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Inhibition of tryptase and chymase induced nucleated cell infiltration by proteinase inhibitors

Acta Pharmacologica Sinica 2004年第12期25卷 111-118页

作者： Shao-heng HE2,3, Han-qiu CHEN, Jian ZHENG Allergy& inflammation research Institute, Shantou University Medical College, Shantou 515031, China 2Immunopharmacology Group, University of Southampton, UK Immunopharmacology Group University of Southampton Allergy & inflammation research Institute Shantou University Medical College Shantou 515031

AIM: To investigate the ability of proteinase inhibitors to modulate nucleated cell infiltration into the peritoneum of mice induced by tryptase and chymase. METHODS: Human lung tryptase and skin chymase were purified by a similar procedure involving high salt extraction, heparinagarose affinity chromatography followedby S-200 Sephacryl gel filtration chromatography. The actions of proteinase inhibitors on tryptase and chymase induced nucleated cell accumulation were examined with a mouse peritoneum model. RESULTS: A selective chymase inhibitor Z-Ile-Glu- Pro-Phe-CO2Me (ZIGPPF) was able to inhibit approximately 90 % neutrophil, 73 % eosinophil, 87 % lymphocyte and 60 % macrophage accumulation induced by chymase at 16 h following injection. Soy bean trypsin inhibitor (SBTI), chymostatin, and α1-antitrypsin showed slightly less potency than ZIGPPF in inhibition of the actions of chymase. While all tryptase inhibitors tested were able to inhibit neutrophil, eosinophil, and macrophage accumu- lation provoked by tryptase at 16 h following injection, only leupeptin, APC366, and aprotinin were capable of inhibiting tryptase induced lymphocyte accumulation. The inhibitiors of tryptase tested were also able to inhibit tryptase induced neutrophil and eosinophil accumulation at 6 h following injection. When being injected alone, all inhibitors of chymase and tryptase at the concentrations tested by themselves had no significant effect on the accumulation of nucleated cells in the peritoneum of mice at both 6 h and 16 h. CONCLUSION: Proteinase inhibitors significantly inhibited tryptase and chymase-induced nucleated cell accumulation in vivo, and therefore they are likely to be developed as a novel class of anti-inflammatory drugs.

关键词： tryptase chymase nucleated cells proteinase inhibitor

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Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

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Neural Regeneration research 2025年第1期20卷 67-81页

作者： Yubo Wang Tingli Yuan Tianjie Lyu Ling Zhang Meng Wang Zhiying He Yongjun Wang Zixiao Li Vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Shanghai Engineering research Center of Stem Cells Translational Medicine ShanghaiChina National Center for Healthcare Quality Management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Institute for Regenerative Medicine Shanghai East HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghaiChina Chinese Institute for Brain research BeijingChina research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering research Center of Digital Healthcare for Neurological Diseases BeijingChina

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger ***,in particular,bears a high burden of stroke *** recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its *** review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and ***,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell ***,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient *** cell therapy may potentially become an important component of ischemic stroke treatment.

关键词： cell therapy immune cell inflammatory ischemic stroke stem cell

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Unveiling phosphofructokinase as the key target: an innovative strategy combining pull-down assays with optical imaging for snail-killing mechanism exploration

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Science China Chemistry 2025年

作者： Yuxun Lu Weisi Wang Le Yu Yuqiang Zhao Ying Chen Yunhai Guo Bingrong Luo Yuhua Liu Shizhu Li Liping Duan Ying Zhou Yunnan Characteristic Plant Extraction Laboratory College of Chemical Science and Technology Yunnan University College of Biological and Chemical Engineering Guangxi University of Science and Technology National Institute of Parasitic Diseases Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research)NHC Key Laboratory of Parasite and Vector Biology WHO Collaborating Centre for Tropical Diseases National Center for International Research on Tropical Diseases School of Chemistry and Environment Yunnan Minzu University Dali Institute of Schistosomiasis Control

The Pomacea canaliculata, also known as apple snail, is an invasive species in China, posing a serious threat to agricultural production and public health. To prevent its rampant infestation, we developed a highly efficient snail-killing lead compound, 1-(4-chlorophenyl)-3-(pyridin-3-yl)urea (PBQ). However, the killing mechanism of PBQ remains unclear. To elucidate this, two novel compounds, B-PBQ and J-PBQ, were developed through structural modification of PBQ and were used, through both protein pull-down assay and confocal laser scanning microscopy imaging, to identify and confirm that phosphofructokinase(PFK) in the apple snail is the primary target protein of PBQ. Further studies revealed that PBQ successfully inhibits the activity,content, and expression of PFK in apple snail, disrupting the glycolysis pathway and leading to abnormal energy *** disruptions impair the snail’s tolerance to low oxygen, resulting in its efficient eradication. These findings offer a promising direction for developing next-generation PFK-targeted snail-killing pesticides. Furthermore, the strategy of combining pull-down assays with optical imaging used in this work provides a novel approach for the exploration of mechanisms of other pesticide candidates.

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Extracellular DNA and autoimmune diseases

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Cellular & Molecular Immunology 2018年第8期15卷 746-755页

作者： Hantao Lou Matthew C Pickering Molecular Immunology Imperial College LondonLondon W120NNUK centre for Complement and inflammation research Imperial College LondonLondon W120NNUK

Extracellular DNA is secreted from various sources including apoptotic cells,NETotic neutrophils and bacterial *** DNA can stimulate innate immune responses to induce type-I IFN production after being *** process is central in antiviral responses but it also plays important role in the pathogenesis of a range of autoimmune diseases such as systemic lupus *** discuss the recent advances in the understanding of the role of extracellular DNA,released from apoptotic and NETotic cells,in autoimmunity.

关键词： DNA type I IFN autoimmunity

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Insufficient MIRO1 contributes to declined oocyte quality during reproductive aging

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Science China Life Sciences 2025年

作者： Zhen-Nan Pan Hao-Lin Zhang Kun-Huan Zhang Jia-Qian Ju Jing-Cai Liu Shao-Chen Sun College of Animal Science and Technology Nanjing Agricultural University Reproductive Medicine centre The Affiliated Yantai Yuhuangding Hospital of Qingdao University

Mitochondrial Rho-GTPase 1 (MIRO1) is an outer mitochondrial membrane protein which regulates mitochondrial transport and mitophagy in mitosis. In present study, we reported the crucial roles of MIRO1 in mammalian oocyte meiosis and its potential relationship with aging. We found that MIRO1 expressed in mouse and porcine oocytes, and its expression decreased in aged mice. MIRO1 deficiency caused the failure of meiotic resumption and polar body extrusion in both mouse and porcine oocytes, which could be rescued by exogenous MIRO1supplementation. Mass spectrometry data indicated that MIRO1 associated with several cytoskeleton and cell cycle-related proteins, and MIRO1 regulated motor protein Dynein for microtubule-organizing centers (MTOCs) dynamics at germinal vesicle (GV) stage, which determined meiotic resumption. Furthermore, we found that MIRO1 regulated Aurora A and kinesin family member 11 (KIF11) for meiotic spindle assembly in oocytes. Besides, MIRO1 associated with several mitochondria-related proteins dynamic-related protein 1 (DRP1),Parkin and lysosomal-associated membrane protein 2 (LAMP2) for mitochondrial dynamics and mitophagy during oocyte meiosis. Taken together, our results suggested that MIRO1 played pivotal roles in meiotic resumption, spindle assembly and mitochondrial function in mouse and porcine oocytes, and its insufficiency might contribute to the oocyte maturation defects during aging.

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Activation of human tonsil and skin mast cells by agonists of proteinase activated receptor-2

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Acta Pharmacologica Sinica 2005年第5期26卷 568-574页

作者： Shao-heng HE~2,Hua XIE,Yi-ling FUAllergy & inflammation research Institute,Shantou University Medical College.Shantou 515031,China Allergy and inflammation research Institute Shantou University Medical College Shantou 515031 China. shoahenghe@***

Aim:To investigate the effects of the agonists of proteinase activated receptor(PAR)-2,and histamine on degranulation of human mast ***:Humanmast cells were enzymatically dispersed from tonsil and skin *** dis-persed cells were then cultured with various stimuli,and tryptase and histaminelevels in cell supernatants collected from challenge tubes were ***:PAR-2 agonist peptide SLIGKV provoked a dose-dependent release of histaminefrom skin mast *** also induced tryptase release from tonsil mast ***-LIGRLO appeared less potent than SLIGKV in induction of release of histamineand *** was able to induce a"bell"shape increase in tryptaserelease from tonsil mast *** was also able to induce a dose-dependent releaseof histamine from both tonsil and skin mast *** actions of trypsin on mastcells were inhibited by soy bean trypsin inhibitor(SBTI)or α1-antitrypsin(α1-AT).Time course study revealed that both stimulated tryptase or histamine releaseinitiated within 10 s and reached their peak release between 4 and 6 ***-ment of cells with metabolic inhibitors or pertussis toxin reduced the ability ofmast cells to release tryptase or ***:It was demonstrated thatthe in vitro tryptase release properties of human tonsil and skin mast cells sug-gested a novel type of mast cell *** activation of mast cells byPAR-2 agonists indicated a self-amplification mechanism of mast cell degranulation.

关键词： tryptase histamine mast cells proteinase activated receptor-2 anti-IgE tonsil skin

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Variability of the Southwest Monsoon since the Last 25 000 Years and Their Possible Causes: Role of Northern Hemisphere versus Tibetan Plateau

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Journal of Earth Science 2013年第3期24卷 428-436页

作者： Anju Pandey Ravi Mishra centre for Climate Change research National centre for Antarctic & Ocean research

High-precision, clay sediment oxygen and hydrogen isotopes analyses of Pleistocene-Holocene deep-sea sediments from the Bay of Bengal （BOB） are presented for the first time. Our study shows that the major source of sediments in the study area, since the last-25 000 years, is likely to be the Higher Himalayan crystalline rocks. Further, the study of these stable isotope data displays the variation of southwest monsoon （SWM） in the BOB region since the last-25 000 years and the cause behind the variation has been interpreted. The δ 18 O values of the clay sediments are compared with δ 18 O values of the BOB seawater. This comparison shows that the clay sediment δ 18 O values of the studied sediment cores temporally vary along with the changes in strength of the SWM. Based on the changes in the clay sediment δ 18 O values of the studied sediment, we evaluate the variance in the SWM since the last 25 000 years in the BOB. Our results are consistent with previous work in the region based on other proxies. To evaluate the factors influencing the intensity of the SWM since the last glacial maxima, we conducted comparative analyses of the studied clay sediment δ 18 O values with δ 18 O values in the Greenland ice cores （GISP2） and Tibetan ice cores （Guliya）. The results from this comparative study show that large-scale changes in the intensity of the SWM since 25 000 years are affected by the climate oscillations of the Northern Hemisphere, but rapid and abrupt fluctuations in the SWM seem to be controlled by the amount of snow cover in the Tibetan Plateau.

关键词： southwest monsoon Bay of Bengal Tibetan Plateau clay stable isotope.

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Novel neuroprotective and hepatoprorective effects of citric acid in acute malathion intoxication

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Asian Pacific Journal of Tropical Medicine 2016年第12期9卷 1157-1169页

作者： Omar M.E.Abdel-Salam Eman R.Youness Nadia A.Mohammed Noha N.Yassen Yasser A.Khadrawy Safinaz Ebrahim El-Toukhy Amany A.Sleem Department of Toxicology and Narcotics National Research Centre Medical Biochemistry National Research Centre Pathology National Research Centre Physiology National Research Centre Pharmacology National Research Centre

Objective: To study the effect of citric acid given alone or combined with atropine on brain oxidative stress, neuronal injury, liver damage, and DNA damage of peripheral blood lymphocytes induced in the rat by acute malathion exposure. Methods: Rats were received intraperitoneal(i.p.) injection of malathion 150 mg/kg along with citric acid(200 or 400 mg/kg, orally), atropine(1 mg/kg, i.p.) or citric acid 200 mg/kg+atropine 1 mg/kg and euthanized 4 h later. Results: Malathion resulted in increased lipid peroxidation(malondialdehyde) and nitric oxide concentrations accompanied with a decrease in brain reduced glutathione, glutathione peroxidase(GPx) activity, total antioxidant capacity(TAC) and glucose concentrations. Paraoxonase-1, acetylcholinesterase(ACh E) and butyrylcholinesterase activities decreased in brain as well. Liver aspartate aminotransferase and alanine aminotransferase activities were raised. The Comet assay showed increased DNA damage of peripheral blood lymphocytes. Histological damage and increased expression of inducible nitric oxide synthase(i NOS) were observed in brain and liver. Citric acid resulted in decreased brain lipid peroxidation and nitric oxide. Meanwhile, glutathione, GPx activity, TAC capacity and brain glucose level increased. Brain ACh E increased but PON1 and butyrylcholinesterase activities decreased by citric acid. Liver enzymes, the percentage of damaged blood lymphocytes, histopathological alterations and i NOS expression in brain and liver was decreased by citric acid. Meanwhile, rats treated with atropine showed decreased brain MDA, nitrite but increased GPx activity, TAC, ACh E and glucose. The drug also decreased DNA damage of peripheral blood lymphocytes, histopathological alterations and i NOS expression in brain and liver. Conclusions: The study demonstrates a beneficial effect for citric acid upon brain oxidative stress, neuronal injury, liver and DNA damage due to acute malathion exposure.

关键词： Citric acid Malathion Oxidative stress Paraoxonase 1 Cholinesterase Comet assay

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Which form of collagen is suitable for nerve cell culture?

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Neural Regeneration research 2013年第23期8卷 2165-2170页

作者： Mohsen Fathi Najafi Saber Zahri Fatemeh Vahedi Leila Esmaililian Toosi Nazila Ariaee Razi Vaccine and Serum research Institute Departamnt of Biology University of Mohaghegh Ardebili inflammation and Inflammatory Diseases research Center Mashhad University of Medical Science

In this study, we investigated the effects of hydrolyzed and non-hydrolyzed collagen and two-di- mensional and three-dimensional collagen matrices on cell survival, attachment and neurite out- growth of primary cultured nerve cells using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide （MTT） colorimetric assay and inverted microscopy. Hydrolyzed collagen facilitated nerve cell survival and neurite outgrowth, but it had no obvious influences on cell attachment. In contrast, non-hydrolyzed two-dimensional collagen matrix had no obvious effects on neurite outgrowth. These findings suggest that hydrolyzed collagen is an ideal nerve cell culture media.

关键词： neural regeneration nerve cells collagen primary culture survival cell attachment growth matrix grants-supported paper neuroregeneration

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An ethanolic extract of Bailian(Radix Ampelopsis Japonicae):demonstration of colorectal cancer treatment efficacy via inhibition of β-catenin signaling in vitro

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Journal of Traditional Chinese Medicine 2019年第3期39卷 339-345页

作者： Su Tao Wang Xinning Li Chunyu Bai Jingxuan Chi-Yan Cheng Fu Xiuqiong Li Ting Yu Zhiling Consun Chinese Medicines research centre for Renal Diseases School of Chinese Medicine Hong Kong Baptist University Kowloon Tong Hong Kong 999077 China HKBU Shenzhen research Institute and Continuing Education Shenzhen 518001 China centre for Cancer and inflammation research School of Chinese Medicine Hong Kong Baptist University Hong Kong999077 China

OBJECTIVE:To investigate the underlying mechanism of Bailian (Radix Ampelopsis Japonicae,BL) extract action on colorectal cancer (CRC).METHODS:We explored the involvement of β-catenin signaling on the anti-CRC effects of an BL ethanolic extract (BLE) in cell models by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay,immunofluorescent staining,luciferase assay,Western blot analysis and real-time quantitative polymerase chain reaction ***-CRC compounds were quantified by high performance liquid ***:The contents of gallic acid,catechin,and epicatechin in the BLE were 0.23,1.25,and 0.18 g/kg,***-mediated cytotoxic and apoptotic effects were accompanied by lowered β-catenin/Tcf transcriptional activity,reduced β-catenin nuclear localization,and downregulated protein and mRNA levels of both β-catenin and molecules regulated by β-***:The mechanism underpinning the anti-CRC effects of BLE may involve inhibition of β-catenin *** studies are necessary to establish the role of β-catenin signaling in the action of BLE-mediated anti-CRC effects.

关键词： Bailian (Radix Ampelopsis Japonicae) Colorectal neoplasms Beta Catenin Cytotoxins Apoptosis

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