摘要：
Polyethyleneimine (PEI) has a good spongy proton effect and is an excellent nonviral gene vector, but its high charge density leads to the instability and toxicity of PEI/DNA complexes. Cell membrane (CM) capsules provide a universal and natural solution for this problem. Here, CM-coated PEI/DNA capsules (CPDcs) were prepared through extrusion, and the extracellular matrix was coated on CPDcs (ECM-CPDcs) for improved targeting. The results showed that compared with PEI/DNA complexes, CPDcs had core-shell structures (PEI/DNA complexes were coated by a 6-10 nm layer), lower cytotoxicity, and obvious homologous targeting. The internalization and transfection efficiency of 293T-CM-coated PEI70k/DNA capsules (293T-CP70Dcs) were 91.8 and 74.5%, respectively, which were higher than those of PEI70k/DNA complexes. Then, the internalization and transfection efficiency of 293T-CP70Dcs were further improved by ECM coating, which were 94.7 and 78.9%, respectively. Then, the internalization and transfection efficiency of 293T-CP70Dcs were further improved by ECM coating, which were 94.7 and 78.9%, respectively. Moreover, the homologous targeting of various CPDcs was improved by ECM coating, and other CPDcs also showed similar effects as 293T-CP70Dcs after ECM coating. These findings suggest that tumor-targeted CPDcs may have considerable advantages in gene delivery.
作者：
Sbarra, Alyssa N.;Rolfe, Sam;Nguyen, Jason Q.;Earl, Lucas;Galles, Natalie C.;...
期刊：
Nature,2021年589(7842):415-+ ISSN：1476-4687
通讯作者：
Hay, Simon I.;Lim, Stephen S.;Mosser, Jonathan F.
作者机构：
[Naghavi, Mohsen; Cunningham, Brandon; Miller-Petrie, Molly K.; Osgood-Zimmerman, Aaron E.; Marks, Ashley; Ikilezi, Gloria; Mayala, Benjamin K.; Munro, Sandra B.; Dandona, Lalit; Cormier, Natalie Maria; Daoud, Farah; Dharmaratne, Samath Dhamminda; Mokdad, Ali H.; Dandona, Rakhi; Rolfe, Sam; LeGrand, Kate E.; Mosser, Jonathan F.; Sbarra, Alyssa N.; Pigott, David M.; Spurlock, Emma Elizabeth; Kinyoki, Damaris K.; Zadey, Siddhesh; Lim, Stephen S.; Mosser, JF; Deshpande, Aniruddha; Henry, Nathaniel J.; Nguyen, Jason Q.; Johnson, Kimberly B.; Fullman, Nancy; Hay, Simon I.; Galles, Natalie C.; Hollerich, Gillian I.; Cook, Aubrey J.; Schaeffer, Lauren E.; Earl, Lucas; Weaver, Nicole Davis; Murray, Christopher J. L.; Larson, Heidi Jane; Wiens, Kirsten E.] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.;[Brady, Oliver J.; Abbas, Kaja M.; Larson, Heidi Jane] London Sch Hyg & Trop Med, Dept Infect Dis Epidemiol, London, England.;[Abbasi-Kangevari, Mohsen] Shahid Beheshti Univ Med Sci, Social Determinants Hlth Res Ctr, Tehran, Iran.;[Abbastabar, Hedayat] Univ Tehran Med Sci, Adv Diagnost & Intervent Radiol Res Ctr, Tehran, Iran.;[Abdelalim, Ahmed; Pana, Adrian; Abd-Allah, Foad; El-Jaafary, Shaimaa I.] Cairo Univ, Dept Neurol, Cairo, Egypt.
通讯机构：
[Hay, SI; Lim, SS; Mosser, JF] U;Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.;Univ Washington, Sch Med, Dept Hlth Metr Sci, Seattle, WA USA.
摘要：
The safe, highly effective measles vaccine has been recommended globally since 1974, yet in 2017 there were more than 17 million cases of measles and 83,400 deaths in children under 5 years old, and more than 99% of both occurred in low- and middle-income countries (LMICs)(1-4). Globally comparable, annual, local estimates of routine first-dose measles-containing vaccine (MCV1) coverage are critical for understanding geographically precise immunity patterns, progress towards the targets of the Global Vaccine Action Plan (GVAP), and high-risk areas amid disruptions to vaccination programmes caused by coronavirus disease 2019 (COVID-19)(5-8). Here we generated annual estimates of routine childhood MCV1 coverage at 5 x 5-km(2) pixel and second administrative levels from 2000 to 2019 in 101 LMICs, quantified geographical inequality and assessed vaccination status by geographical remoteness. After widespread MCV1 gains from 2000 to 2010, coverage regressed in more than half of the districts between 2010 and 2019, leaving many LMICs far from the GVAP goal of 80% coverage in all districts by 2019. MCV1 coverage was lower in rural than in urban locations, although a larger proportion of unvaccinated children overall lived in urban locations; strategies to provide essential vaccination services should address both geographical contexts. These results provide a tool for decision-makers to strengthen routine MCV1 immunization programmes and provide equitable disease protection for all children.
摘要：
Alzheimer’s Disease (AD) is a devastating neurodegenerative disease that affects millions of people in the world. The abnormal aggregation of amyloid β protein (Aβ) is regarded as the key event in AD onset. Meanwhile, the Aβ oligomers are believed to be the most toxic species of Aβ. Recent studies show that the Aβ dimers, which are the smallest form of Aβ oligomers, also have the neurotoxicity in the absence of other oligomers in physiological conditions. In this review, we focus on the pathogenesis, structure and potential therapeutic molecules against small Aβ oligomers, as well as the nanoparticles (NPs) in the treatment of AD. In this review, we firstly focus on the pathogenic mechanism of Aβ oligomers, especially the Aβ dimers. The toxicity of Aβ dimer or oligomers, which attributes to the interactions with various receptors and the disruption of membrane or intracellular environments, were introduced. Then the structure properties of Aβ dimers and oligomers are summarized. Although some structural information such as the secondary structure content is characterized by experimental technologies, detailed structures are still absent. Following that, the small molecules targeting Aβ dimers or oligomers are collected; nevertheless, all of these ligands have failed to come into the market due to the rising controversy of the Aβ-related “amyloid cascade hypothesis”. At last, the recent progress about the nanoparticles as the potential drugs or the drug delivery for the Aβ oligomers are present.
通讯机构：
[Ke, Xiaoyu] D;Department of Emergency, Tongji Hosptial of Tongji Medical College of Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
摘要：
Low dose of NP exposure can alter adipose tissue formation, and the intake of high-fat diet (HFD) can also lead to the fatty liver disease. We investigated the combined effect of NP and HFD on the first offspring of rats, and whether this effect can be passed to the next generation and the possible mechanisms involved. Pregnant rats had access to be treated with 5 μg/kg/day NP and normal diet. The first generation rats were given normal diet and HFD on postnatal day 21, respectively. Then the second generation rats started to only receive normal diet without NP or HFD. Body weight, organ coefficient of liver tissues, lipid profile, biochemical indexes and the expression of genes involved in lipid metabolism, as well as liver histopathology were investigated in male offspring of rats. NP and HFD interaction had significant effect on the birth weight, body weight and liver tissue organ coefficient of first generation male rats. And HFD aggravated abnormal lipid metabolism, even abnormal liver function and liver histopathological damage of first generation male rats produced by the NP. And this effect can be passed on to the second generation rats. HFD also accelerated the mRNA level of fatty acid synthesis genes such as Lpl, Fas, Srebp-1 and Ppar-γ of first generation rats induced by perinatal exposure to NP, even passed on to the second generation of male rats. NP and HFD resulted in synergistical decrease of the protein expression level of ERα in liver tissue in F2 male rats. HFD and NP synergistically accelerated synthesis of fatty acids in liver of male offspring rats through reducing the expression of ERα, which induced abnormal lipid metabolism, abnormal liver function and hepatic steatosis. Moreover, all of these damage passed on to the next generation rats.
期刊：
Life Sciences,2021年265(2):118761 ISSN：0024-3205
通讯作者：
Huang, Kun
作者机构：
[Li, Yang] Wuhan Polytech Univ, Coll Biol & Pharmaceut Engn, Wuhan 430023, Peoples R China.;[Xiao, Yushuo] Hubei Univ Chinese Med, Sch Pharm, Wuhan 430065, Peoples R China.;[Chen, Yuchen; Huang, Kun] Huazhong Univ Sci & Technol, Sch Pharm, Tongji Med Coll, Wuhan 430030, Peoples R China.;[Huang, Kun] Huazhong Univ Sci & Technol, Tongji Sch Pharm, Tongji Med Coll, Wuhan 430030, Peoples R China.
通讯机构：
[Huang, Kun] H;Huazhong Univ Sci & Technol, Tongji Sch Pharm, Tongji Med Coll, Wuhan 430030, Peoples R China.
关键词：
Virus;Infection diseases;Nanomaterials;Antiviral agents and mechanisms;Nanovaccines
摘要：
Outbreaks and the rapid transmission of viruses, such as coronaviruses and influenza viruses, are serious threats to human health. A major challenge in combating infectious diseases caused by viruses is the lack of effective methods for prevention and treatment. Nanotechnology has provided a basis for the development of novel antiviral strategies. Owing to their large modifiable surfaces that can be functionalized with multiple molecules to realize sophisticated designs, nanomaterials have been developed as nanodrugs, nanocarriers, and nano-based vaccines to effectively induce sufficient immunologic memory. From this perspective, we introduce various nanomaterials with diverse antiviral mechanisms and summarize how nano-based antiviral agents protect against viral infection at the molecular, cellular, and organismal levels. We summarize the applications of nanomaterials for defense against emerging viruses by trapping and inactivating viruses and inhibiting viral entry and replication. We also discuss recent progress in nano-based vaccines with a focus on the mechanisms by which nanomaterials contribute to immunogenicity. We further describe how nanotechnology may improve vaccine efficacy by delivering large amounts of antigens to target immune cells and enhancing the immune response by mimicking viral structures and activating dendritic cells. Finally, we provide an overview of future prospects for nano-based antiviral agents and vaccines.
摘要：
Bacterial resistance to the antibiotics develops rapidly and is increasingly serious health concern in the world. It is an insoluble topic due to the multiple resistant mechanisms. The overexpression of relative activities of the efflux pump has proven to be a frequent and important source of bacterial resistance. Efflux transporters in the membrane from the resistant bacteria could play a key role to inhibit the intracellular drug intake and impede the drug activities. However, nanoparticles (NPs), one of the most frequently used encapsulation materials, could increase the intracellular accumulation of the drug and inhibit the transporter activity effectively. The rational and successful application of nanotechnology is a key factor in overcoming bacterial resistance. Furthermore, nanoparticles such as metallic, carbon nanotubes and so on, may prevent the development of drug resistance and be associated with antibiotic agents, inhibiting biofilm formation or increasing the access into the target cell and exterminating the bacteria eventually. In the current study, the mechanisms of bacterial resistance are discussed and summarized. Additionally, the opportunities and challenges in the use of nanoparticles against bacterial resistance are also illuminated. At the same time, the use of nanoparticles to combat multidrug-resistant bacteria is also investigated by coupling natural antimicrobials or other alternatives. In short, we have provided a new perspective for the application of nanoparticles against multidrug-resistant bacteria.
期刊：
Ecotoxicology and Environmental Safety,2021年219:112292 ISSN：0147-6513
通讯作者：
Shaoyong Lu
作者机构：
[Zhang, Yaru; Lu, Shaoyon; Liu, Xiaohui] Chinese Res Inst Environm Sci, State Environm Protect Sci Observat & Res Stn Lak, State Key Lab Environm Criteria & Risk Assessment, Natl Engn Lab Lake Pollut Control & Ecol Restorat, Beijing 100012, Peoples R China.;[Liu, Xianbin; Zhang, Yaru] Tianjin Univ Sci & Technol, Sch Ocean & Environm, Tianjin 300457, Peoples R China.;[Liu, Xiaohui] Tsinghua Univ, Sch Environm, Beijing 100084, Peoples R China.;[Liu, Ying; Xu, Jiamin] Harbin Inst Technol, Sch Environm, Harbin 150001, Peoples R China.;[Guo, Wei] Beijing Univ Technol, Coll Environm & Energy Engn, Beijing 100124, Peoples R China.
通讯机构：
[Shaoyong Lu] S;State Key Laboratory of Environmental Criteria and Risk Assessment, National Engineering Laboratory for Lake Pollution Control and Ecological Restoration, State Environmental Protection Scientific Observation and Research Station for Lake Dongtinghu (SEPSORSLD), Research Centre of Lake Environment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China
作者机构：
[Sun, Wei; Shi, Yuhua; Zhao, Bo; Wu, Lan; Xiang, Li; Xiong, Chao; Chen, Shilin] China Acad Chinese Med Sci, Inst Chinese Mat Med, Key Lab Beijing Identificat & Safety Evaluat Chin, Beijing, Peoples R China.;[Xiong, Chao] Wuhan Polytech Univ, Sch Biol & Pharmaceut Engn, Dept Food & Drug Resources & Hlth Food Innovat, Wuhan, Hubei, Peoples R China.
通讯机构：
[Wei Sun; Shilin Chen] K;Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, PR China<&wdkj&>Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, PR China
关键词：
Ardisia gigantifolia;DNA barcoding;ITS2 and psbA-trnH;Bar-HRM;Rapid identification
摘要：
Recently, biogenic toxins have received increasing attention owing to their high contamination levels in feed and food as well as in the environment. However, there is a lack of an integrative platform for seamless linking of data-driven computational methods with 'wet' experimental validations. To this end, we constructed a novel platform that integrates the technical aspects of toxin biotransformation methods. First, a biogenic toxin database termed ToxinDB (http://www.rxnfinder.org/toxindb/), containing multifaceted data on more than 4836 toxins, was built. Next, more than 8000 biotransformation reaction rules were extracted from over 300,000 biochemical reactions extracted from ~580,000 literature reports curated by more than 100 people over the past decade. Based on these reaction rules, a toxin biotransformation prediction model was constructed. Finally, the global chemical space of biogenic toxins was constructed, comprising ~550,000 toxins and putative toxin metabolites, of which 94.7% of the metabolites have not been previously reported. Additionally, we performed a case study to investigate citrinin metabolism in Trichoderma, and a novel metabolite was identified with the assistance of the biotransformation prediction tool of ToxinDB. This unique integrative platform will assist exploration of the 'dark matter' of a toxin's metabolome and promote the discovery of detoxification enzymes.
期刊：
Ecotoxicology and Environmental Safety,2021年221:112427 ISSN：0147-6513
通讯作者：
Liu, X.;Lu, S.
作者机构：
[Wang, Yongqiang; Lu, Shaoyong; Liu, Xiaohui] Chinese Res Inst Environm Sci, Res Ctr Lake Environm,State Environm Protect Key, State Key Lab Environm Criteria & Risk Assessment, Natl Engn Lab Lake Pollut Control & Ecol Restorat, Beijing 100012, Peoples R China.;[Wang, Yongqiang] Harbin Inst Technol, State Key Lab Urban Water Resource & Environm, Harbin 150090, Peoples R China.;[Liu, Xiaohui] Tsinghua Univ, Beijing 100084, Peoples R China.;[Chen, Jing] Wuhan Polytech Univ, Coll Biol & Pharmaceut Engn, Wuhan 430023, Peoples R China.;[Han, Maozhen] Anhui Med Univ, Sch Life Sci, Hefei 230032, Peoples R China.
通讯机构：
[Shaoyong Lu; Xiaohui Liu] S;State Key Laboratory of Environmental Criteria and Risk Assessment, National Engineering Laboratory for Lake Pollution Control and Ecological Restoration, State Environmental Protection Key Laboratory for Lake Pollution Control, State Environmental Protection Scientific Observation and Research Station for Lake Dongtinghu (SEPSORSLD), Research Centre of Lake Environment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China<&wdkj&>Tsinghua University, Beijing 100084, China<&wdkj&>State Key Laboratory of Environmental Criteria and Risk Assessment, National Engineering Laboratory for Lake Pollution Control and Ecological Restoration, State Environmental Protection Key Laboratory for Lake Pollution Control, State Environmental Protection Scientific Observation and Research Station for Lake Dongtinghu (SEPSORSLD), Research Centre of Lake Environment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China
关键词：
Ebinur Lake Basin;Antibiotics;Antibiotic resistance genes;Microbial community
期刊：
Free Radical Biology and Medicine,2021年173(7):64-69 ISSN：0891-5849
通讯作者：
Chen, Xiuping
作者机构：
[Zhong, Bingling; Hou, Ying; Zhao, Lin; Chen, Xiuping; Yu, Jie; Wang, Xianzhe] Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Macau, Peoples R China.;[Yu, Jie] Wuhan Polytech Univ, Coll Life Sci & Technol, Wuhan, Peoples R China.;[Chen, Xiuping] Univ Macau, Fac Hlth Sci, Dept Pharmaceut Sci, Macau, Peoples R China.
通讯机构：
[Xiuping Chen] S;State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China<&wdkj&>Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Macau, China
摘要：
A novel diarylheptanoid-flavonol dimer (1), named officinin C, was isolated from the rhizomes of Alpinia officinarum Hance. The structure elucidation was accomplished by HR-ESI-MS and 1D and 2D NMR methods. Its xanthine oxidase inhibitory activity was tested along with officinin A (2). At the concentration of 25 mu M, compounds 1 and 2 can reach 57 and 52% inhibition rates against xanthine oxidase.
摘要：
Dietary oils have critical influences on human health, and thermally cooking or frying modify the components and nutritional functions of oils. Palm oil was the most widely used oil in food processing industry, but its health effects remain debatable. In the current study, we aimed to compare the effects of thermally oxidized palm oil and canola oil on gut microbiota. Palm oil or canola oil were heated at 180 degrees C for 10 h to prepare high-fat diets. Rats were fed high-fat diets for 3 months, and hematological properties, gut microflora composition and intestinal gene expression were examined. The results indicated that heated canola oil consumption elevated plasma total cholesterol and LDL-c levels compared with unheated canola oil, but heated palm oil does not had these effects; and consumption of heated palm oil significantly elevated the relative abundance of Lactobacillucs and Roseburia in gut, compared with non-heated palm oil or two canola oil groups. Moreover, intestinal expression of IL-22 was increased in heated palm oil fed animal, though ZO-1 and GPR41 were reduced. In conclusion, heating process may enhance the effects of palm oil on proliferation of probiotics Lactobacillucs, and weaken the effects of canola oil on cholesterol transport and metabolism. (C) 2021 Beijing Academy of Food Sciences. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.
通讯机构：
[Yun Fan] S;[Hong-Xun Wang] C;College of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan 430023, China<&wdkj&>School of Biosciences, University of Birmingham, Birmingham B15 2TT, UK
关键词：
Antioxidant;Dietary supplementation;Fruit fly;In vivo evaluation;Oxidative stress
摘要：
Dietary supplementation with antioxidants provides health benefits by preventing diseases caused by oxidative stress and damage. Consequently, there has been growing interest in the study of antioxidative foods and their active ingredients. Oxidative stress and antioxidative responses are mechanistically conserved from Drosophila to mammals. Therefore, as a well-established model organism with a short life cycle and advantages of genetic manipulation, the fruit fly has been increasingly employed to assess functions of antioxidants in vivo. In this review, the antioxidative defense mechanisms, methods used and assays developed in Drosophila to evaluate antioxidant supplementation, are highlighted. The main manifestations of antioxidation include reduction of reactive species, up-regulation of endogenous antioxidants, inhibition on oxidative damage to biomacromolecules, enhanced resistance against oxidative stress and extension of lifespan, which are related to the activations of nuclear factor erythroid 2-related factor 2-antioxidant response element pathway and other adaptive responses. Moreover, the key considerations and future perspectives for the application of Drosophila models in the studies of food-derived antioxidants are discussed.
关键词：
A20;Entada phaseoloides (L.) merr;Mitogen-activated protein kinases;Pro-inflammatory cytokines;Rheumatoid arthritis;Triterpene saponin
摘要：
ETHNOPHARMACOLOGICAL RELEVANCE: The stems of Entada phaseoloides (L.) Merr commonly named "Guo-gang-long", is a traditional Chinese folk medicine that has been used clinically in China for the treatment of arthritis. Our previous study described that triterpene saponins isolated from "Guo-gang-long" could inhibit the inflammatory response. However, the potential mechanism of "Guo-gang-long" on treatment of arthritis, and whether the triterpene saponins responsible for its anti-arthritic effect are unclear. AIM: To investigate the function and mechanisms of the triterpene saponins from E. phaseoloides (ES) in collagen-induced arthritis (CIA) rats. MATERIALS AND METHODS: The chemical components of ES were analyzed by HPLC. Anti-arthritic activity of ES was investigated in CIA rats, which was established by immunization with bovine type II collagen. Three doses of ES (25, 50 and 100mg/kg) were administrated using oral gavage to CIA rats daily for 3 weeks. The anti-arthritic activity of ES was evaluated by clinical arthritis scoring, paw swelling and mechanical sensitivity, as well as histological changes in CIA rats. The impacts of ES on the regulation of the ubiquintin-editing enzyme A20 and MAPK signaling pathway, and production of pro-inflammatory cytokines in CIA rats were examined by Western blot, quantitative real-time PCR, ELISA, and immunohistochemical staining, respectively. RESULTS: ES treatment relieved the paw swelling, hyperalgesia and joint destruction, and prevented the progression of arthritis in CIA rats. Meanwhile, ES suppressed the excessive mRNA levels and protein expression of TNF-α and IL-17 in synovial tissues and hind paw joints, and reduced the production of IL-1β, TNF-α and IL-17 in serum. Furthermore, ES up-regulated A20 and suppressed the phosphorylation of p38 and ERK1/2 in hind paw joints, as well as inhibiting the activation of spinal p38 in CIA rats. CONCLUSION: ES could relieve rheumatic symptoms and prevent the development of rheumatoid arthritis. The effects of ES may be mediated by reducing proinflammatory cytokine levels, up-regulating A20 expression, reducing p38 and ERK1/2 activation in periphery, and inhibiting of phospho-p38 in spinal cord.
摘要：
Aims The purpose of this study was to investigate the regulatory mechanism of epsilon-PL on Shewanella putrefaciens. Methods and Results Proteomics analysis of inhibitory effect of epsilon-PL against S. putrefaciens was performed by label-free quantitative assay based on high-resolution mass spectrometry (MS). Quantification of 2206 proteins was obtained with high confidence, and a total of 36 differentially expressed proteins (DEPs), with 10 and 26 proteins showing upregulation and downregulation, respectively, were identified. Upon Go functional enrichment, 11, 5 and 8 specific Go terms in biological processes, molecular functions and cellular components were identified, respectively. Six KEGG pathways, including 'ribosome', were significantly enriched. Among the ribosome pathway, there were seven DEPs and all of them were distributed on large and small subunits of ribosome. Conclusions The significant downregulation of proteins, large subunits of ribosomal proteins RP-L18, L30 and L27, small subunits ribosomal proteins S16 and S20, and RNA polymerase beta' subunit protein rpoC were the critical action sites of epsilon-PL to inhibit S. putrefaciens growth. Significance and Impact of the Study Shewanella putrefaciens is one of the representative fish-spoilage bacteria regardless of fish type, and poses significant problems for the fish brewery. A better understanding of the antibacterial mechanism of epsilon-PL on S. putrefaciens could make important contributions to development of biological control strategies of these economically important pathogens.
