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Discovery of antitumor diterpenoids from Casearia graveolens targeting VEGFR-2 to inhibit angiogenesis

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Chinese Journal of Natural Medicines 2024年第9期22卷 842-853页

作者： wang.Sibei LIU Yuhui liang Yue XI Yaru ZHAI Yupeng LEE Dongho XU Jing GUO Yuanqiang State Key Laboratory of Medicinal Chemical Biology College of Pharmacyand Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjin 300350China State Key Laboratory of Functions and Applications of Medicinal Plants Guizhou Medical UniversityGuiyang 550014China Department of Plant Biotechnology College of Life Sciences and BiotechnologyKorea UniversitySeoul 02841South Korea

Eight novel clerodane diterpenoids(1-8)were isolated from the twigs of Casearia *** structures were elucidated through comprehensive nuclear magnetic resonance(NMR),high-resolution electrospray ionization mass spectrometry(HRESI-MS),and electronic circular dichroism(ECD)*** addition to structural determination,surface plasmon resonance(SPR)assays were conducted to investigate molecular interactions,revealing that compound 8 exhibited high affinity for vascular endothelial growth factor receptor 2(VEGFR2),a key regulator of tumor *** in vivo experiments demonstrated that compound 8 effectively inhibited angiogenesis and displayed significant antitumor activity by suppressing tumor proliferation and metastasis in zebrafish xenograft *** findings suggest that compound 8 holds promise as an anticancer lead compound targeting VEGFR-2 to obstruct tumor angiogenesis.

关键词： Clerodane diterpenoids Casearia graveolens Surface plasmon resonance Vascular endothelial growth factor receptor 2 Antitumor activity Zebrafish

Immunomodulation of adipose-derived mesenchymal stem cells on peripheral blood mononuclear cells in colorectal cancer patients with COVID-19

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2113-2122页

作者： Jun-Feng wang.Xiao-Xia Yang Jian Zhang Yan Zheng Fu-Qing Zhang Xiao-Feng Shi Yu-liang wang Department of Colorectal Oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin 300060China Department of Neurology Tianjin First Center HospitalTianjin 300192China Prosthodontics Studio Tianjin Stomatological HospitalTianjin 300041China Department of Clinical Laboratory Medicine Tianjin Institute of UrologyThe Second Hospital of Tianjin Medical UniversityTianjin 300211China Department of Emergency Tianjin First Central HospitalTianjin 300192China

BACKGROUND Accumulating evidence has shown that adipose tissue-derived mesenchymal stem cells(ADSCs)are an effective therapeutic approach for managing coronavirus disease 2019(COVID-19);however,further elucidation is required to determine their underlying immunomodulatory effect on the mRNA expression of T helper cell-related transcription factors(TFs)and cytokine release in peripheral blood mononuclear cells(PBMCs).AIM To investigate the impact of ADSCs on the mRNA expression of TFs and cytokine release in PBMCs from colorectal cancer(CRC)patients with severe COVID-19(CRC^(+)patients).METHODS PBMCs from CRC^(+)patients(PBMCs-C+)and age-matched CRC patients(PBMCs-C)were stimulated and cultured in the presence/absence of *** mRNA levels of T-box TF TBX21(T-bet),GATA binding protein 3(GATA-3),RAR-related orphan receptor C(RORC),and forkhead box P3(FoxP3)in the PBMCs were determined by reverse transcriptase-polymerase chain *** supernatants were evaluated for levels of interferon gamma(IFN-γ),interleukin 4(IL-4),IL-17A,and transforming growth factor beta 1(TGF-β1)using an enzyme-linked immunosorbent *** Compared with PBMCs-C,PBMCs-C+exhibited higher mRNA levels of T-bet and RORC,and increased levels of IFN-γ and ***,a significant decrease in FoxP3 mRNA and TGF-β1,as well as an increase in Tbet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios were observed in PBMCs-C+.Furthermore,ADSCs significantly induced a functional regulatory T cell(Treg)subset,as evidenced by an increase in FoxP3 mRNA and TGF-β1 release *** was accompanied by a significant decrease in the mRNA levels of T-bet and RORC,release of IFN-γ and IL-17A,and T-bet/GATA-3,RORC/FoxP3,IFN-γ/IL-4,and IL-17A/TGF-β1 ratios,compared with the PBMCs-C+*** The present in vitro studies showed that ADSCs contributed to the immunosuppressive effects on PBMCs-C+,favoring Treg ***,ADSC-based cell therapy could be a beneficial approach for p

关键词： Colorectal cancer COVID-19 Adipose-derived mesenchymal stem cells T helper cell Immunomodulation

Exploring centimeter-sized crystals of bismuth-iodide perovskite toward highly sensitive X-ray detection

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Chinese Chemical Letters 2024年第6期35卷 185-188页

作者： Xin Dong Jing liang Zhijin Xu Huajie Wu Lei wang.Shihai You Junhua Luo Lina Li College of Chemistry Fuzhou UniversityFuzhou 350116China State Key Laboratory of Structure Chemistry Fujian Institute of Research on the Structure of MatterChinese Academy of SciencesFuzhou 350002China university of Chinese Academy of Sciences Beijing 100049China

Lead-halide perovskites exhibit outstanding performance in X-ray detection due to their intrinsic features such as high charge carrier mobility,large atomic number,and long carrier lifetime,but the toxicity of lead is regarded as the major factor hindering their ***,we introduce organic molecule(R)-(-)-2-methylpiperazine(R-MPz)into the bismuth-based structure to synthesize lead-free(R)-(H_(2)MPz)BiI_(5)(R-MBI).The high-quality centimeter-sized single crystals have been obtained,which show a low dark current and superior environmental ***,the single-crystal device of R-MBI exhibits a highμτproduct up to 1.88×10^(-4)cm^(2)/V and a low trap density of 1.21×10^(10)cm^(-3).Further,the detector displays excellent detection sensitivity of 263.58μC Gy_(air)^(-1)cm^(-2)and a favorable low detection limit of 4.35μGyair/s,both of which meet the requirement for medical *** findings shed light on the exploration of innovative bismuth-based hybrid perovskites for high-performance X-ray detection.

关键词： Perovskite Lead-free Bismuth-based X-ray detection Sensitivity

Duodenal-jejunal bypass improves hypothalamic oxidative stress and inflammation in diabetic rats via glucagon-like peptide 1-mediated Nrf2/HO-1 signaling

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World Journal of Diabetes 2024年第2期15卷 287-304页

作者： huai-Jie wang.Li-Bin Zhang Si-Peng Sun Qing-Tao Yan Zhi-Qin Gao Fang-Ming Fu Mei-Hua Qu Translational medical Center Weifang Second People's HospitalWeifang 261041Shandong ProvinceChina Department of Endocrinology Weifang Second People's HospitalWeifang 261041Shandong ProvinceChina Department of Pediatric Surgery Weifang People’s HospitalWeifang 261041Shandong ProvinceChina School of Bioscience and Technology Weifang Medical UniversityWeifang 261053Shandong ProvinceChina Department of Endocrinology Jinan Central Hospital Affiliated to Shandong First Medical UniversityJinan 250013Shandong ProvinceChina

BACKGROUND Type 2 diabetes mellitus(T2DM)is often accompanied by impaired glucose utilization in the brain,leading to oxidative stress,neuronal cell injury and *** studies have shown that duodenal jejunal bypass(DJB)surgery significantly improves brain glucose metabolism in T2DM rats,the role and the metabolism of DJB in improving brain oxidative stress and inflammation condition in T2DM rats remain *** To investigate the role and metabolism of DJB in improving hypothalamic oxidative stress and inflammation condition in T2DM *** A T2DM rat model was induced via a high-glucose and high-fat diet,combined with a low-dose streptozotocin injection.T2DM rats were divided into DJB operation and Sham operation *** surgical intervention was carried out on T2DM *** differential expression of hypothalamic proteins was analyzed using quantitative proteomics *** related to oxidative stress,inflammation,and neuronal injury in the hypothalamus of T2DM rats were analyzed by flow cytometry,quantitative real-time PCR,Western blotting,and *** Quantitative proteomics analysis showed significant differences in proteins related to oxidative stress,inflammation,and neuronal injury in the hypothalamus of rats with T2DM-DJB after DJB surgery,compared to the T2DM-Sham groups of *** stress-related proteins(glucagon-like peptide 1 receptor,Nrf2,and HO-1)were significantly increased(P<0.05)in the hypothalamus of rats with T2DM after DJB *** surgery significantly reduced(P<0.05)hypothalamic inflammation in T2DM rats by inhibiting the activation of NF-κB and decreasing the expression of interleukin(IL)-1βand *** surgery significantly reduced(P<0.05)the expression of factors related to neuronal injury(glial fibrillary acidic protein and Caspase-3)in the hypothalamus of T2DM rats and upregulated(P<0.05)the expression of neuroprotective factors(C-fos,Ki67,Bcl-2,and BDNF),thereby reducing hypot

关键词： Duodenal jejunal bypass surgery Type 2 diabetes mellitus Neuron apoptosis Inflammatory Oxidative stress Hypothalamic injury

Diagnosis and therapy of tacrolimus toxicity in a liver transplant recipient during COVID-19 treatment

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Hepatobiliary & Pancreatic Diseases International 2024年第3期23卷 326-330页

作者： Feng Zhu Yi-Ming wang.Ming Ni Yuan liang Jie-Hui Huang Xue-Hao wang.Feng Cheng Ling Lu Hepatobiliary Center The First Affiliated Hospital of Nanjing Medical UniversityKey Laboratory of Liver TransplantationChinese Academy of Medical SciencesNHC Key Laboratory of Liver TransplantationResearch Unit of Liver Transplantation and Transplant ImmunologyChinese Academy of Medical SciencesNanjing 210000China Department of Respiratory and Critical Care Medicine Wuxi Fifth People’s HospitalWuxi 214000China Jiangsu Key Laboratory of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing 210000China

To the Editor:SARS-CoV-2,the pathogen responsible for the pandemic of coronavirus disease 2019(COVID-19),has had profound impacts on human health,and its antagonist Paxlovid is a commonly used treatment option[1].However,treatment selection for immunosuppressed patients,such as liver recipients,remains uncertain due to potential drug interactions and the risk of immunosuppressant dosage adjustment,which can cause liver injury[2].

关键词： dosage treatment antagonist

Improving treatment plan and mental health in children with abdominal infection for broad-spectrum bacterial infections

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World Journal of Psychiatry 2024年第9期14卷 1319-1325页

作者： Gui-Bo wang.Xue-Feng Zhang Bing liang Jie Lei Jun Xue Department of Pediatric Surgery the First Affiliated Hospital of Hebei North UniversityZhangjiakou 075000Hebei ProvinceChina Department of General Surgery the First Affiliated Hospital of Hebei North UniversityZhangjiakou 075000Hebei ProvinceChina

BACKGROUND Pediatric abdominal infection is a common but serious disease that requires timely and effective *** surgical treatment,accurate diagnosis and rational application of antibiotics are the keys to improving treatment *** To investigate the effect of broad-spectrum bacterial detection on postoperative antibiotic *** A total of 100 children with abdominal infection who received surgical treatment in our hospital from September 2020 to July 2021 were *** observation group collected blood samples upon admission and sent them for broad-spectrum bacterial infection nucleic acid testing,and collected pus or exudate during the operation for bacterial culture and drug sensitivity testing;the control group only sent bacterial culture and drug sensitivity testing during the *** White blood cell count,C-reactive protein,procalcitonin,3 days after surgery,showed better postoperative index than the control group(Pmedical costs to some extent.

关键词： Pediatric abdominal infection Nucleic acid detection of broad-spectrum bacterial infection Bacterial culture Drug sensitivity testing Treatment effect Cost Mental health

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石羊河流域多情景土地利用优化及碳储量评估

环境科学 2024年第7期45卷 4164-4176页

作者：杜怀玉俞金凤张媛王家亮西北师范大学社会发展与公共管理学院兰州730300

研究碳储量与土地利用变化的响应关系及空间分布特征,预测未来土地利用类型变化所导致的碳储量变化趋势,可为流域政策制定、土地利用结构调整和“双碳”目标的实现提供一定的借鉴.基于2000年、2010年和2020年三期土地利用数据,运用InVES... 详细信息

研究碳储量与土地利用变化的响应关系及空间分布特征,预测未来土地利用类型变化所导致的碳储量变化趋势,可为流域政策制定、土地利用结构调整和“双碳”目标的实现提供一定的借鉴.基于2000年、2010年和2020年三期土地利用数据,运用InVEST模型和PLUS模型,开展石羊河流域2000~2020年间和2030年自然发展、城镇发展和生态保护这3种情景下土地利用变化及其对碳储量的影响研究.研究发现:(1)2000~2020年石羊河流域主要土地利用类型是耕地、草地和未利用地,且耕地、水域和建设用地的面积呈增加趋势,其中建设用地面积增幅最大.(2)较2020年,2030年自然发展情景下,耕地、水域和建设用地面积均有所增加,分别增加6.15%、9.56%和29.9%;在城镇发展情景下,建设用地面积增加最多;相比其他两种情景,在生态保护情景下林地和草地面积出现了增加.(3)石羊河流域2000~2020年碳储量呈平稳增加的趋势,20年间增加了0.035×10^(8) t,主要源于耕地面积的增加.(4)2030年自然发展、城镇发展和生态保护3种情景下石羊河流域的碳储量分别为5.65×10^(8)、5.64×10^(8)和5.73×10^(8) t,较2020年均有增加,其中生态保护情景下碳储量增加最多,主要是源于草地和林地面积的增加.研究结果表明建设用地的扩张是造成碳储量流失的主要原因,若采取有效的生态保护措施将有助提高流域碳储量,可以解决由于经济发展而导致的碳储量流失问题.

关键词： PLUS-InVEST模型石羊河流域土地利用碳储量多情景

Investigation of Nasal Mucosal IgA Responses in the Population Following COVID-19 Pandemic — china, September 2022–August 2023

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china CDC weekly 2024年第15期6卷 312-317,I0005页

作者： Boyang Li Lei Zhou Zhilong Chen Yanhan Wen Qian wang.Tao Huang Si Chen Wei Wu Mengxuan wang.Lina Sun Mifang liang Shiwen wang.Ling Chen Qun Li National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijingChina National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases Chinese Center for Disease Control and PreventionBeijingChina Xiamen United Institute of Respiratory Health Xiamen CityFujian ProvinceChina Guangzhou Laboratory Guangzhou CityGuangdong ProvinceChina State Key Laboratory of Respiratory Disease Guangzhou Institute of Respiratory HealthThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou CityGuangdong ProvinceChina

What is already known about this topic?Mucosal IgA plays a crucial role in host immunity against respiratory *** studies suggest that it has the potential to mitigate the transmission of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)Omicron ***,a comprehensive population-based analysis examining mucosal IgA levels following the winter 2022 wave of the coronavirus disease 2019(COVID-19)pandemic is yet to be *** is added by this report?In our study involving 3,421 participants,we documented IgA responses subsequent to SARS-CoV-2 infection.A significant proportion of individuals sustained increased levels of IgA for over six *** levels were also observed in individuals with prior infections who underwent asymptomatic reinfections,indicating an active production of IgA ***,individuals with multiple vaccinations or severe symptoms tended to display elevated IgA levels after *** are the implications for public health practice?IgA in the nasal mucosa is crucial for defense against SARS-CoV-2 *** insights can enhance our knowledge of immune responses following infection and have provided certain reference values for disease prevention and control strategies.

关键词： prevention sustained immunity

pH-Responsive polymer boosts cytosolic siRNA release for retinal neovascularization therapy

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Acta Pharmaceutica Sinica B 2024年第2期14卷 781-794页

作者： Shuai Guo Chunhui Li Changrong wang.Xiaowen Cao Xinyue Liu Xing-Jie liang Yuanyu Huang Yuhua Weng School of medical Technology Advanced Research Institute of Multidisciplinary ScienceSchool of Life ScienceKey Laboratory of Molecular Medicine and BiotherapyKey Laboratory of Medical Molecule Science and Pharmaceutics EngineeringBeijing Institute of TechnologyBeijing 100081China School of Pharmacy Shandong New Drug Loading&Release Technology and Preparation Engineering LaboratoryBinzhou Medical UniversityYantai 264003China School of Ophthalmology and Optometry School of Biomedical EngineeringThe Eye HospitalWenzhou Medical UniversityWenzhou 325027China Chinese Academy of Sciences(CAS) Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of ChinaBeijing 100190China

Small interfering RNA(siRNA)has a promising future in the treatment of ocular diseases due to its high efficiency,specificity,and low toxicity in inhibiting the expression of target genes and ***,due to the unique anatomical structure of the eye and various barriers,delivering nucleic acids to the retina remains a significant *** this study,we rationally design PACD,an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block(A),a siRNA binding block(B)and a pH-responsive block(C).PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple *** evaluating its pH-responsive activity,gene silencing efficiency in retinal cells,intraocular distribution,and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis,we demonstrate the efficiency and safety of PACD in delivering siRNA in the *** are surprised to discover that,the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency,excellent gene silencing,and inhibit retinal *** study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.

关键词： SiRNA Oculardeliverysystem Block polymer Endosomalescape Retinal neovascularization Blood-retinal barrier VEGFA Safety