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Science China Chemistry 2024年第3期67卷 953-962页

作者： Yuan-Qing Gu Hong-Xin Long Dan-Dan Zhang Mei-Feng Ruan Guo-Kai Liu school of pharmacy Shenzhen University Medical SchoolShenzhen UniversityShenzhen 518055China

Development of practical and versatile electrophilic difluoromethylating reagent is still a grand challenge so far due to its inherent instability or low ***,we report the design and synthesis of difluoromethyl phenoxathiinium tetrafluoroborate(PT-CF_(2)H^(+)BF_(4)^(-)) as a novel difluoromethylating reagent,which proves to be a bench-stable,general,powerful and versatile reagent with divergent·CF_(2)H,CF_(2)H^(+),and:CF_(2) *** use of this reagent,we demonstrated a vast array of difluoromethyl radical transfer reactions via diverse pathways involving photocatalyst-free visible-light induction,visible-light photoredox catalysis and visible-light mediation single electron transfer of EDA ***,the green and highly effective CF_(2)H^(+) and:CF_(2) transfer reactions were also readily accomplished.

关键词： difluoromethyl phenoxathiinium salt versatile difluoromethylating reagent difluoromethyl radical difluoromthyl cation difluorocarbene

Divergent defluorocarboxylation of α-CF_(3) alkenes with formate via photocatalyzed selective mono-or triple C-F bond cleavage

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Science China Chemistry 2024年第1期67卷 368-373页

作者： Xing-Yu Wang Pei Xu Wen-Wen Liu Hao-Qiang Jiang Song-Lei Zhu Dong Guo Xu Zhu Jiangsu Key Laboratory of New Drug Research and Clinical pharmacy School of PharmacyXuzhou Medical UniversityXuzhou 22100China

Unprecedented divergent synthesis of gem-difluorovinylacetic acid and glutaric acid derivatives fromα-CF_(3)alkenes with formate as the carbonyl source was *** reaction can undergo selective mono-or triple C-F bond cleavage by simply switching the photocatalyst and hydrogen atom transfer(HAT)catalyst under visible-light-induced conditions at room *** acts as both the C1 source and the reductant through the generation of CO_(2)^(·-)species,which underwent Giese radical addition to electron-deficient alkenes to trigger the consecutive C-F bond cleavage and carboxylation process.

关键词： C-F bond activation defluorocarboxylation carbon dioxide radical anion visible light

Cornus officinalis with high pressure wine steaming enhanced anti-hepatic fibrosis: Possible through SIRT3-AMPK axis

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Journal of Pharmaceutical Analysis 2024年第5期14卷 758-771页

作者： Xin Han Yan Ning Xinyue Dou Yiwen Wang Qiyuan Shan Kao Shi Zeping Wang Chuan Ding Min Hao Kuilong Wang Mengyun Peng Haodan Kuang Qiao Yang Xianan Sang Gang Cao school of pharmacy Zhejiang Chinese Medical UniversityHangzhou311400China

Cornus officinalis,a medicinal and edible plant known for its liver-nourishing properties,has shown promise in inhibiting the activation of hepatic stellate cells(HSCs),crucial indicators of hepatic fibrosis,especially when processed by high pressure wine steaming(HPWS).Herein,this study aims to investigate the regulatory effects of cornus officinalis,both in its raw and HPWS forms,on inflammation and apoptosis in liver fibrosis and their underlying *** vivo liver fibrosis models were established by subcutaneous injection of CCl4,while in vitro HSCs were exposed to transforming growth factor-b(TGF-b).These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated histopathological injury,reduced the release of proinflammatory factors,and decreased collagen deposition in CCl4-induced rats compared to its raw *** ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer(UHPLC-QTOF-MS)combined with network analysis,we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS,primarily centered on the adenosine phosphate(AMP)-activated protein kinase(AMPK)*** note,cornus officinalis activated AMPK and sirtuin 3(SIRT3),promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3,caspase6 and *** interfering RNA(siRNA)experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through *** conclusion,cornus officinalis exhibited the ability to reduce inflammation and apoptosis,with the SIRT3-AMPK signaling pathway identified as a potential mechanism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.

关键词： Liver fibrosis SIRT3 Cornus officinalis AMPK Caspase6

Review on analytical technologies and applications in metabolomics

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BIOCELL 2024年第1期48卷 65-78页

作者： XIN MENG YAN LIU SHUJUN XU LIANRONG YANG RUI YIN school of pharmacy Heilongjiang University of Chinese MedicineHarbinChina

Over the past decade,the swift advancement of metabolomics can be credited to significant progress in technologies such as mass spectrometry,nuclear magnetic resonance,and multivariate ***,metabolomics garners widespread application across diverse fields including drug research and development,early disease detection,toxicology,food and nutrition science,biology,prescription,and chinmedomics,among *** serves as an effective characterization technique,offering insights into physiological process alterations in *** changes may result from various exogenous factors like environmental conditions,stress,medications,as well as endogenous elements including genetic and protein-based *** potential scientific outcomes gleaned from these insights have catalyzed the formulation of innovative methods,poised to further broaden the scope of this ***,metabolomics has evolved into a valuable and widely accepted instrument in the life ***,comprehensive reviews focusing on the sample preparation and analytical methodologies employed in metabolomics within the life sciences are surprisingly *** review aims to fill that gap,providing an overview of current trends and recent advancements in *** emphasis is placed on sample preparation,sophisticated analytical techniques,and their applications in life science research.

关键词： Metabolomics Sample preparation Analytical methods Application of metabolomics

LncRNAs unraveling their sponge role in glioblastoma and potential therapeutic applications

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BIOCELL 2024年第3期48卷 387-401页

作者： CAIJUAN LIU XINGHAO LI YUXUAN WU JINHUI YANG MENGHAN WANG YUNQI MA school of pharmacy Binzhou Medical UniversityYantai264003China

Glioblastoma multiforme(GBM),the most common and aggressive primary brain tumor in adults,is the most malignant and still has no ***,the novel role of long non-coding RNAs(lncRNAs)in the pathogenesis of glioblastoma is attracting extensive *** are transcribed RNA molecules over 200 nucleotides long that do not encode *** small non-coding RNAs,such as microRNAs(miRNAs),lncRNAs have more complex secondary and tertiary structures that enable them to interact with DNA,RNA,and proteins and perform multiple regulatory *** act as molecular sponges,absorbing and sequestering other biomolecules,particularly miRNAs,thereby preventing these molecules from performing their normal *** inﬂuence glioblastoma through gene expression regulation,molecular sponge capacity,epigenetic modulation,and signaling pathway *** glioblastoma,a large number of lncRNAs have been found to be abnormally expressed,affecting tumor growth,invasion and resistance to *** to its regulatory role and disease-speciﬁc expression patterns,lncRNA has become a potential biomarker for glioblastoma and a promising new therapeutic *** paper discusses the spongy role of lncRNAs in glioblastoma and its potential therapeutic applications,which will lay a foundation for our understanding of glioblastoma biology and the development of new diagnostic and therapeutic strategies in the future.

关键词： LncRNA miRNA Biomarker Molecular sponges Tumor microenvironment

Granting strength to aerogel fibers through encapsulation

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Science China Materials 2024年第4期67卷 1365-1366页

作者： Wenhui Xu Department of Basic Chemistry School of PharmacyJiangxi University of Chinese MedicineNanchang 330004China

Aerogel fibers, distinguished by their lightweight nature, pronounced porosity, large surface area, and superior thermal insulation properties, have diversified applications in thermal management, energy devices, and environmental remediation[1]. However, compared with monolithic ones, these fibershaped aerogels exhibit limited mechanical strength and resilience due to their one-dimensional small size.

关键词： strength fibers thermal

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Icariin attenuates vascular endothelial dysfunction by inhibiting inflammation through GPER/Sirt1/HMGB1 signaling pathway in type 1 diabetic rats

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Chinese Journal of Natural Medicines 2024年第4期22卷 293-306页

作者： YAO Wenhui TAO Rongpin WANG Kai DING Xuansheng school of Basic Medicine and Clinical pharmacy China Pharmaceutical UniversityNanjing211198China

Icariin, a flavonoid glycoside, is extracted from Epimedium. This study aimed to investigate the vascular protective effects of icariin in type 1 diabetic rats by inhibiting high-mobility group box 1 (HMGB1)-related inflammation and exploring its potential mechanisms. The impact of icariin on vascular dysfunction was assessed in streptozotocin (STZ)-induced diabetic rats through vascular reactivity studies. Western blotting and immunofluorescence assays were performed to measure the expressions of target proteins. The release of HMGB1 and pro-inflammation cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The results revealed that icariin administration enhanced acetylcholine-induced vasodilation in the aortas of diabetic rats. It also notably reduced the release of pro-inflammatory cytokines, including interleukin-8 (IL-8), IL-6, IL-1β, and tumor necrosis factor-alpha (TNF-α) in diabetic rats and high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs). The results also unveiled that the pro-inflammatory cytokines in the culture medium of HUVECs could be increased by rHMGB1. The increased release of HMGB1 and upregulated expressions of HMGB1-related inflammatory factors, including advanced glycation end products (RAGE), Toll-like receptor 4 (TLR4), and phosphorylated p65 (p-p65) in diabetic rats and HG-induced HUVECs, were remarkably suppressed by icariin. Notably, HMGB1 translocation from the nucleus to the cytoplasm in HUVECs under HG was inhibited by icariin. Meanwhile, icariin could activate G protein-coupled estrogen receptor (GPER) and sirt1. To explore the role of GPER and Sirt1 in the inhibitory effect of icariin on HMGB1 release and HMGB-induced inflammation, GPER inhibitor and Sirt1 inhibitor were used in this study. These inhibitors diminished the effects of icariin on HMGB1 release and HMGB1-induced inflammation. Specifically, the GPER inhibitor also negated the activation of Sirt1 by icariin. These findings suggest t

关键词： Icariin Diabetes Inflammation Vascular endothelial dysfunction GPER HMGB1

Pyrimethamine upregulates BNIP3 to interfere SNARE-mediated autophagosome-lysosomal fusion in hepatocellular carcinoma

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Journal of Pharmaceutical Analysis 2024年第2期14卷 211-224页

作者： Jingjing Wang Qi Su Kun Chen Qing Wu Jiayan Ren Wenjuan Tang Yu Hu Zeren Zhu Cheng Cheng Kaihui Tu Huaizhen He Yanmin Zhang school of pharmacy Health Science CenterXi'an Jiaotong UniversityXi'an710061China

Hepatocellular carcinoma (HCC) is one of the most common tumor types and remains a major clinical challenge. Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC. However, few mitophagy inhibitors have been approved for clinical use in humans. Pyrimethamine (Pyr) is used to treat infections caused by protozoan parasites. Recent studies have reported that Pyr may be beneficial in the treatment of various tumors. However, its mechanism of action is still not clearly defined. Here, we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis. Mechanistically, Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells. In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29 (SNAP29)-vesicle-associated membrane protein 8 (VAMP8) interaction. Moreover, Pyr acted synergistically with sorafenib (Sora) to induce apoptosis and inhibit HCC proliferation in vitro and in vivo. Pyr enhances the sensitivity of HCC cells to Sora, a common chemotherapeutic, by inhibiting mitophagy. Thus, these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor. Notably, Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

关键词： Pyrimethamine BNIP3 SNARE Autophagosome-lysosome fusion Hepatocellular carcinoma Sorafenib

Targeted anti-cancer therapy: Co-delivery of VEGF siRNA and Phenethyl isothiocyanate (PEITC) via cRGD-modified lipid nanoparticles for enhanced anti-angiogenic efficacy

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 170-187页

作者： Bao Li Haoran Niu Xiaoyun Zhao Xiaoyu Huang Yu Ding Ke Dang Tianzhi Yang Yongfeng Chen Jizhuang Ma Xiaohong Liu Keda Zhang Huichao Xie Pingtian Ding school of pharmacy Shenyang Pharmaceutical UniversityShenyang 110016China school of Life Science and Biopharmaceutics Shenyang Pharmaceutical University Shenyang 110016 China Department of Basic Pharmaceutical Sciences school of pharmacy Husson University Bangor ME 04401USA College of pharmacy Shenzhen Technology UniversityShenzhen 518118China

Anti-tumor angiogenesis therapy, targeting the suppression of blood vessel growth in tumors, presents a potent approach in the battle against cancer. Traditional therapies have primarily concentrated on single-target techniques, with a specific emphasis on targeting the vascular endothelial growth factor, but have not reached ideal therapeutic efficacy. In response to this issue, our study introduced a novel nanoparticle system known as CS-siRNA/PEITC&L-cRGD NPs. These chitosan-based nanoparticles have been recognized for their excellent biocompatibility and ability to deliver genes. To enhance their targeted delivery capability, they were combined with a cyclic RGD peptide (cRGD). Targeted co-delivery of gene and chemotherapeutic agents was achieved through the use of a negatively charged lipid shell and cRGD, which possesses high affinity for integrin αvβ3 overexpressed in tumor cells and neovasculature. In this multifaceted approach, co-delivery of VEGF siRNA and phenethyl isothiocyanate (PEITC) was employed to target both tumor vascular endothelial cells and tumor cells simultaneously. The co-delivery of VEGF siRNA and PEITC could achieve precise silencing of VEGF, inhibit the accumulation of HIF-1α under hypoxic conditions, and induce apoptosis in tumor cells. In summary, we have successfully developed a nanoparticle delivery platform that utilizes a dual mechanism of action of anti-tumor angiogenesis and pro-tumor apoptosis, which provides a robust and potent strategy for the delivery of anti-cancer therapeutics.

关键词： Anti-angiogenesis Tumor apoptosis Nanoparticles VEGF siRNA Hypoxia inducible factor(HIF)-1 protein Phenethyl isothi ocyanate(PEITC)

Advanced nano drug delivery systems for neuroprotection against ischemic stroke

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Chinese Chemical Letters 2024年第2期35卷 151-162页

作者： Chenchen Xie Jun Liao Ning Zhang Yuhan Sun Yi Li Liyan Xiong Yingnan Zhang Xiaoyan Liu Wei Su Heming Chen Ping Zeng Xiaoqing Zhang Ying Lu Tingfang Wang Chuan Zhang Shanghai Engineering Research Center of Organ Repair School of MedicineShanghai UniversityShanghai 200444China Department of Pharmaceutical Science School of PharmacyNaval Medical UniversityShanghai 200433China Department of pharmacy the International Peace Maternity and Child Health HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200030China school of pharmacy Shanghai Jiao Tong UniversityShanghai 200040China

Ischemic stroke(IS)represents a significant threat to brain health due to its elevated mortality and disability *** efficacy of small-molecule neuroprotective agents has been impeded by challenges associated with traversing the blood-brain barrier(BBB)and limited ***,advanced nano drug delivery systems hold promise for overcoming these obstacles by facilitating efficient transportation across the BBB and maintaining optimal drug *** review aims to explore advanced neuroprotective nano drug delivery systems as a means of effectively administering neuroprotective agents to the brain using pharmaceutical approaches in the treatment of *** examining these systems,researchers and clinicians can gain valuable insights and innovative concepts,illuminating the potential of advanced neuroprotective nano drug delivery *** these advancements can drive the progress of pioneering and efficacious therapeutic interventions for IS.

关键词： Target Blood-brain barrier Ischemic stroke Nano drug delivery Neuroprotection