作者机构:
[Zhang, Fa-Fu; Han, Bin; Meng, Min-Jie] School of Life Science and Biopharmaceutical, Guangdong Pharmaceutical University, Guangzhou, China;[Xu, Run-Hao] Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China;[Zhu, Qing-Qing] School of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, China;[Wu, Qi-Qi] Department of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China;[Wei, Hui-Min] Advanced Institute of Translational Medicine, Tongji University, Shanghai, China
摘要:
This study aimed to measure the expression of SAA2 in plasma and to assess its diagnostic efficacy as a biomarker for non-small cell lung cancer (NSCLC). The gene expression of SAA2 in NSCLC was analyzed based on a database. Then, SAA2 expression was detected by immunohistochemistry in lung tissue and by enzyme-linked immunosorbent assay in 90 patients with NSCLC and 61 normal controls. Finally, the diagnostic performance was assessed in terms of accuracy, sensitivity, and specificity. At the gene and protein levels, the SAA2 expression was significantly higher in the NSCLC group than in the control group (p < 0.01). It was higher in lung squamous carcinoma than in lung adenocarcinoma and in males than in females, and this trend was also observed in the lung squamous carcinoma group. Of note, the expression of SAA2 increased with increasing disease stage. Receiver operating characteristic (ROC) curve analysis revealed that the sensitivity of SAA2 was 83.61%, the specificity was 91.11%, and the area under the curve (AUC) was 0.9252. Its accuracy was 68.89%, which was higher than that of other conventional diagnostic biomarkers, and the combined application can effectively improve the diagnostic efficiency. Based on the results, SAA2 expression was positively correlated with the disease stage of NSCLC. Notably, SAA2 is more concerning in male patients with lung squamous carcinoma, and it can help in the screening and diagnosis of NSCLC. SAA2 may represent a novel diagnostic biomarker in NSCLC.
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:
Lotus root (Nelumbo nucifera G.) is a high economic value crop in the world. In this study, the storage characteristics (color, sensory, texture, and fatty acids) of lotus root ("Elian No.5") were evaluated at different harvest periods (September 2018, October 2018, November 2018, December 2018, and January 2019). Moreover, the storage characteristics were evaluated after the shortterm and long-term storage of lotus root at 4 degrees C and 20 degrees C. The hardness of lotus root significantly decreased at both temperatures (4 degrees C and 20 degrees C) during the first 3 days of storage. In contrast, the decrease in hardness delayed at 4 degrees C (beyond 3 days of storage). Further, genes related to hardness at different storage temperatures were identified using the RNA-seq and qRT-PCR. The results of this study provide a reference for lotus root storage and a basis for the molecular breeding of longterm-storable lotus root.
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.
摘要:
Oxidative stress and inflammation in kidney are the main causes for hyperuricemic nephropathy (HN). Baicalin and baicalein, two flavonoids, have anti-inflammatory and anti-oxidative effects and they are interconvertible in the body. In this study, both baicalin and baicalein were administered by intragastric administration (i.g.) or intraperitoneal injection (i.p.) at the dose of 50 mg kg(-1), once a day for 15 consecutive days to HN mice, a model established by i.g. of yeast extract combined with i.p. of potassium oxonate. In HN mice, baicalin and baicalein reduced serum uric acid (SUA) levels and protected kidneys by anti-inflammatory and anti-oxidative effects. Mechanistically, the effect of baicalin and baicalein on reducing SUA levels might due to their inhibitory effect on xanthine oxidase (XO) activity in vivo and in vitro. Furthermore, the mechanisms of baicalin and baicalein against HN were analyzed with network pharmacology and molecular docking technology. The network pharmacology indicated that the protective effects of baicalin and baicalein against HN were mainly related to their down-regulating effects on TLRs, NF-κB, MAPK, PI3K/AKT and NOD-like receptor signaling pathways. Molecular docking indicated high binding affinity of baicalin/baicalein to targets such as AKT1 and MAPK1. In summary, baicalin and baicalein are promising drug candidates for the treatment of HN by inhibiting XO activity, reducing inflammation and cell apoptosis through down-regulating TLRs/NLRP3/NF-κB, MAPK, PI3K/AKT/NF-κB pathways.
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.
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.