgery Adjunctive treatment

Effect of Size Change on Mechanical Properties of Monolayer Arsenene

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Journal of Wuhan University of Technology(Materials Science) 2024年第1期39卷 206-212页

作者：郭娟刘贵立孙震宇 School of Architecture and Civil Engineering Shenyang University of TechnologyShenyang 110870China

The Young's modulus, shear modulus and Poisson's ratio of monolayer arsenene with different sizes were calculated by finite element method, so as to explore the influence of dimension and orientation on the mechanical properties of monolayer arsenene. The calculation results show that the small size has a significant effect on the mechanical properties of the monolayer arsenene. The smaller the size, the larger the Young's modulus and Poisson's ratio of the monolayer arsenene. The size change has a great influence on the Young's modulus of the arsenene handrail direction, and the Young's modulus of the zigzag direction is not sensitive to the size change. Similarly, the size change has a significant effect on the shear modulus of arsenene in the handrail direction, while the shear modulus in the zigzag direction has no significant effect on its size change. For the Poisson's ratio, the situation is just the opposite, and the effect of the size change on the Poisson's ratio of the arsenene zigzag direction is greater than that of the handrail direction.

关键词： finite element method arsenene size change mechanical properties

Surface Characterization and Tribology Behavior of PMMA Processed by Excimer Laser

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Chinese Journal of Mechanical Engineering 2023年第5期36卷 45-61页

作者： Dong Qin juan guo Ming Liang Ling Chen Weimin He Department of Ophthalmology West China HospitalSichuan UniversityChengdu 610000China Ophthalmology Department The Third People’s Hospital of ChengduChengdu 610031China

Polyoxymethylene methacrylate (PMMA) is widely used in ophthalmic biomaterials. Misuse of PMMA in extreme environments is likely to damage the ocular surface and intraocular structures. The surface characterization and tribological behavior of PMMA processed using an excimer laser were investigated in this study by contrasting diferent lubrication conditions and friction cycles. The results show that the roughness of the material surface increases with laser processing, which changes its physical structure. Under lubrication, the laser-treated PMMA exhibits better hydrophilicity, especially during the use of eye drops. No obvious relationship exists between the laser-processing time and friction behavior. However, the laser treatment may contribute to the formation of friction and wear mechanisms of PMMA materials. Laser-treated PMMA in saline solution exhibits better abrasive resistance by showing a lower wear rate than that in eye drops, although it has a higher friction coefcient. In this study, the diferent friction stages in laser-treated PMMA were clarifed under two lubrication conditions. The wear rates of the laser-treated PMMA were found to decrease with the number of cycles, and the friction coefcient has a similar variation tendency. The wear behavior of the laser-treated PMMA is dominated by the main abrasive wear and secondary transferred flm formation. This study provides a theoretical basis for the development and application of ophthalmic biomaterials in complex environments by examining the material surface interface behavior and wear mechanism after laser processing using PMMA as the research matrix.

关键词： Biocompatible materials Poly(methyl methacrylate) Surface characterization Tribology behavior

The characterization of transmembrane protein 59-like(TMEM59L)reveals its role in the regulating the level of the GDI protein family

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BIOCELL 2022年第12期46卷 2615-2624页

作者： HAIFENG WANG juan guo TIEQIAO WEN School of Environmental Engineering Central Plains Specialty Food Engineering&Technology Research CenterKaifeng Key Laboratory of Food Composition and Quality AssessmentYellow River Conservancy Technical InstituteKaifeng475004China Laboratory of Molecular Neural Biology School of Life SciencesShanghai UniversityShanghai200444China

The characterization and functions of transmembrane protein 59-like(TMEM59L),a type I transmembrane protein,are not clearly understood until now.Some TMEM59L and fluorescent fusion proteins constructs were transfected in cell lines and liposomes,and their localization was observed.The effects of protein constructs were studied by fluorescence microscopy and western blotting.This study reports a novel function of human TMEM59L(hTMEM59L)related to the expression and location of some proteins.In addition,we report two novel splice variants of human TMEM59L(hTMEM59L).The localization of mutants of this protein,lacking a middle region,and a Cterminal deletion,markedly differed from that of full-length hTMEM59L.Intracellular movement assessment in living cells showed the localization of TMEM59L to vesicular structures in the Golgi bodies,and the cell membrane was observed in living cells.Overexpression of TMEM59L markedly increased the level of amyloid precursor protein because of TMEM59L-mediated inhibition of cell membrane transport but did not affect the expression of betasecretase 2.TMEM59L overexpression also significantly increased the levels of Rab GDP dissociation inhibitor alpha and Rab GDP dissociation inhibitor beta proteins.These results suggest that TMEM59L is involved in the packaging of acidic vesicles and thereby functions in the trafficking and processing of intracellular proteins.

关键词： TMEM59L Localization GDI1 GDI2 Protein processing

Ultrasmall Fe-doped carbon dots nanozymes for photoenhanced antibacterial therapy and wound healing

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Bioactive Materials 2022年第6期7卷 246-256页

作者： Yunhang Liu Bolong Xu Mingzhu Lu Shanshan Li juan guo Fangzhou Chen Xiaolu Xiong Zhe Yin Huiyu Liu Dongsheng Zhou Beijing Advanced Innovation Center for Soft Matter Science and Engineering State Key Laboratory of Organic-Inorganic CompositesBionanomaterials&Translational Engineering LaboratoryBeijing Key Laboratory of BioprocessBeijing Laboratory of Biomedical MaterialsBeijing University of Chemical TechnologyBeijing100029China State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyBeijing100071China

Pathogenic bacteria pose a devastating threat to public health.However,because of the growing bacterial antibiotic resistance,there is an urgent need to develop alternative antibacterial strategies to the established antibiotics.Herein,iron-doped carbon dots(Fe-CDs,~3 nm)nanozymes with excellent photothermal conversion and photoenhanced enzyme-like properties are developed through a facile one-pot pyrolysis approach for synergistic efficient antibacterial therapy and wound healing.In particular,Fe doping endows CDs with photoenhanced peroxidase(POD)-like activity,which lead to the generation of heat and reactive oxygen species(ROS)for Gram-positive and Gram-negative bacteria killing.This study demonstrates Fe-CDs have significant wound healing efficiency of Fe-CDs by preventing infection,promoting fibroblast proliferation,angiogenesis,and collagen deposition.Furthermore,the ultrasmall size of Fe-CDs possesses good biocompatibility favoring clinical translation.We believe that the nanozyme-mediated therapeutic platform presented here is expected to show promising applications in antibacterial.

关键词： Carbon dots Nanozymes Photothermal effect Antibacterial therapy Wound healing

Whole Genome Duplication of Intra- and Inter-chromosomes in the Tomato Genome

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Journal of Genetics and Genomics 2012年第7期39卷 361-368页

作者： Chi Song juan guo Wei Sun Ying Wang Key Laboratory of Plant Germplasm Enhancement and Speciality Agriculture Wuhan Botanical GardenChinese Academy of SciencesWuhanHubei 430074China Graduate University of Chinese Academy of Sciences Beijing 100049China South China Botanical Garden Chinese Academy of SciencesGuangzhouGuangdong 510650China

Whole genome duplication （WGD） events have been proven to occur in the evolutionary history of most angiosperms. Tomato is considered a model species of the Solanaceae family. In this study, we describe the details of the evolutionary process of the tomato genome by detecting collinearity blocks and dating the WGD events on the tree of life by combining two different methods： synonymous substitution rates （Ks） and phylogenetic trees. In total, 593 collinearity blocks were discovered out of 12 pseudo-chromosomes con- structed. It was evident that chromosome 2 had experienced an intra-chromosomat duplication event. Major inter-chromosomal dupli- cation occurred among all the pseudo-chromosome. We calculated the Ks value of these collinearity blocks. Two peaks of Ks distribution were found, corresponding to two WGD events occurring approximately 36-82 million years ago （MYA） and 148--205 MYA. Additionally, the results of phylogenetic trees suggested that the more recent WGD event may have occurred after the divergence of the rosidasterid clade, but before the major diversification in Solanaceae. The older WGD event was shown to have occurred before the divergence of the rosid-asterid clade and after the divergence of rice-Arabidopsis （monocot-dicot）.

关键词： Whole genome duplication Collinearity block Phylogenetic tree

Identification of (-)-bornyl diphosphate synthase from Blumea balsamifera and its application for (-)-borneol biosynthesis in Saccharomyces cerevisiae

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Synthetic and Systems Biotechnology 2022年第1期7卷 490-497页

作者： Rui Ma Ping Su Qing Ma juan guo Suiqing Chen Baolong Jin Haiyan Zhang Jinfu Tang Tao Zhou Chenghong Xiao Guanghong Cui Luqi Huang School of Pharmacy Henan University of Chinese MedicineZhengzhouChina State Key Laboratory Breeding Base of Dao-di Herbs National Resource Center for Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijingChina School of Pharmacy Guizhou University of Traditional Chinese MedicineGuiyangChina

Borneol is a precious monoterpenoid with two chiral structures,(-)-borneol and(+)-borneol.Bornyl diphosphate synthase is the key enzyme in the borneol biosynthesis pathway.Many(+)-bornyl diphosphate synthases have been reported,but no(-)-bornyl diphosphate synthases have been identified.Blumea balsamifera leaves are rich in borneol,almost all of which is(-)-borneol.In this study,we identified a high-efficiency(-)-bornyl diphosphate synthase(BbTPS3)from B.balsamifera that converts geranyl diphosphate(GPP)to(-)-bornyl diphosphate,which is then converted to(-)-borneol after dephosphorylation in vitro.BbTPS3 exhibited a K m value of 4.93±1.38μM for GPP,and the corresponding k cat value was 1.49 s−1.Multiple strategies were applied to obtain a high-yielding(-)-borneol producing yeast strain.A codon-optimized BbTPS3 protein was introduced into the GPP high-yield strain MD,and the resulting MD-B1 strain produced 1.24 mg⋅L^(-1)(-)-borneol.After truncating the N-terminus of BbTPS3 and adding a Kozak sequence,the(-)-borneol yield was further improved by 4-fold to 4.87 mg⋅L^(-1).Moreover,the(-)-borneol yield was improved by expressing the fusion protein module of ERG20 F96W-N127W-YRSQI-t14-BbTPS3K2,resulting in a final yield of 12.68 mg⋅L^(-1) in shake flasks and 148.59 mg⋅L^(-1) in a 5-L bioreactor.This work is the first reported attempt to produce(-)-borneol by microbial fermentation.

关键词： Metabolic engineering (-)-borneol (-)-bornyl diphosphate synthase Blumea balsamifera Saccharomyces cerevisiae

西达本胺对骨髓增生异常综合征患者骨髓间充质干细胞成骨分化的影响

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中国实验血液学杂志 2024年第2期32卷 512-519页

作者：赵思达郭娟赵佑山常春康上海交通大学医学院附属第六人民医院血液科上海200233

目的:探索西达本胺对骨髓增生异常综合征(MDS)患者骨髓间充质干细胞(MSC)成骨分化的作用及机制。方法:分离培养正常对照者及MDS患者的骨髓MSC,CCK-8法检测西达本胺对MSC增殖活性的影响,组蛋白去乙酰化酶(HDAC)活性荧光检测试剂盒及Weste... 详细信息

目的:探索西达本胺对骨髓增生异常综合征(MDS)患者骨髓间充质干细胞(MSC)成骨分化的作用及机制。方法:分离培养正常对照者及MDS患者的骨髓MSC,CCK-8法检测西达本胺对MSC增殖活性的影响,组蛋白去乙酰化酶(HDAC)活性荧光检测试剂盒及Western blot检测西达本胺对MSC中HDAC的影响。对MSC成骨诱导分化,在d 3进行碱性磷酸酶活性检测,d 21进行茜素红染色观察钙结节形成情况,在d 7和21分别检测成骨相关早期及后期基因的mRNA表达变化。RT-PCR及Western blot分别检测西达本胺对MSC成骨关键转录因子Runt相关转录因子2(RUNX2)mRNA及蛋白表达的影响。结果:随着西达本胺浓度的增加,MSC增殖受到抑制,但低浓度(1μmol/L)西达本胺对MSC无显著的增殖抑制作用,但可显著抑制HDAC活性。在正常对照组及MDS患者的骨髓MSC中,西达本胺(1μmol/L)可以显著增加碱性磷酸酶活性、促进钙结节形成及上调成骨基因的mRNA表达,从而恢复MDS患者MSC较正常对照组MSC减弱的成骨分化能力。机制研究结果显示,西达本胺促成骨作用可能与RUNX2表达的上调有关。结论:西达本胺可以抑制MDS-MSC的HDAC活性,上调成骨转录因子RUNX2表达,促进MDS-MSC的成骨分化。

关键词：西达本胺骨髓增生异常综合征骨髓间充质干细胞成骨分化