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B-cell lymphoma-2 phosphorylation at Ser70 site-related autophagy mediates puerarin-inhibited the apoptosis of MC3T3-E1 cells during osteoblastogenesis

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Journal of Traditional Chinese Medicine 2024年第1期44卷 27-34页

作者： LI Xi LIN Xiangquan CHEN Dongdong LIU Hui the Third Clinical Medical College Fujian Medical University Department of Orthopedics Fuzhou Second HospitalFuzhou 350007China

OBJECTIVE:To explore the relationship between autophagy and apoptosis regulated by puerarin during ***:In this study,the effects of puerarin on the autophagic activity and apoptosis level of osteoblast precursors(MC3T3-E1 cells)was ***,the roles of puerarin on B-cell lymphoma-2(Bcl-2)phosphorylation at different sites in osteoblast precursors were *** effect of puerarin on the interaction between Bcl-2 and autophagy regulatory molecule or pro-apoptotic molecule was also investigated using Co-immunoprecipitation *** addition,the effect of puerarin on mitochondrial membrane potential of osteoblast precursors was also identified by mitochondrial membrane potential fluorescence probe ***:Our results showed that puerarin can promote the autophagic activity and apoptosis level of *** addition,puerarin promoted Bcl-2phosphorylation at Ser70 site,and the dissociation of Bcl-2-Beclin1 ***,puerarin could enhance the binding of Bcl-2-Bcl-2-Associated X(Bax)complex in MC3T3-E1 ***,puerarin increased the mitochondrial membrane potential of MC3T3-E1 ***:Therefore,puerarin promotes Beclin1into autophagy flux through Bcl-2 phosphorylation at Ser70,thereby enhancing autophagy of osteoblast precursors,which mediates its anti-apoptotic role during ***,the dissociation of Bcl-2-Beclin1 complex is conducive to the binding of Bcl-2-Bax complex,which resists the apoptosis of osteoblast precursors via the increased mitochondrial membrane potential.

关键词： puerarin osteoblasts autophagy apoptosis lymphoma B-cell

WNT7A promotes tumorigenesis of head and neck squamous cell carcinoma via activating FZD7/JAK1/STAT3 signaling

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International Journal of Oral Science 2024年第1期16卷 85-96页

作者： Qingling Huang Yi Xiao Ting Lan Youguang Lu Li Huang Dali Zheng Department of Biochemistry and Molecular Biology School of Basic Medical SciencesFujian Medical UniversityFuzhouChina Fujian Key Laboratory of Oral Diseases School and Hospital of StomatologyFujian Medical UniversityFuzhouChina Department of Preventive Dentistry School and Hospital of StomatologyFujian Medical UniversityFuzhouChina Department of Dentistry The First Affiliated Hospital of Fujian Medical UniversityFuzhouChina

Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor *** findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.

关键词： WNT squamous tumorigenesis

Small extracellular vesicles from hypoxia-preconditioned bone marrow mesenchymal stem cells attenuate spinal cord injury via miR-146a-5p-mediated regulation of macrophage polarization

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Neural Regeneration Research 2024年第10期19卷 2259-2269页

作者： Zeyan Liang Zhelun Yang Haishu Xie Jian Rao Xiongjie Xu Yike Lin Chunhua Wang Chunmei Chen Department of Neurosurgery Fujian Medical University Union HospitalFuzhouFujian ProvinceChina Fujian Neurosurgical Institute FuzhouFujian ProvinceChina

Spinal cord injury is a disabling condition with limited treatment *** studies have provided evidence suggesting that small extracellular vesicles(SEVs)secreted by bone marrow mesenchymal stem cells(MSCs)help mediate the beneficial effects conferred by MSC transplantation following spinal cord ***,hypoxia-preconditioned bone marrow mesenchymal stem cell-derived SEVs(HSEVs)exhibit increased therapeutic *** thus explored the role of HSEVs in macrophage immune regulation after spinal cord injury in rats and their significance in spinal cord *** or HSEVs were isolated from bone marrow MSC supernatants by density gradient *** administration to rats via tail vein injection after spinal cord injury reduced the lesion area and attenuated spinal cord *** regulate macrophage polarization towards the M2 phenotype in vivo and in *** RNA sequencing and bioinformatics analyses of SEVs and HSEVs revealed that mi R-146a-5p is a potent mediator of macrophage polarization that targets interleukin-1 receptor-associated kinase *** mi R-146a-5p expression in HSEVs partially attenuated macrophage *** data suggest that HSEVs attenuate spinal cord inflammation and injury in rats by transporting mi R-146a-5p,which alters macrophage *** study provides new insights into the application of HSEVs as a therapeutic tool for spinal cord injury.

关键词： bone marrow mesenchymal stem cells hypoxia preconditioning interleukin-1 receptor-associated kinase 1 macrophages mesenchymal stem cells small extracellular vesicles spinal cord injury

Emodin suppresses alkali burn-induced corneal inflammation and neovascularization by the vascular endothelial growth factor receptor 2 signaling pathway

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Journal of Traditional Chinese Medicine 2024年第2期44卷 268-276页

作者： ZHENG Xueying GUO Liang LAI Siyi LI Fengyue LIANG Mingli LIU Wanting MENG Chun LIU Guanghui Department of Bioengineering College of Biological Science and BiotechnologyFuzhou UniversityFuzhou 350104China Eye Institute of Integrated Chinese and Western Medicine Fujian University of Traditional Chinese MedicineFuzhou 350004China Department of Ophthalmology Affiliated People's Hospital(Fujian Provincial People's Hospital)Fujian University of Traditional Chinese MedicineFuzhou 350004China

OBJECTIVE:To investigate the effects of emodin on alkali burn-induced corneal inflammation and ***:The ability of emodin to target vascular endothelial growth factor receptor 2(VEGFR2)was predicted by molecular *** effects of emodin on the invasion,migration,and proliferation of human umbilical vein endothelial cells(HUVEC)were determined by cell counting kit-8,Transwell,and tube formation *** of apoptosis was performed by flow ***31 levels were examined by *** abundance and phosphorylation state of VEGFR2,protein kinase B(Akt),signal transducer and activator of transcription 3(STAT3),and P38 were examined by immunoblot *** alkali burn was performed on 40 *** were divided randomly into two groups,and the alkali-burned eyes were then treated with drops of either 10μM emodin or phosphate buffered saline(PBS)four times a *** microscopy was used to evaluate inflammation and corneal neovascularization(CNV)in all eyes on Days 0,7,10,and *** mice were killed humanely 14 d after the alkali burn,and their corneas were removed and preserved at-80℃ until histological study or protein ***:Molecular docking confirmed that emodin was able to target *** findings revealed that emodin decreased the invasion,migration,angiogenesis,and proliferation of HUVEC in a dose-dependent *** mice,emodin suppressed corneal inflammatory cell infiltration and inhibited the development of corneal neovascularization induced by alkali *** to those of the PBS-treated group,lower VEGFR2 expression and CD31 levels were found in the emodintreated *** dramatically decreased the expression of VEGFR2,p-VEGFR2,p-Akt,p-STAT3,and p-P38 in VEGF-treated ***:This study provides a new avenue for evaluating the molecular mechanisms underlying corneal inflammation and *** might be a promising new therapeutic option for corneal alkal

关键词： alkali burn emodin corneal inflammation corneal neovascularisation vascular endothelial growth factor receptor-2 signal transduction

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Meibomian glands segmentation in infrared images with limited annotation

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 401-407页

作者： Jia-Wen Lin Ling-Jie Lin Feng Lu Tai-Chen Lai Jing Zou Lin-Ling Guo Zhi-Ming Lin Li Li College of Computer and Data Science Fuzhou UniversityFuzhou 350108Fujian ProvinceChina Fujian Provincial Key Laboratory of Networking Computing and Intelligent Information Processing Fuzhou UniversityFuzhou 350108Fujian ProvinceChina Shengli Clinical Medical College of Fujian Medical University Fuzhou 350001Fujian ProvinceChina Department of Ophthalmology Fujian Provincial Hospital South BranchFujian Provincial HospitalFuzhou 350001Fujian ProvinceChina

●AIM:To investigate a pioneering framework for the segmentation of meibomian glands(MGs),using limited annotations to reduce the workload on ophthalmologists and enhance the efficiency of clinical diagnosis.●METHODS:Totally 203 infrared meibomian images from 138 patients with dry eye disease,accompanied by corresponding annotations,were gathered for the study.A rectified scribble-supervised gland segmentation(RSSGS)model,incorporating temporal ensemble prediction,uncertainty estimation,and a transformation equivariance constraint,was introduced to address constraints imposed by limited supervision information inherent in scribble *** viability and efficacy of the proposed model were assessed based on accuracy,intersection over union(IoU),and dice coefficient.●RESULTS:Using manual labels as the gold standard,RSSGS demonstrated outcomes with an accuracy of 93.54%,a dice coefficient of 78.02%,and an IoU of 64.18%.Notably,these performance metrics exceed the current weakly supervised state-of-the-art methods by 0.76%,2.06%,and 2.69%,***,despite achieving a substantial 80%reduction in annotation costs,it only lags behind fully annotated methods by 0.72%,1.51%,and 2.04%.●CONCLUSION:An innovative automatic segmentation model is developed for MGs in infrared eyelid images,using scribble annotation for *** model maintains an exceptionally high level of segmentation accuracy while substantially reducing training *** holds substantial utility for calculating clinical parameters,thereby greatly enhancing the diagnostic efficiency of ophthalmologists in evaluating meibomian gland dysfunction.

关键词： infrared meibomian glands images meibomian gland dysfunction meibomian glands segmentation weak supervision scribbled annotation

Total glucosides of paeony alleviates cGAS-STING-mediated diseases by blocking the STING-IRF3 interaction

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Chinese Journal of Natural Medicines 2024年第5期22卷 402-415页

作者： XIU Ye WANG Sihao ZHANG Ping LI Chengwei WU Zhixin WEN Jincai XU Yingjie LV Guiji ZHAO Xiaomei DONG Xu CHEN Yichong LI Junjie WANG Yan ZOU Liang XIAO Xiaohe BAI Zhaofang School of Pharmacy Fujian University of Traditional Chinese MedicineFuzhou 350122China Department of Hepatology The Fifth Medical Center of PLA General HospitalBeijing 100039China China Military Institute of Chinese Materia Fifth Medical Center of Chinese PLA General HospitalBeijing 100039China Department of Pharmacy Medical Supplies Center of PLA General HospitalBeijing 100039China School of Food and Biological Engineering Chengdu UniversityChengdu 610106China National Key Laboratory of Kidney Diseases Chinese PLA General HospitalBeijing 100039China

In the realm of autoimmune and inflammatory diseases,the cyclic GMP-AMP synthase(cGAS)stimulator of interferon genes(STING)signaling pathway has been thoroughly investigated and *** this,the clinical approval of drugs targeting the cGAS-STING pathway has been *** Total glucosides of paeony(TGP)is highly anti-inflammatory and is commonly used in the treatment of rheumatoid arthritis(RA),emerged as a subject of our *** found that the TGP markedly reduced the activation of the cGAS-STING signaling pathway,triggered by various cGAS-STING agonists,in mouse bone marrow-derived macrophages(BMDMs)and Tohoku hospital Pediatrics-1(THP-1)*** inhibition was noted alongside the suppression of interferon regulatory factor 3(IRF3)phosphorylation and the expression of interferon-beta(IFN-β),C-X-C motif chemokine ligand 10(CXCL10),and inflammatory mediators such as tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6).The mechanism of action appeared to involve the TGP’s attenuation of the STING-IRF3 interaction,without affecting STING oligomerization,thereby inhibiting the activation of downstream signaling *** vivo,the TGP hindered the initiation of the cGAS-STING pathway by the STING agonist dimethylxanthenone-4-acetic acid(DMXAA)and exhibited promising therapeutic effects in a model of acute liver injury induced by lipopolysaccharide(LPS)and D-galactosamine(D-GalN).Our findings underscore the potential of the TGP as an effective inhibitor of the cGAS-STING pathway,offering a new treatment avenue for inflammatory and autoimmune diseases mediated by this pathway.

关键词： Total glucosides of gaeony cGAS-STING pathway Inflammation LPS/D-GalN STING inhibitor

Impact of Alcian blue and periodic acid Schiff expression on the prognosis of gastric signet ring cell carcinoma

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 687-698页

作者： Juan Lin Zhu-Feng Chen Guo-Dong Guo Xin Chen Shengli Clinical Medical College Fujian Medical UniversityFuzhou 350001Fujian ProvinceChina Department of Pathology Fujian Provincial HospitalFuzhou 350001Fujian ProvinceChina Department of Internal Medicine Fujian Provincial HospitalFuzhou 350001Fujian ProvinceChina

BACKGROUND The Alcian blue(AB)and periodic acid Schiff(PAS)stains are representative mucus markers in gastric signet ring cell carcinoma(SRCC).They are low-cost special staining methods used to detect acidic mucus and neutral mucus,***,the clinical importance of the special combined AB and PAS stain is *** To investigate AB expression,PAS expression and the AB-to-PAS(A/P)ratio in gastric SRCC patients and to assess patient *** Paraffin-embedded sections from 83 patients with gastric SRCC were stained with AB and PAS,and signet ring cell positivity was assessed ***-histochemical staining for Ki67,protein 53(P53)and human epidermal growth factor receptor 2(HER2)was performed *** cancer-specific survival(CSS)rate was estimated via Kaplan-Meier *** proportional hazards models were used for univariate and multivariate survival *** Kaplan-Meier survival analysis revealed that the 3-year CSS rate was significantly greater in the high-PAS-expression subgroup than in the low-PAS-expression subgroup(P0.5 group(P=0.042).Univariate Cox regression analysis revealed that the factors affecting prognosis included tumor diameter,lymph node metastasis,vessel carcinoma embolus,tumor stage,the A/P ratio and the expression of Ki67,P53 and the *** multivariate regression analysis confirmed that low PAS expression[hazard ratio(HR)=3.809,95%confidence interval(CI):1.563-9.283,P=0.003]and large tumor diameter(HR=2.761,95%CI:1.086-7.020,P=0.033)were independent risk factors for poor *** A/P>0.5 is potentially a risk factor for prognosis,and low PAS expression is an independent risk factor in the prognosis of gastric *** expression and the A/P ratio could help in predicting the clinical prognosis of patients with SRCC.

关键词： Alcian blue Periodic acid-Schiff Prognosis Gastric Signet ring cell carcinoma

Chinese expert consensus on the clinical application of drugcoated balloon(2^(nd) Edition)

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Journal of Geriatric Cardiology 2024年第2期21卷 135-152页

作者： The Expert Writing Committee of the Chinese Expert Consensus on Clinical Applications of Drug-Coated Balloon(2^(nd)Edition) Jun-Bo GE Yun-Dai CHEN 不详 Zhongshan hospital Fudan University Chinese PLA general hospital

Percutaneous coronary interventions have progressed through the era of plain balloon dilation, bare-metal stent insertion to drug-eluting stent treatment, which has significantly reduced the acute occlusion and restenosis rates of target vessels and improved patient prognosis, making drug-eluting stents the mainstream interventional treatment for coronary artery disease. In recent years, drug-coated balloons(DCBs) have become a new treatment strategy for coronary artery disease, and the drugs used in the coating and the coating technology have progressed in the past years. Without permanent implant, a DCB delivers antiproliferative drugs rapidly and uniformly into the vessel wall via the excipient during a single balloon dilation. Many evidence suggests that DCB angioplasty is an effective measure for dealing with in-stent restenosis and de novo lesions in small coronary *** more clinical studies are published, new evidence is emerging for the use of DCB angioplasty in a wide range of coronary diseases, and the indications are expanding internationally. Based on the latest research from China and elsewhere, the Expert Writing Committee of the Chinese Expert Consensus on Clinical Applications of Drug-Coated Balloon has updated the previous DCB consensus after evidence-based discussions and meetings in terms of adequate preparation of in-stent restenosis lesions, expansion of the indications for coronary de novo lesions, and precise guidance of DCB treatment by intravascular imaging and functional evaluation.

关键词： balloon drugs dealing

Activation of the wnt/β-catenin/CYP1B1 pathway alleviates oxidative stress and protects the blood-brain barrier under cerebral ischemia/reperfusion conditions

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Neural Regeneration Research 2024年第7期19卷 1541-1547页

作者： Xingyong Chen Nannan Yao Yanguang Mao Dongyun Xiao Yiyi Huang Xu Zhang Yinzhou Wang Department of Neurology Fujian Provincial HospitalShengli Clinical Medical College of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology Cangzhou Central HospitalCangzhouHebei ProvinceChina Fujian Academy of Medical Science FuzhouFujian ProvinceChina Key Testing Laboratory of Fujian Province FuzhouFujian ProvinceChina

Accumulating evidence suggests that oxidative stress and the Wnt/β-catenin pathway participate in stroke-induced disruption of the blood-brain ***,the potential links between them following ischemic stroke remain largely *** present study found that cerebral ischemia leads to oxidative stress and repression of the Wnt/β-catenin ***,Wnt/β-catenin pathway activation by the pharmacological inhibito r,TWS119,relieved oxidative stress,increased the levels of cytochrome P4501B1(CYP1B1)and tight junction-associated proteins(zonula occludens-1[ZO-1],occludin and claudin-5),as well as brain microvascular density in cerebral ischemia *** r,rat brain microvascular endothelial cells that underwent oxygen glucose deprivation/reoxygenation displayed intense oxidative stress,suppression of the Wnt/β-catenin pathway,aggravated cell apoptosis,downregulated CYP1B1and tight junction protein levels,and inhibited cell prolife ration and *** ofβ-catenin or knockdown ofβ-catenin and CYP1B1 genes in rat brain mic rovascular endothelial cells at least partly ameliorated or exacerbated these effects,*** addition,small interfering RNA-mediatedβ-catenin silencing decreased CYP1B1 expression,whereas CYP1B1 knoc kdown did not change the levels of glycogen synthase kinase 3β,Wnt-3a,andβ-catenin proteins in rat brain microvascular endothelial cells after oxygen glucose deprivatio n/***,the data suggest that CYP1B1 can be regulated by Wnt/β-catenin signaling,and activation of the Wnt/β-catenin/CYP1B1 pathway contributes to alleviation of oxidative stress,increased tight junction levels,and protection of the blood-brain barrier against ischemia/hypoxia-induced injury.

关键词： blood-brain barrier CYP1B1 oxidative stress oxygen glucose deprivation/reoxygenation tight junction vascular endothelial cells Wnt/β-catenin pathway β-catenin