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Signal Transduction and Targeted Therapy 2022年第7期7卷 2533-2544页

作者： Xi Shi Zihao Wang Wei Ren Long Chen Cong Xu Menghua Li Shiyong Fan Yuru Xu Mengbing Chen Fanjun Zheng Wenyuan Zhang Xinbo Zhou Yue Zhang Shiwei Qiu Liyuan Wu Peng Zhou Xinze Lv Tianyu Cui Yuehua Qiao Hui Zhao Weiwei Guo Wei Chen Song Li Wu Zhong Jian Lin Shiming Yang Department of Pharmacy Peking University Third HospitalBeijingChina Artificial Auditory Laboratory of Jiangsu Province Xuzhou Medical UniversityXuzhouChina National Engineering Research Center for the Emergency Drug Beijing Institute of Pharmacology and ToxicologyBeijingChina College of Otolaryngology Head and Neck Surgery Chinese PLA General HospitalBeijingChina National clinical Research Center for Otolaryngologic Diseases BeijingChina Key Lab of Hearing Science Ministry of EducationBeijingChina Beijing Key Lab of Hearing Impairment for Prevention and Treatment BeijingChina Synthetic and Functional Biomolecules Center Beijing National Laboratory for Molecular SciencesKey Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of EducationCollege of Chemistry and Molecular EngineeringInnovation Center for GenomicsPeking UniversityBeijingChina

Inner ear disorders are a cluster of diseases that cause hearing loss in more than 1.5 billion people ***,the presence of the blood-labyrinth barrier(BLB)on the surface of the inner ear capillaries greatly hinders the effectiveness of systemic drugs for prevention and intervention due to the low permeability,which restricts the entry of most drug compounds from the bloodstream into the inner ear ***,we report the finding of a novel receptor,low-density lipoprotein receptor-related protein 1(LRP1),that is expressed on the BLB,as a potential target for shuttling therapeutics across this *** a proof-ofconcept,we developed an LRP1-binding peptide,IETP2,and covalently conjugated a series of model small-molecule compounds to it,including potential drugs and imaging *** compounds were successfully delivered into the inner ear and inner ear lymph,indicating that targeting the receptor LRP1 is a promising strategy to enhance the permeability of the *** discovery of the receptor LRP1 will illuminate developing strategies for crossing the BLB and for improving systemic drug delivery for inner ear disorders.

关键词： drugs prevention barrier

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Effects of Urban and Industrial Waste on Some Soil Properties of Agricultural Soils in Kano Metropolis, Kano State, Nigeria

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Journal of Environmental Science and Engineering 2010年第3期4卷 54-63页

作者： J.C. Akan F.I. Abdulrahman O.A. Sodipo V.O. Ogugbuaja Department of chemistry Faculty of Science University of Maiduguri P.M.B. 1069 Maiduguri Borno State Nigeria Department of clinical pharmacology and Therapeutics College of Medical Sciences University of Maiduguri P.M.B 1069Maiduguri Borno State Nigeria

The potential impact of the addition of untreated sewage sludge from domestic waste and effluent from textile and tannery industries on agricultural soils is a common practice in this area of study. A proportion of heavy metals in sewage sludge will be present in the soil solution. Soil samples from three Agricultural Site were collected at three depths （0-10 cm, 10-20 cm and 20-30 cm） from the months of June to September, 2007 （Rainy season）, February - May, 2008 （Dry season） for the determination of pH, electrical conductivity, organic matter, organic carbon, salinity, cation exchanged capacity, Ca, Na, K and heavy metals using standard procedures. Levels of the above parameters were higher in the dry season than in the rainy season. It was also observed from the result of this study that the levels of pH and organic carbon influenced the solubility and mobility of heavy metals. Generally, the levels of heavy metals, pH and organic carbon for the three agricultural sites increases significantly （P 〈 0.05） to a depth of 30 cm, while Conductivity, salinity, organic matter, CEC （Cation exchanged capacity）, Ca, Na and K decreased to a depth of 30 cm. The concentrations of heavy metals in the soil samples were higher than the Interim Canadian Environmental quality criteria and FAO （Food and Agriculture Organization） for contaminated site. Based on the above results, the study underscores the need for immediate remediation programme to control the use of untreated sewage sludge and waste water from tannery and textile industries by farmers in the study areas for crop production.

关键词： Accumulation heavy metals sewage sludge wastewater soil properties.

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低氧诱导因子-1α和血管内皮生长因子-C及podoplanin在乳腺癌中的表达及其临床意义

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中华检验医学杂志 2008年第9期31卷 1028-1029页

作者：魏江朱江罗光华汤艳红郑璐牟琴峰陈陆俊张俊徐宁江苏省常州市第一人民医院综合实验室 213003 Section of clinical chemistry & pharmacology Institute of Laboratory MedicineLund University Sweden

肿瘤诱导淋巴管生成是许多肿瘤生长及肿瘤转移的关键。由于缺乏特异的淋巴内皮细胞标志物，肿瘤诱导淋巴管生成及在肿瘤转移中的作用未被充分认识。podoplanin是一种膜性黏蛋白，可特异性表达在淋巴管内皮。在podoplanin敲除的动物模型... 详细信息

肿瘤诱导淋巴管生成是许多肿瘤生长及肿瘤转移的关键。由于缺乏特异的淋巴内皮细胞标志物，肿瘤诱导淋巴管生成及在肿瘤转移中的作用未被充分认识。podoplanin是一种膜性黏蛋白，可特异性表达在淋巴管内皮。在podoplanin敲除的动物模型中，已经证实podoplanin缺失可导致淋巴管生成受损和淋巴水肿。本研究检测乳腺癌患者组织标本中低氧诱导因子-1α（HIF-1α），血管内皮生长因子-C（VEGF-C）和podoplanin的表达水平，并结合临床资料进行相关性分析，以探讨低氧可能对肿瘤淋巴管生成的影响。

关键词： podoplanin 血管内皮生长因子-C 低氧诱导因子-1α 乳腺癌患者临床意义淋巴管生成特异性表达肿瘤转移

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Gut microbiota contribution to hepatocellular carcinoma manifestation in non-alcoholic steatohepatitis

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World Journal of Hepatology 2022年第7期14卷 1277-1290页

作者： Valentina Liakina Sandra Strainiene Ieva Stundiene Vaidota Maksimaityte Edita Kazenaite Centre of Hepatology Gastroenterology and DieteticsClinic of GastroenterologyNephrourology and SurgeryInstitute of Clinical MedicineFaculty of MedicineVilnius UniversityVilnius 01513Lithuania Department of chemistry and Bioengineering Faculty of Fundamental SciencesVilnius Gediminas Technical University(VILNIUS TECH)Vilnius 10223Lithuania Faculty of Medicine Vilnius UniversityVilnius 01513Lithuania Therapeutic and Radiological Department Antakalnis PolyclinicVilnius 10207Lithuania Department of Pathology Forensic Medicine and PharmacologyInstitute of Biomedical SciencesFaculty of MedicineVilnius UniversityVilnius 01513Lithuania

Recently,the gut microbiota has been recognized as an obvious active player in addition to liver steatosis/steatohepatitis in the pathophysiological mechanisms of the development of hepatocellular carcinoma(HCC),even in the absence of *** from clinical and experimental studies shows the association of specific changes in the gut microbiome and the direct contribution to maintaining liver inflammation and/or cancerogenesis in nonalcoholic fatty liver disease-induced *** composition of the gut microbiota differs significantly in obese and lean individuals,especially in the abundance of pro-inflammatory lipopolysaccharide-producing phyla,and,after establishing steatohepatitis,it undergoes minor changes during the progression of the disease toward advanced *** studies proved that the microbiota of obese subjects can induce steatohepatitis in normally fed *** the contrary,the transplantation of healthy microbiota to obese mice relieves ***,further studies are needed to confirm these findings and the mechanisms *** this review,we have evaluated well-documented clinical and experimental research on the role of the gut microbiota in the manifestation and promotion of HCC in nonalcoholic steatohepatitis(NASH).Furthermore,a literature review of microbiota alterations and consequences of dysbiosis for the promotion of NASH-induced HCC was performed,and the advantages and limitations of the microbiota as an early marker of the diagnosis of HCC were discussed.

关键词： Gut microbiota Hepatocellular carcinoma Non-alcoholic steatohepatitis Non-alcoholic fatty liver disease Microbiome

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In-Vivo Anti-Hyperlipidemic Activity and Preliminary Phytochemical Screening of Canephora robusta

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American Journal of Molecular Biology 2020年第1期10卷 44-50页

作者： Kishan Pavani Jankuti Anusha Govindula Rajkumar Jampala Mohammad Arif Pasha Aligeti Sravan Kumar Sunayana Soorammagari Chinnela Satish Mahankali Naga Ganesh Department of Pharmaceutics Vaageswari College of Pharmacy Karimnagar India Department of pharmacology Vaageswari College of Pharmacy Karimnagar India Department of Pharmaceutical chemistry Vaageswari College of Pharmacy Karimnagar India Department of clinical Pharmacy Vaageswari College of Pharmacy Karimnagar India Department of Pharmaceutics Geethanjali College of Pharmacy Hyderabad India

The main aim of this study is to determine the anti-hyerlipidemic and anti-obesity activity of Canephora robusta in hyperlipidemia induced rats. Prepared coffee bean extract (GCE) was procured from the market which is unroasted and contains more quantity of caffeine and chlorogenic acid when compared to roasted coffee. Male albino Wister rats are fed with high fat diet (HFD) for weeks to induce hyperlipidemia in rats, which are divided into 4 groups with 4 animals in each group. Test GCBE was given in doses of 200 mg/kg and 400 mg/kg to III and IV groups which are fed with HFD for 30 days. Then blood samples were collected through retro-orbital sinus by capillaries and serum is separated for analysis. The result obtained from lipid profile which includes total cholesterol, triglycerides, very low density lipoproteins, and low density lipoproteins shows the decreased level when compared to the hyperlipidemic control. This shows the significant reduction of total body weight (p < 0.05) when given with dose of 200 mg/kg and 400 mg/kg. The present study suggests that GCBE has anti-obesity and anti-hyperlipidemic activity, where 400 mg/kg is more effective to reduce the total body weight and lipid levels when compared to 200 mg/kg. Further studies on this extract may lead to identify the possible mechanism of action and isolation of active principle from the same.

关键词： Anti-Hyerlipidemic Anti-Obesity Lipoproteins Hyperlipidemia

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Physical-Chemical Aggressiveness of Solutions of Medicines as a Factor in the Rheology of the Blood inside Veins and Catheters

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Journal of chemistry and Chemical Engineering 2014年第1期8卷 61-65页

作者： Aleksandr Urakov Natalia Urakova Anton Kasatkin Leisan Chernova Department of the Deformed Solid Body Institute of Mechanics of the Ural Branch of the RAS Izhevsk 426067 Russia Department of General and clinical pharmacology Izhevsk State Medical Academy Izhevsk 426034 Russia

In experiments in vitro and observations in the clinic in vivo studied the state of the lumen of subcutaneous veins and blood rheology of patients after their interaction with vascular catheters and solutions of medicines based on the values of temperature, volume, concentration, osmotic activity and pH. It is shown that heparin injection in blood not prevent, but solution of 4% sodium bicarbonate injection prevents blood clotting, blood clots and blockage blood clots of veins and of catheters. It is shown that the heating to a temperature of＋42 ℃ with the solution of 4% sodium bicarbonate provides softening action on old dry blood clots in 1 min, and their subsequent irrigation with a warm solution of 4% sodium bicarbonate and 3% hydrogen peroxide provides complete destruction and discoloration of the remaining spots of blood during 2 s. Proposed new medicines and hygiene products for the protection of the veins and installed in them vascular catheters from blockage of blood clots, and for removing blood stains from clothes and body surface patients.

关键词： New drugs hygiene products physical-chemical properties rheology blood.

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Computational Exploration of Rh（Ⅲ）-Catalyzed C-H Cyclopropanation via “Dual-Intramolecular-Hydrogen-Transfer”

Computational Exploration of Rh（Ⅲ）-Catalyzed C-H Cyclopro...

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2019中国化学会第十五届全国计算（机）化学学术会议

作者： Huiying Xu Zhi Zhou Guoxun Zhu Xingwei Li Hui Gao Wei Yi Key Laboratory of Molecular Target and clinical pharmacology & State Key Laboratory of Respiratory Disease School of Pharmaceu-tical Sciences & the Fifth Affiliated Hospital Guangzhou Medical University Key Laboratory of Applied Surface and Colloid chemistry of MOE School of Chemistry and Chemical Engineering Shaanxi Normal University(SNNU)

By virtue of a dual-directing-group-assisted C–H activation strategy, the first Cp*RhIII-catalyzed redox-neutral and diastereoselective C–H cyclopropanation that uses versatile cyclopropenyl alcohols as the coupling partners has been realized at room temperature for constructing the exclusive trans-cyclopropanation products. Driven by the above experimental results, we conducted a set of density functional theory studies to clarify the reaction pathways, in particular, to reveal the role of the dual directing groups and the origin of the specific trans-diastereoselectivity. In the Cp*RhIII-catalytic mechanism, the initial N–H deprotonation of N-phenoxytosylamide followed by facile C–H bond cleavage process was involved to provide a five-membered rhodacycle intermediate. The subsequent regioselective and stereo-determining alkene insertion and oxidative addition gives a seven-membered Rh（V） alkyl complex. This complex then undergoes β–H elimination via two concerted intramolecular hydrogen transfers. Finally, C–H reductive elimination and protonolysis regenerates the Rh（Ⅲ） catalyst and releases the final product.

关键词： DFT study Cp*Rh Ⅲ catalyst intramolecular hydrogen transfer trans-cyclopropanation cyclopropenyl alcohols

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RIG-I immunotherapy overcomes radioresistance in p53-positive malignant melanoma

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分子细胞生物学报:英文版 2023年第1期15卷 13-26页

作者： Silke Lambing Yu Pan Tan Paraskevi Vasileiadou Stefan Holdenrieder Patrick Müller Christian Hagen Stephan Garbe Rayk Behrendt Martin Schlee Jasper G.van den Boorn Eva Bartok Marcel Renn Gunther Hartmann Institute of clinical chemistry and clinical pharmacology University Hospital BonnBonn 53127Germany Institute of Laboratory Medicine German Heart CentreMunich 80636Germany Department of Radiation Oncology University Hospital BonnBonn 53127Germany Unit of Experimental Immunology Department of Biomedical SciencesInstitute of Tropical MedicineAntwerp 2000Belgium Institute of Experimental Haematology and Transfusion Medicine University Hospital BonnBonn 53127Germany Mildred Scheel School of Oncology BonnUniversity Hospital BonnMedical FacultyBonn 53127Germany

Radiotherapy induces DNA damage,resulting in cell cycle arrest and activation of cell-intrinsic death ***,the radioresistance of some tumour entities such as malignant melanoma limits its clinical *** innate immune sensing receptor retinoic acid-inducible gene I(RIG-I)is ubiquitously expressed and upon activation triggers an immunogenic form of cell death in a variety of tumour cell types including *** date,the potential of RIG-I ligands to overcome radioresistance of tumour cells has not been ***,we demonstrate that RIG-I activation enhanced the extent and immunogenicity of irradiation-induced tumour cell death in human and murine melanoma cells in vitro and improved survival in the murine B16 melanoma model in *** analysis pointed to a central role for p53,which was confirmed using p53^(-/-)B16 *** vivo,the additional effect of RIG-I in combination with irradiation on tumour growth was absent in mice carrying p53^(-/-)B16 tumours,while the antitumoural response to RIG-I stimulation alone was *** results identify p53 as a pivotal checkpoint that is triggered by RIG-I resulting in enhanced irradiation-induced tumour cell ***,the combined administration of RIG-I ligands and radiotherapy is a promising approach to treating radioresistant tumours with a functional p53 pathway,such as melanoma.

关键词： RIG-I p53 melanoma immunotherapy irradiation radiotherapy radioresistance

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Kaempferol from Drynaria fortunei Promotes Kidney Tubular Cell Proliferation and the Secretion of a Bone Growth Factor

Kaempferol from Drynaria fortunei Promotes Kidney Tubular Ce...

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自主创新与持续增长第十一届中国科协年会

作者： FRANCIS Johnson Departments of pharmacology and chemistry Stony Brook University

Patients with Chronic kidney disease associated with bone deficiency are observed in clinical. This article reports the finding that kidney cells secrete a bone growth factor that is stimulated by kaempferol from flavones fraction (FF) Rhizoma Drynariae (Gu Sui Bu, GSB).The FF was extracted from GSB by 50% ethanol, and isolated by macroporous resin, silica gel and sephadex LH-20 column chromatography. Four components were isolated and identified to be naringin (I), neoeriocitrin (II) , Kaempferol (III) and naringenin-7-O-β-D-glucoside (IV). The activity of the components was examined by studying the proliferation and bio-function of Opossum Kidney (OK), osteoblast (MC3T3 E1) and human fibroblast (HF) cells. Kaempferol was found to be active in promoting OK cell growth, the increase in rates being 1.16-1.3 fold, and 12.6 fold respectively in the presence of gentamicin. Kaempferol promoted neither MC3T3 E1 nor HF cell proliferation. OK cell-conditioned culture medium (OKM) promoted MC3T3 E1 growth 2.98 fold. At 70nM kaempferol-conditioned OKM, MC3T3E1 cell growth increased to 2.27fold in comparison to control OKM. Both OKMs failed to show any significant effect on HF cell growth. The results of OKM promoted osteoblast proliferation indicate that the kidney cell secretes a bone growth factor (BGF). Kaempferol stimulates kidney cells proliferation and increases secretion of BGF. The data suggest that patients with CKD associated with deficiency of bone may have a lower level of BGF. Kaempferol may serve to stimulate kidney repair and up-regulate bone formation and may be useful in treating CKD and osteoporosis.

关键词： Kaempferol renal tubular cell osteoblast bone growth factor (BGF) Rhizoma Drynariae Gu Sui Bu

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Tubular-Cell Secrets Osteoblast Growth Factor and Kaempferol from Drynaria fortunei Promotes the Secretion

Tubular-Cell Secrets Osteoblast Growth Factor and Kaempferol...

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2009年中国药学大会暨第九届中国药师周

作者： Johnson Francis Departments of pharmacology and chemistry Stony Brook University

Patients with Chronic kidney disease （CKD） associated with bone deficiency are observed in clinical practice. This article reports the finding that kidney cells secrete a bone growth factor that is stimulated by kaempferol found in the flavones fraction （FF） of Rhizoma Drynariae （Gu Sui Bu, GSB）. The FF was extracted from GSB by 50% ethanol, and isolated by macroporous resin, silica gel and Sephadex LH-20 column chromatography. Four components were isolated and identified to be naringin （1）, neoeriocitrin （2） , kaempferol （3） and naringenin-7-O-β-D-glucoside （4）. The activity of the components was examined by studying the proliferation and bio-function of Opossum Kidney （OK）, osteoblast （MC3T3 E1） and human fibroblast （HF） cells. Kaempferol was found to be active in promoting OK cell growth, which increased by 16-30% and 11.6% respectively in the absence or presence of gentamicin. Kaempferol promoted neither MC3T3 E1 nor HF cell proliferation. OK cell-conditioned culture medium （OKM） increased MC3T3 E1 growth by 198%. At 70 nmol·L-1 kaempferol-conditioned OKM, MC3T3E1 cell growth additionally increased by 127% in comparison to control OKM. Both OKMs failed to show any significant effect on HF cell growth. The results of OKM promoted osteoblast proliferation indicate that the kidney cell secretes a bone-growth factor （BGF）. Kaempferol stimulates kidney cells proliferation and increases secretion of BGF. The data suggest that patients with CKD associated with bone deficiency, may have a lower level of BGF. Kaempferol may serve to stimulate kidney repair and up-regulate bone formation and may be useful in treating CKD and osteoporosis.

关键词： kaempferol renal tubular cell osteoblast bone growth factor (BGF) Rhizoma Drynariae Gusuibu

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