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IKKβ mediates homeostatic function in inflammation via competitively phosphorylating AMPK and IκBα

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Acta Pharmaceutica Sinica B 2022年第2期12卷 651-664,F0004页

作者： Juan Liu Yuxin Zhuang Jianlin Wu Qiang Wu Meixian Liu Yue Zhao Zhongqiu Liu Caiyan Wang Linlin Lu Yingjiao Meng Kawai Lei Xiaojuan Li Qibiao Wu Elaine Lai-Han Leung Zhengyang Guo Liang Liu Ting Li State Key Laboratory of Quality Research in Chinese Medicine/Macao Institute for Applied Research in Medicine and Health Macao University of Science and TechnologyMacao SAR 999078China International Institute for Translational Chinese Medicine Guangzhou University of Chinese MedicineGuangzhou 510006China Guangdong Provincial Key Laboratory of New Drug Screening/Laboratory of Anti-inflammatory and Immunomodulatory Pharmacology School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory infectious Disease Macao University of Science and TechnologyMacao SAR 999078China Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People’s Republic of China Macao University of Science and TechnologyMacao SAR 999078China

Inhibitor of nuclear factor kappa-B kinase subunit beta(IKKβ)is one of important kinases in inflammation to phosphorylate inhibitor of nuclear factor kappa-B(IκBα)and then activate nuclear factor kappa-B(NF-κB).Inhibition of IKKβhas been a therapeutic strategy for inflammatory and autoimmune *** we report that IKKβis constitutively activated in healthy donors and healthy Ikkβ^(C46A)(cysteine 46 mutated to alanine)knock-in mice although they possess intensive IKKβ-IκBα-NF-κB signaling *** indicate that IKKβactivation probably plays homeostatic role instead of causing *** to IkkβWTlittermates,lipopolysaccharides(LPS)could induce high mortality rate in Ikkβ^(C46A) mice which is correlated to breaking the homeostasis by intensively activating p-IκBα-NF-κB signaling and inhibiting phosphorylation of 5’adenosine monophosphate-activated protein kinase(p-AMPK)*** then demonstrated that IKKβkinase domain(KD)phosphorylates AMPKa1 via interacting with residues Thr183,Ser184,and Thr388,while IKKβhelix-loop-helix motifs is essential to phosphorylate IκBαaccording to the previous *** assay further demonstrated that IKKβsimultaneously catalyzes phosphorylation of AMPK and IκBαto mediate ***,activation of AMPK rather than inhibition of IKKβcould substantially rescue LPS-induced mortality in Ikkβ^(C46A) mice by rebuilding the *** conclude that IKKβactivates AMPK to restrict inflammation and IKKβmediates homeostatic function in inflammation via competitively phosphorylating AMPK and IκBα.

关键词： IKKβ Homeostasis Kinase domain AMPK Inflammation IκBα Anti-inflammatory drug Phosphorylation

Biliary complications in orthotopic liver transplantation:mechanism,diagnosis and treatment

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Journal of Nanjing Medical University 2009年第2期23卷 87-92页

作者： Xiaochen Shi Zhihai Peng department of General Surgery Shanghai First People' s Hospital Shanghai 200080 China

Biliary complicationsfBC） are a major cause of morbidity in liver transplant recipients with an incidence of 10-30% following orthotopic liver transplantation（OLT）, and a mortality rate of up to 10%. The most common biliary complications are bile leaks, biliary strictures, ampullary dysfunction, and stones. Leaks predominate in the early posttransplant period; while stricture formation typically develops gradually over time. Risk factors for biliary complications comprise technical failure, T-tube-related complications, hepatic artery thrombosis, bleeding, ischemia/reperfusion injury, primary diseases, and other immunological, non-immunological, and infectious complications. Cholangiography, such as endoscopic retrograde cholangiopancreatograpby（ERCP） or percutaneous transhepatic cholangiogram（PTC）, is considered the gold standard for identifying post-transplant BC. The management of biliary complications after OLT requires a multidisciplinary approach, in which interventional radiology and endoscopic techniques are emerging as the preferred treatment option, but in a selected majority of patients, surgery is still necessary.

关键词： liver transplantation bile-duct complication ischemic-type biliary lesions.

Rheumatologic manifestations of hepatic diseases

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Hepatobiliary & Pancreatic diseases International 2003年第1期2卷 32-37页

作者： Zhao-Chun Chi Su-Zhen Ma the Division of Gastroenterologr, department of Medicine, People’s Hospital, Qingdao 266001, China the department of infectious diseases, Qingdao University College of Medicine, Qingdao 266012, China Division of Gastroenterology Department of Medicine People's Hospital Qingdao 266001 China.

A possible link is suggested between hepatic diseases and rheumatic disease. Polyarthralgia and polyarthritis may be seen during the prodromal period of acute viral hepatitis, especially in hepatitis B virus (HBV). The symptoms of arthritis, mild, localized or generalized, mostly involve the small joints of hands. Joint symptoms frequently precede the onset of jaundice, no residual joint deformities. Circulating immune complexes are believed to play a causative role in the development of vasculitis and arthritis. Hemochromatosis is an antosomal recessive disorder of iron. About 43%-81% of patients with hemochromatosis have arthritis. The common extrahepatic manifestations of autoimmune hepatitis are arthralgia and skin rash. The reported prevalence of symptomatic inflammatory arthropathy in patients with primary biliary cirrhosis ranges from 4% to 50%. Skeletal involvement with Wilson's disease is common. Such patients may complain of pain and stiffness, mainly in the knee, wrist, or other large joints. Shwachman's syndrome is a disorder of pancreatic exocrine. Symmetric bone lesions have been reported in 10% to 15% of patients. They are involved predominantly at the femoral neck. Rheumatic symptoms are seen in one third of adult patients with cystic fibrosis and arthritis in 2.5% to 12% of patients. The arthritis caused by pancreatic panniculitis is usually symmetrical and involves the small joints of the hand, wrist, and feet, but may involve such larger joints as the elbow, ankle, and knee.

关键词： hepatic diseases rheumatologic manifestation

Global output of research on epidermal parasitic skin diseases from 1967 to 2017

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infectious diseases of Poverty 2018年第1期7卷 730-739页

作者： Waleed M.Sweileh department of Physiology Pharmacology/ToxicologyDivision of Biomedical SciencesCollege of Medicine and Health SciencesAn-Najah National UniversityNablusPalestine

Background:Epidermal parasitic skin diseases(EPSD)occur in most countries and cause a considerable health and economic burden,particularly in the tropics and *** aim of this study was to assess and analyse peerreviewed literature on EPSD in *** results of this study serve as an indicator of the extent the scientific community,health authorities,and international health agencies interact with EPSD as a health problem that is commonly associated with poverty and poor ***:A bibliometric analysis methodology was *** Scopus database was used to retrieve documents about EPSD for the study period(1967-2017).The study focused on scabies,tungiasis,pediculosis,hookwormrelated cutaneous larva migrans(HrCLM),myiasis,and cutaneous *** that specifically and explicitly discuss EPSD in animals,aquatic organisms,and birds were ***:In total,4186 documents were retrieved.A fluctuated growth of publications on EPSD in the past five decades was *** retrieved documents received 43301 citations,an average of 10.3 citations per article and an h-index of *** keywords“scabies”and was the most commonly encountered keyword followed by the keywords“head lice”and“pediculosis”.The most active journal involved in publishing articles on EPSD was the International Journal of Dermatology(164;3.9%).Researchers from 93 different countries published the retrieved *** USA led with 735(17.6%)documents,followed by the UK(274;6.5%),and Germany(259;6.2%).In terms of institutions,the Charite-Universitätsmedizin Berlin in Germany was the most active in this field with 78(1.9%)publications,followed by the Universidade Federal do Cearáin Brazil with 52(1.2%)***:Research on scabies and pediculosis dominated the field of EPSD research to the expense of tungiasis,HrCLM,myiasis,and cutaneous *** was an underrepresentation of literature from the tropics and subtropics despite EPSD being com

关键词： Epidermal parasitic skin diseases Bibliometric analysis Keyword mapping Scopus

Three-dimensional Culture of Human Airway Epithelium in Matrigel for Evaluation of Human Rhinovirus C and Bocavirus Infections

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Biomedical and Environmental Sciences 2018年第2期31卷 136-145页

作者： CHEN Ya Xiong XIE Guang Cheng PAN Dong DU Ya Rong PANG Li Li SONG Jing Dong DUAN Zhao Jun HU Bu Rong Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences & Key Laboratory of Space Radiobiology of Gansu Province Institute of Modern Physics Chinese Academy of Sciences department of Pathogenic Biology Chengde Medical University department for Viral Diarrhea National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and Prevention

Objective Newly identified human rhinovirus C （HRV-C） and human bocavirus （HBoV） cannot propagate in vitro in traditional cell culture models; thus obtaining knowledge about these viruses and developing related vaccines are difficult. Therefore, it is necessary to develop a novel platform for the propagation of these types of *** A platform for culturing human airway epithelia in a three-dimensional （3D） pattern using Matrigel as scaffold was developed. The features of 3D culture were identified by immunochemical staining and transmission electron microscopy. Nucleic acid levels of HRV-C and HBoV in 3D cells at designated time points were quantitated by real-time polymerase chain reaction {PCR）. Levels of cytokines, whose secretion was induced by the viruses, were measured by *** Properties of bronchial-like tissues, such as the expression of biomarkers CK5, ZO-2, and PCK, and the development of cilium-like protuberances indicative of the human respiration tract, were observed in 3D-cultured human airway epithelial （HAE） cultures, but not in monolayer-cultured cells. Nucleic acid levels of HRV-C and HBoV and levels of virus-induced cytokines were also measured using the 3D culture *** Our data provide a preliminary indication that the 3D culture model of primary epithelia using a Matrigel scaffold in vitro can be used to propagate HRV-C and HBoV.

关键词： 3D cell culture Human airway epithelium (HAE) Human rhinovirus C Human bocavirus Propagation

Chemical constituents, in vitro antimicrobial and cytotoxic potentials of the extracts from Macaranga barteri Mull-Arg

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Asian Pacific Journal of Tropical Biomedicine 2017年第7期7卷 654-659页

作者： Akintayo Ogundajo Benjamin Okeleye Anofi Omotayo Ashafa Phytomedicine and Phytopharmacology Research Group Department of Plant Sciences University of the Free State Qwaqwa Campus Phuthaditjhaba 9866 South Africa

Objectives: To investigate antimicrobial and cytotoxic potentials as well as chemical constituents of extracts from Macaranga barteri(M. barteri).Methods: Antimicrobial activity was carried out using micro-dilution, cell culture and GC–MS methods were employed to determine the cytotoxicity and chemical constituents of the extracts ***: Marked activity was observed in methanol(ME) fraction [MIC_(50):(0.097 7–6.250 0) mg/mL] compared to hexane and ethyl acetate fractions. Aeromonas hydrophila(environmental strain) and Shigella sonnei(ATCC 29930) were the most susceptible pathogens to ME and ciprofloxacin(Cl) at MIC_(50) value of 0.097 7 and infectious diseases.

关键词： Macaranga barteri GC–MS Antimicrobial Cytotoxicity

Assessment of net lending strategy to better reach mobile and migrant populations in malaria endemic areas of Cambodia

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infectious diseases of Poverty 2018年第1期7卷 1131-1143页

作者： Dysoley Lek Deyer Gopinath Sovann Ek Sopheab Heng Sreng Bun Chy Say Nguon Sokomar Kheang Soy Ty Huy Rekol National Center for Parasitology Entomology and Malaria Control Corner St.92village Trapeng SvayPhnom Penh ThmeySen SokPhnom PenhCambodia School of Public Health National Institute of Public HealthPhnom PenhCambodia World Health Organization Country Office for Thailand NonthaburiThailand University Research Co LLCPhnom PenhCambodia department of Communicable diseases Control Ministry of HealthPhnom PenhCambodia

Background:In Cambodia,internal migration involves migrants moving from non-malaria endemic areas to malaria endemic areas and vice *** majority of them work in farms or forests with various malaria transmission *** Cambodia,as one of the national approaches to ensure LLIN accessibility and use among mobile and migrant populations(MMPs),a lending scheme of long lasting insecticide treated nets(LLINs)was initiated among farm *** this net lending program,LLINs and long-lasting insecticide treated hammock nets(LLIHNs)will be distributed annually at workplace(*** farms,plantations,industrial sites,as identified by operational district and health center staff)on a ratio of one LLIN per one *** main objective of this study is to assess MMPs’accessibility to LLINs through a lending scheme with plantation owners in remote malaria endemic areas of ***:The study used a cross-sectional survey among MMPs using two-stage cluster sampling *** sampling frame is the list of farms in the four provinces of Banteay Meanchey,Battambang,Pailin,and Pursat in western and northwestern Cambodia bordering with Thailand where the LLIN lending scheme was implemented and where an estimated 100000 MMPs worked *** assessment was carried out from January to February 2013 in these four *** was estimated that 768 workers would be ***:A total of 702 MMPs were *** ratio of male:female is 1:*** age group of 21-60 was the largest accounting for 77.6%.About 91%of the MMPs stayed on the farm for less than 6 months.93.2%of them owned either untreated or insecticide treated *** and LLIHNs accounted for 89.5%;and 46.6%of them borrowed the nets from a lending *** those workers who have LLINs/LLIHNs,99%slept under LLINs/LLIHNs the night ***,only 87.4%knew that sleeping under LLINs/LLIHNs protects against ***:LLIN lending scheme provides an important delivery ch

关键词： Cambodia Malaria Mobile and migrant population Net Lending

人免疫缺陷病毒感染孕妇奈韦拉平毒性的队列研究

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世界核心医学期刊文摘（妇产科学分册） 2006年第4期2卷 13-13页

作者： Joāo E.C. Calvet G.A. Menezes J.A. 李奎 infectious diseases department Hospital Dos Servidores Do Estado R. Sacadura Cabral 178-Saude 5 Andar DIP Rio de Janeiro RJ 20221903 Brazil Dr.

Objective: The purpose of this study was to complete an evaluation of nevirapine (NVP) toxicity in a cohort of HIV+pregnant women. Study design: This was a retrospective study of 611 women followed from January 1996 to December 2003. All women who used NVP for > 7 days were included. Multivariate logistic regression was used to test independent association of CD4 and hepatitis C virus (HCV) infection related to the outcome of toxic effects of NVP. Results: One hundred ninety seven women were exposed to NVP for > 7 days, and toxicity occurred in 11 (5.6%), leading to drug discontinuation in 7 patients. One case of Stevens-Johnson syndrome occurred. No serious liver toxicity occurred except for 1 grade 4 cholestasis. Median CD4 was 344 in women without toxicities and 298 in women with toxicities. HCV was the only significant factor associated to toxicity by logistic regression (odds ratio [OR] 15.61, P = .001). Conclusion: NVP toxicities occurred in a very small fraction of patients and were not associated with fatalities.

关键词：人免疫缺陷病毒奈韦拉平感染孕妇队列研究肝炎病毒毒效 Stevens 胆汁淤积研究设计死

Bioconjugated Nanomaterial for Targeted Diagnosis of SARS-CoV‑2

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Accounts of Materials Research 2022年第2期3卷 134-148页

作者： Avijit Pramanik Ye Gao Shamily Patibandla Kalein Gates Paresh Chandra Ray department of Chemistry and Biochemistry Jackson State UniversityJacksonMississippi 39217United States

CONSPECTUS:infectious diseases by pathogenic microorganisms are one of the leading causes of mortality *** and socio-economic development have been seriously affected for different civilizations because of bacterial and viral *** to the Centers for Disease Control and Prevention(CDC),pandemic in 1918 by the Influenza A virus of the H1N1 subtype was responsible for 50 to 100 million deaths ***,the Asian flu pandemic in 1957,Hong Kong flu in 1968,and H1N1pdm09 flu pandemic in 2009 were responsible for more than 1 million deaths across the globe each *** per the World Health Organization(WHO),the current pandemic by coronavirus disease 2019(COVID-19)due to the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus is responsible for more than 4.8 M death worldwide until *** the gold standard polymerase chain reaction(PCR)test is more time-consuming,the health care system cannot test all symptomatic and asymptomatic Covid patients every day,which is extremely important to tackle the *** of the significant challenges during the current pandemic is developing mass testing tools,which is critical to control the virus spread in the ***,it is highly desirable to develop advanced material-based approaches that can provide a rapid and accurate diagnosis of COVID-19,which will have the capability to save millions of human lives.

关键词： diagnosis consuming deaths