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Post-acute ischemic stroke hyperglycemia aggravates destruction of the blood-brain barrier

Neural Regeneration Research 2024年第6期19卷 1344-1350页

作者： Tianqi Xu Jianhong Yang Yao Xu Xiaofeng Wang Xiang Gao Jie Sun Chenhui Zhou Yi Huang Department of Neurology The First Affiliated Hospital of Ningbo University Department of General Surgery The First Affiliated Hospital of Ningbo University Department of Neurosurgery The First Affiliated Hospital of Ningbo University Key Laboratory of Precision Medicine for Atherosclerotic Diseases of Zhejiang Province

Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation, which is associated with blood-brain barrier disruption. Brain microvascular endothelial cells are a major component of the blood-brain barrier. Intercellular mitochondrial transfer has emerged as a novel paradigm for repairing cells with mitochondrial dysfunction. In this study, we first investigated whether mitochondrial transfer exists between brain microvascular endothelial cells, and then investigated the effects of post-acute ischemic stroke hyperglycemia on mitochondrial transfer between brain microvascular endothelial cells. We found that healthy brain microvascular endothelial cells can transfer intact mitochondria to oxygen glucose deprivation-injured brain microvascular endothelial cells. However, post-oxygen glucose deprivation hyperglycemia hindered mitochondrial transfer and exacerbated mitochondrial dysfunction. We established an in vitro brain microvascular endothelial cell model of the blood-brain barrier. We found that post-acute ischemic stroke hyperglycemia reduced the overall energy metabolism levels of brain microvascular endothelial cells and increased permeability of the blood-brain barrier. In a clinical study, we retrospectively analyzed the relationship between post-acute ischemic stroke hyperglycemia and the severity of hemorrhagic transformation. We found that post-acute ischemic stroke hyperglycemia serves as an independent predictor of severe hemorrhagic transformation. These findings suggest that post-acute ischemic stroke hyperglycemia can aggravate disruption of the blood-brain barrier by inhibiting mitochondrial transfer.

关键词： acute ischemic stroke blood-brain barrier brain microvascular endothelial cells mitochondrial transfer stress hyperglycemia

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Predictive value of neutrophil-to-lymphocyte ratio in coronary chronic total occlusion patients

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Journal of Geriatric Cardiology 2024年第5期21卷 542-549页

作者： Qian LI Yue YU Ya-Qiong ZHOU Yi ZHAO Jin WU Yuan-Jing WU Bin DU Pei-Jian WANG Tao ZHENG Department of Cardiovascular Medicine the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina Department of Cardiology First Affiliated Hospital of Chengdu Medical CollegeChengduChina Department of Neurology the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anChina

BACKGROUND The neutrophil to lymphocyte ratio(NLR)has been reported as a novel predictor for atherosclerosis and car-diovascular *** study aimed to determine the effects of NLR on long-term clinical outcomes of chronic total occlusion(CTO)*** A total of 670 patients with CTO who met the inclusion criteria were included at the end of the follow-up *** were divided into tertiles according to their baseline NLR levels at admission:low(n=223),intermediate(n=223),and high(n=224).The incidence of major adverse cardiac events(MACEs)during the follow-up period,including all-cause death,nonfatal myocardial infarction(MI),or ischemia-driven revascularization,were compared among the three *** Major adverse cardiac events were observed in 27 patients(12.1%)in the low tertile,40(17.9%)in the intermediate tertile,and 61(27.2%)in the high NLR tertile(P<0.001).Kaplan-Meier analysis demonstrated a significantly higher incidence of MACE,ischemia-driven coronary revascularization,non-fatal MI,and mortality in patients within the high tertile than those in the low and intermediate groups(all P<0.001).Multivariable COX regression analysis showed that the high tertile of baseline NLR level showed a strong association with the risk of MACE(hazard ratio[HR]=2.21;95%confidence interval[CI]:1.21-4.03;P=0.009),ischemia-driven coronary revascularization(HR=3.19;95%CI:1.56-6.52;P=0.001),MI(HR=2.61;95%CI:1.35-5.03;P=0.043)and mortality(HR=3.78;95%CI:1.65-8.77;P=0.001).CONCLUSION Our findings suggest that NLR is an inexpensive and readily available biomarker that can independently pre-dict cardiovascular risk in patients with CTO.

关键词： patients coronary occlusion

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Sonodynamic therapy for the treatment of atherosclerosis

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Journal of Pharmaceutical Analysis 2024年第5期14卷 666-677页

作者： Yan Zhang Ying Yang Yudi Feng Xueyan Gao Liping Pei Xiaopan Li Bingxin Gao Lin Liu Chengzeng Wang Shuochen Gao The Department of Ultrasound The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China The Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China

Atherosclerosis(AS)is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease,stroke,and peripheral vascular *** the current treatments,mortality and disability still remain *** therapy(SDT),a non-invasive and localized methodology,has been developed as a promising new treatment for inhibiting atherosclerotic progression and stabilizing *** progress has been made through cell and animal assays,as well as clinical *** example,the effect of SDT on apoptosis and autophagy of cells in AS,especially macrophages,and the concept of non-lethal SDT has also been *** this review,we summarize the ultrasonic parameters and known sonosensitizers utilized in SDT for AS;we elaborate on SDT's therapeutic effects and mechanisms in terms of macrophages,T lymphocytes,neovascularization,smooth muscle cells,lipid,extracellular matrix and efferocytosis within plaques;additionally,we discuss the safety of SDT.A comprehensive summary of the confirmed effects of SDT on AS is conducted to establish a framework for future researchers.

关键词： Atherosclerosis Sonodynamic therapy Sonosensitizer Ultrasound Reactive oxygen species

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NIR-triggered on-site NO/ROS/RNS nanoreactor:Cascade-amplified photodynamic/photothermal therapy with local and systemic immune responses activation

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Opto-Electronic Advances 2024年第6期7卷 58-73页

作者： Ziqing Xu Yakun Kang Jie Zhang Jiajia Tang Hanyao Sun Yang Li Doudou He Xuan Sha Yuxia Tang Ziyi Fu Feiyun Wu Shouju Wang Laboratory of Molecular Imaging Department of RadiologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Department of Breast Surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Department of Women&Children Research Center The First Affiliated HospitalNanjing Medical UniversityNanjing 210029China

Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune *** these challenges,we present a novel near-infrared(NIR)-triggered RNS nanoreactor(PBNO-Ce6)to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer(TNBC).The designed PBNOCe6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS *** not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses,protecting mice from tumor *** in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62%decrease in regulatory T cells in comparison to the control PB-Ce6(Prussian Blue nanoparticles loaded with Chlorin e6),marking a substantial improvement over traditional PTT/*** such,the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.

关键词： photothermal therapy photodynamic therapy nitric oxide reactive nitrogen species triple-negative breast cancer immune response nanoreactor

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Conquer coronary artery perforation with magic hands

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Journal of Geriatric Cardiology 2024年第4期21卷 379-386页

作者： Yi-Lun ZOU Jian-Qiang LI Ding-Yu WANG Yong-Tai GONG Li SHENG Yue LI Department of Cardiology the First Affiliated Hospital of Harbin Medical UniversityHarbinChina

Coronary artery perforation(CAP) poses a significant challenge for interventional cardiologists. Management of CAP depends on the location and severity of the perforation. The conventional method for addressing the perforation of large vessels involves the placement of a covered stent, while the perforation of distal and collateral vessels is typically managed using coils, autologous skin, subcutaneous fat, microspheres, gelatin sponge, thrombin or other substances. However, the above techniques have certain limitations and are not applicable in all scenarios. Our team has developed a range of innovative strategies for effectively managing CAP. This article provides an insightful review of the various tips and tricks for the treatment of CAP.

关键词： coronary sponge perforation

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Diagnosis and treatment of biliary mucinous cystic neoplasms: A single-center experience

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 495-501页

作者： Jun-Jun Jia Ya-Fen Cheng Mei-Bao Feng Li Liu Ming-Qi Shuai Xiao-Dong Shen Xiao-Feng Tang Shu-Sen Zheng Division of Hepatobiliary and Pancreatic Surgery Department of Surgerythe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of International Healthcare Center the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Pathology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Library the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Background: Biliary mucinous cystic neoplasms(BMCNs) are rare hepatobiliary cystic tumors, which can be divided into noninvasive and invasive types. This study aimed to investigate the diagnosis, treatment, and prognosis of BMCNs in a large single center. Methods: We analyzed 49 patients with BMCNs confirmed by postoperative pathology at the first Afflliated hospital, Zhejiang University School of Medicine between January 2007 and December 2021. Results: Among the 49 patients, 37 were female(75.5%), and the average age was 57.04 years. Common symptoms included abdominal discomfort, jaundice and fever, while 22 patients(44.9%) had no symptoms. Serum carbohydrate antigen(CA) 19-9 and CA125 concentrations were elevated in 34.8% and 19.6% of patients, respectively. Forty-eight patients had tumors in the intrahepatic bile ducts and only one had a tumor in the extrahepatic bile duct. Forty-eight patients with noninvasive intrahepatic BMCNs were further analyzed in terms of pathological features: 34(70.8%) had low-grade intraepithelial neoplasms(LGINs), and 14(29.2%) had high-grade intraepithelial neoplasms(HGINs). The potential immunohistochemical markers of BMCNs were cytokeratin(CK) 19, CK7, estrogen receptor and progesterone receptor. Follow-up data for 37 patients with intrahepatic BMCNs were obtained. The median overall survival(OS) of BMCNs was not reached. The longest survival time was 137 *** 5-and 10-year OS rates were 100% and 85.4%, respectively. The 5-and 10-year recurrence-free survival(RFS) rates were 93.9% and 80.2%, respectively. Conclusions: BMCNs are rare cystic neoplasms that commonly occur in middle-aged females. BMCNs can only be diagnosed and classified by postoperative pathology, as there are no specific clinical presentations, serological indicators or imaging modalities for preoperative diagnosis. Complete surgical resection is necessary for BMCNs, and the postoperative prognosis is favorable.

关键词： Biliary mucinous cystic neoplasms Low-grade intraepithelial neoplasms High-grade intraepithelial neoplasms Overall survival Recurrence-free survival

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New pimarane diterpenoids with antibacterial activity from fungus Arthrinium ***03

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Chinese Journal of Natural Medicines 2024年第4期22卷 356-364页

作者： ZHAO Songfeng JING Ziwei Department of Pharmacy the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

A comprehensive chemical study of the endophytic fungus Arthrinium sp. ZS03, associated with Acorus tatarinowii Schott, yielded eleven pimarane diterpenoids (compounds 1–11), including seven novel compounds designated arthrinoids A–G (1–7). The determination of their structures and absolute configurations was achieved through extensive spectroscopic techniques, quantum chemical calculations of electronic circular dichroism (ECD), and single-crystal X-ray diffraction analysis. Furthermore, 7 demonstrated inhibitory activity against Klebsiella pneumoniae, comparable to the reference antibiotic amikacin, with a minimum inhibitory concentration (MIC) of 8 μg·mL^(−1).

关键词： Arthrinium sp.ZS03 Pimarane diterpenoids Structural elucidation Antibacterial activity

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Natural long-chain saturated fatty acids doped LNPs enabling spleen selective mRNA translation and potent cancer immunotherapy

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Nano Research 2024年第3期17卷 1804-1817页

作者： Fazhan Wang Meng Zhang Meiling Tian Jia Lou Longze Pan Xiaoke Gao Lijing Zhang Xiaohan Lou Linyu Zhu Yuqiao Sheng Ming Wang Rui Xue Wenjing Deng Shuai Shao Zhihai Qin Medical Research Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Translational Medical Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Department of Neuro-Intensive Care Unit The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Academy of Medical Sciences Zhengzhou UniversityZhengzhou 450052China

Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA *** expression of antigenic protein in lymphoid tissues/organs could improve the immunostimulatory efficacy and safety of LNPs-based mRNA *** by the metabolic behavior that long-chain saturated fatty acids tending to enter lymphoid tissue rather than the liver,we developed fatty acid-doped LNPs capable of mediating differential protein expressions in the liver and spleen when administered *** the molar ratio of saturated fatty acid located 60%–70%,the doped LNPs achieved the spleen selective mRNA *** mechanism could be attributed to the different cellular uptake behaviors of saturated fatty acids in *** with a model antigen(ovalbumin)mRNA-loaded spleen selective LNPs,we observed enhanced antigen-specific T cell immune responses,and potent immunotherapeutic and immunoprophylactic efficacy in the mouse lymphoma *** natural long-chain saturated fatty acids metabolic characteristics-inspired design of LNPs for spleen-selective mRNA vaccines delivery will provide references for designing mRNA vaccines with high efficacy and safety for tumor immunotherapy.

关键词： mRNA vaccine lipid nanoparticles spleen long-chain saturated fatty acid cancer immunotherapy

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MGMT activated by Wnt pathway promotes cisplatin tolerance through inducing slow-cycling cells and nonhomologous end joining in colorectal cancer

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Journal of Pharmaceutical Analysis 2024年第6期14卷 863-877页

作者： Haowei Zhang Qixin Li Xiaolong Guo Hong Wu Chenhao Hu Gaixia Liu Tianyu Yu Xiake Hu Quanpeng Qiu Gang Guo Junjun She Yinnan Chen Department of General Surgery The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an710061China Center for Gut Microbiome Research Med-X InstituteThe First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an710061China Department of High Talent The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an710061China

Chemotherapy resistance plays a pivotal role in the prognosis and therapeutic failure of patients with colorectal cancer(CRC).Cisplatin(DDP)-resistant cells exhibit an inherent ability to evade the toxic chemotherapeutic drug effects which are characterized by the activation of slow-cycle programs and DNA *** the elements that lead to DDP resistance,O^(6)-methylguanine(O^(6)-MG)-DNA-methyltransferase(MGMT),a DNA-repair enzyme,performs a quintessential *** this study,we clarify the significant involvement of MGMT in conferring DDP resistance in CRC,elucidating the underlying mechanism of the regulatory actions of MGMT.A notable upregulation of MGMT in DDP-resistant cancer cells was found in our study,and MGMT repression amplifies the sensitivity of these cells to DDP treatment in vitro and in ***,in cancer cells,MGMT overexpression abolishes their sensitivity to DDP ***,the interaction between MGMT and cyclin dependent kinase 1(CDK1)inducing slow-cycling cells is attainted via the promotion of ubiquitination degradation of ***,to achieve nonhomologous end joining,MGMT interacts with XRCC6 to resist chemotherapy *** transcriptome data from samples of 88 patients with CRC suggest that MGMT expression is co-related with the Wnt signaling pathway activation,and several Wnt inhibitors can repress drug-resistant *** summary,our results point out that MGMT is a potential therapeutic target and predictive marker of chemoresistance in CRC.

关键词： Colorectal cancer MGMT Chemotherapy resistance Slow-cycling cells Nonhomologous end joining Wnt pathway

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Profibrotic role of the SOX9-MMP10-ECM biosynthesis axis in the tracheal fibrosis after injury and repair

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Genes & Diseases 2024年第5期11卷 360-373页

作者： Lei Gu Anmao Li Chunyan He Rui Xiao Jiaxin Liao Li Xu Junhao Mu Xiaohui Wang Mingjin Yang Jinyue Jiang Yang Bai Xingxing Jin Meiling Xiao Xia Zhang Tairong Tan Yang Xiao Jing Lin Yishi Li Shuliang Guo Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Soochow UniversitySuzhou 215006China Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Infection Disease The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang 325000China

Fibroblast activation and extracellular matrix(ECM)deposition play an important role in the tracheal abnormal repair process and *** a transcription factor,SOX9 is involved in fibroblast activation and ECM ***,the mechanism of how SOX9 regulates fibrosis after tracheal injury remains *** investigated the role of SOX9 in TGF-b1-induced fibroblast activation and ECM deposition in rat tracheal fibroblast(RTF)***9 overexpression adenovirus(Ad-SOX9)and siRNA were transfected into RTF *** found that SOX9 expression was up-regulated in RTF cells treated with ***9 overexpression activated fibroblasts and promoted ECM *** SOX9 inhibited cell proliferation,migration,and ECM deposition,induced G2 arrest,and increased apoptosis in RTF ***-seq and chromatin immunoprecipitation sequencing(ChIP-seq)assays identified MMP10,a matrix metalloproteinase involved in ECM deposition,as a direct target of SOX9,which promotes ECM degradation by increasing MMP10 expression through the Wnt/b-catenin signaling ***,in vivo,SOX9 knockdown ameliorated granulation proliferation and tracheal fibrosis,as manifested by reduced tracheal *** conclusion,our findings indicate that SOX9 can drive fibroblast activation,cell proliferation,and apoptosis resistance in tracheal fibrosis via the Wnt/b-catenin signaling *** SOX9eMMP10 eECM biosynthesis axis plays an important role in tracheal injury and *** SOX9 and its downstream target MMP10 may represent a promising therapeutic approach for tracheal fibrosis.

关键词： Extracellular matrix deposition Fibroblast activation MMP10 SOX9 Tracheal fibrosis

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