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1.
Chengming Ding Jun He Jun Zhao Junhua Li Jie Chen Wenyan Liao Yi Zeng Jing Zhong Chaoying Wei Liming Zhang Mei Zhou Zeming Jia Yaoting Zhang Hui Li Yuzheng Zhou Xiaolong Xiao Dong Han Chong Li Zhu Zhu Zanxian Xia Jian Peng 《Cell proliferation》2018,51(5)
Objective
β‐catenin is one of the most critical oncogenes associated with many kinds of human cancers, especially in the human CRC. Innate immunity recognizes tumour derived damage‐associated molecular patterns (DAMPs) and primes the anti‐tumour adaptive responses. While the function of β‐catenin in CRC tumourigenesis is well established, its impact on innate immune evasion is largely unknown. The aim of this study is to characterize the role of β‐catenin in inhibiting RIG‐I‐like receptor (RLR)‐mediated IFN‐β signalling in colorectal cancer.Materials and Methods
Immunohistochemical staining and western blotting were conducted to study the expression of β‐catenin, IRF3 and phospho‐IRF3 (p‐IRF3) in CRC samples and cell lines. Plaque assay determining virus replication was performed to assess the regulation of β‐catenin on IFN‐β signalling. The inhibition of β‐catenin on RLR‐mediated IFN‐β signalling was further studied by real‐time analyses and reporter assays in the context of lentiviral‐mediated β‐catenin stably knocking down. Lastly, co‐immunoprecipitation and nuclear fractionation assay were conducted to monitor the interaction between β‐catenin and IRF3.Results
We found that high expression of β‐catenin positively correlated with the expression of IRF3 in CRC cells. Overexpression of β‐catenin increased the viral replication. Conversely knocking down of β‐catenin inhibited viral replication. Furthermore, our data demonstrated that β‐catenin could inhibit the expression of IFN‐β and interferon‐stimulated gene 56 (ISG56). Mechanistically, we found that β‐catenin interacted with IRF3 and blocked its nuclear translocation.Conclusion
Our study reveals an unprecedented role of β‐catenin in enabling innate immune evasion in CRC.2.
Finasteride accelerates prostate wound healing after thulium laser resection through DHT and AR signalling
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Ruizhe Zhao Xingjie Wang Chenyi Jiang Fei Shi Yiping Zhu Boyu Yang Jian Zhuo Yifeng Jing Guangheng Luo Shujie Xia Bangmin Han 《Cell proliferation》2018,51(3)
Objectives
Urinary tract infection, urinary frequency, urgency, urodynia and haemorrhage are common post‐operative complications of thulium laser resection of the prostate (TmLRP). Our study mainly focuses on the role of finasteride in prostate wound healing through AR signalling.Materials and methods
TmLRP beagles were randomly distributed into different treatment groups. Serum and intra‐prostatic testosterone and DHT level were determined. Histological analysis was conducted to study the re‐epithelialization and inflammatory response of the prostatic urethra in each group. We investigated the role of androgen in proliferation and inflammatory response in prostate. In addition, the effects of TNF‐α on prostate epithelium and stromal cells were also investigated.Results
Testosterone and DHT level increased in testosterone group and DHT decreased in finasteride group. Accelerated wound healing of prostatic urethra was observed in the finasteride group. DHT suppressed proliferation of prostate epithelium and enhanced inflammatory response in prostate. We confirmed that DHT enhanced macrophages TNF‐α secretion through AR signalling. TNF‐α suppressed proliferation of prostate epithelial cells and retarded cell migration. TNF‐α also played a pivotal role in suppressing fibroblasts activation and contraction.Conclusion
Testosterone treatment repressed re‐epithelialization and wound healing of prostatic urethra. Finasteride treatment may be an effective way to promote prostate re‐epithelialization.3.
Ecological and cultural shifts of hunter‐gatherers of the Jomon period paralleled with environmental changes
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Soichiro Kusaka Yasuhiro Yamada Minoru Yoneda 《American journal of physical anthropology》2018,167(2):377-388
Objectives
Holocene hunter‐gatherers adapted to climatic and environmental changes over time. Carbon and nitrogen stable isotope analysis of human skeletal remains from the Inariyama shell mound of the Final Jomon period have revealed large dietary variations in the population. This study analyzed radiocarbon dates of these individuals to test temporal changes in diet and its relationship with tooth ablation.Materials and Methods
Twenty‐nine human skeletal remains from Inariyama were included in this study. Extracted bone collagen samples were purified to graphite. Then, radiocarbon dating of these samples was performed using the accelerator mass spectrometer.Results
The radiocarbon ages of Inariyama ranged about, 3,230–2,140 cal BP and showed three peaks of occupation. In the early and late phases, terrestrial resource consumption and incisor extraction were observed, while marine resource consumption and canine extraction were observed in the middle phase.Discussion
These temporal changes of diet and tooth ablation types occurred in parallel with climatic cooling and environmental change and help reveal how Holocene hunter‐gatherers adapted to the changing environments.4.
Jacinda R. Larson Mange F. Manyama Joanne B. Cole Paula N. Gonzalez Christopher J. Percival Denise K. Liberton Tracey M. Ferrara Sheri L. Riccardi Emmanuel A. Kimwaga Joshua Mathayo Jared A. Spitzmacher Campbell Rolian Heather A. Jamniczky Seth M. Weinberg Charles C. Roseman Ophir Klein Ken Lukowiak Richard A. Spritz Benedikt Hallgrimsson 《American journal of physical anthropology》2018,165(2):327-342
Objectives
In group‐living primates, it has been reported that the alpha male exhibits high concentrations of cortisol and testosterone in the context of mating competition. We investigated how the presence of females affected salivary cortisol and testosterone levels in males from a small captive group of chimpanzees (Pan troglodytes). Specifically, we assessed whether the presence of females resulted in a rapid increase in salivary cortisol and testosterone levels in the alpha male.Materials and methods
We compared the social behavior and salivary hormone concentrations of four males before and after the presentation of receptive females. Three times a day, we collected saliva samples, a useful matrix for investigating short‐term hormonal changes, and measured cortisol and testosterone concentration by liquid chromatography–tandem mass spectrometry (LC–MS/MS).Results
The frequency of inter‐male aggression increased in the presence of females, indicating intense competition among males. Salivary cortisol levels increased in all males in the presence of females; however, the increase was significantly more pronounced in the alpha male. We found a complex three‐way interaction among the presence of females, sampling timings, and male dominance rank in the analysis of salivary testosterone. Contrary to our prediction, a post hoc analysis revealed that salivary testosterone levels decreased after female introduction and that the alpha male did not show a higher level of salivary testosterone.Conclusions
Our study provides experimental evidence suggesting that the presence of females plays a significant role in the rank‐related variation in the cortisol levels in male chimpanzees. Furthermore, our findings demonstrate the usefulness of salivary hormones for detecting short‐term physiological changes in studies of socioendocrinology.5.
Luca Fiorenza Robin Yong Sarbin Ranjitkar Toby Hughes Michelle Quayle Paul G. McMenamin John Kaidonis Grant C. Townsend Justin W. Adams 《American journal of physical anthropology》2018,167(2):400-406
Objectives
Rapid prototyping (RP) technology is becoming more affordable, faster, and is now capable of building models with a high resolution and accuracy. Due to technological limitations, 3D printing in biological anthropology has been mostly limited to museum displays and forensic reconstructions. In this study, we compared the accuracy of different 3D printers to establish whether RP can be used effectively to reproduce anthropological dental collections, potentially replacing access to oftentimes fragile and irreplaceable original material.Methods
We digitized specimens from the Yuendumu collection of Australian Aboriginal dental casts using a high‐resolution white‐light scanning system and reproduced them using four different 3D printing technologies: stereolithography (SLA); fused deposition modeling (FDM); binder‐jetting; and material‐jetting. We compared the deviations between the original 3D surface models with 3D print scans using color maps generated from a 3D metric deviation analysis.Results
The 3D printed models reproduced both the detail and discrete morphology of the scanned dental casts. The results of the metric deviation analysis demonstrate that all 3D print models were accurate, with only a few small areas of high deviations. The material‐jetting and SLA printers were found to perform better than the other two printing machines.Conclusions
The quality of current commercial 3D printers has reached a good level of accuracy and detail reproduction. However, the costs and printing times limit its application to produce large sample numbers for use in most anthropological studies. Nonetheless, RP offers a viable option to preserve numerically constraint fragile skeletal and dental material in paleoanthropological collections.6.
Trabecular architecture and joint loading of the proximal humerus in extant hominoids,Ateles, and Australopithecus africanus
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Tracy L. Kivell Rebecca Davenport Jean‐Jacques Hublin J. Francis Thackeray Matthew M. Skinner 《American journal of physical anthropology》2018,167(2):348-365
Objectives
Several studies have investigated potential functional signals in the trabecular structure of the primate proximal humerus but with varied success. Here, we apply for the first time a “whole‐epiphyses” approach to analysing trabecular bone in the humeral head with the aim of providing a more holistic interpretation of trabecular variation in relation to habitual locomotor or manipulative behaviors in several extant primates and Australopithecus africanus.Materials and methods
We use a “whole‐epiphysis” methodology in comparison to the traditional volume of interest (VOI) approach to investigate variation in trabecular structure and joint loading in the proximal humerus of extant hominoids, Ateles and A. africanus (StW 328).Results
There are important differences in the quantification of trabecular parameters using a “whole‐epiphysis” versus a VOI‐based approach. Variation in trabecular structure across knuckle‐walking African apes, suspensory taxa, and modern humans was generally consistent with predictions of load magnitude and inferred joint posture during habitual behaviors. Higher relative trabecular bone volume and more isotropic trabeculae in StW 328 suggest A. africanus may have still used its forelimbs for arboreal locomotion.Discussion
A whole‐epiphysis approach to analysing trabecular structure of the proximal humerus can help distinguish functional signals of joint loading across extant primates and can provide novel insight into habitual behaviors of fossil hominins.7.
Loss‐of‐function of miR‐142 by hypermethylation promotes TGF‐β‐mediated tumour growth and metastasis in hepatocellular carcinoma
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Qiangfeng Yu Leyang Xiang Libo Yin Xincheng Liu Dinghua Yang Jianyin Zhou 《Cell proliferation》2017,50(6)
Objectives
Hypermethylation‐induced epigenetic silencing of tumour suppressor genes (TSGs) are frequent events during carcinogenesis. MicroRNA‐142 (miR‐142) is found to be dysregulated in cancer patients to participate into tumour growth, metastasis and angiogenesis. However, the tumour suppressive role of miR‐142 and the status of methylation are not fully understood in hepatocellular carcinoma (HCC).Methods
Hepatocellular carcinoma tissues and corresponding non‐neoplastic tissues were collected. The expression and function of miR‐142 and TGF‐β in two HCC cell lines were determined. The miRNA‐mRNA network of miR‐142 was analysed in HCC cell lines.Results
We found that the miR‐142 expression was reduced in tumour tissues and two HCC cell lines HepG2 and SMMC7721, which correlated to higher TNM stage, metastasis and differentiation. Moreover, miR‐142 was identified to directly target and inhibit transforming growth factor β (TGF‐β), leading to decreased cell vitality, proliferation, EMT and the ability of pro‐angiogenesis in TGF‐β‐dependent manner. Interestingly, the status of methylation of miR‐142 was analysed and the results found the hypermethylated miR‐142 in tumour patients and cell lines. The treatment of methylation inhibitor 5‐Aza could restore the expression of miR‐142 to suppress the TGF‐β expression, which impaired TGF‐β‐induced tumour growth.Conclusion
These findings implicated that miR‐142 was a tumour suppressor gene in HCC and often hyermethylated to increase TGF‐β‐induced development of hepatocellular carcinoma.8.
9.
Long bone diaphyseal shape follows different ontogenetic trajectories in captive and wild gorillas
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Stephanie L. Canington Adam D. Sylvester M. Loring Burgess Juho‐Antti Junno Christopher B. Ruff 《American journal of physical anthropology》2018,167(2):366-376
Objectives
A number of studies have demonstrated the ontogenetic plasticity of long bone diaphyseal structure in response to mechanical loading. Captivity should affect mechanical loading of the limbs, but whether captive apes grow differently than wild apes has been debated. Here, we compare captive and wild juvenile and adult Gorilla to ascertain whether growth trajectories in cross‐sectional diaphyseal shape are similar in the two environments.Materials and methods
A sample of young juvenile (n = 4) and adult (n = 10) captive Gorilla gorilla gorilla specimens, with known life histories, were compared with age‐matched wild G.g. gorilla (n = 62) and G. beringei beringei (n = 75) in relative anteroposterior to mediolateral bending strength of the femur, tibia, and humerus. Cross sections were obtained using peripheral quantitative CT.Results
Captive and wild adult G.g. gorilla differed in bending strength ratios for all three bones, but these differences were not present in young juvenile G.g. gorilla. In comparisons across taxa, captive juvenile G.g. gorilla were more similar to wild G.g. gorilla than to G.b. beringei, while captive adult G.g. gorilla were more similar in shape to G.b. beringei in the hind limb.Discussion
Captive and wild G. gorilla follow different ontogenetic trajectories in long bone diaphyseal shape, corresponding to environmental differences and subsequent modified locomotor behaviors. Differences related to phylogeny are most evident early in development.10.
Concurrence of autophagy with apoptosis in alveolar epithelial cells contributes to chronic pulmonary toxicity induced by methamphetamine
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Yun Wang Yu‐Han Gu Li‐Ye Liang Ming Liu Bin Jiang Mei‐Jia Zhu Xin Wang Lin Shi 《Cell proliferation》2018,51(5)
Objectives
Methamphetamine (MA) abuse evokes pulmonary toxicity. The aim of our study is to investigate if autophagy is induced by MA and if autophagy‐initiated apoptosis in alveolar epithelial cells is involved in MA‐induced chronic pulmonary toxicity.Materials and Methods
The rats in Control group and MA group were tested by Doppler and HE staining. The alveolar epithelial cells were treated with MA, following by western blot, RT‐PCR and immunofluorescence assay.Results
Chronic exposure to MA resulted in lower growth ratio of weight and in higher heart rate and peak blood flow velocity of the main pulmonary artery of rats. MA induced infiltration of inflammatory cells in lungs, more compact lung parenchyma, thickened alveolar septum and reduction in the number of alveolar sacs. In alveolar epithelial cells, the autophagy marker LC3 and per cent of cells containing LC3‐positive autophagosome were significantly increased. MA dose dependently suppressed the phosphorylation of mTOR to inactivate mTOR, elicited autophagy regulatory proteins LC3 and Beclin‐1, accelerated the transformation from LC3 I to LC3 II and initiated apoptosis by decreasing Bcl‐2 and increasing Bax, Bax/Bcl‐2 and cleaved Caspase 3. The above results suggest that sustained autophagy was induced by long‐term exposure to MA and that the increased Beclin‐1 autophagy initiated apoptosis in alveolar epithelial cells.Conclusions
Concurrence of autophagy with apoptosis in alveolar epithelial cells contributes to chronic pulmonary toxicity induced by MA.11.
Critical role of inflammatory mast cell in fibrosis: Potential therapeutic effect of IL‐37
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P. Conti Al. Caraffa F. Mastrangelo L. Tettamanti G. Ronconi I. Frydas S. K. Kritas T. C. Theoharides 《Cell proliferation》2018,51(5)
Background
Fibrosis involves the activation of inflammatory cells, leading to a decrease in physiological function of the affected organ or tissue.Aims
To update and synthesize relevant information concerning fibrosis into a new hypothesis to explain the pathogenesis of fibrosis and propose potential novel therapeutic approaches.Materials and Methods
Literature was reviewed and relevant information is discussed in the context of the pathogenesis of fibrosis.Results
A number of cytokines and their mRNA are involved in the circulatory system and in organs of patients with fibrotic tissues. The profibrotic cytokines are generated by several activated immune cells, including fibroblasts and mast cells (MCs), which are important for tissue inflammatory responses to different types of injury. MC‐derived TNF, IL‐1, and IL‐33 contribute crucially to the initiation of a cascade of the host defence mechanism(s), leading to the fibrosis process. Inhibition of TNF and inflammatory cytokines may slow the progression of fibrosis and improve the pathological status of the affected subject. IL‐37 is generated by various types of immune cells and is an IL‐1 family member protein. IL‐37 is not a receptor antagonist; it binds IL‐18 receptor alpha (IL‐18Rα) and delivers the inhibitory signal by using TIR8. It has been shown that IL‐37 can be protective in inflammation and injury, and inhibits both innate and adaptive immunity.Discussion
IL‐37 may be useful for suppression of inflammatory diseases induced by inhibiting MyD88‐dependent TLR signalling. In addition, IL‐37 downregulates NF‐κB induced by TLR2 or TLR4 through a mechanism dependent on IL‐18Rα.Conclusion
This review summarizes current knowledge on the role of MC in inflammation and tissue/organ fibrosis, with a focus on the therapeutic potential of IL‐37‐targeting cytokines.12.
Loss of PPM1F expression predicts tumour recurrence and is negatively regulated by miR‐590‐3p in gastric cancer
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Jing Zhang Ming Jin Xiaoyu Chen Rui Zhang Yanxia Huang Hui Liu Jinshui Zhu 《Cell proliferation》2018,51(4)
Objectives
MicroRNAs (miRNAs) as small non‐coding RNA molecules act by negatively regulating their target genes. Recent studies have shown that protein phosphatase Mg2+/Mn2+‐dependent 1F (PPM1F) plays a critical role in cancer metastasis. But, the regulation mechanisms of PPM1F by miRNAs in gastric cancer (GC) remain undefined.Methods
The correlation of PPM1F or miR‐590‐3p (miR‐590) expression with clinicopathological features and prognosis of the patients with GC was analysed by TCGA RNA‐sequencing data. The miRNAs that target PPM1F gene were identified by bioinformatics and Spearman correlation analysis, and the binding site between miR‐590 and PPM1F 3′UTR was confirmed by dual luciferase assay. MTT and Transwell assays were conducted to evaluate the effects of miR‐590 or (and) PPM1F on cell proliferation and invasion.Results
We found that PPM1F expression was downregulated in GC tissues and cell lines and was correlated with tumour recurrence in patients with GC. The decreased expression of PPM1F was attributed to the dysregulation of miR‐590 expression rather than its genetic or epigenetic alterations. Overexpression of miR‐590 promoted cell proliferation and invasion capability of GC cells, while knockdown of miR‐590 reversed these effects. Moreover, PPM1F was validated as a direct target of miR‐590 and counteracted the tumour‐promoting effects caused by miR‐590. The expression of miR‐590 presented the negative correlation with PPM1F expression and acted as an independent prognostic factor for tumour recurrence in patients with GC.Conclusion
PPM1F may function as a suppressive factor and is negatively regulated by miR‐590 in GC.13.
Jaime Fagúndez 《植被学杂志》2018,29(4):765-774
Questions
What is the general pattern of species co‐occurrence in managed heathlands? Is the pattern consistent among functional groups? Is it ruled by species competition, or by contrasting environments at a fine scale? Does grazing pressure and herbivore species condition species interactions?Location
Erica mackayana wet heaths, Galicia, NW Iberian Peninsula.Methods
A null model approach was used to compare species co‐occurrence with generated random matrices from 54 10‐m transects. The C‐score was obtained from the multispecies presence/absence matrix for each transect of shrubs and graminoids recorded at 25‐cm intervals. Differences in canopy height were recorded to assess the importance of the environment compared to inter‐specific competition. Results were linked to different levels of grazing pressure and herbivore species.Results
Species segregation was the main pattern for all species, but mainly among graminoid species compared to shrubs. Graminoids showed an even proportion of segregated pairs explained by different canopy heights and competition. These differences were mainly species environmental requirements of canopy height. Levels of grazing pressure enhanced species segregation in graminoids but had no effect on shrubs or the total species set.Conclusions
Competition and canopy height affect the E. mackayana heathland composition, but differently for functional groups. A heterogeneous vegetation profile with shrub mats and open gaps created by light grazing promotes species co‐existence within mats and competition in gaps. I suggest this is an optimum structure for the habitat to be targeted through management.14.
FBXW7 suppresses epithelial‐mesenchymal transition and chemo‐resistance of non‐small‐cell lung cancer cells by targeting snai1 for ubiquitin‐dependent degradation
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Guodong Xiao Yuan Li Meng Wang Xiang Li Sida Qin Xin Sun Rui Liang Boxiang Zhang Ning Du Chongwen Xu Hong Ren Dapeng Liu 《Cell proliferation》2018,51(5)
Objectives
FBXW7 acts as a tumour suppressor by targeting at various oncoproteins for ubiquitin‐mediated degradation. However, the clinical significance and the involving regulatory mechanisms of FBXW7 manipulation of NSCLC regeneration and therapy response are not clear.Materials and Methods
Immunohistochemical staining and qRT‐PCR were applied to detect FBXW7 and Snai1 expression in 100 samples of NSCLC and matched tumour‐adjacent tissues. FBXW7 manipulation of cancer biological functions were studied by using MTT assay, immunoblotting, flow cytometry, transwells, wound healing assay, and sphere‐formation assays. Immunofluorescence and co‐immunoprecipitation were used to analyse the possible interaction between Snai1 and FBXW7.Results
We detected the decreased FBXW7 expression in majority of the NSCLC tissues, and lower FBXW7 level was correlated with advanced TNM stage. Furthermore, those patients with decreased FBXW7 expression tend to have both poorer 5‐year survival outcomes, and shorter disease‐free survival, comparing to those with higher FBXW7 levels. Functionally, we found that FBXW7 enforcement suppressed NSCLC progression by inducing cell growth arrest, increasing chemo‐sensitivity and inhibiting Epithelial‐mesenchymal Transition (EMT) progress. Results further showed that FBXW7 could interact with Snai1 directly to degrade its expression through ubiquitylating alternation in NSCLC, which could be partially abrogated by restoring Snai1 expression.Conclusions
FBXW7 conduction of tumour suppression was partly through degrading Snai1 directly for ubiquitylating regulation in NSCLC15.
Kate McGrath Sireen El‐Zaatari Debbie Guatelli‐Steinberg Margaret A. Stanton Donald J. Reid Tara S. Stoinski Michael R. Cranfield Antoine Mudakikwa Shannon C. McFarlin 《American journal of physical anthropology》2018,166(2):337-352
Objectives
The approximately 250 years old remains of the Kwäd?y Dän Ts'ìnch? man were found in a glacier in Canada. Studying the state of preservation of the corpse, we observed black deposits in his lung. Following this observation we wanted to determine: (1) location of the deposits in the lung tissue, (2) composition and origins of the deposits.Methods
By light microscopy (LM) and transmission electron microscopy (TEM), we studied the deposits in the Kwäd?y Dän Ts'ìnch? man’ s lung and compared it with distribution of anthracotic deposits in contemporary samples from the David Harwick Pathology Centre (DHPC). To determine chemical composition of the inclusions we used Raman spectroscopy. Scanning electron microscopy and elemental mapping was used for determine the chemical elements.Results
The histopathological identification of anthracosis in the Kwäd?y Dän Ts'ìnch? man's lung allowed us to distinguish crushed parenchyma from conducting airway tissue and identification of particles using LM and TEM. Crystal particles were found using TEM. Ordered carbonaceous material (graphene and graphite), disordered carbonaceous material (soot) and what might be minerals (likely conglomerates) were found with Raman spectrometry. Gold and lead particles in the lung were discovered with scanning electron microscopy and elemental mapping.Conclusions
Presence of soot particles in anthracotic areas in the Kwäd?y Dän Ts'ìnch? man's lung probably were due to an inhalation of particles in open fires. Gold and lead particles are most likely of an environmental origin and may have been inhaled and could have impacted his health and his Champagne and Aishihik First Nations (CAFN) contemporaries.16.
17.
Measurements of auto‐antibodies to α‐synuclein in the serum and cerebral spinal fluids of patients with Parkinson's disease
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Rizwan S. Akhtar Joseph P. Licata Kelvin C. Luk Leslie M. Shaw John Q. Trojanowski Virginia M.‐Y. Lee 《Journal of neurochemistry》2018,145(6):489-503
18.
Association of tumor necrosis factor alpha gene polymorphisms with Helicobacter pylori infection in dyspeptic patients in Sri Lanka
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Piyumali Sandareka Arachchi Manjula Manoji Weerasekera Bimalka Senevirathna Deepaka Weerasekera Neluka Fernando Chinthika Prabhashinie Gunasekara 《Microbiology and immunology》2018,62(7):429-435
19.
Li Z Yao H Ma Y Dong Q Chen Y Peng Y Zheng BJ Huang JD Chan CY Lin MC Sung JJ Yuen KY Kung HF He ML 《The journal of gene medicine》2008,10(6):619-627
Background
Interferon‐α2 (IFNα2) is routinely used for anti‐hepatitis B virus (HBV) treatment. However, the therapeutic efficiency is unsatisfactory, particularly in East Asia. Such inefficiency might be a result of the short half‐life, relatively low local concentration and strong side‐effects of interferons. Frequent and repeated injection is also a big burden for patients. In the present study, a single dose of vector‐delivered IFNα1 was tested for its anti‐HBV effects.Methods
Adeno‐associated viral vector (AAV‐IFNα1) was generated to deliver the IFNα1 gene into hepatocytes. IFNα1, hepatitis B surface (HBsAg) and e (HBeAg) antigens were measured by enzyme‐linked immunosorbent assay and/or western blotting. The level of viral DNA was measured by quantitative real‐time polymerase chain reaction.Results
AAV‐IFNα1 effectively transduced HBV‐producing cells (HepAD38) and mouse hepatocytes, where IFNα1 was expressed in a stable manner. Both intracellular and extracellular HBsAg and HBeAg were significantly reduced in vitro. In the HBV‐producing mice, the concentration of IFNα1 in the liver was eight‐fold higher than that in plasma. Compared with control groups, HBeAg/HBsAg antigen levels were reduced by more than ten‐fold from day 1–5, and dropped to an undetectable level on day 9 in the AAV‐IFNα1 group. Concurrently, the level of viral DNA decreased over 30‐fold for several weeks.Conclusions
A single dose administration of AAV‐IFNα1 viral vector displayed prolonged transgene expression and superior antiviral effects both in vitro and in vivo. Therefore, the use of AAV‐IFNα1 might be a potential alternative strategy for anti‐HBV therapy. Copyright © 2008 John Wiley & Sons, Ltd.20.
Wnt signaling loss accelerates the appearance of neuropathological hallmarks of Alzheimer's disease in J20‐APP transgenic and wild‐type mice
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