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Genetic dissection of glutathione S-transferase omega-1:identification of novel downstream targets and Alzheimer's disease pathways

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Neural Regeneration Research 2022年第11期17卷 2452-2458页

作者： Yue jia Meng-Die Gao yun-Fang Liu Lu Lu Gang chen Ying chen Department of Histology and Embryology Medical CollegeNantong UniversityNantongJiangsu ProvinceChina Key Laboratory of Neuroregeneration of jiangsu and the Ministry of Education Co-innovation Center of NeuroregenerationNantong UniversityNantongJiangsu ProvinceChina Department of Genetics Genomics and InformaticsUniversity of Tennessee Health Science CenterMemphisTNUSA Department of Anesthesiology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina

Alzheimer's disease(AD)is affected by genetic factors.Polymorphisms in the glutathione S-transfe rase omega-1(Gsto1)gene have been shown by genetic correlation analyses performed in different ethnic populations to be genetic risk factors for AD.Gene expression profile data from BXD recombinant inbred mice were used in combination with genetic and bioinformatic analyses to chara cterize the mechanisms underlying regulation of Gstol variation regulation and to identify network membe rs that may contribute to AD risk or progression.Allele-specific assays confirmed that variation in Gstol expression is controlled by cis-expression quantitative trait loci.We found that Gstol mRNA levels were related to several central nervous system traits,such as glial acidic fibrillary protein levels in the caudate putamen,co rtical gray matter volume,and hippocampus mossy fiber pathway volume.We identified 2168 genes whose expression was highly correlated with that of Gsto1.Some genes were enriched for the most common neurodegenerative diseases.Some Gsto1-related genes identified in this study had previously been identified as susceptibility genes for AD,such as APP,Grin2 b,Ide,and Psenen.To evaluate the relationships between Gstol and candidate network members,we transfected astrocytes with Gstol siRNA and assessed the effect on putative downstream effecto rs.We confirmed that knockdown of Gstol had a significant influence on Pa2g4 expression,suggesting that Pa2g4 may be a downstream effector of Gstol,and that both genes intera ct with other genes in a network during AD pathogenesis.

关键词： Alzheimer's disease BXD recombinant inbred mice co-expression correlation analysis expression quantitative trait locus expression variation genetic dissection glutathione S-transferase omega-1 hippocampus proliferation-associated 2G4

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Liobagrus chengduensis,a new species of torrent catfish(Teleostei:Siluriformes:Amblycipitidae)from the upper Changjiang River basin in southwest China

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Zoological Research 2022年第4期43卷 679-682页

作者： Zhong-Guang chen Yan-Shu Guo jia-yun Wu An-Xiang Wen College of Life Sciences Sichuan Agricultural UniversityYa’anSichuan 625014China Ecological Restoration and Conservation on Forest and Wetland Key Laboratory of Sichuan Province Sichuan Academy of Forestry SciencesChengduSichuan 610081China

DEAR EDITOR,A new torrent catfish species,Liobagrus chengduensis sp.nov.,is described from the Xihe River,a tributary of the Minjiang River,Qionglai City,chengdu City,Sichuan Province,China.It can be distinguished from all other congeneric species by a unique combination of the following characters:3-4 serrations on posterior edge of pectoral-fin spine;anal fin with 15-16 rays;upper jaw obviously shorter than lower jaw;caudal fin rounded,with 42-44 rays;vertebral column with 36-37 post-Weberian elements;anus close to pelvic-fin insertion;adipose fin posteriorly continuous with caudal fin,with marked incision at confluence;body generally brownish yellow;all fins lacking well-defined light-colored margins,with color fading towards edge.

关键词： southwest colored insertion

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Sangguayin preparation prevents palmitate-induced apoptosis by suppressing endoplasmic reticulum stress and autophagy in db/db mice and MIN6 pancreatic β-cells

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Chinese Journal of Natural Medicines 2020年第6期18卷 472-480页

作者： XING Qi-Chang LIU Xiang LI Wei chen yun-Zhong chen jia Department of pharmacy Xiangtan Central HospitalXiangtan 411100China College of pharmacy Hubei University of Chinese MedicineWuhan 430065China

Sangguayin preparation(SGY-P) is refined from the traditional Chinese medicinal compound Sangguayin, which"clears heat and promotes fluid" and "tonifies kidney and spleen" for "Xiaoke", commonly known as ‘Diabetes mellitus’ in clinics.Previous studies have shown that SGY-P could reduce insulin resistance and repair damaged pancreas in db/db mice, but the underlying mechanisms were unclear. Here, we investigated whether treatment with SGY-P could protect pancreatic β-cells from apoptosis and uncovered the underlying mechanisms. db/db mice were used to observe the hypoglycemic and islet protective effect in vivo. Apoptosis was induced in mouse insulinoma 6(MIN6) cells by palmitate, following which the cells were treated with SGY-P for elucidating the anti-apoptotic mechanism in vitro. Cell viability and nuclear morphology were detected by CCK-8 assay and Hoechst 33258 staining. The expression levels of apoptosis-, endoplasmic reticulum(ER) stress-, and autophagy-related proteins were measured by western blot. The results showed that SGY-P reduced fasting blood glucose, pancreatic pathological changes, and islet β-cell apoptosis in db/db mice. Palmitate-induced apoptosis in MIN6 cells was decreased by SGY-P treatment. Hence, SGY-P therapy exhibited a protective effect on pancreatic β-cells by decreasing the expression of cleaved caspase-3, cleaved PARP and Bax, and increasing Bcl-2 by suppressing ER stress(Bip/XBP1/IRE1α/CHOP/Caspase-12) and autophagy(LC3/p62/Atg5) pathways.2/Atg5 pathways.

关键词： Sangguayin preparation MIN6 cells Apoptosis Endoplasmic reticulum(ER)stress Autophagy Lipotoxicity

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Identification of a cytochrome P450 from Tripterygium hypoglaucum(Levl.)Hutch that catalyzes polpunonic acid formation in celastrol biosynthesis

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Chinese Journal of Natural Medicines 2022年第9期20卷 691-700页

作者： chen Xiao-Chao LU yun LIU Yuan ZHOU jia-Wei ZHANG Yi-Feng GAO Hai-yun LIDan GAO Wei School of Traditional Chinese Medicine Capital Medical UniversityBeijing 100069China Beijing Shijitan Hospital Capital Medical UniversityBeijing 100038China

Tripterygium hypoglaucum(Levl.)Hutch,a traditional Chinese medicinal herb with a long history of use,is widely distributed in China.One of its main active components,celastrol,has great potential to be developed into anti-cancer and anti-obesity drugs.Although it exhibits strong pharmacological activities,there is a lack of sustainable sources of celastrol and its derivatives,making it crucial to develop novel sources of these drugs through synthetic biology.The key step in the biosynthesis of celastrol is considered to be the cyclization of 2,3-oxidosqualene into friedelin under the catalysis of 2,3-oxidosqualene cyclases.Friedelin was speculated to be oxidized into celastrol by cytochrome P450 oxidases(CYP450s).Here,we reported a cytochrome P450 ThCYP712K1 from Tripterygium hypoglaucum(Levl.)Hutch that catalyzed the oxidation of friedelin into polpuonic acid when heterologously expressed in yeast.Through substrate supplementation and in vitro enzyme analysis,ThCYP712K1 was further proven to catalyze the oxidation of friedelin at the C-29 position to produce polpunonic acid,which is considered a vital step in the biosynthesis of celastrol,and will lay a foundation for further analysis of its biosynthetic pathway.

关键词： Tripterygium hypoglaucum Cytochrome P450 Polpunonic acid Celastrol Biosynthesis

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Safety of Thread Embedding Acupuncture Therapy:A Systematic Review

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Chinese Journal of Integrative Medicine 2021年第12期27卷 947-955页

作者： HUANG jia-jia LIANG Jun-quan XU Xiao-kang XU yun-xiang chen Gui-zhen Clinical Medical School of Acupuncture Moxibustion and RehabilitationGuangzhou University of Chinese MedicineGuangzhou(510405)China Shenzhen Bao'an Traditional Chinese Medicine Hospital The Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou University of Chinese MedicineShenzhenGuangdong Province(518101)China

Objective To evaluate the safety of thread embedding acupuncture therapy(TEAT)and discuss the prevention and treatment of some adverse events(AEs).Methods Review of databases,including China National Knowledge Infrastructure(CNKI),CBMdisc,Wanfang,VIP databases and English literature published in PubMed,MEDLINE,EMBASE and Web of Science,were searched from their inception to January 2020,randomized controlled trials(RCTs)and case reports in which AEs with TEAT were included.Cochrane Collaboration’s tool and RevMan V.5.3.3 software were used to evaluate the quality of the studies.Results A total of 61 studies(45 RCTs and 16 case reports)with 620 cases of AEs were included in this review.These studies were published in two countries:China and South Korea.Twenty eight kinds of AEs were summarized.The most common AEs were induration,bleeding and ecchymosis,redness and swelling,fever,and pain.They were accounted for 75.35%(425/564)in the review,and most of them were mild.The rarest AEs were epilepsy,irregular menstruation,skin ulcer,thread malabsorption,and fat liquefaction,with 1 case each.But not all of them had clear causal relationship with TEAT.Most of the AEs were local reactions[with incidence of 9.83%(480/4,882)]and systemic reactions accounted for only 1.27%(62/4,882).Although the included studies showed that AEs were very commonly encountered(11.09%),only 5 cases of severe AEs reported from 2013 to 2017(0.1%)by using catgut thread,which are rarely seen nowdays with the wide use of new absorbable surgical suture.All of the severe AEs were recovered after symptomatic treatment with no sequelae.Conclusions The evidence showed that TEAT is a relatively safe and convenient therapy especially since application of new absorbable surgical suture.Improving practitioner skills,regulating operations,and paying attention to the patients’conditions may reduce the incidence of AEs and improve safety of TEAT.

关键词： thread embedding acupuncture systematic review safety adverse events Chinese Medicine

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Neurophysiological predictors of aphasia recovery in patients with large left-hemispheric infarction: a mismatch negativity study

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Chinese Medical Journal 2019年第19期132卷 2300-2307页

作者： Qing-Xia jia Ying-Ying Su Gang Liu Zhong-yun chen Department of Neurology Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Department of Neurology Xuanwu HospitalCapital Medical UniversityBeijing 100053China

Background:Although the rehabilitation of aphasia has been extensively studied,the prediction of language outcome still has not received sufficient attention.The aim of this study was to predict the language outcome using mismatch negativity(MMN)in patients with large left-hemispheric infarction.Methods:MMN was elicited by an oddball paradigm in which a standard tone(1000 Hz)and deviant tone(1500 Hz)were presented at 90%and 10%of the number of tones,respectively.The mean amplitudes and laterality indexes(LIs)of MMN were measured over the prefrontal,frontal,central,parietal,temporal,and perisylvian electrodes and both hemispheres during the first 7 days(session 1)and 10 to 20 days(session 2)post-onset.Mixed three-way analysis of variance(ANOVA)was used to investigate differences in these factors between two aphasia groups(the good recovery group and poor recovery group).The predictive value of the most significant LI was also compared with the score of National Institutes of Health Stroke Scale score and low-density volume on computed tomography.Results:A total of 18 patients were enrolled in this study.Mixed three-way ANOVA showed no interaction effect of session×region of interest(ROI)×group(F[3.59,57.38]=1.301,P=0.282)and no interaction effect of ROI×group(F[1.81,29.01]=0.71,P=0.487)and session×group(F[1.00,16.00]=0.084,P=0.776)for MMN amplitude.No interaction effect of session×ROI×group(F[1.79,28.58]=0.62,P=0.530),but an interaction effect of session×group(F[1.00,16.00]=5.21,P=0.036)was found for LIs.In the poor recovery group,the LIs of MMN over all the ROIs,except the parietal area,became more negative at session 2 than those at session 1(P-0.36 over the perisylvian area sugge

关键词： Mismatch negativity Stroke Laterality index Aphasia

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Sparing lung tissue with virtual block method in VMAT planning for locally advanced non-small cell lung cancer

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Nuclear Science and Techniques 2022年第4期33卷 136-150页

作者： Jia-Yun Chen Da-Quan Wang Xiao-Dong Zhang Qi Fu Xue-Na Yan Kuo Men jian-Rong Dai Nan Bi Department of Radiation Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Department of Radiation Oncology State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineSun Yat-Sen University Cancer CenterGuangzhou 510060China Department of Radiation Physics The University of Texas MD Anderson Cancer CenterHoustonTXUSA

This study aimed to exploit a new virtual block method to spare normal lung tissue in VMAT planning for patients with locally advanced non-small cell lung cancer(LA-NSCLC).The previous method was used to manually restrict the angle of the beam passing through,which ignored the location and shape of large targets that varied between different slices and did not block the beamlets precisely.Unlike the previous method,this new virtual block method was used to block the beamlets when necessary by closing the multi-leaf collimator(MLC)at prerequisite angles.The algorithm for closing the MLC depended on the thickness of the beamlets passing through the lungs and avoided only the entrance radiation beamlet.Moreover,this block can be automatically contoured.A retrospective study was performed to compare the VMAT plans with and without the virtual block method for 17 LANSCLC patients,named the block plan(B-plan)/non-block plan(N-plan).All cases were selected in this study because of the large tumor size and unmet dose constraints of the lungs.In addition to the maximum dose constraint for the virtual block,B-plans adopted identical optimization parameters to N-plans for each patient.These two types of plans were compared in terms of dosimetric indices and plan scores.The results were statistically analyzed using the Wilcoxon nonparametric signed-rank test.B-plans have advantages in the following dosimetric metrics that have statistical significance(p<0.05):(1)lower V_(5)/V_(10)/D_(mean)/normal tissue complication probability(NTCP)of total lungs;(2)reductions in V_(5)/V_(10)for the contralateral lung;(3)decrease in Dmean/V_(40)of the heart;(4)decrease in esophagus V_(40);(5)reductions in Dmean,V_(5)/V_(10) of normal tissue.B-plans(82.51±7.07)achieved higher-quality scores than N-plans(80.74±7.22).The new virtual block spared the lungs as well as other normal structures in VMAT planning for LA-NSCLC.Thus,the block method may decrease the risk of radiation-related toxicity in patients.

关键词： Virtual block VMAT Normal tissue sparing Lung cancer

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A non-invasive diagnostic method of cavity detuning based on a convolutional neural network

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Nuclear Science and Techniques 2022年第7期33卷 25-35页

作者： Liu-Yuan Zhou Hao Zha jia-Ru Shi jia-Qi Qiu Chuan-Jing Wang yun-Sheng Han Huai-Bi chen Department of Engineering Physics Tsinghua UniversityBeijing100084China Key Laboratory of Particle and Radiation Imaging Tsinghua UniversityBeijing100084China

As modern accelerator technologies advance toward more compact sizes,conventional invasive diagnostic methods of cavity detuning introduce negligible interference in measurements and run the risk of harming structural surfaces.To overcome these difficulties,this study developed a non-invasive diagnostic method using knowledge of scattering parameters with a convolutional neural network and the interior point method.Meticulous construction and training of the neural network led to remarkable results on three typical acceleration structures:a 13-cell S-band standing-wave linac,a 12-cell X-band traveling-wave linac,and a 3-cell X-band RF gun.The trained networks significantly reduced the burden of the tuning process,freed researchers from tedious tuning tasks,and provided a new perspective for the tuning of side-coupling,semi-enclosed,and total-enclosed structures.

关键词： Cavity detuning Convolutional neural network Equivalent circuit

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A modified three-incision approach to treating three-column Lisfranc injuries

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Chinese Journal of Traumatology 2022年第6期25卷 362-366页

作者： Ting-Hu Zhao Han-Xin chen Bin jia yun-Bo Bai Jike Lu Wei Ren Department of Foot and Ankle Shen Zhen Ping Le Orthopaedic HospitalShenzhen518118Guangdong ProvinceChina Department of Orthopaedic Trauma Shen Zhen Ping Le Orthopaedic HospitalShenzhen518118Guangdong ProvinceChina Department of Orthopedic Surgery United Family HospitalBeijing100015China

Purpose:The most popular surgical approach to manage Lisfranc fracture-dislocations is the double-incision approach,which frequently causes a variety of complications,such as skin necrosis,rotational malreduction of the first tarsometatarsal joint(TMTJ)and lateral column dorsoplantar malreduction of the TMTJ.We introduce a three-incision approach to treat Lisfranc fracture-dislocations with only minor postoperative complications and good foot function.Methods:We prospectively selected 30 previously healthy patients,ranging from 18 to 60 years of age,but only 23 patients completed the follow-up and thus were finally included,with an average age of 38.1±12.9 years.All patients have sustained Lisfranc fracture-dislocations involving all three-column;13.0%(3/23)were Myerson classification type A(medial),47.8%(11/23)were type A(lateral),and 39.1%(9/23)were type C2.All patients were treated via a three-incision approach:a long incision made along the lateral border of the second ray was used as a working incision to visualize and reduce the first three TMTJs,as well as to apply internal fixation instrumentation;a 2 cm medial incision was made at the medial side of the first TMTJ as an inspecting incision,ensuring good reduction of the first TMTJ in medial and plantar view;another 1 cm inspecting incision was made at the dorsal side of the fourth/fifth TMTJ to prevent sagittal subluxation of the lateral column.Mean±SD was used for quantitative data such as operation time,follow-up time and foot function scores.Postoperative complications were documented,and foot function was evaluated using the American orthopaedic foot&ankle society score,foot function index and Maryland foot score at follow-up.The foot function of the injured foot and contralateral foot of the same patient was at the end of follow-up,and independent samplet-test was used for statistical analysis.Results:The median operation time was 117.9±14.6 min(range 93-142 min).All complications occurred within three months after the operation,and included delayed

关键词： Surgical approach Three-incision approach Complication Three-column Lisfranc fracture-dislocation Foot function

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Celastrol mitigates inflammation in sepsis by inhibiting the PKM2-dependent Warburg effect

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Military Medical Research 2023年第1期10卷 17-31页

作者： Piao Luo Qian Zhang Tian-Yu Zhong Jia-Yun Chen Jun-Zhe Zhang Ya Tian Liu-Hai Zheng Fan Yang Ling-yun Dai Chang Zou Zhi-Jie Li Jing-Hua Liu Ji-Gang Wang Artemisinin Research Center and Institute of Chinese Materia MedicaChinese Academy of Chinese Medical SciencesBeijing 100700China Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Laboratory Medicine the First Affiliated Hospital of Gannan Medical UniversityGanzhou 341000JiangxiChina Department of Geriatric Medicine Shenzhen People’s Hospitalthe Second Clinical Medical CollegeJinan University and the First Affiliated HospitalSouthern University of Science and TechnologyShenzhen 518020GuangdongChina Guangdong Provincial Key Laboratory of Proteomics School of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China Center for Reproductive Medicine Dongguan Maternal and Child Health Care HospitalSouthern Medical UniversityDongguan 523125GuangdongChina Central People’s Hospital of Zhanjiang Zhanjiang 524037GuangdongChina

Background: Sepsis involves life-threatening organ dysfunction and is caused by a dysregulated host response to infection. No specific therapies against sepsis have been reported. Celastrol(Cel) is a natural anti-inflammatory compound that shows potential against systemic inflammatory diseases. This study aimed to investigate the pharmacological activity and molecular mechanism of Cel in models of endotoxemia and sepsis.Methods: We evaluated the anti-inflammatory efficacy of Cel against endotoxemia and sepsis in mice and macrophage cultures treated with lipopolysaccharide(LPS). We screened for potential protein targets of Cel using activity-based protein profiling(ABPP). Potential targets were validated using biophysical methods such as cellular thermal shift assays(CETSA) and surface plasmon resonance(SPR). Residues involved in Cel binding to target proteins were identified through point mutagenesis, and the functional effects of such binding were explored through gene knockdown.Results: Cel protected mice from lethal endotoxemia and improved their survival with sepsis, and it significantly decreased the levels of pro-inflammatory cytokines in mice and macrophages treated with LPS(P <0.05). Cel bound to Cys424 of pyruvate kinase M2(PKM2), inhibiting the enzyme and thereby suppressing aerobic glycolysis(Warburg effect). Cel also bound to Cys106 in high mobility group box 1(HMGB1) protein, reducing the secretion of inflammatory cytokine interleukin(IL)-1β. Cel bound to the Cys residues in lactate dehydrogenase A(LDHA).Conclusions: Cel inhibits inflammation and the Warburg effect in sepsis via targeting PKM2 and HMGB1 protein.

关键词： Celastrol Sepsis Pyruvate kinase M2 High mobility group box 1 Aerobic glycolysis

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