Borneol, as a traditional natural permeation enhancer, has been widely used to promote the transdermal absorption of active ingredients. In this review, the mechanism of borneol in promoting permeation by destroying t...Borneol, as a traditional natural permeation enhancer, has been widely used to promote the transdermal absorption of active ingredients. In this review, the mechanism of borneol in promoting permeation by destroying the highly ordered lipid structure of the lipid layer and by destroying the hydrogen-bond network was described. The application of borneol in promoting the transdermal absorption of the active ingredients of traditional Chinese medicine and chemical drugs was introduced. The application of borneol as a natural ingredient added to functional cosmetics was summarized, and its effects on skin-spot treatment, acne skin care, eczema skin care, skin repair and anti-oxidation were introduced. Finally, the possible problems in the application of borneol in cosmetics were put forward, and the application prospect of borneol in the development of cosmetics was given.展开更多
Expanding in the oral care business, being passionately driven by innovative and scientific products, functional toothpaste has recently become more popular for functionality, variety, and efficacy. Many new types of ...Expanding in the oral care business, being passionately driven by innovative and scientific products, functional toothpaste has recently become more popular for functionality, variety, and efficacy. Many new types of toothpaste are commercially manufactured with diverse fragrances, colors, probiotics, and pharmaceutical ingredients to enhance the functionalities of toothpaste. Our study attempted to create a toothpaste formulation that might facilitate the intraoral delivery of vitamin D3 into the bloodstream. Simply brushing our teeth with toothpaste should be easy to take the essential vitamin regularly. In this study, an emulsion-based toothpaste mixed with an azone compound and sodium dodecyl sulfate as penetration enhancers blended thoroughly with other ingredients and then with vitamin D. Multiple toothpaste characteristic tests were performed, such as abrasiveness, scratchiness, spreadability, pH, foaming, cleaning, and antibacterial strength with our vitamin D toothpaste, and compared with those of other commercial brand toothpaste. To confirm the intraoral delivery of vitamin D through the oral cavity, an earthworm transport study and TEER value test were conducted using L. terrestris skin. Our data demonstrated the high feasibility of intraoral delivery of vitamin D based on those two skin studies with various experimental support;our vitamin D toothpaste had comparable characteristics with other commercial toothpaste for cleaning functionality.展开更多
Borneol,as a traditional natural permeation enhancer,has been widely used to promote the transdermal absorption of active ingredients.The mechanism of borneol in promoting permeation by destroying the highly ordered l...Borneol,as a traditional natural permeation enhancer,has been widely used to promote the transdermal absorption of active ingredients.The mechanism of borneol in promoting permeation by destroying the highly ordered lipid structure of the lipid layer and by destroying the hydrogen-bond network was described.The application of borneol in promoting the transdermal absorption of the active ingredients of traditional Chinese medicine and chemical drugs was introduced.The application of borneol as a natural ingredient added to functional cosmetics was summarized,and its effects on skin-spot treatment,acne skin care,eczema skin care,skin repair and anti-oxidation were introduced.Finally,the possible problems in the application of borneol in cosmetics were put forward,and the application prospect of borneol in the development of cosmetics was given。展开更多
Unmanned aerial vehicle (UAV) target tracking tasks can currently be successfully completed in daytime situations with enough lighting, but they are unable to do so in nighttime scenes with inadequate lighting, poor c...Unmanned aerial vehicle (UAV) target tracking tasks can currently be successfully completed in daytime situations with enough lighting, but they are unable to do so in nighttime scenes with inadequate lighting, poor contrast, and low signal-to-noise ratio. This letter presents an enhanced low-light enhancer for UAV nighttime tracking based on Zero-DCE++ due to its ad-vantages of low processing cost and quick inference. We developed a light-weight UCBAM capable of integrating channel information and spatial features and offered a fully considered curve projection model in light of the low signal-to-noise ratio of night scenes. This method significantly improved the tracking performance of the UAV tracker in night situations when tested on the public UAVDark135 and compared to other cutting-edge low-light enhancers. By applying our work to different trackers, this search shows how broadly applicable it is.展开更多
Enhancer is a positive regulator for spatiotemporal development in eukaryotes. As a cluster, super-enhancer is closely related to cell identity- and fate-determined processes. Both of them function tightly depending o...Enhancer is a positive regulator for spatiotemporal development in eukaryotes. As a cluster, super-enhancer is closely related to cell identity- and fate-determined processes. Both of them function tightly depending on their targeted transcription factors, cofactors, and genes through distal genomic interactions. They have been recognized as critical components and played positive roles in transcriptional regulatory network or factory. Recent advances of next-generation sequencing have dramatically expanded our ability and knowledge to interrogate the molecular mechanism of enhancer and super-enhancer for transcription. Here, we review the history, importance, advances and challenges on enhancer and super-enhancer field.This will benefit our understanding of their function mechanism for transcription underlying precise gene expression.展开更多
Transdermal drug delivery has been accepted as a potential non-invasive route of drug administration,with advantages of prolonged therapeutic action,decreased side effect,easy use and better patient compliance.However...Transdermal drug delivery has been accepted as a potential non-invasive route of drug administration,with advantages of prolonged therapeutic action,decreased side effect,easy use and better patient compliance.However,development of transdermal products is primarily hindered by the low permeability of the skin.To overcome this barrier effect,numerous new chemicals have been synthesized as potential permeation enhancers for transdermal drug delivery.In this review,we presented an overview of the investigations in this field,and further implications on selection or design of suitable permeation enhancers for transdermal drug delivery were also discussed.展开更多
Polycomb group proteins represent a global silencing system involved in development regulation.In specific,they regulate the transition from proliferation to differentiation,contributing to stem-cell maintenance and i...Polycomb group proteins represent a global silencing system involved in development regulation.In specific,they regulate the transition from proliferation to differentiation,contributing to stem-cell maintenance and inhibiting an inappropriate activation of differentiation programs.Enhancer of Zeste Homolog 2(EZH2) is the catalytic subunit of Polycomb repressive complex 2,which induces transcriptional inhibition through the tri-methylation of histone H3,an epigenetic change associated with gene silencing.EZH2 expression is high in precursor cells while its level decreases in differentiated cells.EZH2 is upregulated in various cancers with high levels associated with metastatic cancer and poor prognosis.Indeed,aberrant expression of EZH2 causes the inhibition of several tumor suppressors and differentiation genes,resulting in an uncontrolled proliferation and tumor formation.This editorial explores the role of Polycomb repressive complex 2 in cancer,focusing in particular on EZH2.The canonical function of EZH2 in gene silencing,the non-canonical activities as the methylation of other proteins and the role in gene transcriptional activation,were summarized.Moreover,mutations of EZH2,responsible for an increased methyltransferase activity in cancer,were recapitulated.Finally,various drugs able to inhibit EZH2 with different mechanism were described,specifically underscoring the effects in several cancers,in order to clarify the role of EZH2 and understand if EZH2 blockade could be a new strategy for developing specific therapies or a way to increase sensitivity of cancer cells to standard therapies.展开更多
Objective To investigate the cell-type-specific enhancer (CTSE) in HPV16 and its variation in cervical carcinoma. Methods CTSEs were detected by polymerase chain reaction (PCR) in 58 cervical carcinoma from Shaanxi pr...Objective To investigate the cell-type-specific enhancer (CTSE) in HPV16 and its variation in cervical carcinoma. Methods CTSEs were detected by polymerase chain reaction (PCR) in 58 cervical carcinoma from Shaanxi province; in addition variation of CTSEs was analyzed through single-strand conformation polymorphisms (SSCP). Results HPV16 CTSEs were detectable in 34 of 58 (57%) specimens and mutant rate was 41%(14/34) and the main mutations of chosen randomly variant CTSE (CTSEv) happened at YY1 binding sites in addition to glucocoticoid response elements (GRE). Conclusion CTSE in some specimens of Shaanxi province was obviously different from that in HPV16 wild type and variant CTSE might affect the transcriptional regulation of LCR on viral P97, which regulates over-expression of viral oncogenes in cervical carcinoma.展开更多
This study aimed to develop niosomes of ellagic acid(EA),a potent antioxidant phytochemical substance,for dermal delivery and to investigate the influence of chemical penetration enhancers on the physicochemical prope...This study aimed to develop niosomes of ellagic acid(EA),a potent antioxidant phytochemical substance,for dermal delivery and to investigate the influence of chemical penetration enhancers on the physicochemical properties of EA-loaded niosomes.The EA niosomes were prepared by reverse phase evaporation method using Span 60,Tween 60 and cholesterol as vesicle forming agents and Solulan C24 as a steric stabilizer.Polyethylene glycol 400(PEG)was used as a solubilizer while dimethylsulfoxide(DMSO)or Nmethyl-2-pyrrolidone(NMP)was used as a skin penetration enhancer.It was found that the mean particle sizes of EA-loaded niosomes were in the range of 312e402 nm with PI values of lower than 0.4.The niosomes were determined to be spherical multilamellar vesicles as observed by transmission electron microscope and optical microscopy.All niosomes were stable after 4 months storage at 4C.In vitro skin permeation through human epidermis revealed that the skin enhancers affected the penetration of EA from the niosomes at 24 h.The DMSO niosomes showed the highest EA amount in epidermis;whereas the NMP niosomes had the highest EA amount in the acceptor medium.Concomitantly,the skin distribution by confocal laser scanning microscopy showed the high fluorescence intensity of the DMSO niosomes and NMP niosomes at a penetration depth of between 30e90 mm(the epidermis layer)and 90e120 mm(the dermis layer)under the skin,respectively.From the results,it can be concluded that the DMSO niosomes are suitable for epidermis delivery of EA while the NMP niosomes can be used for dermis delivery of EA.展开更多
Background:The pig is an economically important livestock species and is a widely applied large animal model in medical research.Enhancers are critical regulatory elements that have fundamental functions in evolution,...Background:The pig is an economically important livestock species and is a widely applied large animal model in medical research.Enhancers are critical regulatory elements that have fundamental functions in evolution,development and disease.Genome-wide quantification of functional enhancers in the pig is needed.Results:We performed self-transcribing active regulatory region sequencing(STARR-seq)in the porcine kidney epithelial PK15 and testicular ST cell lines,and reliably identified 2576 functional enhancers.Most of these enhancers were located in repetitive sequences and were enriched within silent and lowly expressed genes.Enhancers poorly overlapped with chromatin accessibility regions and were highly enriched in chromatin with the repressive histone modification H3K9me3,which is different from predicted pig enhancers detected using ChIP-seq for H3K27ac or/and H3K4me1 modified histones.This suggests that most pig enhancers identified with STARR-seq are endogenously repressed at the chromatin level and may function during cell type-specific development or at specific developmental stages.Additionally,the PPP3CA gene is associated with the loin muscle area trait and the QKI gene is associated with alkaline phosphatase activity that may be regulated by distal functional enhancers.Conclusions:In summary,we generated the first functional enhancer map in PK15 and ST cells for the pig genome and highlight its potential roles in pig breeding.展开更多
Amh (anti-Müllerian hormone) is a single copy gene which is expressed strongly in Sertoli cells in the foetal testis and participates in the onset of sexual differentiation. Its promoter driving the expression of...Amh (anti-Müllerian hormone) is a single copy gene which is expressed strongly in Sertoli cells in the foetal testis and participates in the onset of sexual differentiation. Its promoter driving the expression of a reporter gene (d2EGFP) has been used to analyse the role of certain defined putative elements and a downstream enhancer element in gene expression. These experiments were carried out in vitro using a line of pre-pubertal mouse Sertoli cells, transienly transfected with circular DNA constructs with variously mutated promoter elements. A downstream enhancer element, situated immediately 3’ of the polyadenylation (PA) signal for Amh, has been inserted in an equivalent position in the d2EGFP construct. When the Amh promoter is unmodified, the downstream enhancer (DE) is positively associated with a large increase in EGFP expression. This is at least partly the consequence of an increased rate of expression by individual cells. Experiments using variously truncated Amh promoters indicate that an upstream region (-214 to -336) may play a minor role in facilitating enhancement. However mutation of the Wilms tumour factor-1 element, situated between the tata box and the start of translation, results in an almost complete suppression of enhancement.展开更多
Currently,enhancers have key transcriptional regulatory roles in muscle development.Skeletal muscle formation involves various molecules,and in animals,enhancers are one of the main types of transcriptional regulatory...Currently,enhancers have key transcriptional regulatory roles in muscle development.Skeletal muscle formation involves various molecules,and in animals,enhancers are one of the main types of transcriptional regulatory regions that are of great importance to regulate myogenic gene expression.In muscle development,enhancers can generate enhancer RNAs(eRNAs)that are involved in the regulation of gene transcription.The regulation of gene expression by eRNAs offers great potential in improving animal production traits.Herein we comprehensively review the roles of enhancers in muscle formation and its potential function in skeletal muscle development.This review will describe the future application of enhancers in skeletal muscle development and discuss the prospects that enhancer studies offer for agriculture,biotechnology,and animal breeding.展开更多
BACKGROUND Inflammatory bowel disease(IBD)is a prevalent worldwide health problem featured by relapsing,chronic gastrointestinal inflammation.Enhancer of zeste homolog 2(EZH2)is a critical epigenetic regulator in diff...BACKGROUND Inflammatory bowel disease(IBD)is a prevalent worldwide health problem featured by relapsing,chronic gastrointestinal inflammation.Enhancer of zeste homolog 2(EZH2)is a critical epigenetic regulator in different pathological models,such as cancer and inflammation.However,the role of EZH2 in the IBD development is still obscure.AIM To explore the effect of EZH2 on IBD progression and the underlying mechanism.METHODS The IBD mouse model was conducted by adding dextran sodium sulfate(DSS),and the effect of EZH2 on DSS-induced colitis was assessed in the model.The function of EZH2 in regulating apoptosis and permeability was evaluated by Annexin V-FITC Apoptosis Detection Kit,transepithelial electrical resistance analysis,and Western blot analysis of related markers,including Zona occludens 1,claudin-5,and occludin,in NCM460 and fetal human colon(FHC)cells.The mechanical investigation was performed by quantitative reverse transcriptionpolymerase chain reaction,Western blot analysis,and chromatin immunoprecipitation assays.RESULTS The colon length was inhibited in the DSS-treated mice and was enhanced by the EZH2 depletion in the system.DSS treatment caused a decreased histological score in the mice,which was reversed by EZH2 depletion.The inflammatory cytokines,such as tumor necrosis factor-α,interleukin-6,and interleukin-1β,were induced in the DSS-treated mice,in which the depletion of EZH2 could reverse this effect.Moreover,the tumor necrosis factor-αtreatment induced the apoptosis of NCM460 and FHC cells,in which EZH2 depletion could reverse this effect in the cells.Moreover,the depletion of EZH2 attenuated permeability of colonic epithelial cells.Mechanically,the depletion of EZH2 or EZH2 inhibitor GSK343 was able to enhance the expression and the phosphorylation of janus kinase 2(JK2)and signal transducer and activator of transcription in the NCM460 and FHC cells.Specifically,EZH2 inactivated JAK2 expression by regulating histone H3K27me3.JAK2 inhibitor TG101348 was able to reverse EZH2 knockdownmediated colonic epithelial cell permeability and apoptosis.CONCLUSION Thus,we concluded that EZH2 contributed to apoptosis and inflammatory response by inactivating JAK2/signal transducer and activator of transcription signaling in IBD.EZH2 may be applied as a potential target for IBD therapy.展开更多
AIM:To investigate the role of procollagen C-proteinase enhancer 1(PCPE1)in retinal angiogenesis and relevant mechanisms.METHODS:The Pcolce1-knockout(KO)mice were used to explore the effect of PCPE1 on retinal angioge...AIM:To investigate the role of procollagen C-proteinase enhancer 1(PCPE1)in retinal angiogenesis and relevant mechanisms.METHODS:The Pcolce1-knockout(KO)mice were used to explore the effect of PCPE1 on retinal angiogenesis in vivo.Pcolce1 si RNA were designed,cell count kit 8(CCK8)assays and tube formation assays were performed to investigate the cell proliferation and tube formation abilities of retinal microvascular endothelial cells(h RMECs)in vitro.Mouse embryo fibroblasts(MEF)cells were isolated and cultured to analyze the effect of PCPE1 on enhancing procollagen cleavage.RESULTS:In vivo studies showed that the retinal vascular density of Pcolce1-/-mice was significantly lower than that of the control group.Furthermore,silencing of Pcolce1 inhibited cell proliferation and tube formation abilities of h RMECs in vitro.Additionally,much more procollagen was found in Pcolce1-/-MEF cells,compared to wild type MEF cells.CONCLUSION:PCPE1 may promote physiological retinal angiogenesis by regulating the processing of collagen,which may provide a potential therapeutic target of retinal vascular disease.展开更多
BACKGROUND Heart diseases are the primary cause of death all over the world.Following myocardial infarction,billions of cells die,resulting in a huge loss of cardiac function.Stem cell-based therapies have appeared as...BACKGROUND Heart diseases are the primary cause of death all over the world.Following myocardial infarction,billions of cells die,resulting in a huge loss of cardiac function.Stem cell-based therapies have appeared as a new area to support heart regeneration.The transcription factors GATA binding protein 4(GATA-4)and myocyte enhancer factor 2C(MEF2C)are considered prominent factors in the development of the cardiovascular system.AIM To explore the potential of GATA-4 and MEF2C for the cardiac differentiation of human umbilical cord mesenchymal stem cells(hUC-MSCs).METHODS hUC-MSCs were characterized morphologically and immunologically by the presence of specific markers of MSCs via immunocytochemistry and flow cytometry,and by their potential to differentiate into osteocytes and adipocytes.hUC-MSCs were transfected with GATA-4,MEF2C,and their combination to direct the differentiation.Cardiac differentiation was confirmed by semiquant itative real-time polymerase chain reaction and immunocytochemistry.RESULTS hUC-MSCs expressed specific cell surface markers CD105,CD90,CD44,and vimentin but lack the expression of CD45.The transcription factors GATA-4 and MEF2C,and their combination induced differentiation in hUC-MSCs with significant expression of cardiac genes i.e.,GATA-4,MEF2C,NK2 homeobox 5(NKX2.5),MHC,and connexin-43,and cardiac proteins GATA-4,NKX2.5,cardiac troponin T,and connexin-43.CONCLUSION Transfection with GATA-4,MEF2C,and their combination effectively induces cardiac differentiation in hUC-MSCs.These genetically modified MSCs could be a promising treatment option for heart diseases in the future.展开更多
Currently,the growth of micro and nano(very large scale integration-ultra large-scale integration)electronics technology has greatly impacted biomedical signal processing devices.These high-speed micro and nano techno...Currently,the growth of micro and nano(very large scale integration-ultra large-scale integration)electronics technology has greatly impacted biomedical signal processing devices.These high-speed micro and nano technology devices are very reliable despite their capacity to operate at tremendous speed,and can be designed to consume less power in minimum response time,which is particularly useful in biomedical products.The rapid technological scaling of the metal-oxide-semi-conductor(MOS)devices aids in mapping multiple applications for a specific purpose on a single chip which motivates us to design a sophisticated,small and reliable application specific integrated circuit(ASIC)chip for future real time medical signal separation and processing(digital stetho-scopes and digital microelectromechanical systems(MEMS)microphone).In this paper,ASIC level implementation of the adaptive line enhancer design using adaptive filtering algorithms(least mean square(LMS)and normalized least mean square(NLMS))integrated design is used to separate the real-time auscultation sound signals effectively.Adaptive line enhancer(ALE)design is imple-mented in Verilog hardware description language(HDL)language to obtain both the network and adaptive algorithm in cadence Taiwan Semiconductor Manufacturing Company(TSMC)90 nm standard cell library environment for ASIC level implementation.Native compiled simulator(NC)sim and RC lab were used for functional verification and design constraints and the physical design is implemented in Encounter to obtain the Geometric Data Stream(GDS II).In this architecture,the area occupied is 0.08 mm,the total power consumed is 5.05 mW and the computation time of the proposed system is 0.82μs for LMS design and the area occupied is 0.14 mm,the total power consumed is 4.54 mW and the computation time of the proposed system is 0.03μs for NLMS design that will pave a better way in future electronic stethoscope design.展开更多
The P19CL6 mouse embryonic carcinoma cells efficiently differentiate into cardiac muscle cells in the presence of DMSO. A reporter plasmid for cardiac muscle differentiation was constructed by connecting the CMV enhan...The P19CL6 mouse embryonic carcinoma cells efficiently differentiate into cardiac muscle cells in the presence of DMSO. A reporter plasmid for cardiac muscle differentiation was constructed by connecting the CMV enhancer and a 250 bp MLC-2v promoter in front of the GFP gene to further evaluate the role of the CMV enhancer. This plasmid (pCBVenh/MLC-2vpro/EGFP) was stably introduced into P19CL6 cells, and the transfectant differentiated into cardiomyocytes with DMSO. Upon DMSO addition, GFP was immediately transcribed (within 2 days) and the amount of the transcript increased with cultivation. Concomitantly, GFP fluorescence was detected in the cells under a microscope. However, native MLC-2v was transcribed later on day 4. This expression time course is different from that of GFP. Clearly the CMV enhancer responded immediately to DMSO. Since GATA DNA-binding proteins play crucial roles in the initiation of cardiomyocyte differentiation, such a response could be ascribed to the presence of multiple GATA motifs in the enhancer sequence but not in the native MLC-2v promoter. Thus the CMV enhancer may be not only useful for gene therapy and monitoring cell differentiation but also the study of the role of GATA transcription factors expressed in P19CL6 cells.展开更多
The purpose of this study was to identify factors that enhance and hinder interdisciplinary collaborative practice (ICP) among doctors and nurses at the Nnamdi Azikiwe teaching hospital, Nnewi, southeast Nigeria. The ...The purpose of this study was to identify factors that enhance and hinder interdisciplinary collaborative practice (ICP) among doctors and nurses at the Nnamdi Azikiwe teaching hospital, Nnewi, southeast Nigeria. The study was a cross-sectional descriptive survey and the quantitative method of data collection was employed. The population was all doctors irrespective of area of specialty and all nurses employed and working in the hospital as at the time of study. Proportionate stratified and convenience sampling methods were used to select study participants according to their categories. Using validated structured questionnaire, data were collected from 110 doctors and 95 nurses in the teaching hospital on their perception on ICP and factors that enhance/hinder ICP. Data were analyzed using both descriptive and inferential statistics. Specifically, frequencies, percentages, standard deviation and graphic presentation were used for descriptive analysis of scores while the unpaired t test of mean score using Graph Pad Prism, Version 5.30 was used to determine the influence of profession, gender, and years of experience on perception of ICP at 0.05 level of significance. The study found that both doctors and nurses have positive perception on ICP. Their years of experience have significant influence on their perception. Clear individual roles and good working relationships enhance ICP while giving priority to professional status rather than expertise was seen as a prominent hindrance to ICP. The study recommends collaborative continuing education for doctors and nurses to enhance ICP in patient care. In addition, the inclusion of interdisciplinary collaborative practice programmme into the curriculum of medical and nursing students (where it does not exist) would go a long way to strengthen ICP and decrease hindrances when they graduate.展开更多
To explore the structure-activity connections of amphiphilic permeation enhancers containing the length of the hydrophobic chains as well as the properties of the polar head,O-acylgeraniol and O-acylnerol derivatives ...To explore the structure-activity connections of amphiphilic permeation enhancers containing the length of the hydrophobic chains as well as the properties of the polar head,O-acylgeraniol and O-acylnerol derivatives were synthesized from geraniol/nerol(cis-isomer of geraniol) and pharmaceutical excipient acids in this research. Their promotion of the percutaneous absorption of three drugs as the model, flurbiprofen(FP), isosorbide dinitrate(ISDN) and donepezil(DNP), which were selected based on their physicochemical properties,was tested by in vitro skin penetration and in vivo. Molecular simulation, ATR-FTIR, CLSM and histological observation were implement to evaluate the mode of action of the enhancers.The results indicated that(E)-3,7-dimethyl-2,6-octadien-1-yl tetradecanoate(GER-C14, trans-)achieved the highest enhancement ability for the three drugs;additionally, the in vivo results obtained were in good correlation with the in vitro data. Molecular docking results suggested that enhancers loosen the hydrogen bonds between ceramides, and the results of molecular simulation indicated that GER-C14, NER-C14 could insert into the middle of the lipid bilayer to form an independent phase. According to ATR-FTIR and histological evaluation, the enhancers extracted lipids and influenced the protein region, thereby disturbing the skin array. In addition, CLSM described the dynamic effects of enhancers on lipids between stratum corneum(SC) cells. In conclusion, GER-C14 had a better penetration promotion effect, which broadened our understanding of stereoisomeric penetration enhancers.展开更多
文摘Borneol, as a traditional natural permeation enhancer, has been widely used to promote the transdermal absorption of active ingredients. In this review, the mechanism of borneol in promoting permeation by destroying the highly ordered lipid structure of the lipid layer and by destroying the hydrogen-bond network was described. The application of borneol in promoting the transdermal absorption of the active ingredients of traditional Chinese medicine and chemical drugs was introduced. The application of borneol as a natural ingredient added to functional cosmetics was summarized, and its effects on skin-spot treatment, acne skin care, eczema skin care, skin repair and anti-oxidation were introduced. Finally, the possible problems in the application of borneol in cosmetics were put forward, and the application prospect of borneol in the development of cosmetics was given.
文摘Expanding in the oral care business, being passionately driven by innovative and scientific products, functional toothpaste has recently become more popular for functionality, variety, and efficacy. Many new types of toothpaste are commercially manufactured with diverse fragrances, colors, probiotics, and pharmaceutical ingredients to enhance the functionalities of toothpaste. Our study attempted to create a toothpaste formulation that might facilitate the intraoral delivery of vitamin D3 into the bloodstream. Simply brushing our teeth with toothpaste should be easy to take the essential vitamin regularly. In this study, an emulsion-based toothpaste mixed with an azone compound and sodium dodecyl sulfate as penetration enhancers blended thoroughly with other ingredients and then with vitamin D. Multiple toothpaste characteristic tests were performed, such as abrasiveness, scratchiness, spreadability, pH, foaming, cleaning, and antibacterial strength with our vitamin D toothpaste, and compared with those of other commercial brand toothpaste. To confirm the intraoral delivery of vitamin D through the oral cavity, an earthworm transport study and TEER value test were conducted using L. terrestris skin. Our data demonstrated the high feasibility of intraoral delivery of vitamin D based on those two skin studies with various experimental support;our vitamin D toothpaste had comparable characteristics with other commercial toothpaste for cleaning functionality.
文摘Borneol,as a traditional natural permeation enhancer,has been widely used to promote the transdermal absorption of active ingredients.The mechanism of borneol in promoting permeation by destroying the highly ordered lipid structure of the lipid layer and by destroying the hydrogen-bond network was described.The application of borneol in promoting the transdermal absorption of the active ingredients of traditional Chinese medicine and chemical drugs was introduced.The application of borneol as a natural ingredient added to functional cosmetics was summarized,and its effects on skin-spot treatment,acne skin care,eczema skin care,skin repair and anti-oxidation were introduced.Finally,the possible problems in the application of borneol in cosmetics were put forward,and the application prospect of borneol in the development of cosmetics was given。
文摘Unmanned aerial vehicle (UAV) target tracking tasks can currently be successfully completed in daytime situations with enough lighting, but they are unable to do so in nighttime scenes with inadequate lighting, poor contrast, and low signal-to-noise ratio. This letter presents an enhanced low-light enhancer for UAV nighttime tracking based on Zero-DCE++ due to its ad-vantages of low processing cost and quick inference. We developed a light-weight UCBAM capable of integrating channel information and spatial features and offered a fully considered curve projection model in light of the low signal-to-noise ratio of night scenes. This method significantly improved the tracking performance of the UAV tracker in night situations when tested on the public UAVDark135 and compared to other cutting-edge low-light enhancers. By applying our work to different trackers, this search shows how broadly applicable it is.
基金China Postdoctoral Science Foundation,Grant/Award Number:2017M620977,2018T110169Technology Research and Development Project of Dapeng New Zone,Grant/Award Number:KY20160308the Agricultural Science and Technology Innovation Program Cooperation and Innovation Mission,Grant/Award Number:CAAS-XTCX2016001-3
文摘Enhancer is a positive regulator for spatiotemporal development in eukaryotes. As a cluster, super-enhancer is closely related to cell identity- and fate-determined processes. Both of them function tightly depending on their targeted transcription factors, cofactors, and genes through distal genomic interactions. They have been recognized as critical components and played positive roles in transcriptional regulatory network or factory. Recent advances of next-generation sequencing have dramatically expanded our ability and knowledge to interrogate the molecular mechanism of enhancer and super-enhancer for transcription. Here, we review the history, importance, advances and challenges on enhancer and super-enhancer field.This will benefit our understanding of their function mechanism for transcription underlying precise gene expression.
基金National Natural Science Foun-dation of China(No:30973654 and No:81173007).
文摘Transdermal drug delivery has been accepted as a potential non-invasive route of drug administration,with advantages of prolonged therapeutic action,decreased side effect,easy use and better patient compliance.However,development of transdermal products is primarily hindered by the low permeability of the skin.To overcome this barrier effect,numerous new chemicals have been synthesized as potential permeation enhancers for transdermal drug delivery.In this review,we presented an overview of the investigations in this field,and further implications on selection or design of suitable permeation enhancers for transdermal drug delivery were also discussed.
文摘Polycomb group proteins represent a global silencing system involved in development regulation.In specific,they regulate the transition from proliferation to differentiation,contributing to stem-cell maintenance and inhibiting an inappropriate activation of differentiation programs.Enhancer of Zeste Homolog 2(EZH2) is the catalytic subunit of Polycomb repressive complex 2,which induces transcriptional inhibition through the tri-methylation of histone H3,an epigenetic change associated with gene silencing.EZH2 expression is high in precursor cells while its level decreases in differentiated cells.EZH2 is upregulated in various cancers with high levels associated with metastatic cancer and poor prognosis.Indeed,aberrant expression of EZH2 causes the inhibition of several tumor suppressors and differentiation genes,resulting in an uncontrolled proliferation and tumor formation.This editorial explores the role of Polycomb repressive complex 2 in cancer,focusing in particular on EZH2.The canonical function of EZH2 in gene silencing,the non-canonical activities as the methylation of other proteins and the role in gene transcriptional activation,were summarized.Moreover,mutations of EZH2,responsible for an increased methyltransferase activity in cancer,were recapitulated.Finally,various drugs able to inhibit EZH2 with different mechanism were described,specifically underscoring the effects in several cancers,in order to clarify the role of EZH2 and understand if EZH2 blockade could be a new strategy for developing specific therapies or a way to increase sensitivity of cancer cells to standard therapies.
基金The study was supported by National Natural Science Foundation of China (No.39970035) .
文摘Objective To investigate the cell-type-specific enhancer (CTSE) in HPV16 and its variation in cervical carcinoma. Methods CTSEs were detected by polymerase chain reaction (PCR) in 58 cervical carcinoma from Shaanxi province; in addition variation of CTSEs was analyzed through single-strand conformation polymorphisms (SSCP). Results HPV16 CTSEs were detectable in 34 of 58 (57%) specimens and mutant rate was 41%(14/34) and the main mutations of chosen randomly variant CTSE (CTSEv) happened at YY1 binding sites in addition to glucocoticoid response elements (GRE). Conclusion CTSE in some specimens of Shaanxi province was obviously different from that in HPV16 wild type and variant CTSE might affect the transcriptional regulation of LCR on viral P97, which regulates over-expression of viral oncogenes in cervical carcinoma.
基金This project is supported by the Office of the High Education Commission and Mahidol University under the National Research Universities Initiative.
文摘This study aimed to develop niosomes of ellagic acid(EA),a potent antioxidant phytochemical substance,for dermal delivery and to investigate the influence of chemical penetration enhancers on the physicochemical properties of EA-loaded niosomes.The EA niosomes were prepared by reverse phase evaporation method using Span 60,Tween 60 and cholesterol as vesicle forming agents and Solulan C24 as a steric stabilizer.Polyethylene glycol 400(PEG)was used as a solubilizer while dimethylsulfoxide(DMSO)or Nmethyl-2-pyrrolidone(NMP)was used as a skin penetration enhancer.It was found that the mean particle sizes of EA-loaded niosomes were in the range of 312e402 nm with PI values of lower than 0.4.The niosomes were determined to be spherical multilamellar vesicles as observed by transmission electron microscope and optical microscopy.All niosomes were stable after 4 months storage at 4C.In vitro skin permeation through human epidermis revealed that the skin enhancers affected the penetration of EA from the niosomes at 24 h.The DMSO niosomes showed the highest EA amount in epidermis;whereas the NMP niosomes had the highest EA amount in the acceptor medium.Concomitantly,the skin distribution by confocal laser scanning microscopy showed the high fluorescence intensity of the DMSO niosomes and NMP niosomes at a penetration depth of between 30e90 mm(the epidermis layer)and 90e120 mm(the dermis layer)under the skin,respectively.From the results,it can be concluded that the DMSO niosomes are suitable for epidermis delivery of EA while the NMP niosomes can be used for dermis delivery of EA.
基金supported by the National Natural Science Foundation of China(32100502)the Ministry of Agriculture of China(2016ZX08009003-006)Science&Technology Department of Yunnan Province(202102AE090039).
文摘Background:The pig is an economically important livestock species and is a widely applied large animal model in medical research.Enhancers are critical regulatory elements that have fundamental functions in evolution,development and disease.Genome-wide quantification of functional enhancers in the pig is needed.Results:We performed self-transcribing active regulatory region sequencing(STARR-seq)in the porcine kidney epithelial PK15 and testicular ST cell lines,and reliably identified 2576 functional enhancers.Most of these enhancers were located in repetitive sequences and were enriched within silent and lowly expressed genes.Enhancers poorly overlapped with chromatin accessibility regions and were highly enriched in chromatin with the repressive histone modification H3K9me3,which is different from predicted pig enhancers detected using ChIP-seq for H3K27ac or/and H3K4me1 modified histones.This suggests that most pig enhancers identified with STARR-seq are endogenously repressed at the chromatin level and may function during cell type-specific development or at specific developmental stages.Additionally,the PPP3CA gene is associated with the loin muscle area trait and the QKI gene is associated with alkaline phosphatase activity that may be regulated by distal functional enhancers.Conclusions:In summary,we generated the first functional enhancer map in PK15 and ST cells for the pig genome and highlight its potential roles in pig breeding.
文摘Amh (anti-Müllerian hormone) is a single copy gene which is expressed strongly in Sertoli cells in the foetal testis and participates in the onset of sexual differentiation. Its promoter driving the expression of a reporter gene (d2EGFP) has been used to analyse the role of certain defined putative elements and a downstream enhancer element in gene expression. These experiments were carried out in vitro using a line of pre-pubertal mouse Sertoli cells, transienly transfected with circular DNA constructs with variously mutated promoter elements. A downstream enhancer element, situated immediately 3’ of the polyadenylation (PA) signal for Amh, has been inserted in an equivalent position in the d2EGFP construct. When the Amh promoter is unmodified, the downstream enhancer (DE) is positively associated with a large increase in EGFP expression. This is at least partly the consequence of an increased rate of expression by individual cells. Experiments using variously truncated Amh promoters indicate that an upstream region (-214 to -336) may play a minor role in facilitating enhancement. However mutation of the Wilms tumour factor-1 element, situated between the tata box and the start of translation, results in an almost complete suppression of enhancement.
基金This work was supported by the Key R&D Programmes of Guangdong Province,China(2018B020203003)the National Natural Science Foundation of China(31830090)+1 种基金the Shenzhen Science Technology and Innovation Commission,China(JCYJ20170307160516413)and the Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences(CAAS-ZDRW202006).We appreciate Postdoctoral Fellow AdeyinkaAbiolaAdetula,for grammar checking and suggestions.
文摘Currently,enhancers have key transcriptional regulatory roles in muscle development.Skeletal muscle formation involves various molecules,and in animals,enhancers are one of the main types of transcriptional regulatory regions that are of great importance to regulate myogenic gene expression.In muscle development,enhancers can generate enhancer RNAs(eRNAs)that are involved in the regulation of gene transcription.The regulation of gene expression by eRNAs offers great potential in improving animal production traits.Herein we comprehensively review the roles of enhancers in muscle formation and its potential function in skeletal muscle development.This review will describe the future application of enhancers in skeletal muscle development and discuss the prospects that enhancer studies offer for agriculture,biotechnology,and animal breeding.
基金Supported by National Natural Science Foundation of China,No.81900498.
文摘BACKGROUND Inflammatory bowel disease(IBD)is a prevalent worldwide health problem featured by relapsing,chronic gastrointestinal inflammation.Enhancer of zeste homolog 2(EZH2)is a critical epigenetic regulator in different pathological models,such as cancer and inflammation.However,the role of EZH2 in the IBD development is still obscure.AIM To explore the effect of EZH2 on IBD progression and the underlying mechanism.METHODS The IBD mouse model was conducted by adding dextran sodium sulfate(DSS),and the effect of EZH2 on DSS-induced colitis was assessed in the model.The function of EZH2 in regulating apoptosis and permeability was evaluated by Annexin V-FITC Apoptosis Detection Kit,transepithelial electrical resistance analysis,and Western blot analysis of related markers,including Zona occludens 1,claudin-5,and occludin,in NCM460 and fetal human colon(FHC)cells.The mechanical investigation was performed by quantitative reverse transcriptionpolymerase chain reaction,Western blot analysis,and chromatin immunoprecipitation assays.RESULTS The colon length was inhibited in the DSS-treated mice and was enhanced by the EZH2 depletion in the system.DSS treatment caused a decreased histological score in the mice,which was reversed by EZH2 depletion.The inflammatory cytokines,such as tumor necrosis factor-α,interleukin-6,and interleukin-1β,were induced in the DSS-treated mice,in which the depletion of EZH2 could reverse this effect.Moreover,the tumor necrosis factor-αtreatment induced the apoptosis of NCM460 and FHC cells,in which EZH2 depletion could reverse this effect in the cells.Moreover,the depletion of EZH2 attenuated permeability of colonic epithelial cells.Mechanically,the depletion of EZH2 or EZH2 inhibitor GSK343 was able to enhance the expression and the phosphorylation of janus kinase 2(JK2)and signal transducer and activator of transcription in the NCM460 and FHC cells.Specifically,EZH2 inactivated JAK2 expression by regulating histone H3K27me3.JAK2 inhibitor TG101348 was able to reverse EZH2 knockdownmediated colonic epithelial cell permeability and apoptosis.CONCLUSION Thus,we concluded that EZH2 contributed to apoptosis and inflammatory response by inactivating JAK2/signal transducer and activator of transcription signaling in IBD.EZH2 may be applied as a potential target for IBD therapy.
基金Supported by the National Natural Science Foundation of China(No.81770963No.81770964)。
文摘AIM:To investigate the role of procollagen C-proteinase enhancer 1(PCPE1)in retinal angiogenesis and relevant mechanisms.METHODS:The Pcolce1-knockout(KO)mice were used to explore the effect of PCPE1 on retinal angiogenesis in vivo.Pcolce1 si RNA were designed,cell count kit 8(CCK8)assays and tube formation assays were performed to investigate the cell proliferation and tube formation abilities of retinal microvascular endothelial cells(h RMECs)in vitro.Mouse embryo fibroblasts(MEF)cells were isolated and cultured to analyze the effect of PCPE1 on enhancing procollagen cleavage.RESULTS:In vivo studies showed that the retinal vascular density of Pcolce1-/-mice was significantly lower than that of the control group.Furthermore,silencing of Pcolce1 inhibited cell proliferation and tube formation abilities of h RMECs in vitro.Additionally,much more procollagen was found in Pcolce1-/-MEF cells,compared to wild type MEF cells.CONCLUSION:PCPE1 may promote physiological retinal angiogenesis by regulating the processing of collagen,which may provide a potential therapeutic target of retinal vascular disease.
基金Supported by the Higher Education Commission(HEC),Pakistan Scholarship for Ph.D.Studies to Razzaq SS,No.520-148390-2BS6-011.
文摘BACKGROUND Heart diseases are the primary cause of death all over the world.Following myocardial infarction,billions of cells die,resulting in a huge loss of cardiac function.Stem cell-based therapies have appeared as a new area to support heart regeneration.The transcription factors GATA binding protein 4(GATA-4)and myocyte enhancer factor 2C(MEF2C)are considered prominent factors in the development of the cardiovascular system.AIM To explore the potential of GATA-4 and MEF2C for the cardiac differentiation of human umbilical cord mesenchymal stem cells(hUC-MSCs).METHODS hUC-MSCs were characterized morphologically and immunologically by the presence of specific markers of MSCs via immunocytochemistry and flow cytometry,and by their potential to differentiate into osteocytes and adipocytes.hUC-MSCs were transfected with GATA-4,MEF2C,and their combination to direct the differentiation.Cardiac differentiation was confirmed by semiquant itative real-time polymerase chain reaction and immunocytochemistry.RESULTS hUC-MSCs expressed specific cell surface markers CD105,CD90,CD44,and vimentin but lack the expression of CD45.The transcription factors GATA-4 and MEF2C,and their combination induced differentiation in hUC-MSCs with significant expression of cardiac genes i.e.,GATA-4,MEF2C,NK2 homeobox 5(NKX2.5),MHC,and connexin-43,and cardiac proteins GATA-4,NKX2.5,cardiac troponin T,and connexin-43.CONCLUSION Transfection with GATA-4,MEF2C,and their combination effectively induces cardiac differentiation in hUC-MSCs.These genetically modified MSCs could be a promising treatment option for heart diseases in the future.
文摘Currently,the growth of micro and nano(very large scale integration-ultra large-scale integration)electronics technology has greatly impacted biomedical signal processing devices.These high-speed micro and nano technology devices are very reliable despite their capacity to operate at tremendous speed,and can be designed to consume less power in minimum response time,which is particularly useful in biomedical products.The rapid technological scaling of the metal-oxide-semi-conductor(MOS)devices aids in mapping multiple applications for a specific purpose on a single chip which motivates us to design a sophisticated,small and reliable application specific integrated circuit(ASIC)chip for future real time medical signal separation and processing(digital stetho-scopes and digital microelectromechanical systems(MEMS)microphone).In this paper,ASIC level implementation of the adaptive line enhancer design using adaptive filtering algorithms(least mean square(LMS)and normalized least mean square(NLMS))integrated design is used to separate the real-time auscultation sound signals effectively.Adaptive line enhancer(ALE)design is imple-mented in Verilog hardware description language(HDL)language to obtain both the network and adaptive algorithm in cadence Taiwan Semiconductor Manufacturing Company(TSMC)90 nm standard cell library environment for ASIC level implementation.Native compiled simulator(NC)sim and RC lab were used for functional verification and design constraints and the physical design is implemented in Encounter to obtain the Geometric Data Stream(GDS II).In this architecture,the area occupied is 0.08 mm,the total power consumed is 5.05 mW and the computation time of the proposed system is 0.82μs for LMS design and the area occupied is 0.14 mm,the total power consumed is 4.54 mW and the computation time of the proposed system is 0.03μs for NLMS design that will pave a better way in future electronic stethoscope design.
文摘The P19CL6 mouse embryonic carcinoma cells efficiently differentiate into cardiac muscle cells in the presence of DMSO. A reporter plasmid for cardiac muscle differentiation was constructed by connecting the CMV enhancer and a 250 bp MLC-2v promoter in front of the GFP gene to further evaluate the role of the CMV enhancer. This plasmid (pCBVenh/MLC-2vpro/EGFP) was stably introduced into P19CL6 cells, and the transfectant differentiated into cardiomyocytes with DMSO. Upon DMSO addition, GFP was immediately transcribed (within 2 days) and the amount of the transcript increased with cultivation. Concomitantly, GFP fluorescence was detected in the cells under a microscope. However, native MLC-2v was transcribed later on day 4. This expression time course is different from that of GFP. Clearly the CMV enhancer responded immediately to DMSO. Since GATA DNA-binding proteins play crucial roles in the initiation of cardiomyocyte differentiation, such a response could be ascribed to the presence of multiple GATA motifs in the enhancer sequence but not in the native MLC-2v promoter. Thus the CMV enhancer may be not only useful for gene therapy and monitoring cell differentiation but also the study of the role of GATA transcription factors expressed in P19CL6 cells.
文摘The purpose of this study was to identify factors that enhance and hinder interdisciplinary collaborative practice (ICP) among doctors and nurses at the Nnamdi Azikiwe teaching hospital, Nnewi, southeast Nigeria. The study was a cross-sectional descriptive survey and the quantitative method of data collection was employed. The population was all doctors irrespective of area of specialty and all nurses employed and working in the hospital as at the time of study. Proportionate stratified and convenience sampling methods were used to select study participants according to their categories. Using validated structured questionnaire, data were collected from 110 doctors and 95 nurses in the teaching hospital on their perception on ICP and factors that enhance/hinder ICP. Data were analyzed using both descriptive and inferential statistics. Specifically, frequencies, percentages, standard deviation and graphic presentation were used for descriptive analysis of scores while the unpaired t test of mean score using Graph Pad Prism, Version 5.30 was used to determine the influence of profession, gender, and years of experience on perception of ICP at 0.05 level of significance. The study found that both doctors and nurses have positive perception on ICP. Their years of experience have significant influence on their perception. Clear individual roles and good working relationships enhance ICP while giving priority to professional status rather than expertise was seen as a prominent hindrance to ICP. The study recommends collaborative continuing education for doctors and nurses to enhance ICP in patient care. In addition, the inclusion of interdisciplinary collaborative practice programmme into the curriculum of medical and nursing students (where it does not exist) would go a long way to strengthen ICP and decrease hindrances when they graduate.
基金The Natural Science Foundation of Hebei Province [grant numbers H2019209254]North China University of Science and Technology Foundation for Distinguished Young Scholars[grant numbers JQ201713]Distinguished Young Scholars of Hebei Province。
文摘To explore the structure-activity connections of amphiphilic permeation enhancers containing the length of the hydrophobic chains as well as the properties of the polar head,O-acylgeraniol and O-acylnerol derivatives were synthesized from geraniol/nerol(cis-isomer of geraniol) and pharmaceutical excipient acids in this research. Their promotion of the percutaneous absorption of three drugs as the model, flurbiprofen(FP), isosorbide dinitrate(ISDN) and donepezil(DNP), which were selected based on their physicochemical properties,was tested by in vitro skin penetration and in vivo. Molecular simulation, ATR-FTIR, CLSM and histological observation were implement to evaluate the mode of action of the enhancers.The results indicated that(E)-3,7-dimethyl-2,6-octadien-1-yl tetradecanoate(GER-C14, trans-)achieved the highest enhancement ability for the three drugs;additionally, the in vivo results obtained were in good correlation with the in vitro data. Molecular docking results suggested that enhancers loosen the hydrogen bonds between ceramides, and the results of molecular simulation indicated that GER-C14, NER-C14 could insert into the middle of the lipid bilayer to form an independent phase. According to ATR-FTIR and histological evaluation, the enhancers extracted lipids and influenced the protein region, thereby disturbing the skin array. In addition, CLSM described the dynamic effects of enhancers on lipids between stratum corneum(SC) cells. In conclusion, GER-C14 had a better penetration promotion effect, which broadened our understanding of stereoisomeric penetration enhancers.
