Emily Dickinson is widely regarded as one of American's premier poets of the nineteenth century.In both style and content,her verse was,"revolutionary" in her day.Owing to the deep exploration of death a...Emily Dickinson is widely regarded as one of American's premier poets of the nineteenth century.In both style and content,her verse was,"revolutionary" in her day.Owing to the deep exploration of death and immortality,Emily Dickinson has become a puzzle in literary.As show in her poems,Dickinson's spiritual journey led her from na?ve nature-mysticism through disappointment,to a sacramental approach to immortality afterlife and further discouragement,culminating in a mature attitude of faithful unknowing and even more interrogating the immortality.This paper will base on the theory of the death and immortality through common people's fear to death,the essence of death,the significance of death to show the poetess's whole life-childhood,love,life condition,spiritual contradiction,and mainly her skeptical concept of death and immortality.展开更多
In an effort to find out how Nabokov manages to achieve aesthetic immortality in Speak Memory,a detailed text analysis is conducted on the techniques he has utilized.Afterwards,it draws the conclusion that Nabokov,fir...In an effort to find out how Nabokov manages to achieve aesthetic immortality in Speak Memory,a detailed text analysis is conducted on the techniques he has utilized.Afterwards,it draws the conclusion that Nabokov,firmly grounded on his own con⁃sciousness,manages to command memory with the help of imagination,thus,transforming this recreation of memory into a work of aesthetic eternity.展开更多
Photobiomodulation,originally used red and near-infrared lasers,can alter cellular metabolism.It has been demonstrated that the visible spectrum at 451-540 nm does not necessarily increase cell proliferation,near-infr...Photobiomodulation,originally used red and near-infrared lasers,can alter cellular metabolism.It has been demonstrated that the visible spectrum at 451-540 nm does not necessarily increase cell proliferation,near-infrared light promotes adipose stem cell proliferation and affects adipose stem cell migration,which is necessary for the cells homing to the site of injury.In this in vitro study,we explored the potential of adipose-derived stem cells to differentiate into neurons for future translational regenerative treatments in neurodegenerative disorders and brain injuries.We investigated the effects of various biological and chemical inducers on trans-differentiation and evaluated the impact of photobiomodulation using 825 nm near-infrared and 525 nm green laser light at 5 J/cm2.As adipose-derived stem cells can be used in autologous grafting and photobiomodulation has been shown to have biostimulatory effects.Our findings reveal that adipose-derived stem cells can indeed trans-differentiate into neuronal cells when exposed to inducers,with pre-induced cells exhibiting higher rates of proliferation and trans-differentiation compared with the control group.Interestingly,green laser light stimulation led to notable morphological changes indicative of enhanced trans-differentiation,while near-infrared photobiomodulation notably increased the expression of neuronal markers.Through biochemical analysis and enzyme-linked immunosorbent assays,we observed marked improvements in viability,proliferation,membrane permeability,and mitochondrial membrane potential,as well as increased protein levels of neuron-specific enolase and ciliary neurotrophic factor.Overall,our results demonstrate the efficacy of photobiomodulation in enhancing the trans-differentiation ability of adipose-derived stem cells,offering promising prospects for their use in regenerative medicine for neurodegenerative disorders and brain injuries.展开更多
Alzheimer's disease(AD)is characterized by complex etiology,long-lasting pathogenesis,and celltype-specific alterations.Currently,there is no cure for AD,emphasizing the urgent need for a comprehensive understandi...Alzheimer's disease(AD)is characterized by complex etiology,long-lasting pathogenesis,and celltype-specific alterations.Currently,there is no cure for AD,emphasizing the urgent need for a comprehensive understanding of cell-specific pathology.Astrocytes,principal homeostatic cells of the central nervous system,are key players in the pathogenesis of neurodegenerative diseases,including AD.Cellular models greatly facilitate the investigation of cell-specific pathological alterations and the dissection of molecular mechanisms and pathways.Tumor-derived and immortalized astrocytic cell lines,alongside the emerging technology of adult induced pluripotent stem cells,are widely used to study cellular dysfunction in AD.Surprisingly,no stable cell lines were available from genetic mouse AD models.Recently,we established immortalized hippocampal astroglial cell lines from amyloid-βprecursor protein/presenilin-1/Tau triple-transgenic(3xTg)-AD mice(denominated as wild type(WT)-and 3Tg-iAstro cells)using retrovirus-mediated transduction of simian virus 40 large T-antigen and propagation without clonal selection,thereby maintaining natural heterogeneity of primary cultures.Several groups have successfully used 3Tg-iAstro cells for single-cell and omics approaches to study astrocytic AD-related alterations of calcium signaling,mitochondrial dysfunctions,disproteostasis,altered homeostatic and signaling support to neurons,and blood-brain barrier models.Here we provide a comparative overview of the most used models to study astrocytes in vitro,such as primary culture,tumor-derived cell lines,immortalized astroglial cell lines,and induced pluripotent stem cell-derived astrocytes.We conclude that immortalized WT-and 3Tg-iAstro cells provide a noncompetitive but complementary,low-cost,easy-to-handle,and versatile cellular model for dissection of astrocyte-specific AD-related alterations and preclinical drug discovery.展开更多
The majestic Taibai Mountain boasts nature’s magic and wisdom, and has been known as the“Immortal Mountain”since ancient times.THE Taibai Mountain in Baoji,Shaanxi Province, is a range of major mountain peaks in th...The majestic Taibai Mountain boasts nature’s magic and wisdom, and has been known as the“Immortal Mountain”since ancient times.THE Taibai Mountain in Baoji,Shaanxi Province, is a range of major mountain peaks in the famous Qinling Mountains in China, having the highest peak east of the QinghaiTibet Plateau. Rising from the plains.展开更多
Shakespeare’s Sonnet 12 is about the destructive effect of time on the beauty of the nature as well as human beings and how one can be immortal. This paper analyzes the theme of this sonnet and the way the poet prese...Shakespeare’s Sonnet 12 is about the destructive effect of time on the beauty of the nature as well as human beings and how one can be immortal. This paper analyzes the theme of this sonnet and the way the poet presents this theme.展开更多
Through analyzing the relationship between immortal cultures and tourist activities, the authors proposed that birth of immortal thought was closely related to early tourist activities. The core idea of immortal cultu...Through analyzing the relationship between immortal cultures and tourist activities, the authors proposed that birth of immortal thought was closely related to early tourist activities. The core idea of immortal cultures was in conformity with modern leisure cultures. Tourist resources in Ancient Xianshi Township were re-explored, and application of immortal cultures in tourism development of the town was studied. The authors proposed that both "immortal" and "salt" should be valued in the tourism development of ancient Xianshi Township, interaction and integration of immortal stories, immortal traces and scenic areas should be stressed in the application of immortal cultures, so as to incorporate "immortal bath" and modern salt bath, and to combine creation of fairyland with modern sightseeing and leisure agriculture.展开更多
Death is a common theme of literature and most of writers eulogize noble death to heaven and belittle some souls to heaven.Emily Dickinson,the great American poetess,wrote more than 600 poems about death and immortali...Death is a common theme of literature and most of writers eulogize noble death to heaven and belittle some souls to heaven.Emily Dickinson,the great American poetess,wrote more than 600 poems about death and immortality with her unique ideas.The paper will analyze Emily Dickinson’s unusual belief about death from her poems and the influence of her growing environment on her.展开更多
Colorectal cancer is the third most common form of cancer and the second leading cause of cancer-related death in the western world.Tumour cells acquire the hallmarks of cancer during the carcinogenic selection proces...Colorectal cancer is the third most common form of cancer and the second leading cause of cancer-related death in the western world.Tumour cells acquire the hallmarks of cancer during the carcinogenic selection process.Cell immortality is one of the principal features acquired during this process which involves the stabilization of telomere length.It is achieved mainly,by telomerase activation.Thus,the discovery of telomeres and telomerase allowed an understanding of the mechanisms by which cells can become immortalized.Different studies have shown that tumour cells have shorter telomeres than nontumour cells and have detected telomerase activity in the majority of tumours.Survival studies have determined that telomere maintenance and telomerase activity are associated with poor prognosis.Taking into account all the results achieved by different groups,quantification and evaluation of telomerase activity and measurement of telomere length may be useful methods for additional biologic and prognostic staging of colorectal carcinoma.展开更多
The paper explores the symbolic meanings of roses in Shakespeare’s sonnets. In Shakespeare’s 154 sonnets, therose imagery is placed in a dominant position among all the other flower imagery. In general, rose is one ...The paper explores the symbolic meanings of roses in Shakespeare’s sonnets. In Shakespeare’s 154 sonnets, therose imagery is placed in a dominant position among all the other flower imagery. In general, rose is one of themost conventional images in the sonnet. But in addition to the traditional symbol of beauty and love, rose in thesonnet shows more symbolic meanings: a symbol of vitality and reproduction, a symbol of friendship and devotion,and a symbol of fidelity and immortality. The symbolic rose, to a great extent, reflects the Renaissance humanistShakespeare’s values and ideals of humanism. By successfully employing the rose imagery, Shakespeare extols thevirtues of reproduction, displays his faith in the immortality of his verse, and conveys the message of appreciatingand cherishing the beauty, goodness, and truth.展开更多
First of all, the article identifies the highlights of the documentary The Romantic Shudao.It adopts a panoramic view of the broad Chinese cultural community and depicts the tangible Shudao(road to the Shu area) and t...First of all, the article identifies the highlights of the documentary The Romantic Shudao.It adopts a panoramic view of the broad Chinese cultural community and depicts the tangible Shudao(road to the Shu area) and the intangible "Romance" associated with it by combining the oral history and collective memory as perceived by common people.The vivid stories can easily reach a wide audience and can thus help to enhance people's confidence in the ever-prospering local Ba-Shu culture.Secondly, the article explains the ten major characteristics of the Ba-Shu culture by looking at the wonderful ecological landscape, the mystical culture and literature, and the magic spiritual aesthetics of the area in an international and modern context.It also studies the Ba-Shu cultural community and the origins, historical development, and main features of the city clusters within the Chengdu-Chongqing economic circle and analyzes the historical and practical values of building a cultural corridor connecting Chengdu and Chongqing.展开更多
Emily Dickinson,one of America's great poets and a precursor of the Imagist movement in American literature,who was born on December 10,1830 and died unmarried in 1886 in Amherst,lived her life in complete shadow,...Emily Dickinson,one of America's great poets and a precursor of the Imagist movement in American literature,who was born on December 10,1830 and died unmarried in 1886 in Amherst,lived her life in complete shadow,abnormally shy and even not leaved her house.Confining herself exclusively to poetry.In her life, she was nobody (only several poems got published), but after her death she gained the recognition of the world and so became somebody.Emily Dickinson's poetry had been controversially discussed because of the unique style.As three aspects which are related to religion affected her poetic personality,there are profound characteristics of religious culture in her poem.she finally establishes her own unique religious outlook.展开更多
BACKGROUND: Orthotopic liver transplantation (OLT) is the most effective therapy for liver failure. However, OLT is severely limited by the shortage of liver donors. Bioartificial liver (BAL) shows great potential as ...BACKGROUND: Orthotopic liver transplantation (OLT) is the most effective therapy for liver failure. However, OLT is severely limited by the shortage of liver donors. Bioartificial liver (BAL) shows great potential as an alternative therapy for liver failure In recent years, progress has been made in BAL regarding genetically engineered cell lines, immortalized human hepatocytes, methods for preserving the phenotype of primary human hepatocytes, and other functional hepatocytes derived from stem cells. DATA SOURCES: A systematic search of PubMed and ISI Web of Science was performed to identify relevant studies in English language literature using the Key words such as liver failure bioartificial liver, hepatocyte, stem cells, differentiation, and immortalization. More than 200 articles related to the cell sources of hepatocyte in BAL were systematically reviewed. RESULTS: Methods for preserving the phenotype of primary human hepatocytes have been successfully developed. Many genetically engineered cell lines and immortalized human hepatocytes have also been established. Among these cell lines the incorporation of BAL with GS-HepG2 cells or alginate encapsulated HepG2 cells could prolong the survival time and improve pathophysiological parameters in an animal model of liver failure. The cBAL111 cells were evaluated using the AMC-BAL bioreactor, which could eliminate ammonia and lidocaine, and produce albumin. Importantly, BAL loading with HepLi-4 cells could significantly improve the blood biochemical parameters, and prolong the survival time in pigs with liver failure. Other functional hepatocytes differentiated from stem cells, such as human liver progenitor cells, have been successfully achieved. CONCLUSIONS: Aside from genetically modified liver cell lines and immortalized human hepatocytes, other functionalhepatocytes derived from stem cells show great potential as cell sources for BAL. BAL with safe and effective liver cells may be achieved for clinical liver failure in the near future.展开更多
AIM: To develop a hepatocyte cell line, we immortalized primary porcine hepatocytes with a retroviral vector SSR#69 containing the Simian Virus 40 T antigen (SV40T ag). METHODS: We first established a method of porcin...AIM: To develop a hepatocyte cell line, we immortalized primary porcine hepatocytes with a retroviral vector SSR#69 containing the Simian Virus 40 T antigen (SV40T ag). METHODS: We first established a method of porcine hepatocyte isolation with a modified four-step retrograde perfusion technique. Then the porcine hepatocytes were immortalized with retroviral vector SSR#69 expressing SV40T and hygromycin-resistance genes flanked by paired loxP recombination targets. SV40T cDNA in the expanded cells was subsequently excised by Cre/LoxP site-specific recombination. RESULTS: The resultant hepatocytes with high viability (97%) were successfully immortalized with retroviral vector SSR#69. One of the immortalized clones showed the typical morphological appearance, TJPH-1, and was selected by clone rings and expanded in culture. After excision of the SV40T gene with Cre-recombinase, cells stopped growing. The population of reverted cells exhibited the characteristics of differentiated hepatocytes. CONCLUSION: In conclusion, we herein describe a modified method of hepatocyte isolation and subsequently established a porcine hepatocyte cell line mediated by retroviral transfer and site-specific recombination.展开更多
Objective Cytochrome P450 2E1 (CYP2E1) is an important metabolizing enzyme involved in oxidative stress responses to benzene, a chemical associated with bone marrow toxicity and leukemia, We aimed to identify the CY...Objective Cytochrome P450 2E1 (CYP2E1) is an important metabolizing enzyme involved in oxidative stress responses to benzene, a chemical associated with bone marrow toxicity and leukemia, We aimed to identify the CYP2E1 genetic biomarkers of susceptibility to benzene toxicity in support of environmental and occupational exposure prevention, and to test whether a model using immortal human lymphocytes might be an efficient tool for detecting genetic biomarkers. Methods Immortalized human lymphocyte cell lines with independent genotypes on four CYP2E1 SNP sites were induced with 0.01% phenol, a metabolite of benzene. CYP2E1 gene function was evaluated by mRNA expression and enzyme activity. DNA damage was measured by Single-Cell Gel Electrophoresis (SCGE). Results Among the four SNPs, cells with rs2070673TT and rs2030920CC showed higher levels of ~YP2E1 transcription and enzymatic activity than the other genotypes in the same SNP site. Cells with higher gene expression genotypes also showed higher comet rates compared with lower gene expression genotypes. Conclusion These results suggest that CYP2E1 rs2070673 and rs2030920 might be the genetic biomarkers of susceptibility to benzene toxicity and that the immortalized human lymphocytes model might be an efficient tool for the detection of genetic biomarkers of susceptibility to chemicals.展开更多
AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of...AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of corneas against viruses.METHODS: The herpes viral keratitis model was utilized in BALB/c mice with inoculation of herpes simplex virus-1(HSV-1). Corneal tissues removed during therapy of patients with viral keratitis as well as a Simian vacuolating virus 40(SV40)-immortalized human corneal epithelial cell line were also examined.Immunohistochemistry was used to detect NLRP3 in these subjects, focusing on their distribution in tissue or cells. Western blot was used to measure the level of NLRP3 and another two related molecules in NLPR3 inflammasome, namely caspase-1 and IL-1β.RESULTS: The NLRP3 activation induced by HSV-1infection in corneas was accompanied with redistribution of NLRP3 from the cytoplasm to the nucleus in both murine and human corneal epithelial cells. Furthermore,in the SV40-immortalized human corneal epithelial cells,NLRP3 was exclusively located in the nucleus, and treatment of the cells with high concentration of extracellular potassium(known as an inhibitor of NLRP3activation) effectively drove NLRP3 back to the cytoplasm as reflected by both immunohistochemistry and Western blot.· CONCLUSION: It is proposed that herpes virus infection activates and causes redistribution of NLRP3 to nuclei. Whether this NLRP3 translocation occurs with other viral infections and in other cell types merit further study.展开更多
Conophylline, is a bis (indole) alkaloid consisting of two pentacyclic aspidosperma skeletons, isolated from Tabernaemontana divaricata, which has been found to induce β-cell differentiation in rat pancreatic acina...Conophylline, is a bis (indole) alkaloid consisting of two pentacyclic aspidosperma skeletons, isolated from Tabernaemontana divaricata, which has been found to induce β-cell differentiation in rat pancreatic acinar carcinoma cells and in cultured rat pancreatic tissue. However, the precise role of conophylline in the growth and survival of immortalized pancreatic mesenchymal stem cells (iPMSCs) derived from fetal porcine pancreas were not understood at present. To determine whether this molecule is involved in controlling the proliferation of iPMSCs, we examined the effects of conophylline on iPMSCs. We found that conophylline can robustly stimulate iPMSCs proliferation, even promote their potential differentiation into islet-like clusters analyzed by cell counting, morphology, RT-PCR and real-time PCR, Western blotting, glucose-stimulated insulin release and insulin content analysis. The effects of conophylline were inhibited by LY294002, which is the inhibitor of the PI3K pathway. These results suggest that conophylline plays a key role in the regulation of cell mass proliferation, maintenance of the undifferentiated state of iPMSCs and also promotes iPMSCs differentiated into insulin-producing cells.展开更多
文摘Emily Dickinson is widely regarded as one of American's premier poets of the nineteenth century.In both style and content,her verse was,"revolutionary" in her day.Owing to the deep exploration of death and immortality,Emily Dickinson has become a puzzle in literary.As show in her poems,Dickinson's spiritual journey led her from na?ve nature-mysticism through disappointment,to a sacramental approach to immortality afterlife and further discouragement,culminating in a mature attitude of faithful unknowing and even more interrogating the immortality.This paper will base on the theory of the death and immortality through common people's fear to death,the essence of death,the significance of death to show the poetess's whole life-childhood,love,life condition,spiritual contradiction,and mainly her skeptical concept of death and immortality.
文摘In an effort to find out how Nabokov manages to achieve aesthetic immortality in Speak Memory,a detailed text analysis is conducted on the techniques he has utilized.Afterwards,it draws the conclusion that Nabokov,firmly grounded on his own con⁃sciousness,manages to command memory with the help of imagination,thus,transforming this recreation of memory into a work of aesthetic eternity.
基金supported by the National Research Foundation(NRF)S&F-Scarce Skills Postdoctoral Fellowship,No.120752(to AC)the Global Excellence and Stature,Fourth Industrial Revolution(GES 4.0)Postgraduate Scholarship(to MJR)the South African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation of South Africa(SARChI/NRF-DST),No.146290(to DDS and HA).
文摘Photobiomodulation,originally used red and near-infrared lasers,can alter cellular metabolism.It has been demonstrated that the visible spectrum at 451-540 nm does not necessarily increase cell proliferation,near-infrared light promotes adipose stem cell proliferation and affects adipose stem cell migration,which is necessary for the cells homing to the site of injury.In this in vitro study,we explored the potential of adipose-derived stem cells to differentiate into neurons for future translational regenerative treatments in neurodegenerative disorders and brain injuries.We investigated the effects of various biological and chemical inducers on trans-differentiation and evaluated the impact of photobiomodulation using 825 nm near-infrared and 525 nm green laser light at 5 J/cm2.As adipose-derived stem cells can be used in autologous grafting and photobiomodulation has been shown to have biostimulatory effects.Our findings reveal that adipose-derived stem cells can indeed trans-differentiate into neuronal cells when exposed to inducers,with pre-induced cells exhibiting higher rates of proliferation and trans-differentiation compared with the control group.Interestingly,green laser light stimulation led to notable morphological changes indicative of enhanced trans-differentiation,while near-infrared photobiomodulation notably increased the expression of neuronal markers.Through biochemical analysis and enzyme-linked immunosorbent assays,we observed marked improvements in viability,proliferation,membrane permeability,and mitochondrial membrane potential,as well as increased protein levels of neuron-specific enolase and ciliary neurotrophic factor.Overall,our results demonstrate the efficacy of photobiomodulation in enhancing the trans-differentiation ability of adipose-derived stem cells,offering promising prospects for their use in regenerative medicine for neurodegenerative disorders and brain injuries.
基金supported by fellowship to a grant from CRT Foundation,No.1393-2017(to LT)grants from the Fondazione Cariplo,Nos.2013-0795(to AAG),2014-1094(to DL)grants from The Universitàdel Piemonte Orientale,Nos.FAR-2016(to DL),FAR-2019(to DL)。
文摘Alzheimer's disease(AD)is characterized by complex etiology,long-lasting pathogenesis,and celltype-specific alterations.Currently,there is no cure for AD,emphasizing the urgent need for a comprehensive understanding of cell-specific pathology.Astrocytes,principal homeostatic cells of the central nervous system,are key players in the pathogenesis of neurodegenerative diseases,including AD.Cellular models greatly facilitate the investigation of cell-specific pathological alterations and the dissection of molecular mechanisms and pathways.Tumor-derived and immortalized astrocytic cell lines,alongside the emerging technology of adult induced pluripotent stem cells,are widely used to study cellular dysfunction in AD.Surprisingly,no stable cell lines were available from genetic mouse AD models.Recently,we established immortalized hippocampal astroglial cell lines from amyloid-βprecursor protein/presenilin-1/Tau triple-transgenic(3xTg)-AD mice(denominated as wild type(WT)-and 3Tg-iAstro cells)using retrovirus-mediated transduction of simian virus 40 large T-antigen and propagation without clonal selection,thereby maintaining natural heterogeneity of primary cultures.Several groups have successfully used 3Tg-iAstro cells for single-cell and omics approaches to study astrocytic AD-related alterations of calcium signaling,mitochondrial dysfunctions,disproteostasis,altered homeostatic and signaling support to neurons,and blood-brain barrier models.Here we provide a comparative overview of the most used models to study astrocytes in vitro,such as primary culture,tumor-derived cell lines,immortalized astroglial cell lines,and induced pluripotent stem cell-derived astrocytes.We conclude that immortalized WT-and 3Tg-iAstro cells provide a noncompetitive but complementary,low-cost,easy-to-handle,and versatile cellular model for dissection of astrocyte-specific AD-related alterations and preclinical drug discovery.
文摘The majestic Taibai Mountain boasts nature’s magic and wisdom, and has been known as the“Immortal Mountain”since ancient times.THE Taibai Mountain in Baoji,Shaanxi Province, is a range of major mountain peaks in the famous Qinling Mountains in China, having the highest peak east of the QinghaiTibet Plateau. Rising from the plains.
文摘Shakespeare’s Sonnet 12 is about the destructive effect of time on the beauty of the nature as well as human beings and how one can be immortal. This paper analyzes the theme of this sonnet and the way the poet presents this theme.
文摘Through analyzing the relationship between immortal cultures and tourist activities, the authors proposed that birth of immortal thought was closely related to early tourist activities. The core idea of immortal cultures was in conformity with modern leisure cultures. Tourist resources in Ancient Xianshi Township were re-explored, and application of immortal cultures in tourism development of the town was studied. The authors proposed that both "immortal" and "salt" should be valued in the tourism development of ancient Xianshi Township, interaction and integration of immortal stories, immortal traces and scenic areas should be stressed in the application of immortal cultures, so as to incorporate "immortal bath" and modern salt bath, and to combine creation of fairyland with modern sightseeing and leisure agriculture.
文摘Death is a common theme of literature and most of writers eulogize noble death to heaven and belittle some souls to heaven.Emily Dickinson,the great American poetess,wrote more than 600 poems about death and immortality with her unique ideas.The paper will analyze Emily Dickinson’s unusual belief about death from her poems and the influence of her growing environment on her.
基金Supported by Grants from Ministerio de Sanidad y Consumo (FIS PI080033)Fundación de Investigación Médica Mutua Madrilea,and RTICC RD06/0020/0021
文摘Colorectal cancer is the third most common form of cancer and the second leading cause of cancer-related death in the western world.Tumour cells acquire the hallmarks of cancer during the carcinogenic selection process.Cell immortality is one of the principal features acquired during this process which involves the stabilization of telomere length.It is achieved mainly,by telomerase activation.Thus,the discovery of telomeres and telomerase allowed an understanding of the mechanisms by which cells can become immortalized.Different studies have shown that tumour cells have shorter telomeres than nontumour cells and have detected telomerase activity in the majority of tumours.Survival studies have determined that telomere maintenance and telomerase activity are associated with poor prognosis.Taking into account all the results achieved by different groups,quantification and evaluation of telomerase activity and measurement of telomere length may be useful methods for additional biologic and prognostic staging of colorectal carcinoma.
文摘The paper explores the symbolic meanings of roses in Shakespeare’s sonnets. In Shakespeare’s 154 sonnets, therose imagery is placed in a dominant position among all the other flower imagery. In general, rose is one of themost conventional images in the sonnet. But in addition to the traditional symbol of beauty and love, rose in thesonnet shows more symbolic meanings: a symbol of vitality and reproduction, a symbol of friendship and devotion,and a symbol of fidelity and immortality. The symbolic rose, to a great extent, reflects the Renaissance humanistShakespeare’s values and ideals of humanism. By successfully employing the rose imagery, Shakespeare extols thevirtues of reproduction, displays his faith in the immortality of his verse, and conveys the message of appreciatingand cherishing the beauty, goodness, and truth.
文摘First of all, the article identifies the highlights of the documentary The Romantic Shudao.It adopts a panoramic view of the broad Chinese cultural community and depicts the tangible Shudao(road to the Shu area) and the intangible "Romance" associated with it by combining the oral history and collective memory as perceived by common people.The vivid stories can easily reach a wide audience and can thus help to enhance people's confidence in the ever-prospering local Ba-Shu culture.Secondly, the article explains the ten major characteristics of the Ba-Shu culture by looking at the wonderful ecological landscape, the mystical culture and literature, and the magic spiritual aesthetics of the area in an international and modern context.It also studies the Ba-Shu cultural community and the origins, historical development, and main features of the city clusters within the Chengdu-Chongqing economic circle and analyzes the historical and practical values of building a cultural corridor connecting Chengdu and Chongqing.
文摘Emily Dickinson,one of America's great poets and a precursor of the Imagist movement in American literature,who was born on December 10,1830 and died unmarried in 1886 in Amherst,lived her life in complete shadow,abnormally shy and even not leaved her house.Confining herself exclusively to poetry.In her life, she was nobody (only several poems got published), but after her death she gained the recognition of the world and so became somebody.Emily Dickinson's poetry had been controversially discussed because of the unique style.As three aspects which are related to religion affected her poetic personality,there are profound characteristics of religious culture in her poem.she finally establishes her own unique religious outlook.
基金supported by grants from the Chinese High-Tech Research & Development (863) Program (2011AA020104)Science Fund for Creative Research Groups of the National Natural Science Foundation of China (81121002)+1 种基金the Fundamental Research Funds for the Central Universitiesthe Technology Group Project for Infectious Disease Control of Zhejiang Province (2009R50041)
文摘BACKGROUND: Orthotopic liver transplantation (OLT) is the most effective therapy for liver failure. However, OLT is severely limited by the shortage of liver donors. Bioartificial liver (BAL) shows great potential as an alternative therapy for liver failure In recent years, progress has been made in BAL regarding genetically engineered cell lines, immortalized human hepatocytes, methods for preserving the phenotype of primary human hepatocytes, and other functional hepatocytes derived from stem cells. DATA SOURCES: A systematic search of PubMed and ISI Web of Science was performed to identify relevant studies in English language literature using the Key words such as liver failure bioartificial liver, hepatocyte, stem cells, differentiation, and immortalization. More than 200 articles related to the cell sources of hepatocyte in BAL were systematically reviewed. RESULTS: Methods for preserving the phenotype of primary human hepatocytes have been successfully developed. Many genetically engineered cell lines and immortalized human hepatocytes have also been established. Among these cell lines the incorporation of BAL with GS-HepG2 cells or alginate encapsulated HepG2 cells could prolong the survival time and improve pathophysiological parameters in an animal model of liver failure. The cBAL111 cells were evaluated using the AMC-BAL bioreactor, which could eliminate ammonia and lidocaine, and produce albumin. Importantly, BAL loading with HepLi-4 cells could significantly improve the blood biochemical parameters, and prolong the survival time in pigs with liver failure. Other functional hepatocytes differentiated from stem cells, such as human liver progenitor cells, have been successfully achieved. CONCLUSIONS: Aside from genetically modified liver cell lines and immortalized human hepatocytes, other functionalhepatocytes derived from stem cells show great potential as cell sources for BAL. BAL with safe and effective liver cells may be achieved for clinical liver failure in the near future.
基金Supported by The Major Scientific and Technological Project of Hubei Province, No. 2007ABD005
文摘AIM: To develop a hepatocyte cell line, we immortalized primary porcine hepatocytes with a retroviral vector SSR#69 containing the Simian Virus 40 T antigen (SV40T ag). METHODS: We first established a method of porcine hepatocyte isolation with a modified four-step retrograde perfusion technique. Then the porcine hepatocytes were immortalized with retroviral vector SSR#69 expressing SV40T and hygromycin-resistance genes flanked by paired loxP recombination targets. SV40T cDNA in the expanded cells was subsequently excised by Cre/LoxP site-specific recombination. RESULTS: The resultant hepatocytes with high viability (97%) were successfully immortalized with retroviral vector SSR#69. One of the immortalized clones showed the typical morphological appearance, TJPH-1, and was selected by clone rings and expanded in culture. After excision of the SV40T gene with Cre-recombinase, cells stopped growing. The population of reverted cells exhibited the characteristics of differentiated hepatocytes. CONCLUSION: In conclusion, we herein describe a modified method of hepatocyte isolation and subsequently established a porcine hepatocyte cell line mediated by retroviral transfer and site-specific recombination.
基金supported by the National Natural Science Foundation of China (Grant No: 30671731, 30901168)the Doctoral Program of Higher Education of China (Grant No: 20070286069)
文摘Objective Cytochrome P450 2E1 (CYP2E1) is an important metabolizing enzyme involved in oxidative stress responses to benzene, a chemical associated with bone marrow toxicity and leukemia, We aimed to identify the CYP2E1 genetic biomarkers of susceptibility to benzene toxicity in support of environmental and occupational exposure prevention, and to test whether a model using immortal human lymphocytes might be an efficient tool for detecting genetic biomarkers. Methods Immortalized human lymphocyte cell lines with independent genotypes on four CYP2E1 SNP sites were induced with 0.01% phenol, a metabolite of benzene. CYP2E1 gene function was evaluated by mRNA expression and enzyme activity. DNA damage was measured by Single-Cell Gel Electrophoresis (SCGE). Results Among the four SNPs, cells with rs2070673TT and rs2030920CC showed higher levels of ~YP2E1 transcription and enzymatic activity than the other genotypes in the same SNP site. Cells with higher gene expression genotypes also showed higher comet rates compared with lower gene expression genotypes. Conclusion These results suggest that CYP2E1 rs2070673 and rs2030920 might be the genetic biomarkers of susceptibility to benzene toxicity and that the immortalized human lymphocytes model might be an efficient tool for the detection of genetic biomarkers of susceptibility to chemicals.
基金Supported by National Natural Science Foundation of China(No.81273212,81100651)Project of Science and Technology of Shandong Province(No.2014GSF118044)
文摘AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of corneas against viruses.METHODS: The herpes viral keratitis model was utilized in BALB/c mice with inoculation of herpes simplex virus-1(HSV-1). Corneal tissues removed during therapy of patients with viral keratitis as well as a Simian vacuolating virus 40(SV40)-immortalized human corneal epithelial cell line were also examined.Immunohistochemistry was used to detect NLRP3 in these subjects, focusing on their distribution in tissue or cells. Western blot was used to measure the level of NLRP3 and another two related molecules in NLPR3 inflammasome, namely caspase-1 and IL-1β.RESULTS: The NLRP3 activation induced by HSV-1infection in corneas was accompanied with redistribution of NLRP3 from the cytoplasm to the nucleus in both murine and human corneal epithelial cells. Furthermore,in the SV40-immortalized human corneal epithelial cells,NLRP3 was exclusively located in the nucleus, and treatment of the cells with high concentration of extracellular potassium(known as an inhibitor of NLRP3activation) effectively drove NLRP3 back to the cytoplasm as reflected by both immunohistochemistry and Western blot.· CONCLUSION: It is proposed that herpes virus infection activates and causes redistribution of NLRP3 to nuclei. Whether this NLRP3 translocation occurs with other viral infections and in other cell types merit further study.
基金supported by the grants from the National Natural Science Foundation of China(31272518, 31101775, 30972097)the Doctoral Fund of Ministry of Education of China (20100204120020)+4 种基金the Program for New Century Excellent Talents of State Ministry of Education (NCET-09-0654)the Scientific Research Program of Shaanxi Province (2011K02-06, 2008K02-05)the Scientific Research Program of Shaanxi Province, China(2011K02-06)the Fundamental Research Funds for the Central Universities, China (QN2011012)the Graduate Education Innovation Projects of Henan University of Technology, China (11YJCX45)
文摘Conophylline, is a bis (indole) alkaloid consisting of two pentacyclic aspidosperma skeletons, isolated from Tabernaemontana divaricata, which has been found to induce β-cell differentiation in rat pancreatic acinar carcinoma cells and in cultured rat pancreatic tissue. However, the precise role of conophylline in the growth and survival of immortalized pancreatic mesenchymal stem cells (iPMSCs) derived from fetal porcine pancreas were not understood at present. To determine whether this molecule is involved in controlling the proliferation of iPMSCs, we examined the effects of conophylline on iPMSCs. We found that conophylline can robustly stimulate iPMSCs proliferation, even promote their potential differentiation into islet-like clusters analyzed by cell counting, morphology, RT-PCR and real-time PCR, Western blotting, glucose-stimulated insulin release and insulin content analysis. The effects of conophylline were inhibited by LY294002, which is the inhibitor of the PI3K pathway. These results suggest that conophylline plays a key role in the regulation of cell mass proliferation, maintenance of the undifferentiated state of iPMSCs and also promotes iPMSCs differentiated into insulin-producing cells.