Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant...Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant,anticoagulant,and anti-diabetic effects.Growth/differentiation factor-15(GDF-15),a member of the transforming growth factorβsuperfamily,is considered a potential therapeutic target for metabolic disorders.This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism.The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo,and determined the involvement of endoplasmic reticulum(ER)stress signaling in this process.Luciferase reporter assays,chromatin immunoprecipitation,and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4(ATF4),CCAAT enhancer binding proteinγ(CEBPG),and CCCTC-binding factor(CTCF).The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene,as well as the influence of single nucleotide polymorphisms(SNPs)on magnolol and ATF4-induced transcription activity.Results demonstrated that magnolol triggers GDF-15 production in endothelial cells(ECs),hepatoma cell line G2(HepG2)and hepatoma cell line 3B(Hep3B)cell lines,and primary mouse hepatocytes.The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene.SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15.In high-fat diet ApoE^(-/-)mice,administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15.These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity,indicating its potential as a drug for the treatment of metabolic disorders.展开更多
The increasing challenges of environmental degradation,soil erosion,and climate change have driven interest in sustainable solutions like enhanced weathering(EW)and phytoremediation.Elephant Grass(Cenchrus purpureus),...The increasing challenges of environmental degradation,soil erosion,and climate change have driven interest in sustainable solutions like enhanced weathering(EW)and phytoremediation.Elephant Grass(Cenchrus purpureus),a fast-growing perennial species,shows promise as a bioaccumulator and agent for soil weathering.This study assessed the potential of C.purpureus to improve soil quality through heavy metal(HM)uptake and EW facilitation.A 60-day greenhouse pot experiment at Jackson State University evaluated plant performance in soils amended with metabasalt rock powder at 1:1 and 2:1 rock-to-soil ratios.Biomass,growth,and HM concentrations in roots and shoots were measured via ICP-MS after wet digestion.Soil pH and magnesium(Mg)release were also monitored to assess weathering and carbon drawdown.Results showed that C.purpureus accumulated more HMs in roots at higher amendment levels,while at lower levels,metals like As,Cd,and Cr were more translocated to shoots,enhancing phytoextraction potential.High treatment favored Fe and Al uptake,possibly reducing toxic metal accumulation in edible parts.Notably,C.purpureus contributed to the weathering of 38%of metabasalt rock,leading to a 42%increase in Mg release.With high biomass,HM tolerance,and weathering capacity,C.purpureus offers a sustainable strategy for soil remediation,improved soil health,and potential support for renewable energy systems.展开更多
Objective:In recent decades,studies have underscored nuclear proteins and signaling pathways in prostate cancer(PCa)development.Key biomarkers like Enhancer of zeste homolog 2(EZH2)and Forkhead box M1(FOXM1)are expres...Objective:In recent decades,studies have underscored nuclear proteins and signaling pathways in prostate cancer(PCa)development.Key biomarkers like Enhancer of zeste homolog 2(EZH2)and Forkhead box M1(FOXM1)are expressed in both healthy and malignant prostate cells.This study aimed to demonstrate the relationship between pathological characteristics,survival,recurrence,and tissue expression of EZH2 and FOXM1 in high-risk PCa patients.Methods:PCa tissues were used in a retrospective analysis that spanned from September 2009 to August 2019.Inclusion criteria comprised pathological tumor stage(pT)3 patients with positive surgical margins or tumor proximity to inked margins within 5 mm.After case selection,tissue slides were stained for EZH2 and FOXM1 antibodies,and Allred scores were calculated.Patients or relatives of deceased patients were contacted for signed agreements and disease follow-ups.Results:The pT3b,ductal carcinoma component,and moderate EZH2 expression were associated with relapse(odds ratio[OR]6.21,95%confidence interval[CI]1.41-27.27,p=0.016;OR 7.29,95%CI 1.03-51.43,p=0.046;OR 5.96,95%CI 1.09-32.48,p=0.039;respectively).The unilateral and bilateral seminal vesicle invasion increased the likelihood of recurrence by 9.98 times and 5.36 times,and the risk of death by around 9.78 times and 10.79 times,respectively.The pT3b was linked to higher death likelihood(OR 7.16,95%CI 1.38-37.23,p=0.019),while moderate EZH2 expression did not show statistical significance(OR 4.54,95%CI 0.87-23.60,p=0.072,marginally).Pathological regional lymph node stage(pN)1 had significantly higher probability of mortality than pN unknown(3.9%vs.27%,p<0.001).PCa in the neck and apex of the prostate gland increased death risk tenfold.Conclusion:Sufficient immunoexpression of EZH2,ductal carcinoma component,and neoplastic proliferation in the seminal vesicles,apex and neck of the prostate gland correlates with elevated risks of recurrence and mortality.Clinicians should use these criteria for appropriate patient referrals,and a multicenter trial could provide accurate classifications.展开更多
Plp1-lineage Schwann cells(SCs)of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing,and the abnormal plasticity of SCs would jeopardize ...Plp1-lineage Schwann cells(SCs)of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing,and the abnormal plasticity of SCs would jeopardize the bone regeneration.However,how Plp1-lineage cells respond to injury and initiate the vascularized osteogenesis remains incompletely understood.Here,by employing single-cell transcriptional profiling combined with lineage-specific tracing models,we uncover that Plp1-lineage cells undergoing injury-induced glia-to-MSCs transition contributed to osteogenesis and revascularization in the initial stage of bone injury.Importantly,our data demonstrated that the Sonic hedgehog(Shh)signaling was responsible for the transition process initiation,which was strongly activated by c-Jun/SIRT6/BAF170 complex-driven Shh enhancers.Collectively,these findings depict an injuryspecific niche signal-mediated Plp1-lineage cells transition towards Gli1+MSCs and may be instructive for approaches to promote bone regeneration during aging or other bone diseases.展开更多
Background:Dysregulation of enhancer transcription occurs in multiple cancers.Enhancer RNAs(eRNAs)are transcribed products from enhancers that play critical roles in transcriptional control.Characterizing the genetic ...Background:Dysregulation of enhancer transcription occurs in multiple cancers.Enhancer RNAs(eRNAs)are transcribed products from enhancers that play critical roles in transcriptional control.Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers.Methods:Initially,a comprehensive analysis of eRNA quantitative trait loci(eRNAQTLs)was performed in The Cancer Genome Atlas(TCGA),and functional features were characterized using multi-omics data.To establish the first eRNAQTL profiles for colorectal cancer(CRC)in China,epigenomic data were used to define active enhancers,which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples.Finally,largescale case-control studies(34,585 cases and 69,544 controls)were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk.Results:A total of 300,112 eRNAQTLs were identified across 30 different cancer types,which exert their influence on eRNA transcription by modulating chromatin status,binding affinity to transcription factors and RNA-binding proteins.These eRNAQTLs were found to be significantly enriched in cancer risk loci,explaining a substantial proportion of cancer heritability.Additionally,tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer.Moreover,the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer,highlighting their potential as therapeutic targets.Furthermore,multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China(OR=0.91,95%CI 0.88–0.95,P=2.92×10^(-7))and Europe(OR=0.92,95%CI 0.88–0.95,P=4.61×10^(-6)).Mechanistically,rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786,which functioned as a transcriptional activator promoting the expression of its target gene SENP7.These two genes synergistically suppressed tumor cell proliferation.Our curated list of variants,genes,and drugs has been made available in CancereRNAQTL(http://canernaqtl.whu.edu.cn/#/)to serve as an informative resource for advancing this field.Conclusion:Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability,pinpointing the potential of eRNA-based therapeutic strategies in cancers.展开更多
The abnormality of the p53 tumor suppressor is crucial in lung cancer development,because p53 regulates target gene promoters to combat cancer.Recent studies have shown extensive p53 binding to enhancer elements.Howev...The abnormality of the p53 tumor suppressor is crucial in lung cancer development,because p53 regulates target gene promoters to combat cancer.Recent studies have shown extensive p53 binding to enhancer elements.However,whether p53 exerts a tumor suppressor role by shaping the enhancer landscape remains poorly understood.In the current study,we employed several functional genomics approaches to assess the enhancer activity at p53 binding sites throughout the genome based on our established TP53 knockout(KO)human bronchial epithelial cells(BEAS-2B).A total of 943 active regular enhancers and 370 super-enhancers(SEs)disappeared upon the deletion of p53,indicating that p53 modulates the activity of hundreds of enhancer elements.We found that one p53-dependent SE,located on chromosome 9 and designated as KLF4-SE,regulated the expression of the Krüppel-like factor 4(KLF4)gene.Furthermore,the deletion of p53 significantly decreased the KLF4-SE enhancer activity and the KLF4 expression,but increased colony formation ability in the nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced cell transformation model.Subsequently,in TP53 KO cells,the overexpression of KLF4 partially reversed the increased clonogenic capacity caused by p53 deficiency.Consistently,KLF4 expression also decreased in lung cancer tissues and cell lines.It appeared that overexpression of KLF4 significantly suppressed the proliferation and migration of lung cancer cells.Collectively,our results suggest that the regulation of enhancer formation and activity by p53 is an integral component of the p53 tumor suppressor function.Therefore,our findings offer some novel insights into the regulation mechanism of p53 in lung oncogenesis and introduce a new strategy for screening therapeutic targets.展开更多
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
The effects of some commonly used penetration enhancers such as laurocapram (AZ), oleic acid (OA), poloxamer (POL) and propylene glycol (PG) on the in vitro transdermal iontophoretic delivery of insulin through fu...The effects of some commonly used penetration enhancers such as laurocapram (AZ), oleic acid (OA), poloxamer (POL) and propylene glycol (PG) on the in vitro transdermal iontophoretic delivery of insulin through full-thickness mouse skin were investigated. The results showed that AZ had a synergistic effect on iontophoretic ability to enhance skin permeation of insulin, and PG could further increase this effect. 5% AZ / PG increased the iontophoretic steady state flux of insulin by a factor of 2.75 compared to that treated with iontophoresis alone. OA did not further enhance iontophoretic effect to increase skin permeation of insulin. The combination of iontophoresis and some enhancer provided a novel idea and possibility for transdermal delivery of insulin.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
The aim of this present study is to investigate the effect of Zanthoxylum bungeanum oil （essential oil from Z. bungeanum Maxim.） on cytotoxicity and the transdermal permeation of 5-fluorouracil and indomethacin. The...The aim of this present study is to investigate the effect of Zanthoxylum bungeanum oil （essential oil from Z. bungeanum Maxim.） on cytotoxicity and the transdermal permeation of 5-fluorouracil and indomethacin. The cy- totoxicity of Z. bungeanum oil on dermal fibroblasts and epidermal keratinocytes was studied using an MTT （3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） assay. The rat skin was employed to determine the percutaneous penetration enhancement effect of Z. bungeanum oil on hydrophilic and lipophilic model drugs, i.e., 5-fluorouracil and indomethacin. The secondary structure changes of the rat stratum comeum （SC） were determined using attenuated total reflectance-Fourier transform infrared spectroscopy （ATR-FTIR）, and saturated solubilities and SC/vehicle partition coefficients of two model drugs with and without Z. bungeanum oil were also measured to un- derstand its related mechanisms of action. It was found that the half maximal inhibitory concentration （ICs0） values of Z. bungeanum oil were significantly lower in HaCaT and CCC-ESF-1 cell lines compared to the well-established and standard penetration enhancer Azone. The Z. bungeanum oil at various concentrations effectively facilitated the percutaneous penetration of two model drugs across the rat skin. In addition, the mechanisms of permeation en- hancement by Z. bungeanum oil could be explained with saturated solubility, SC/vehicle partition coefficient, and secondary structure changes of SC.展开更多
In recent decades, a growing worldwide trend of developing the biodegradable lubricants has been prevailing to form a specific field of green chemistry and green engineering. Enhancement of biodegradability of unreadi...In recent decades, a growing worldwide trend of developing the biodegradable lubricants has been prevailing to form a specific field of green chemistry and green engineering. Enhancement of biodegradability of unreadily biodegradable petroleum-based lubricants has as such become an urgent must. For over a decade the authors have been focusing on the improvement of biodegradability of unreadily biodegradable lubricants such as petroleum-based lubricating oils and greases. A new idea of lubricant biodegradation enhancer was put forward by the authors with the aim to stimulate the biodegradation of unreadily biodegradable lubricants by incorporating the enhancer into the lubricants in order to turn the lubricants into greener biodegradable ones and to help in situ bioremediation of lubricant-contaminated environment. This manuscript summarizes our recent efforts relating to the chemistry and technology of biodegradation enhancers for lubricants. Firstly, the chemistry of lubricant biodegradation enhancers was designed based on the principles of bioremediation for the treatment of hydrocarbon contaminated environment. Secondly, the ability of the designed biodegradation enhancers for increasing the biodegradability of unreadily biodegradable industrial lubricants was investigated through biodegradability evaluation tests, microbial population analysis, and biodegradation kinetics modeling. Finally, the impact of biodegradation enhancers on some crucial performance characteristics of lubricants such as lubricity and oxidation stability was tested via tribological evaluation and oxidation determinations. Our results have shown that the designed chemistry of nitrogenous and/or phosphorous compounds such as lauroyl glutamine, oleoyl glycine, oleic diethanolamide phosphate and lauric diethanolamide borate was outstanding in boosting biodegradation of petroleum-based lubricants which was ascribed to increase the microbial population and decrease the oil-water interfacial tension during the biodegradation process. Lubricants doped with the biodegradation enhancers exhibited much better biodegradability and higher biodegradation rate in the surrounding soils which could be well modeled by the exponential biodegradation kinetics. Furthermore, as lubricant dopants, the biodegradation enhancers also provided excellent capability in reducing friction and wear and in retarding oxidation of lubricants. In the nature of things, lubricant biodegradation enhancers, which are multi-functional not only in the improvement of biodegradability, but also in the fortification of lubricity and in the inhibition of oxidation of lubricants, are expected to be promising as a new category of lubricant additives.展开更多
Insertion mutagenesis has become one of the most popular methods for gene functions analysis.Here we report a two-element Ac/Ds transposon system containing enhancer trap and gene trap for gene tagging in rice.The exc...Insertion mutagenesis has become one of the most popular methods for gene functions analysis.Here we report a two-element Ac/Ds transposon system containing enhancer trap and gene trap for gene tagging in rice.The excision of Ds element was examined by PCR amplification.The excision frequency of Ds element varied from 0% to 40% among 20 F2 populations derived from 11 different Ds parents.Southern blot analysis revealed that more than 70% of excised Ds elements reinserted into rice genome and above 70% of the reinserted Ds elements were located at different positions of the chromosome in rice.The result of histochemical GUS analysis indicated that 28% of enhancer trap and 22% of gene trap tagging plants displayed GUS activity in leaves, roots,flowers or seeds.The GUS positive lines will be useful for identifying gene function in rice.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
Osteosarcoma is the most common primary bone sarcoma that mostly occurs in young adults. The causes of osteosarcoma are heterogeneous and still not fully understood. Identification of novel, important oncogenic factor...Osteosarcoma is the most common primary bone sarcoma that mostly occurs in young adults. The causes of osteosarcoma are heterogeneous and still not fully understood. Identification of novel, important oncogenic factors in osteosarcoma and development of better, effective therapeutic approaches are in urgent need for better treatment of osteosarcoma patients. In this study, we uncovered that the oncogene MYC is significantly upregulated in metastastic osteosarcoma samples. In addition, high MYC expression is associated with poor survival of osteosarcoma patients. Analysis of MYC targets in osteosarcoma revealed that most of the osteosarcoma super enhancer genes are bound by MYC. Treatment of osteosarcoma cells with super enhancer inhibitors THZ1 and JQ1 effectively suppresses the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically,THZ1 treatment suppresses a large group of super enhancer containing MYC target genes including CDK6 and TGFB2. These findings revealed that the MYC-driven super enhancer signaling is crucial for the osteosarcoma tumorigenesis and targeting the MYC/super enhancer axis represents as a promising therapeutic strategy for treatment of osteosarcoma patients.展开更多
Our previous studies had confirmed that the essential oil from Zanthoxylum bungeanum Maxim. （Z. bungeanum oil） could effectively enhance the percutaneous permeation of drug molecules as a natural transdermal penetra...Our previous studies had confirmed that the essential oil from Zanthoxylum bungeanum Maxim. （Z. bungeanum oil） could effectively enhance the percutaneous permeation of drug molecules as a natural transdermal penetration enhancer. The aim of the present study is to investigate and compare the skin penetration enhancement effect of Z. bungeanum oil and its main components on traditional Chinese medicine （TCM） active components. Toxicities of Z. bungeanum oil and three selected terpene compounds （terpinen-4-ol, 1,8-cineole, and limonene） in epidermal keratinocytes （HaCaT） and dermal flbroblast （CCC-ESF-1） cell lines were measured using an MTT （3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） assay. Five model drugs in TCM external preparations, namely osthole （OT）, tetramethylpyrazine （TMP）, ferulic acid （FA）, puerarin （PR）, and geniposide （GP）, which were selected based on their lipophilicity denoted by IogKo^w, were tested using in vitro permeation studies in which vertical Franz diffusion ceils and rat abdominal skin were employed. The secondary structure changes of skin stratum corneum （SC） and drug thermodynamic activities were investigated to understand their mechanisms of action using Fourier transform infrared （FTIR） spectroscopy and saturation solubility studies, respectively. It was found that Z. bungeanum oil showed lower toxicities in both HaCaT cells and CCC-ESF-1 cells compared with three terpene compounds used alone. The enhancement permeation capacities by all tested agents were in the following increasing order： terpinen-4-ol=1,8-cineole〈limonene〈Z, bungeanum oil. The mechanisms of permeation enhancement suggested that these enhancers promoted the skin permeation of drugs mainly by affecting SC lipids. These results indicated that Z. bungeanum oil exhibited better performance in enhancing the skin permeation of active components in TCM preparations.展开更多
Integration of human papillomavirus(HPV)DNA into the human genome is a reputed key driver of cervical cancer.However,the effects of HPV integration on chromatin structural organization and gene expression are largely ...Integration of human papillomavirus(HPV)DNA into the human genome is a reputed key driver of cervical cancer.However,the effects of HPV integration on chromatin structural organization and gene expression are largely unknown.We studied a cohort of 61 samples and identified an integration hot spot in the CCDC106 gene on chromosome 19.We then selected fresh cancer tissue that contained the unique integration loci at CCDC106 with no HPV episomal DNA and performed whole-genome,RNA,chromatin immunoprecipitation and high-throughput chromosome conformation capture(Hi-C)sequencing to identify the mechanisms of HPV integration in cervical carcinogenesis.Molecular analyses indicated that chromosome 19 exhibited significant genomic variation and differential expression densities,with correlation found between three-dimensional(3D)structural change and gene expression.Importantly,HPV integration divided one topologically associated domain(TAD)into two smaller TADs and hijacked an enhancer from PEG3 to CCDC106,with a decrease in PEG3 expression and an increase in CCDC106 expression.This expression dysregulation was further confirmed using 10 samples from our cohort,which exhibited the same HPV-CCDC106 integration.In summary,we found that HPV-CCDC106 integration altered local chromosome architecture and hijacked an enhancer via 3D genome structure remodeling.Thus,this study provides insight into the 3D structural mechanism underlying HPV integration in cervical carcinogenesis.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
Connected a segment of CMV enhancer to the front of MyoG gene promoter and then constructed the corresponding dual luciferase expression vector pGL3-CMV-MyoGpro. We set four eukaryotic expression vectors including pGL...Connected a segment of CMV enhancer to the front of MyoG gene promoter and then constructed the corresponding dual luciferase expression vector pGL3-CMV-MyoGpro. We set four eukaryotic expression vectors including pGL3-CMV, pGL3MyoGpro, pGL3-CMV-MyoGpro, and pGL3-Basic which contained CMV promoter, MyoG promoter, CMV-MyoG synthesis promoter, and a promoterless negative control, respectively. Then the four vectors and internal control Renilla luciferase report gene vector phRL-TK were transfected into bovine skeletal muscle satellite cells, mouse C2C12 cells and bovine fetal fibroblast cells to detect the promoter activity with dual luciferase report system. The results showed that CMV enhancer could significantly improve the transcription activity of bovine MyoG gene promoter in muscle satellite cells and mouse C2C12 cells, and it had certain specificity. This study provided experimental materials for increasing the high expression of exogenous gene in bovine muscle cells, and also laid the molecular theoretical basis for obtaining the high specific promoter of bovine muscle and the transgenic beef cattle.展开更多
Muscle-derived stem cells were isolated from the skeletal muscle of Sprague-Dawley neonatal rats aged 3 days old. Cells at passage 5 were incubated in Dulbecco＇s modified Eagle＇s medium supplemented with 10% （v/v）...Muscle-derived stem cells were isolated from the skeletal muscle of Sprague-Dawley neonatal rats aged 3 days old. Cells at passage 5 were incubated in Dulbecco＇s modified Eagle＇s medium supplemented with 10% （v/v） fetal bovine serum, 20 IJg/L nerve growth factor, 20 pg/L basic fibroblast growth factor and 1% （v/v） penicillin for 6 days. Cells presented with long processes, similar to nerve cells. Connections were formed between cell processes. Immunocytochemical staining with neuron specific enolase verified that cells differentiated into neuron-like cells. Immunofluorescence cytochemistry and western blot results revealed that the expression of protein hairy enhancer of split-1 was significantly reduced. These results indicate that low expression of protein hairy enhancer of split-1 participates in the differentiation of muscle-derived stem cells into neuron-like cells.展开更多
基金supported by the National Natural Science Foundation of China(Nos.82171552 and 82170479)the Natural Science Foundation of Shanghai Ctiy(No.21ZR1457500)the Science and Technology Bureau of Shanghai Putuo District(No.ptkwws202102).
文摘Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant,anticoagulant,and anti-diabetic effects.Growth/differentiation factor-15(GDF-15),a member of the transforming growth factorβsuperfamily,is considered a potential therapeutic target for metabolic disorders.This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism.The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo,and determined the involvement of endoplasmic reticulum(ER)stress signaling in this process.Luciferase reporter assays,chromatin immunoprecipitation,and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4(ATF4),CCAAT enhancer binding proteinγ(CEBPG),and CCCTC-binding factor(CTCF).The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene,as well as the influence of single nucleotide polymorphisms(SNPs)on magnolol and ATF4-induced transcription activity.Results demonstrated that magnolol triggers GDF-15 production in endothelial cells(ECs),hepatoma cell line G2(HepG2)and hepatoma cell line 3B(Hep3B)cell lines,and primary mouse hepatocytes.The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene.SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15.In high-fat diet ApoE^(-/-)mice,administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15.These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity,indicating its potential as a drug for the treatment of metabolic disorders.
文摘The increasing challenges of environmental degradation,soil erosion,and climate change have driven interest in sustainable solutions like enhanced weathering(EW)and phytoremediation.Elephant Grass(Cenchrus purpureus),a fast-growing perennial species,shows promise as a bioaccumulator and agent for soil weathering.This study assessed the potential of C.purpureus to improve soil quality through heavy metal(HM)uptake and EW facilitation.A 60-day greenhouse pot experiment at Jackson State University evaluated plant performance in soils amended with metabasalt rock powder at 1:1 and 2:1 rock-to-soil ratios.Biomass,growth,and HM concentrations in roots and shoots were measured via ICP-MS after wet digestion.Soil pH and magnesium(Mg)release were also monitored to assess weathering and carbon drawdown.Results showed that C.purpureus accumulated more HMs in roots at higher amendment levels,while at lower levels,metals like As,Cd,and Cr were more translocated to shoots,enhancing phytoextraction potential.High treatment favored Fe and Al uptake,possibly reducing toxic metal accumulation in edible parts.Notably,C.purpureus contributed to the weathering of 38%of metabasalt rock,leading to a 42%increase in Mg release.With high biomass,HM tolerance,and weathering capacity,C.purpureus offers a sustainable strategy for soil remediation,improved soil health,and potential support for renewable energy systems.
文摘Objective:In recent decades,studies have underscored nuclear proteins and signaling pathways in prostate cancer(PCa)development.Key biomarkers like Enhancer of zeste homolog 2(EZH2)and Forkhead box M1(FOXM1)are expressed in both healthy and malignant prostate cells.This study aimed to demonstrate the relationship between pathological characteristics,survival,recurrence,and tissue expression of EZH2 and FOXM1 in high-risk PCa patients.Methods:PCa tissues were used in a retrospective analysis that spanned from September 2009 to August 2019.Inclusion criteria comprised pathological tumor stage(pT)3 patients with positive surgical margins or tumor proximity to inked margins within 5 mm.After case selection,tissue slides were stained for EZH2 and FOXM1 antibodies,and Allred scores were calculated.Patients or relatives of deceased patients were contacted for signed agreements and disease follow-ups.Results:The pT3b,ductal carcinoma component,and moderate EZH2 expression were associated with relapse(odds ratio[OR]6.21,95%confidence interval[CI]1.41-27.27,p=0.016;OR 7.29,95%CI 1.03-51.43,p=0.046;OR 5.96,95%CI 1.09-32.48,p=0.039;respectively).The unilateral and bilateral seminal vesicle invasion increased the likelihood of recurrence by 9.98 times and 5.36 times,and the risk of death by around 9.78 times and 10.79 times,respectively.The pT3b was linked to higher death likelihood(OR 7.16,95%CI 1.38-37.23,p=0.019),while moderate EZH2 expression did not show statistical significance(OR 4.54,95%CI 0.87-23.60,p=0.072,marginally).Pathological regional lymph node stage(pN)1 had significantly higher probability of mortality than pN unknown(3.9%vs.27%,p<0.001).PCa in the neck and apex of the prostate gland increased death risk tenfold.Conclusion:Sufficient immunoexpression of EZH2,ductal carcinoma component,and neoplastic proliferation in the seminal vesicles,apex and neck of the prostate gland correlates with elevated risks of recurrence and mortality.Clinicians should use these criteria for appropriate patient referrals,and a multicenter trial could provide accurate classifications.
基金supported by the National Natural Science Foundation of China(grants 81970910 and 82370931)Jiangsu Province Capability Improvement Project through Science,Technology and Education-Jiangsu Provincial Research Hospital Cultivation Unit(YJXYYJSDW4)Jiangsu Provincial Medical Innovation Center(CXZX202227).
文摘Plp1-lineage Schwann cells(SCs)of peripheral nerve play a critical role in vascular remodeling and osteogenic differentiation during the early stage of bone healing,and the abnormal plasticity of SCs would jeopardize the bone regeneration.However,how Plp1-lineage cells respond to injury and initiate the vascularized osteogenesis remains incompletely understood.Here,by employing single-cell transcriptional profiling combined with lineage-specific tracing models,we uncover that Plp1-lineage cells undergoing injury-induced glia-to-MSCs transition contributed to osteogenesis and revascularization in the initial stage of bone injury.Importantly,our data demonstrated that the Sonic hedgehog(Shh)signaling was responsible for the transition process initiation,which was strongly activated by c-Jun/SIRT6/BAF170 complex-driven Shh enhancers.Collectively,these findings depict an injuryspecific niche signal-mediated Plp1-lineage cells transition towards Gli1+MSCs and may be instructive for approaches to promote bone regeneration during aging or other bone diseases.
基金supported by the National Science Fund for Excellent Young Scholars(NSFC-82322058)the Program of National Natural Science Foundation of China(NSFC-82103929,NSFC-82273713)+10 种基金the Young Elite Scientists Sponsorship Program by CAST(2022QNRC001)the National Science Fund for Distinguished Young Scholars of Hubei Province of China(2023AFA046)the Fundamental Research Funds for the Central Universities(WHU:2042022kf1205)Fundamental Research Funds for the Central Universities(WHU:2042022kf1031)for Ying Zhuthe Fundamental Research Funds for the Central Universities(2042022rc0026,2042023kf1005)for Xiao-Ping Miaothe Knowledge Innovation Program of Wuhan(whkxjsj011,2023020201010073)for Jian-Bo Tianthe Science and Technology Innovation Seed Fund of Zhongnan Hospital of Wuhan University(znpy2019060)for Yong-Chang Weithe Distinguished Young Scholars of China(NSFC-81925032)the Key Program of National Natural Science Foundation of China(NSFC-82130098)the Youth Program of National Natural Science Foundation of China(NSFC-82003547)the Program of Health Commission of Hubei Province(WJ2023M045)。
文摘Background:Dysregulation of enhancer transcription occurs in multiple cancers.Enhancer RNAs(eRNAs)are transcribed products from enhancers that play critical roles in transcriptional control.Characterizing the genetic basis of eRNA expression may elucidate the molecular mechanisms underlying cancers.Methods:Initially,a comprehensive analysis of eRNA quantitative trait loci(eRNAQTLs)was performed in The Cancer Genome Atlas(TCGA),and functional features were characterized using multi-omics data.To establish the first eRNAQTL profiles for colorectal cancer(CRC)in China,epigenomic data were used to define active enhancers,which were subsequently integrated with transcription and genotyping data from 154 paired CRC samples.Finally,largescale case-control studies(34,585 cases and 69,544 controls)were conducted along with multipronged experiments to investigate the potential mechanisms by which candidate eRNAQTLs affect CRC risk.Results:A total of 300,112 eRNAQTLs were identified across 30 different cancer types,which exert their influence on eRNA transcription by modulating chromatin status,binding affinity to transcription factors and RNA-binding proteins.These eRNAQTLs were found to be significantly enriched in cancer risk loci,explaining a substantial proportion of cancer heritability.Additionally,tumor-specific eRNAQTLs exhibited high responsiveness to the development of cancer.Moreover,the target genes of these eRNAs were associated with dysregulated signaling pathways and immune cell infiltration in cancer,highlighting their potential as therapeutic targets.Furthermore,multiple ethnic population studies have confirmed that an eRNAQTL rs3094296-T variant decreases the risk of CRC in populations from China(OR=0.91,95%CI 0.88–0.95,P=2.92×10^(-7))and Europe(OR=0.92,95%CI 0.88–0.95,P=4.61×10^(-6)).Mechanistically,rs3094296 had an allele-specific effect on the transcription of the eRNA ENSR00000155786,which functioned as a transcriptional activator promoting the expression of its target gene SENP7.These two genes synergistically suppressed tumor cell proliferation.Our curated list of variants,genes,and drugs has been made available in CancereRNAQTL(http://canernaqtl.whu.edu.cn/#/)to serve as an informative resource for advancing this field.Conclusion:Our findings underscore the significance of eRNAQTLs in transcriptional regulation and disease heritability,pinpointing the potential of eRNA-based therapeutic strategies in cancers.
基金the National Natural Science Foundation of China(Grant No.82072580).
文摘The abnormality of the p53 tumor suppressor is crucial in lung cancer development,because p53 regulates target gene promoters to combat cancer.Recent studies have shown extensive p53 binding to enhancer elements.However,whether p53 exerts a tumor suppressor role by shaping the enhancer landscape remains poorly understood.In the current study,we employed several functional genomics approaches to assess the enhancer activity at p53 binding sites throughout the genome based on our established TP53 knockout(KO)human bronchial epithelial cells(BEAS-2B).A total of 943 active regular enhancers and 370 super-enhancers(SEs)disappeared upon the deletion of p53,indicating that p53 modulates the activity of hundreds of enhancer elements.We found that one p53-dependent SE,located on chromosome 9 and designated as KLF4-SE,regulated the expression of the Krüppel-like factor 4(KLF4)gene.Furthermore,the deletion of p53 significantly decreased the KLF4-SE enhancer activity and the KLF4 expression,but increased colony formation ability in the nitrosamines 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced cell transformation model.Subsequently,in TP53 KO cells,the overexpression of KLF4 partially reversed the increased clonogenic capacity caused by p53 deficiency.Consistently,KLF4 expression also decreased in lung cancer tissues and cell lines.It appeared that overexpression of KLF4 significantly suppressed the proliferation and migration of lung cancer cells.Collectively,our results suggest that the regulation of enhancer formation and activity by p53 is an integral component of the p53 tumor suppressor function.Therefore,our findings offer some novel insights into the regulation mechanism of p53 in lung oncogenesis and introduce a new strategy for screening therapeutic targets.
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The effects of some commonly used penetration enhancers such as laurocapram (AZ), oleic acid (OA), poloxamer (POL) and propylene glycol (PG) on the in vitro transdermal iontophoretic delivery of insulin through full-thickness mouse skin were investigated. The results showed that AZ had a synergistic effect on iontophoretic ability to enhance skin permeation of insulin, and PG could further increase this effect. 5% AZ / PG increased the iontophoretic steady state flux of insulin by a factor of 2.75 compared to that treated with iontophoresis alone. OA did not further enhance iontophoretic effect to increase skin permeation of insulin. The combination of iontophoresis and some enhancer provided a novel idea and possibility for transdermal delivery of insulin.
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supported by the National Natural Science Foundation of China(No.81073059)the Beijing Natural Science Foundation(No.7132127)the Innovative Research Team in Beijing University of Chinese Medicine(No.2011-CXTD-13),China
文摘The aim of this present study is to investigate the effect of Zanthoxylum bungeanum oil （essential oil from Z. bungeanum Maxim.） on cytotoxicity and the transdermal permeation of 5-fluorouracil and indomethacin. The cy- totoxicity of Z. bungeanum oil on dermal fibroblasts and epidermal keratinocytes was studied using an MTT （3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） assay. The rat skin was employed to determine the percutaneous penetration enhancement effect of Z. bungeanum oil on hydrophilic and lipophilic model drugs, i.e., 5-fluorouracil and indomethacin. The secondary structure changes of the rat stratum comeum （SC） were determined using attenuated total reflectance-Fourier transform infrared spectroscopy （ATR-FTIR）, and saturated solubilities and SC/vehicle partition coefficients of two model drugs with and without Z. bungeanum oil were also measured to un- derstand its related mechanisms of action. It was found that the half maximal inhibitory concentration （ICs0） values of Z. bungeanum oil were significantly lower in HaCaT and CCC-ESF-1 cell lines compared to the well-established and standard penetration enhancer Azone. The Z. bungeanum oil at various concentrations effectively facilitated the percutaneous penetration of two model drugs across the rat skin. In addition, the mechanisms of permeation en- hancement by Z. bungeanum oil could be explained with saturated solubility, SC/vehicle partition coefficient, and secondary structure changes of SC.
基金the financial support provided by the National Natural Science Foundation of China (project Nos.50975282 and 50275147)the Natural Science Foundation of Chongqing, China (project No. CSTC 2008BA4037)
文摘In recent decades, a growing worldwide trend of developing the biodegradable lubricants has been prevailing to form a specific field of green chemistry and green engineering. Enhancement of biodegradability of unreadily biodegradable petroleum-based lubricants has as such become an urgent must. For over a decade the authors have been focusing on the improvement of biodegradability of unreadily biodegradable lubricants such as petroleum-based lubricating oils and greases. A new idea of lubricant biodegradation enhancer was put forward by the authors with the aim to stimulate the biodegradation of unreadily biodegradable lubricants by incorporating the enhancer into the lubricants in order to turn the lubricants into greener biodegradable ones and to help in situ bioremediation of lubricant-contaminated environment. This manuscript summarizes our recent efforts relating to the chemistry and technology of biodegradation enhancers for lubricants. Firstly, the chemistry of lubricant biodegradation enhancers was designed based on the principles of bioremediation for the treatment of hydrocarbon contaminated environment. Secondly, the ability of the designed biodegradation enhancers for increasing the biodegradability of unreadily biodegradable industrial lubricants was investigated through biodegradability evaluation tests, microbial population analysis, and biodegradation kinetics modeling. Finally, the impact of biodegradation enhancers on some crucial performance characteristics of lubricants such as lubricity and oxidation stability was tested via tribological evaluation and oxidation determinations. Our results have shown that the designed chemistry of nitrogenous and/or phosphorous compounds such as lauroyl glutamine, oleoyl glycine, oleic diethanolamide phosphate and lauric diethanolamide borate was outstanding in boosting biodegradation of petroleum-based lubricants which was ascribed to increase the microbial population and decrease the oil-water interfacial tension during the biodegradation process. Lubricants doped with the biodegradation enhancers exhibited much better biodegradability and higher biodegradation rate in the surrounding soils which could be well modeled by the exponential biodegradation kinetics. Furthermore, as lubricant dopants, the biodegradation enhancers also provided excellent capability in reducing friction and wear and in retarding oxidation of lubricants. In the nature of things, lubricant biodegradation enhancers, which are multi-functional not only in the improvement of biodegradability, but also in the fortification of lubricity and in the inhibition of oxidation of lubricants, are expected to be promising as a new category of lubricant additives.
文摘Insertion mutagenesis has become one of the most popular methods for gene functions analysis.Here we report a two-element Ac/Ds transposon system containing enhancer trap and gene trap for gene tagging in rice.The excision of Ds element was examined by PCR amplification.The excision frequency of Ds element varied from 0% to 40% among 20 F2 populations derived from 11 different Ds parents.Southern blot analysis revealed that more than 70% of excised Ds elements reinserted into rice genome and above 70% of the reinserted Ds elements were located at different positions of the chromosome in rice.The result of histochemical GUS analysis indicated that 28% of enhancer trap and 22% of gene trap tagging plants displayed GUS activity in leaves, roots,flowers or seeds.The GUS positive lines will be useful for identifying gene function in rice.
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.
基金supported by National Natural Science Foundation of China (81670874, 81500354, and 81772999)Shenzhen Science Foundation (JCYJ20160308104109234)
文摘Osteosarcoma is the most common primary bone sarcoma that mostly occurs in young adults. The causes of osteosarcoma are heterogeneous and still not fully understood. Identification of novel, important oncogenic factors in osteosarcoma and development of better, effective therapeutic approaches are in urgent need for better treatment of osteosarcoma patients. In this study, we uncovered that the oncogene MYC is significantly upregulated in metastastic osteosarcoma samples. In addition, high MYC expression is associated with poor survival of osteosarcoma patients. Analysis of MYC targets in osteosarcoma revealed that most of the osteosarcoma super enhancer genes are bound by MYC. Treatment of osteosarcoma cells with super enhancer inhibitors THZ1 and JQ1 effectively suppresses the proliferation, migration, and invasion of osteosarcoma cells. Mechanistically,THZ1 treatment suppresses a large group of super enhancer containing MYC target genes including CDK6 and TGFB2. These findings revealed that the MYC-driven super enhancer signaling is crucial for the osteosarcoma tumorigenesis and targeting the MYC/super enhancer axis represents as a promising therapeutic strategy for treatment of osteosarcoma patients.
基金supported by the Beijing Natural Science Foundation(No.7132127)the Innovative Research Team in Beijing University of Chinese Medicine(No.2011-CXTD-13),China
文摘Our previous studies had confirmed that the essential oil from Zanthoxylum bungeanum Maxim. （Z. bungeanum oil） could effectively enhance the percutaneous permeation of drug molecules as a natural transdermal penetration enhancer. The aim of the present study is to investigate and compare the skin penetration enhancement effect of Z. bungeanum oil and its main components on traditional Chinese medicine （TCM） active components. Toxicities of Z. bungeanum oil and three selected terpene compounds （terpinen-4-ol, 1,8-cineole, and limonene） in epidermal keratinocytes （HaCaT） and dermal flbroblast （CCC-ESF-1） cell lines were measured using an MTT （3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide） assay. Five model drugs in TCM external preparations, namely osthole （OT）, tetramethylpyrazine （TMP）, ferulic acid （FA）, puerarin （PR）, and geniposide （GP）, which were selected based on their lipophilicity denoted by IogKo^w, were tested using in vitro permeation studies in which vertical Franz diffusion ceils and rat abdominal skin were employed. The secondary structure changes of skin stratum corneum （SC） and drug thermodynamic activities were investigated to understand their mechanisms of action using Fourier transform infrared （FTIR） spectroscopy and saturation solubility studies, respectively. It was found that Z. bungeanum oil showed lower toxicities in both HaCaT cells and CCC-ESF-1 cells compared with three terpene compounds used alone. The enhancement permeation capacities by all tested agents were in the following increasing order： terpinen-4-ol=1,8-cineole〈limonene〈Z, bungeanum oil. The mechanisms of permeation enhancement suggested that these enhancers promoted the skin permeation of drugs mainly by affecting SC lipids. These results indicated that Z. bungeanum oil exhibited better performance in enhancing the skin permeation of active components in TCM preparations.
基金supported by the National Natural Science Foundation of China(81630060 to P.W.,31771402 to G.L.,81830074 and 81772786 to H.W.,81572569 to G.C.,and 81772775 to J.W.)National Science and Technology Major Project(2019YFC1005202 and 2019YFC1005201 to K.L.,and 2018ZX10301402-002 to Q.G.)the research-oriented clinician funding program of Tongji Medical College,Huazhong University of Science and Technology for P.W
文摘Integration of human papillomavirus(HPV)DNA into the human genome is a reputed key driver of cervical cancer.However,the effects of HPV integration on chromatin structural organization and gene expression are largely unknown.We studied a cohort of 61 samples and identified an integration hot spot in the CCDC106 gene on chromosome 19.We then selected fresh cancer tissue that contained the unique integration loci at CCDC106 with no HPV episomal DNA and performed whole-genome,RNA,chromatin immunoprecipitation and high-throughput chromosome conformation capture(Hi-C)sequencing to identify the mechanisms of HPV integration in cervical carcinogenesis.Molecular analyses indicated that chromosome 19 exhibited significant genomic variation and differential expression densities,with correlation found between three-dimensional(3D)structural change and gene expression.Importantly,HPV integration divided one topologically associated domain(TAD)into two smaller TADs and hijacked an enhancer from PEG3 to CCDC106,with a decrease in PEG3 expression and an increase in CCDC106 expression.This expression dysregulation was further confirmed using 10 samples from our cohort,which exhibited the same HPV-CCDC106 integration.In summary,we found that HPV-CCDC106 integration altered local chromosome architecture and hijacked an enhancer via 3D genome structure remodeling.Thus,this study provides insight into the 3D structural mechanism underlying HPV integration in cervical carcinogenesis.
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.
基金Supported by the Major Special Projects of New Product Training of Transgenic Organisms(zx080072008-2008)
文摘Connected a segment of CMV enhancer to the front of MyoG gene promoter and then constructed the corresponding dual luciferase expression vector pGL3-CMV-MyoGpro. We set four eukaryotic expression vectors including pGL3-CMV, pGL3MyoGpro, pGL3-CMV-MyoGpro, and pGL3-Basic which contained CMV promoter, MyoG promoter, CMV-MyoG synthesis promoter, and a promoterless negative control, respectively. Then the four vectors and internal control Renilla luciferase report gene vector phRL-TK were transfected into bovine skeletal muscle satellite cells, mouse C2C12 cells and bovine fetal fibroblast cells to detect the promoter activity with dual luciferase report system. The results showed that CMV enhancer could significantly improve the transcription activity of bovine MyoG gene promoter in muscle satellite cells and mouse C2C12 cells, and it had certain specificity. This study provided experimental materials for increasing the high expression of exogenous gene in bovine muscle cells, and also laid the molecular theoretical basis for obtaining the high specific promoter of bovine muscle and the transgenic beef cattle.
基金supported by a grant from the Distinguished Young Scholars in Universities in Liaoning Province Development Plan, No. LJQ2011090
文摘Muscle-derived stem cells were isolated from the skeletal muscle of Sprague-Dawley neonatal rats aged 3 days old. Cells at passage 5 were incubated in Dulbecco＇s modified Eagle＇s medium supplemented with 10% （v/v） fetal bovine serum, 20 IJg/L nerve growth factor, 20 pg/L basic fibroblast growth factor and 1% （v/v） penicillin for 6 days. Cells presented with long processes, similar to nerve cells. Connections were formed between cell processes. Immunocytochemical staining with neuron specific enolase verified that cells differentiated into neuron-like cells. Immunofluorescence cytochemistry and western blot results revealed that the expression of protein hairy enhancer of split-1 was significantly reduced. These results indicate that low expression of protein hairy enhancer of split-1 participates in the differentiation of muscle-derived stem cells into neuron-like cells.
