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Non-viral factors contributing to hepatocellular carcinoma

World Journal of Hepatology 2013年第6期5卷 311-322页

作者： Manal A Hamed Sanaa A Ali Therapeutic Chemistry Department Pharmaceutical and Drug Industries Division National Research Centre

Hepatocellular carcinoma (HCC) is a major cause of cancer death worldwide, accounting for over half a million deaths per year. The geographic pattern of HCC incidence is parallel to exposure to viral etiologic factors. Its incidence is increasing, ranging between 3% and 9% annually depending on the geographical location, and variability in the incidence rates correspond closely to the prevalence and pattern of the primary etiologic factors. Chronic infections with hepatitis B viruses or hepatitis C viruses have both been recognized as human liver carcinogens with a combined attributable fraction of at least 75% of all HCC cases. Multiple non-viral factors have been implicated in the development of HCC. Increased body mass index and diabetes with subsequent development of non-alcoholic steatohepatitis represent significant risk factors for HCC. Other non-viral causes of HCC include iron overload syndromes, alcohol use, tobacco, oral contraceptive, aflatoxin, pesticides exposure and betel quid chewing, a prevalent habit in the developing world. Wilson disease, α-1 antitrypsin deficiency, Porphyrias, autoimmune hepatitis, Schistosoma japonicum associated with positive hepatitis B surface antigen, and thorotrastray are also contributing hepatocellualar carcinoma. In addition, primary biliary cirrhosis, congestive liver disease and family history of liver cancer increase the risk of HCC incident. In conclusion,clarification of relevant non-viral causes of HCC will help to focus clinicians on those risk factors that are modifiable. The multilevel preventative approach will hopefully lead to a reduction in incidence of non-viral HCC, and a decrease in the patient morbidity and mortality as well as the societal economic burden associated with HCC.

关键词： Hepatocellular carcinoma Viral etiologic factors Non viral factors

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Causal Relationship Between Gut Microbiota and Liver Cirrhosis:16S rRNA Sequencing and Mendelian Randomization Analyses

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Journal of Clinical and Translational Hepatology 2024年第2期12卷 123-133页

作者： Mengqin Yuan Xue Hu Lichao Yao Ping Chen Zheng Wang Pingji Liu Zhiyu Xiong Yingan Jiang Lanjuan Li Department of Infectious Diseases Renmin Hospital of Wuhan UniversityWuhanHubeiChina State Key Laboratory for Diagnosis and treatment of Infectious Diseases National Clinical Research Centre for Infectious DiseasesCollaborative Innovation Centre for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina

Background and Aims:Accumulating evidence highlights the association between the gut microbiota and liver ***,the role of the gut microbiota in liver cirrhosis remains ***:We first assessed the differences in the composition of the bacterial community between CCl4-induced liver cirrhosis and control mice using 16S rRNA *** then performed a two-sample Mendelian randomization(MR)analysis to reveal the underlying causal relationship between the gut microbiota and liver *** relationships were analyzed using primary inverse variance weighting(IVW)and other supplemental MR ***,fecal samples from liver cirrhosis patients and healthy controls were collected to validate the results of the MR ***:Analysis of 16S rRNA sequencing indicated significant differences in gut microbiota composition between the cirrhosis and control *** analyses suggested that Alphaproteobacteria,Bacillales,NB1n,Rhodospirillales,Dorea,Lachnospiraceae,and Rhodospirillaceae were positively correlated with the risk of liver cirrhosis,whereas Butyricicoccus,Hungatella,Marvinbryantia,and Lactobacillaceae displayed the opposite ***,the weighted median and MR-PRESSO estimates further showed that only Butyricicoccus and Marvinbryantia presented stable negative associations with liver *** significant heterogeneity or horizontal pleiotropy was observed in the sensitivity ***,the result of 16S rRNA sequencing also showed that healthy controls had a higher relative abundance of Butyricicoccus and Marvinbryantia than liver cirrhosis ***:Our study provides new causal evidence for the link between gut microbiota and liver cirrhosis,which may contribute to the discovery of novel strategies to prevent liver cirrhosis.

关键词： 16S rRNA gene sequencing Liver cirrhosis Gut microbiota Causality Two-sample Mendelian randomization study

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Nanoparticles for targeted delivery of therapeutics and small interfering RNAs in hepatocellular carcinoma

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World Journal of Gastroenterology 2015年第42期21卷 12022-12041页

作者： Jaleh Varshosaz Maryam Farzan Department of Pharma-ceutics Faculty of Pharmacy and Novel Drug Delivery Systems Research Centre Isfahan University of Medical Sciences

Hepatocellular carcinoma(HCC) is the 5th most common malignancy which is responsible for more than half million annual mortalities; also, it is the third leading cause of cancer related death. Unfavorablesystemic side-effects of chemotherapeutic agents and susceptibility to the degradation of small interfering RNAs(si RNAs), which can knock down a specific gene involved in the disease, have hampered their clinical application. So, it could be beneficial to develop an efficient carrier for the stabilization and specific delivery of drugs and si RNA to cells. Targeted nanoparticles have gained considerable attention as an efficient drug and gene delivery system, which is due to their capability in achieving the highest accumulation of cytotoxic agents in tumor tissue, modifiable drug pharmacokinetic- and bio-distribution, improved effectiveness of treatment, and limited sideeffects. Recent studies have shed more light on the advantages of novel drug loaded carrier systems vs free drugs. Most of the animal studies have reported improvement in treatment efficacy and survival rate using novel carrier systems. Targeted delivery may be achieved passively or actively. In passive targeting, no ligand as homing device is used, while targeting is achieved by incorporating the therapeutic agent into a macromolecule or nanoparticle that passively reaches the target organ. However, in active targeting, the therapeutic agent or carrier system is conjugated to a tissue or cell-specific receptor which is overexpressed in a special malignancy using a ligand called a homing device. This review covers a broad spectrum of targeted nanoparticles as therapeutic and nonviral si RNA delivery systems, which are developed for enhanced cellular uptake and targeted gene silencing in vitro and in vivo and their characteristics and opportunities for the clinical applications of drugs and therapeutic si RNA are discussed in this article. Asialoglycoprotein receptors, low-density lipoprotein, gangl

关键词： Small interfering RNA Targeted delivery Nanopartic

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An active RUNX1-ID1/ID3 axis governs differentiation and chemoresistance of cancer stem cell population in epithelial ovarian cancer cells

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BIOCELL 2022年第1期46卷 75-86页

作者： AJIT CDHADVE PRITHA RAY Imaging Cell Signaling&Therapeutics Laboratory Advanced Centre for TreatmentResearch and Education in CancerTata Memorial CentreNavi Mumbai410210India Homi Bhabha National Institute Mumbai400094India

Progression,relapse,and therapy resistance are the most challenging features of cancer therapy that have been postulated to be driven by Cancer Stem Cell(CSC)*** enigmatic subpopulation of cancer cells has therefore emerged as promising therapeutic *** earlier reported enrichment of CSC-like side population(SP)with increasing resistance towards Cisplatin and Paclitaxel either alone or in combination in epithelial ovarian cancer(EOC)*** SP population is a small proportion of the total population of cancer cells characterised with high expression of drug transporters,a unique feature of stem cells and thereby can be isolated through their efflux properties of DNA binding *** the bulk non-SP(NSP)population of the cancer cells lack overexpression of the drug transporters and thus can be identified as the dye containing *** this study,we show that increased expression of Runt related transcription factor 1(RUNX1)maintains undifferentiated state of CSC-like SP cells through upregulation of inhibitors of DNA binding/differentiation genes(ID1 and ID3)in late cisplatinpaclitaxel resistant *** RUNX1 expression was found to correlate with decreased median overall survival and disease-free survival in The Cancer Genome Atlas(TCGA)data set of high grade serous ovarian cancer(HGSOC)*** protein-protein interaction network analysis of 397 upregulated genes in RUNX1-high samples of TCGA data show significant enrichment of pathways known to negatively regulate CSC *** RUNX1 inhibition not only induces CSC differentiation but also downregulates anti-apoptotic protein BCL2 in both SP and NSP cells and potentiates cytotoxic effects of Cisplatin-Paclitaxel in chemoresistant EOC *** of BCL2 through Venetoclax treatment,a small molecule BH3 mimic,sensitized these cells to platinum taxol ***,our data reveal new regulatory roles by RUNX1 to modulate CSC differentiation via ID

关键词： Cancer stem cells Differentiation RUNX1 ID1 ID2 BCL2 Chemoresistance Ovarian cancer

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Inhibition of lysine-specific demethylase 1(LSD1)prevented tumor growth and metastasis by downregulating PD-L1 expression in lung adenocarcinoma

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Genes & Diseases 2023年第5期10卷 1779-1782页

作者： Pengxing He Linna Du Pan Hao Han Yang Yufei Ren Huiqin Kang Yanli Ding Wen Zhao Yichao Xu Hongmin Liu Key Laboratory of Advanced drug Preparation Technologies Ministry of Education of ChinaInstitute of Drug Discovery&DevelopmentSchool of Pharmaceutical SciencesZhengzhou UniversityZhengzhouHenan 450001China State Key Laboratory of Esophageal Cancer Prevention&treatment Zhengzhou UniversityZhengzhouHenan 450001China

Lysine-specific demethylase 1(LSD1),as a histone lysine demethylase,demethylates monomethyl and dimethyl of histone H3 on lysine 4(H3K4)and lysine 9(H3K9).Studies have reported that high LSD1 expression promotes cell proliferation,migration,and invasion by regulating chromatin morphology and gene expression,and is closely related to the development of non-small cell lung cancer(NSCLC).1 However,the underlying mechanism of LSD1 on cell proliferation and migration remains unclear.

关键词： lung invasion metastasis

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Highly active antiretroviral therapy per se decreased mortality and morbidity of advanced human immunodeficiency virus disease in Hong Kong

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Chinese Medical Journal 2005年第16期118卷 1338-1345页

作者： CHAN Chi-wai CHENG Lai-sim CHAN Wai-kit WONG Ka-hing Integrated treatment centre Department of Health Hong Kong China

Background Morbidity and mortality of advanced human immunodeficiency virus infection （HIV） have declined in Western industrialized countries since the availability of highly active antiretroviral therapy （HAART）. It is unclear if this has also happened in Hong Kong. Methods We studied a retrospective cohort of patients with advanced HIV disease in Hong Kong, China. First, the mortality of advanced HIV disease per year was calculated for the decade 1993 to 2002, both annually and according to patient observation before and after 1997. Second, the event rates were estimated for the clinical end points of acquired immune deficiency syndrome （AIDS） and death. Univariate and multivariate analyses were then performed to identify associated factors. Results The crude mortality of advanced HIV disease declined from 10. 8 - 30. 4 per 100 patients during 1993 - 1996, to 0. 8 - 6. 9 per 100 patients during 1997 - 2002. A rate ratio of 4. 04 （95% CI, 2. 52 - 6. 47） was evident for those observed in 1993 - 1996, compared to those in 1997 - 2002. In a multivariate analysis where calendar period was adjusted, use of＇highly active antiretroviral therapy was associated with rate ratios of 0. 13 （95% CI, 0. 05 -0. 33） for death after AIDS, 0. 08 （95% CI, 0. 04 -0. 19） for AIDS after a CD4 cell count 〈200/μ1, and 0.21 （95% CI, 0.07 -0.67） for death after CD4 cell count 〈200/μl. In the same analysis, calendar period ceased to be a significant factor after adjustment for use of HAART. Conclusions The mortality and morbidity of advanced human immunodeficiency virus disease have declined in Hong Kong. This improved prognosis was attributable to the use of highly active antiretroviral therapy.

关键词： highly active antiretroviral therapy mortality· morbidity acquired immunodeficiency syndrome

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A rapid reporter assay for recombinant human brain natriuretic peptide(rhBNP)by GloSensor technology

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Journal of Pharmaceutical Analysis 2018年第5期8卷 297-301页

作者： Lei Yu Xinchang Shi Chunmei Han Chunming Rao Junzhi Wang National Institutes for Food and drug Control Beijing 100050China WHO CoUahoration centre for Biologicals Standardization and Evaluation Beijing 100050China

Accurate determination of biological activity is essential in quality control of recombinant human brain natriuretic peptide （rhBNP）. In previous study, we successfully developed a genetically modified cell line 293GCAC3-based ELISA assay for rhBNP. But ELISA procedure is still tedious, so this study was aimed to develop a rapid and simple bioassay for rhBNP using GloSensor technology, which provides a platform of flexible luciferase-based biosensors for real-time detection of signaling events in live cells, including cGMP production. A reporter cell line 293GCAGIo-G1 was constructed by transfecting pGloSensorTM 40 F plasmid into 293GCAC3. The reporter assay based on 293GCAGIo-G1 showed high precision with intraassay CV being 8.3% and inter-assay CV being 14.1%; high accuracy with 80%, 100% and 120% recovery rate being 99.2%, 102.4% and 99.0% respectively; and great linearity with R^2 of linear fitting equation being 0.99. Besides, no significant difference was found in test results of reporter assay and 293GCAC3-based ELISA assay （paired t test,p = 0.630）. All these results suggested that the reporter assay was a viable assay for biological determination of rhBNP.

关键词： RhBNP cGMP GloSensor technology Reporter assay

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Synthesis and evaluation of monoclonal antibody against Plasmodium falciparum merozoite surface antigen 2

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Asian Pacific Journal of Tropical Medicine 2013年第10期6卷 798-803页

作者： Afra Khosravi Eghbaleh Asadollahy Sobhan Ghafourian Nourkhoda Sadeghifard Reza Mohebi Immunology Department Faculty of MedicineIlam University of Medical Sciences Food and drug Department Food and Drug DeputyIlam University of Medical Sciences Clinical Microbiology research centre Ilam University of Medical Sciences

Objective:To assess the quality of expressed MSP-2 and also to confirm the immune response against different domains of these ***:Mice were immunized with a schizont extract to stimulate the immune system to make antibodies against different antigens of the late stage parasite including production of antibodies against different domains of Plasmodium falciparum(***)MSP-2.B lymphocytes of immunized mice were extracted from the spleen and the fusion was performed using NS-1 myeloma cells and the hybridoma cells were assayed by ELISA either with a schizont extract or different domains of MSP-2 and/or by IFAT with whole schizont *** of NS-1 and spleen cells was *** positive hybrids were cloned and ELISA was applied against different *** positive clones were transferred to a small tissue culture flask and after developing they were assayed against schizont extract and the different MSP-2 *** positive clones were expanded to large(75 cm^2)flask and cultured under the same conditions,checking them using both ELISA and IFAT and the positive cells were frozen as soon as ***:A total number of 7 fusions including 26 plates(2496 wells)were performed,of which 1336 hybrids were produced and the overall efficiency(1336/24%×100)was about 53%.ELISA was performed to detect the positive hybrids against crude schizont extract by which the highest frequency to crude schizont extract was found for the supernatant of the hybrids produced in fusion number 3(66 out of 315 hybrids).The supernatant of both B5 and Ft hybridoma cells were more positive against domain 2 of the MSP-2 recombinant protein in Western blotting *** blotting results also showed that different domains of the MSP-2 recombinant protein and also the MSP-2 of the *** parasite were recognized by some of the positive clones and also immune ***:Bringing together all the results of this study it has been confirmed that s

关键词： MSP-2 Monoclonal antibody Malaria Diagnosis

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Study on the mechanism of copper-ammonia complex decomposition in struvite formation process and enhanced ammonia and copper removal

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Journal of Environmental Sciences 2017年第1期29卷 222-233页

作者： Cong Peng Liyuan Chai Chongjian Tang Xiaobo Min Yuxia Song Chengshan Duan Cheng Yu Department of Environmental Engineering School of Metallurgy and EnvironmentCentral South UniversityChangsha 410083China Chinese National Engineering Research centre for Control and treatment of Heavy Metal Pollution Changsha 410083China

Heavy metals and ammonia are difficult to remove from wastewater,as they easily combine into refractory *** struvite formation method（SFM） was applied for the complex decomposition and simultaneous removal of heavy metal and *** results indicated that ammonia deprivation by SFM was the key factor leading to the decomposition of the copper-ammonia complex *** was separated from solution as crystalline struvite,and the copper mainly co-precipitated as copper hydroxide together with *** bonding and electrostatic attraction were considered to be the main surface interactions between struvite and copper *** bonding was concluded to be the key factor leading to the *** addition,incorporation of copper ions into the struvite crystal also occurred during the treatment process.

关键词： Copper-ammonia complex Ammonia removal Copper hydroxide Co-precipitation Struvite formation Heavy-metal-containing wastewater

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Changes of Anti-tuberculosis Herbs Formula during Past Three Decades in Contrast to Ancient Ones

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Chinese Journal of Integrative Medicine 2021年第5期27卷 388-393页

作者： XU Yu-hui Dai Guang-ming TANG Shi-huan YANG Hong-jun SUN Zhao-gang Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China Translational Medicine Center Beijing Chest HospitalCapital Medical UniversityBeijing 101149China Beijing Key Laboratory in drug resistant Tuberculosis Research Beijing Tuberculosis&Thoracic Tumor Research InstituteBeijing 101149China

Objective:To investigate the evolution of herbal medicine in treating tuberculosis(TB)and encourage anti-TB drug discovery and ***:In this study,477 ancient traditional Chinese medicine formulae were collected from the Dictionary of Traditional Chinese Medicine Prescriptions and 172 modern Chinese medicine formulae(from 1986 to 2016)were collected by searching 4 databases:Wan Fang Data Knowledge Service Platform,China National Knowledge Infrastructure Database(CNKI),China Science and Technology Journal Database(VIP)and Chinese Bio-medical Literature and Retrieval System(Sino Med)in *** restricted the search to publications in *** data analysis was done using the Traditional Chinese Medicine Inheritance Support System version 2 ***:There were 425 herbs in the 477 ancient formulae and 257 herbs in the 172 modern *** of the top 30 herbs were shared by both modern and ancient *** are Radix Ophiopogonis,Astragalus membranaceus,Fritillaria cirrhosa,Dried rehmannia glutinosa,Poria cocos,Angelica sinensis,Prepared rehmannia glutinosa,Platycodon Root,Radix paeoniae alba,Schisandra chinensis,Bighead atractylodes rhizome,Rhizoma anemarrhenae,Cortex lycii radicis and Radix *** two groups of herbs with a high correlation coefficient were found in both modern and ancient prescriptions,the Dried rehmannia glutinosa with Radix ophiopogonis,and Radix ophiopogonis with Prepared rehmannia *** were 9 and 15 core herb combinations in modern and ancient prescriptions,respectively,but no one was found simutaniously in both modern and ancient ***:Although there were wide variations in the herb groups and herb combinations in the formulae,half of the top 30 herbs were found in both modern and ancient *** core herb combinations in modern and ancient prescriptions could help us to improve the priscription for treatment of TB.

关键词： herbal formula tuberculosis Chinese materia medica anti-tuberculosis herbs

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