1.Crystal structure of SMU.2055 protein from Streptococcus mutans and its small molecule inhibitors design and selection.
Xiaodan CHEN ; Xiurong ZHAN ; Xinyu WU ; Chunyan ZHAO ; Wanghong ZHAO
West China Journal of Stomatology 2015;33(2):182-186
OBJECTIVEThe aim of this study is to analyze the three-dimensional crystal structure of SMU.2055 protein, a putative acetyltransferase from the major caries pathogen Streptococcus mutans (S. mutans). The design and selection of the structure-based small molecule inhibitors are also studied.
METHODSThe three-dimensional crystal structure of SMU.2055 protein was obtained by structural genomics research methods of gene cloning and expression, protein purification with Ni²⁺-chelating affinity chromatography, crystal screening, and X-ray diffraction data collection. An inhibitor virtual model matching with its target protein structure was set up using computer-aided drug design methods, virtual screening and fine docking, and Libdock and Autodock procedures.
RESULTSThe crystal of SMU.2055 protein was obtained, and its three-dimensional crystal structure was analyzed. This crystal was diffracted to a resolution of 0.23 nm. It belongs to orthorhombic space group C222(1), with unit cell parameters of a = 9.20 nm, b = 9.46 nm, and c = 19.39 nm. The asymmetric unit contained four molecules, with a solvent content of 56.7%. Moreover, five small molecule compounds, whose structure matched with that of the target protein in high degree, were designed and selected.
CONCLUSIONProtein crystallography research of S. mutans SMU.2055 helps to understand the structures and functions of proteins from S. mutans at the atomic level. These five compounds may be considered as effective inhibitors to SMU.2055. The virtual model of small molecule inhibitors we built will lay a foundation to the anticaries research based on the crystal structure of proteins.
Bacterial Proteins ; chemistry ; Cloning, Molecular ; Crystallization ; Crystallography, X-Ray ; Dental Caries ; Humans ; Streptococcus mutans ; chemistry ; X-Ray Diffraction
2.Role of epigenetic regulation in cerebral ischemia
Xinyu LI ; Lixuan ZHAN ; Long LONG ; En XU
International Journal of Cerebrovascular Diseases 2016;24(4):371-377
The interaction between genetic and environmental factors influences the onset,development and prognosis of cerebral ischemia.Recently,epigenetic regulation is increasingly becoming a research focus on cerebral ischemia,and there has been great progress in research on DNA methylation,histone modification and miRNA network.Epigenetic regulation provides a new idea for identifying potential therapeutic targets of cerebral ischemia.
3.MRI Features of Encephalitis in Children with Severe Hand-foot-mouth Disease
Jing YANG ; Jubao SUN ; Yongwen HUANG ; Xinyu LI ; Haohui ZHAN ; Haiqiao SONG ; Ke LI
Chinese Journal of Medical Imaging 2014;(9):670-673
Purpose To investigate MRI features of encephalitis in children with severe hand-foot-mouth disease (HFMD). Materials and Methods The MR images of 85 cases of clinically diagnosed encephalitis in severe HFMD patients were retrospectively reviewed. Results In 85 patients, plain MRI was negative in 28;57 cases were positive including 10 cases showing punctate or patchy lesions in cerebral hemisphere, callosum, thalamus and cerebellar vermis with isointensity or slightly hypointensity on T1WI, isointensity or slightly hyperintensity on T2WI, and hyperintensity on T2FLAIR and DWI. In 47 cases, the lesions were located in the brainstem, tegmentum of pons and medulla oblongata. MRI features included symmetric high signal on DWI in posterior portions of brainstem, hypointensity or isointensity on T1WI and hyperintensity or isointensity on T2WI and T2FLAIR (n=17);patchy long T1, long T2 signal in posterior portions of brainstem, normal or mild hyperintensity on DWI, hyperintensity on T2FLAIR (n=30); lesion extending around the fourth ventricle in 9 patients, one of which involved bilateral cerebral peduncles. Conclusion Encephalitis in children with severe HFMD has characteristic MRI features. The lesions are mostly located in the posterior portion of the brainstem. DWI and T2FLAIR can better detection lesions.
4.The role of endoplasmic reticulum stress in regulating macrophage immune response in liver diseases
Yiyun GAO ; Xinyu ZHAN ; Haoming ZHOU
Organ Transplantation 2024;15(6):889-894
Endoplasmic reticulum stress refers to a cellular stress response triggered when cells are stimulated,which is manifested as the disruption of endoplasmic reticulum homeostasis and dysfunction in various pathological conditions,resulting in the accumulation of a large number of misfolded and unfolded proteins within the endoplasmic reticulum and an imbalance of calcium ions.Macrophages are the most abundant immune cells in the liver and play an important role in maintaining liver homeostasis and various liver diseases.Recent studies have confirmed that the unfolded protein response caused by endoplasmic reticulum stress plays an important role in regulating macrophage immune response.This article reviews the mechanisms of endoplasmic reticulum stress regulating macrophage immune response and its role in liver diseases such as ischemia-reperfusion injury during organ transplantation,liver fibrosis,and hepatocellular carcinoma,in order to deepen the understanding of the mechanism of macrophage immune regulation and provide new ideas for research and interventional treatment related to liver diseases.
5.Crystal structure of SMU.2055 protein fromStreptococcus mutans and its small molecule inhibitors design and selec- tion
Xiaodan CHEN ; Xiurong ZHAN ; Xinyu WU ; Chunyan ZHAO ; Wanghong ZHAO
West China Journal of Stomatology 2015;(2):182-186
ObjectiveThe?aim?of?this?study?is?to?analyze?the?three-dimensional?crystal?structure?of?SMU.2055?protein,?a?putative?acetyltransferase?from?the?major?caries?pathogen?Streptococcus mutans(S.mutans).?The?design?and?selection?of?the?structure-based?small?molecule?inhibitors?are?also?studied.?Methods???The?three-dimensional?crystal?structure?of?SMU.2055?protein?was?obtained?by?structural?genomics?research?methods?of?gene?cloning?and?expression,?protein?purification?with?Ni2+-chelating?affinity?chromatography,?crystal?screening,?and?X-ray?diffraction?data?collection.?An?inhibitor?virtual?model?matching?with?its?target?protein?structure?was?set?up?using?computer-aided?drug?design?methods,?virtual?screening?and?fine?docking,?and?Libdock?and?Autodock?procedures.?Results???The?crystal?of?SMU.2055?protein?was?obtained,?and?its?three-dimensional?crystal?structure?was?analyzed.?This?crystal?was?diffracted?to?a?resolution?of?0.23?nm.?It?belongs?to?orthorhombic?space?group?C2221,?with unit cell parameters of a=9.20nm, b=9.46nm, and c=19.39nm. The asymmetric unit contained four molecules, with a solvent?content?of?56.7%.?Moreover,?five?small?molecule?compounds,?whose?structure?matched?with?that?of?the?target?protein?in?high?degree,?were?designed?and?selected.?Conclusion???Protein?crystallography?research?of?S. mutans?SMU.2055?helps?to?under-stand?the?structures?and?functions?of?proteins?from?S. mutans?at?the?atomic?level.?These?five?compounds?may?be?considered?as?effec-tive?inhibitors?to?SMU.2055.?The?virtual?model?of?small?mole-cule?inhibitors?we?built?will?lay?a?foundation?to?the?anticaries?research?based?on?the?crystal?structure?of?proteins.
6.Construction of microRNA-21 terahertz metamaterial sensing method based on duplex-specific nuclease triggered rolling circle amplification
Xinyu ZHAN ; Sha YANG ; Yang ZHANG ; Xiang YANG ; Weiling FU
Chinese Journal of Preventive Medicine 2021;55(2):212-218
Objective:To construct of a terahertz metamaterial sensing method for detection of microRNA-21 (miRNA-21) based on duplex-specific nuclease triggered rolling circle amplification.Methods:First, a THz metamaterial sensing method was constructed, and verified by polyacrylamide gel electrophoresis and zeta potential; after optimizing the detection conditions of the sensor, different concentrations of miRNA-21 and other different miRNAs were detected. And this biosensor was compared with other miRNA detection methods; finally, the recovery rate of the biosensor was evaluated.Results:Under the optimal experimental conditions, through the dual signal amplification strategy of duplex-specific nuclease (DSN) cycle recognition and rolling circle amplification (RCA), the THz metamaterial sensor has a response range of 10 fmol/L to 10 nmol/L to the target miRNA-21, with a detection limit of 8.49 fmol/L. And the biosensor has good specificity with the ability to recognize the target miRNA-21 from a variety of microRNAs. And the experiment with recovery rate from 94.33% to 115.33% has been further verified in commercial human serum samples.Conclusion:The terahertz biosensor can achieve highly sensitive and specific detection of the target miRNA-21, which proves the potential for label-free diagnosis and early warning of miRNA-related diseases.
7.Construction of microRNA-21 terahertz metamaterial sensing method based on duplex-specific nuclease triggered rolling circle amplification
Xinyu ZHAN ; Sha YANG ; Yang ZHANG ; Xiang YANG ; Weiling FU
Chinese Journal of Preventive Medicine 2021;55(2):212-218
Objective:To construct of a terahertz metamaterial sensing method for detection of microRNA-21 (miRNA-21) based on duplex-specific nuclease triggered rolling circle amplification.Methods:First, a THz metamaterial sensing method was constructed, and verified by polyacrylamide gel electrophoresis and zeta potential; after optimizing the detection conditions of the sensor, different concentrations of miRNA-21 and other different miRNAs were detected. And this biosensor was compared with other miRNA detection methods; finally, the recovery rate of the biosensor was evaluated.Results:Under the optimal experimental conditions, through the dual signal amplification strategy of duplex-specific nuclease (DSN) cycle recognition and rolling circle amplification (RCA), the THz metamaterial sensor has a response range of 10 fmol/L to 10 nmol/L to the target miRNA-21, with a detection limit of 8.49 fmol/L. And the biosensor has good specificity with the ability to recognize the target miRNA-21 from a variety of microRNAs. And the experiment with recovery rate from 94.33% to 115.33% has been further verified in commercial human serum samples.Conclusion:The terahertz biosensor can achieve highly sensitive and specific detection of the target miRNA-21, which proves the potential for label-free diagnosis and early warning of miRNA-related diseases.
8.Cellular composition and anatomic distribution in nonfunctioning pancreatic endocrine tumors: immunohistochemical study of 30 cases
Xinyu ZHENG ; Kejian GUO ; Yulin TIAN ; Jiguang LI ; Renxuan GUO ; Yong ZHAN ; Maomin SONG ; Kui SHEN
Chinese Medical Journal 1998;111(4):0-0
Objective To investigate the cytological pattern and distribution in nonfunctioning pancreatic endocrine tumors.Methods Using labeled streptavidin-biotin (LSAB), immunohistochemical staining for insulin, glucagon, somatostatin, pancreatic polypeptide and gastrin was performed on 30 nonfunctioning pancreatic endocrine tumors from 30 patients. The cellular composition and anatomic distribution in these tumors were analyzed.Results Of 30 tumor tissues, 22 (73.3%) were found to contain cells immunoreactive to 1-4 kinds of peptide hormones; 17 (56.7%) showed positive staining for more than one peptide and up to 4 peptides; and 8 (26.7%) showed negative immunoreaction to all antiserum applied. No tumor was found to contain immunoreactive gastrin. Among 17 multihormonal tumors, 4 contained 2 kinds of peptide hormones, 8 had 3 kinds, and 5 harbored 4 kinds of peptide hormones. In addition, the difference in the number and type of positive endocrine cells between the tumors arising from the head of the pancreas and those arising from the body and tail of the pancreas were statistically significant (P<0.05).Conclusions Immunohistochemically, the high positive rate to peptide hormones suggests that the nonfunctioning pancreatic endocrine tumors are actually not nonfunctioning; they are asymptomatic pancreatic endocrine tumors. Moreover, an uneven distribution of positive endocrine cells in the nonfunctioning pancreas endocrine tumors within the pancreas was identified.
9.Vascular anatomy of the stomach and its application in gastric tube reconstruction dur-ing esophagectomy
Tian JIANG ; Ming LI ; Mengnan ZHAO ; Xinyu YANG ; Xiyu DAI ; Cheng ZHAN ; Mingxiang FENG
Chinese Journal of Clinical Oncology 2019;46(3):126-129
Objective: To investigate the vascular anatomy of the stomach, especially the right gastroepiploic artery for the reconstruc-tion of a gastric tube during esophagectomy. Methods: The vascular anatomy of the stomach was studiing in 28 embalmed human specimens provided by the Department of Anatomy, Shanghai Medical College, Fudan University, included 10 female and 18 male spec-imens. The length and diameter of gastric vessels were measured. The ratio of the length of the right gastroepiploic artery to the length of the greater curvature was calculated. Anastomosis between the left and right gastroepiploic arteries was also assessed. Re-sults: Twenty-five left gastric arteries were observed in the autopsies, with the mean diameter of 3.40 (2.10-6.40) mm. Twenty-one right gastric arteries were measured, with the mean diameter of 1.97 (0.68-3.56) mm. Twenty-six left gastroepiploic arteries were ob-served, with the mean diameter of 1.87 (0.80-2.96) mm. Twenty-eight right gastroepiploic arteries were measured, with the mean di-ameter of 2.82 (1.58-4.80) mm. The mean lengths of the 28 right gastroepiploic arteries and their greater curvatures were 216.71 (120-318) mm and 356.39 (248-487) mm, respectively. The ratio of the length of right gastroepiploic arteries and greater curvatures was 0.61 (0.45-0.82). The anastomosis between the left and right gastroepiploic arteries was observed in 60.7% (17/28) of the specimens. Conclusions: The length and diameter of gastric vessels were calculated. It was assumed that the right gastroepiploic artery provides an average of 61% of the blood supply for the great curvature. In addition, the anastomotic branch of the right and left gastroepiploic arteries was observed in 60.7% specimens. These anatomical data allow surgeons to estimate the blood supply and to choose an opti-mal method of gastric tube reconstruction during esophagectomy.
10.Application and advancement of digital teaching materials in teaching epidemiology
Xinyu YANG ; Ziqi DONG ; Xiaoqun WANG ; Yuntao LIU ; Siyan ZHAN ; Shengfeng WANG
Chinese Journal of Epidemiology 2024;45(4):597-601
This study aims at examining the application and development of digital teaching materials in the field of epidemiology, encompassing both China and international contexts. The research involved conducting search on websites and literature databases to assess the status of digital teaching materials in epidemiology, nationally and internationally. At present, in China, digital teaching materials used in epidemiology are primarily presented in the form of printed books with added QR codes, providing teaching resources such as videos and exercises. However, issues with the level of interactivity have been identified. In foreign countries, with stronger emphasis placed on personalization, interactivity, and the use of rich media technologies in the digital teaching materials, epidemiologically. Enhanced digitization regarding materials and learning outcomes is achieved through features such as real-time notes, interactive animations, and quizzes. These approaches are considered worth considering for adoption. This study provides valuable insights for the digital transformation of epidemiology education.