RESUMO
BACKGROUND: Colonoscopic enteral tube placement using current methods has some shortcomings, such as the complexity of the procedure and tube dislodgement. The magnetic navigation technique (MNT) has been proven effective for nasoenteral feeding tube placement, and is associated with reduced cost and time to initiation of nutrition. This study attempted to develop a novel method for enteral tube placement using MNT. METHODS: The MNT device consisted of an external magnet and a 12 Fr tube with a magnet at the end. Ten swine were used, and bowel cleansing was routinely performed before colonoscopy. Intravenous anesthesia with propofol and ketamine was administered. A colonoscopic enteral tube was placed using the MNT. The position of the end of the enteral tube was determined by radiography, and angiography was performed to check for colonic perforations. Colonoscopy was used to detect intestinal mucosal damage after tube removal. RESULTS: MNT-assisted colonoscopic enteral tube placement was successfully completed in all pigs. The median operating time was 30 (26-47) min. No colon perforation was detected on colonography after enteral tube placement, and no colonic mucosal bleeding or injury was detected after the removal of the enteral tube. CONCLUSIONS: MNT-assisted colonoscopic enteral tube placement is feasible and safe in swine and may represent a valuable method for microbial therapy, colonic drainage, and host-microbiota interaction research in the future.
Assuntos
Colonoscopia , Intubação Gastrointestinal , Animais , Colonoscopia/métodos , Suínos , Intubação Gastrointestinal/métodos , Nutrição Enteral/métodos , Nutrição Enteral/instrumentação , Imãs , Colo/diagnóstico por imagem , Estudos de Viabilidade , Feminino , Duração da CirurgiaRESUMO
Background: Calvatia gigantea (CG) is widely used as a traditional Chinese medicine for wound treatment. In this study, we aimed to determine the effects of CG extract (CGE) on diabetic wound healing and the commensal wound microbiome. Method: A wound model was established using leptin receptor-deficient db/db mice, with untreated mice as the control group and CGE-treated mice as the treatment group. The wound healing rate, inflammation and histology were analyzed. Additionally, wound microbiome was evaluated via 16S ribosomal RNA (rRNA) gene sequencing. Results: CGE significantly accelerated the healing of diabetic ulcer wounds, facilitated re-epithelialization, and downregulated the transcription levels of the inflammatory cytokines, interleukin-1ß and tumor necrosis factor-α. Furthermore, CGE treatment positively affected the wound microbiome, promoting diversity of the microbial community and enrichment of Escherichia-Shigella bacteria in the CGE-treated group. Conclusions: Overall, CGE enhanced diabetic wound healing by modulating the wound microbiome and facilitating macrophage polarization during inflammation. These findings suggest modulation of the commensal wound microbiome using medicinal plants as a potential therapeutic strategy for diabetic wounds.
RESUMO
The main chemical constituents from Acori Tatarinowii Rhizoma were isolated and purified using the macroporous resin,microporous resin(MCI) and octadecylsilyl silica gel(ODS) column chromatography, as well as semi-preparative high performance liquid chromatography. Their chemical structures were elucidated by spectroscopic analyses including mass spectrometry(MS),nuclear magnetic resonance(NMR), ultraviolet(UV), infrared(IR) and circular dichoism(CD) combined with literature data.A total of 11 compounds were isolated and identified, including 4 lignan glycosides, 2 benzyl alcohol glycosides, 4 flavonoid glycosides, and 1 α-tetralone glycoside:(7S,8R)-dihydrodehydrodiconiferyl alcohol 9-O-ß-D-glucopyranosyl-9'-O-ß-D-glucopyranosyl-(1 â 6)-ß-D-glucopyranoside(1),(7S, 8R)-dihydrodehydrodiconiferyl alcohol 9-O-ß-D-glucopyranoside(2),(7S, 8R)-dihydrodehydrodiconiferyl alcohol di-9, 9'-O-ß-D-glucopyranoside(3),(+)-lyoniresinol 3α-O-ß-D-glucopyranoside(4), benzyl alcohol O-ß-D-glucopyranosyl-(1â6)-ß-D-glucopyranoside(5), benzyl alcohol O-ß-D-xylopyranosyl-(1â6)-ß-D-glucopyranoside(6), 3'-O-methylepicatechin 7-O-ß-D-glucopyranoside(7), 3'-O-methylcatechin 7-O-ß-D-glucopyranoside(8), apigenin 6-C-ß-D-glucopyranosyl-7-O-ß-D-glucopyranoside(9), isoscoparin 7-O-ß-D-glucopyranoside(10), and(4R)-8-hydroxy-α-tetralone-4-O-ß-D-glucopyranoside(11). Compound 1 is a new neolignan glycoside, and compounds 2-5 and 7-11 are isolated from genus Acorus for the first time.
Assuntos
Medicamentos de Ervas Chinesas , Glicosídeos , Lignanas , Rizoma , Glicosídeos/química , Glicosídeos/isolamento & purificação , Rizoma/química , Medicamentos de Ervas Chinesas/química , Lignanas/química , Lignanas/isolamento & purificação , Estrutura Molecular , Espectroscopia de Ressonância Magnética , Cromatografia Líquida de Alta PressãoRESUMO
The incidences of metabolic syndrome (MetS), denoting insulin resistance-associated various metabolic disorders, are increasing. This study aimed to identify new biomarkers for predicting MetS and provide a novel diagnostic approach. Herein, the expression profiles of c-Jun (JUN) and FBJ murine osteosarcoma viral oncogene homolog B (FOSB) in individuals with obesity and patients with MetS from the Gene Expression Omnibus database. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to evaluate the messenger RNA levels of JUN and FOSB in the peripheral blood of healthy volunteers (lean and obese) and patients with MetS (lean and obese), along with that in the adipose tissue and peripheral blood of obese mouse model. Furthermore, receiver operating characteristic (ROC) curve and logistic regression analyses were performed to determine the diagnostic value of JUN and FOSB in MetS. The expression profiles and RT-qPCR results showed that JUN and FOSB were highly expressed in individuals with obesity, obese mouse models, and patients with MetS. The ROC analysis results showed an area under the curve values of 0.872 and 0.879 for JUN, 0.802 and 0.962 for FOSB, and 0.946 and 0.979 for JUN-FOSB in the lean group and the group with obesity, respectively, in predicting MetS. Logistic regression analysis showed that the p-values of both JUN and FOSB as MetS-affecting factors were <0.05. Altogether, the findings of this study indicate that both JUN and FOSB, abnormally expressed in individuals with obesity, are good biomarkers of MetS.
RESUMO
Land conversion to agriculture is an important factor affecting soil ecological processes in the desert grasslands of northern China. However, soil fungal-community structure and function in response to Land conversion remain unclear. In this study, desert grassland, artificial shrubland, and land conversion were investigated in the western part of the Mu Us Sandland (Yanchi, Ningxia; Dingbian, Shaanxi). We found that land conversion significantly increased soil total carbon, nitrogen, and phosphorus, and available phosphorous and potassium contents. In the early stage of conversion to agricultural (April), soil fungal operational taxonomic units and abundance-based coverage estimator were lower than those of dessert grasslands and shrubland plots and had significant correlations with pH, electric conductivity, and available phosphorus and potassium. The dominant phyla strongly correlated with soil physicochemical properties. Concomitantly, the relative abundance of Glomeromycota was significantly lower, and the complexity of the network in the land conversion plots was lower than that in the shrubland plots. In the late stage of land conversion (September), soil fungal operational taxonomic units and abundance-based coverage estimator were lower in the conversion plots than in the desert grassland plots, with more complex network relationships compared to the desert grassland or shrubland plots. Symbiotrophic groups, a functional group of desert grassland soil fungi, can be used as a predictor of environmental change; in addition, land conversion decreases the relative abundance of arbuscular mycorrhizal functional groups. Our study highlights the response of soil fungal communities and functions to human disturbances in desert grasslands. Considering the potential of land conversion to agriculture to influence soil secondary salinization, there is a need for continued observation of soil ecological health over the time continuum of land conversion to agriculture.
RESUMO
Target identification is crucial for elucidating the mechanisms of bioactive molecules in drug discovery. However, traditional methods assess compounds individually, making it challenging to efficiently examine multiple compounds in parallel, especially for structurally diverse compounds. This study reports a novel strategy called chemical genomics-facilitated chemical proteomics (CGCP) for multiplexing the target identification of bioactive small molecules. CGCP correlates compounds' perturbation of global transcription, or chemical genomic profiles, with their reactivity toward target proteins, enabling simultaneous identification of targets. We demonstrated the utility of CGCP by studying the targets of celastrol (Cel) and four other electrophilic compounds with varying levels of similarity to Cel based on their chemical genomic profiles. We identified multiple novel targets and binding sites shared by the compounds in a single experiment. CGCP enabled multiplexity and improved the efficiency of target identification for structurally distinct compounds, indicating its potential to accelerate drug discovery.
RESUMO
There is an increasing need for determining 3D structures of DNAs, e.g., for increasing the efficiency of DNA aptamer selection. Recently, we have proposed a computational method of 3D structure prediction of DNAs, called 3dDNA, which has been integrated into our original web server 3dRNA, now renamed 3dRNA/DNA (http://biophy.hust.edu.cn/new/3dRNA). Currently, 3dDNA can only output the predicted DNA 3D structures for users but cannot rank them as an energy function for assessing DNA 3D structures is still lacking. Here, we first provide a brief introduction to 3dDNA and then introduce a new energy function, 3dDNAscore, for the assessment of DNA 3D structures. 3dDNAscore is an all-atom knowledge-based potential by integrating 86 atomic types from nucleic acids. Benchmarks demonstrate that 3dDNAscore can effectively identify near-native structures from the decoys generated by 3dDNA, thus enhancing the completeness of 3dDNA.
Assuntos
DNA , Modelos Moleculares , Conformação de Ácido Nucleico , RNA , DNA/química , RNA/química , Software , Biologia Computacional/métodosRESUMO
With the rapid progress in deciphering the pathogenesis of Alzheimer's disease (AD), it has been widely accepted that the accumulation of misfolded amyloid ß (Aß) in the brain could cause the neurodegeneration in AD. Although much evidence demonstrates the neurotoxicity of Aß, the role of Aß in the nervous system are complex. However, more comprehensive studies are needed to understand the physiological effect of Aß40 monomers in depth. To explore the physiological mechanism of Aß, we employed mass spectrometry to investigate the altered proteomic events induced by a lower submicromolar concentration of Aß. Human neuroblastoma SH-SY5Y cells were exposed to five different concentrations of Aß1-40 monomers and collected at four time points. The proteomic analysis revealed the time-course behavior of proteins involved in biological processes, such as RNA splicing, nuclear transport and protein localization. Further biological studies indicated that Aß40 monomers may activate PI3K/AKT signaling to regulate p-Tau, Ezrin and MAP2. These three proteins are associated with dendritic morphogenesis, neuronal polarity, synaptogenesis, axon establishment and axon elongation. Moreover, Aß40 monomers may regulate their physiological forms by inhibiting the expression of BACE1 and APP via activation of the ERK1/2 pathway. A comprehensive exploration of pathological and physiological mechanisms of Aß is beneficial for exploring novel treatment.
Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Proteômica , Humanos , Peptídeos beta-Amiloides/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Proteômica/métodos , Linhagem Celular Tumoral , Ácido Aspártico Endopeptidases/metabolismo , Ácido Aspártico Endopeptidases/genética , Fragmentos de Peptídeos/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Proteínas do Citoesqueleto/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas tau/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Transdução de Sinais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Proteoma/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Sistema de Sinalização das MAP QuinasesRESUMO
OBJECTIVE: Aggregating evidence highlights the strong genetic basis underpinning congenital heart disease (CHD). Here BMP4 was chosen as a prime candidate gene causative of human CHD predominantly because BMP4 was amply expressed in the embryonic hearts and knockout of Bmp4 in mice led to embryonic demise mainly from multiple cardiovascular developmental malformations. The aim of this retrospective investigation was to discover a novel BMP4 mutation underlying human CHD and explore its functional impact. METHODS: A sequencing examination of BMP4 was implemented in 212 index patients suffering from CHD and 236 unrelated non-CHD individuals as well as the family members available from the proband carrying a discovered BMP4 mutation. The impacts of the discovered CHD-causing mutation on the expression of NKX2-5 and TBX20 induced by BMP4 were measured by employing a dual-luciferase analysis system. RESULTS: A new heterozygous BMP4 mutation, NM_001202.6:c.318T>G;p.(Tyr106*), was found in a female proband affected with familial CHD. Genetic research of the mutation carrier's relatives unveiled that the truncating mutation was in co-segregation with CHD in the pedigree. The nonsense mutation was absent from 236 unrelated non-CHD control persons. Quantitative biologic measurement revealed that Tyr106*-mutant BMP4 failed to induce the expression of NKX2-5 and TBX20, two genes whose expression is lost in CHD. CONCLUSION: The current findings indicate BMP4 as a new gene predisposing to human CHD, allowing for improved prenatal genetic counseling along with personalized treatment of CHD patients.
RESUMO
Highland barley (HB) is an intriguing plateau cereal crop with high nutrition and health benefits. However, abundant dietary fiber and deficient gluten pose challenges to the processing and taste of whole HB products. Extrusion technology has been proved to be effective in overcoming these hurdles, but the association between the structure and physicochemical properties during extrusion remains inadequately unexplored. Therefore, this study aims to comprehensively understand the impact of extrusion conditions on the physicochemical properties of HB flour (HBF) and the multi-scale structure of starch. Results indicated that the nutritional value of HBF were significantly increased (soluble dietary fiber and ß-glucan increased by 24.05%, 19.85% respectively) after extrusion. Typical underlying mechanisms based on starch structure were established. High temperature facilitated starch gelatinization, resulting in double helices unwinding, amylose leaching, and starch-lipid complexes forming. These alterations enhanced the water absorption capacity, cold thickening ability, and peak viscosity of HBF. More V-type complexes impeded amylose rearrangement, thus enhancing resistance to retrogradation and thermal stability. Extrusion at high temperature and moisture exhibited similarities to hydrothermal treatment, partly promoting amylose rearrangement and enhancing HBF peak viscosity. Conversely, under low temperature and high moisture, well-swelled starch granules were easily broken into shorter branch-chains by higher shear force, which enhanced the instant solubility and retrogradation resistance of HBF as well as reduced its pasting viscosity and the capacity to form gel networks. Importantly, starch degradation products during this condition were experimentally confirmed from various aspects. This study provided some reference for profiting from extrusion for further development of HB functional food and "clean label" food additives.
Assuntos
Amilose , Farinha , Manipulação de Alimentos , Hordeum , Amido , Hordeum/química , Amido/química , Farinha/análise , Viscosidade , Amilose/química , Manipulação de Alimentos/métodos , Valor Nutritivo , Fibras na Dieta/análise , Solubilidade , beta-Glucanas/química , Fenômenos Químicos , Temperatura AltaRESUMO
Four pairs of undescribed enantiomeric guaiane sesquiterpenoids, (±)-alismaenols A-D (1a/1b, 3a/3b-5a/5b), together with a pair of known ones (2a/2b) were isolated from the rhizomes of Alisma plantago-aquatica. The structures and relative configurations of the isolates were established by analysis of their 1D, 2D-NMR and HRESIMS data. Their absolute configurations were determined by comparison of their experimental CD spectra and calculated electronic circular dichroism (ECD) spectra or by single-crystal X-ray diffraction analysis. All compounds (1a/1b-5a/5b) were evaluated for their inhibitory effects on nitric oxide (NO) production in LPS-induced RAW 264.7 cells, and compound 1a exhibited stronger activity (IC50 = 12.89 µM) than indomethacin (IC50 = 14.03 µM).
Assuntos
Alisma , Óxido Nítrico , Compostos Fitoquímicos , Rizoma , Sesquiterpenos de Guaiano , Rizoma/química , Camundongos , Células RAW 264.7 , Estrutura Molecular , Óxido Nítrico/metabolismo , Animais , Alisma/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Sesquiterpenos de Guaiano/isolamento & purificação , Sesquiterpenos de Guaiano/farmacologia , Sesquiterpenos de Guaiano/química , China , Estereoisomerismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/químicaRESUMO
INTRODUCTION: Current anti-rheumatic drugs are primarily modulating immune cell activation, yet their effectiveness remained suboptimal. Therefore, novel therapeutics targeting alternative mechanisms, such as synovial activation, is urgently needed. OBJECTIVES: To explore the role of Midline-1 (Mid1) in synovial activation. METHODS: NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice were used to establish a subcutaneous xenograft model. Wild-type C57BL/6, Mid1-/-, Dpp4-/-, and Mid1-/-Dpp4-/- mice were used to establish a collagen-induced arthritis model. Cell viability, cell cycle, qPCR and western blotting analysis were used to detect MH7A proliferation, dipeptidyl peptidase-4 (DPP4) and Mid1 levels. Co-immunoprecipitation and proteomic analysis identified the candidate protein of Mid1 substrates. Ubiquitination assays were used to determine DPP4 ubiquitination status. RESULTS: An increase in Mid1, an E3 ubiquitin ligase, was observed in human RA synovial tissue by GEO dataset analysis, and this elevation was confirmed in a collagen-induced mouse arthritis model. Notably, deletion of Mid1 in a collagen-induced arthritis model completely protected mice from developing arthritis. Subsequent overexpression and knockdown experiments on MH7A, a human synoviocyte cell line, unveiled a previously unrecognized role of Mid1 in synoviocyte proliferation and migration, the key aspects of synovial activation. Co-immunoprecipitation and proteomic analysis identified DPP4 as the most significant candidate of Mid1 substrates. Mechanistically, Mid1 promoted synoviocyte proliferation and migration by inducing ubiquitin-mediated proteasomal degradation of DPP4. DPP4 deficiency led to increased proliferation, migration, and inflammatory cytokine production in MH7A, while reconstitution of DPP4 significantly abolished Mid1-induced augmentation of cell proliferation and activation. Additionally, double knockout model showed that DPP4 deficiency abolished the protective effect of Mid1 defect on arthritis. CONCLUSION: Overall, our findings suggest that the ubiquitination of DPP4 by Mid1 promotes synovial cell proliferation and invasion, exacerbating synovitis in RA. These results reveal a novel mechanism that controls synovial activation, positioning Mid1 as a promising target for therapeutic intervention in RA.
Assuntos
Artrite Experimental , Artrite Reumatoide , Dipeptidil Peptidase 4 , Camundongos Endogâmicos C57BL , Processamento de Proteína Pós-Traducional , Sinovite , Ubiquitina-Proteína Ligases , Animais , Humanos , Masculino , Camundongos , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Artrite Reumatoide/metabolismo , Proliferação de Células , Dipeptidil Peptidase 4/metabolismo , Dipeptidil Peptidase 4/genética , Camundongos Endogâmicos NOD , Camundongos Knockout , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , Sinoviócitos/metabolismo , Sinoviócitos/patologia , Sinovite/metabolismo , Sinovite/patologia , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , UbiquitinaçãoRESUMO
BACKGROUND AND AIMS: Iron overload, oxidative stress and ferroptosis are associated with liver injury in alcohol-associated liver disease (ALD), however, the crosstalk among these regulatory pathways in ALD development is unclear. METHODS: ALD mouse model and general control of amino acid synthesis 5 like 1 (GCN5L1) liver knockout mice were generated to investigate the role of GCN5L1 in ALD development. Proteomic screening tests were performed to identify the key factors mediating GCN5L1 loss-induced ALD. RESULTS: Gene Expression Omnibus data set analysis indicates that GCN5L1 expression is negatively associated with ALD progression. GCN5L1 hepatic knockout mice develop severe liver injury and lipid accumulation when fed an alcohol diet. Screening tests identified that GCN5L1 targeted the mitochondrial iron transporter CISD1 to regulate mitochondrial iron homeostasis in ethanol-induced ferroptosis. GCN5L1-modulated CISD1 acetylation and activity were crucial for iron accumulation and ferroptosis in response to alcohol exposure. CONCLUSION: Pharmaceutical modulation of CISD1 activity is critical for cellular iron homeostasis and ethanol-induced ferroptosis. The GCN5L1/CISD1 axis is crucial for oxidative stress and ethanol-induced ferroptosis in ALD and is a promising avenue for novel therapeutic strategies.
Assuntos
Modelos Animais de Doenças , Ferroptose , Hepatopatias Alcoólicas , Camundongos Knockout , Estresse Oxidativo , Animais , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/genética , Hepatopatias Alcoólicas/patologia , Camundongos , Ferro/metabolismo , Fígado/metabolismo , Fígado/patologia , Masculino , Etanol , Camundongos Endogâmicos C57BL , Humanos , Proteínas do Tecido Nervoso , Proteínas MitocondriaisRESUMO
Mounting evidence suggests that high-fat diet (HFD) consumption increases the risk for depression, but the neurophysiological mechanisms involved remain to be elucidated. Here, we demonstrated that HFD feeding of C57BL/6J mice during the adolescent period (from 4 to 8 weeks of age) resulted in increased depression- and anxiety-like behaviors concurrent with changes in neuronal and myelin structure in the hippocampus. Additionally, we showed that hippocampal microglia in HFD-fed mice assumed a hyperactive state concomitant with increased PSD95-positive and myelin basic protein (MBP)-positive inclusions, implicating microglia in hippocampal structural alterations induced by HFD consumption. Along with increased levels of serum free fatty acids (FFAs), abnormal deposition of lipid droplets and increased levels of HIF-1α protein (a transcription factor that has been reported to facilitate cellular lipid accumulation) within hippocampal microglia were observed in HFD-fed mice. The use of minocycline, a pharmacological suppressor of microglial overactivation, effectively attenuated neurobehavioral abnormalities and hippocampal structural alterations but barely altered lipid droplet accumulation in the hippocampal microglia of HFD-fed mice. Coadministration of triacsin C abolished the increases in lipid droplet formation, phagocytic activity, and ROS levels in primary microglia treated with serum from HFD-fed mice. In conclusion, our studies demonstrate that the adverse influence of early-life HFD consumption on behavior and hippocampal structure is attributed at least in part to microglial overactivation that is accompanied by an elevated serum FFA concentration and microglial aberrations represent a potential preventive and therapeutic target for HFD-related emotional disorders.
Assuntos
Ansiedade , Dieta Hiperlipídica , Ácidos Graxos não Esterificados , Hipocampo , Camundongos Endogâmicos C57BL , Microglia , Animais , Hipocampo/metabolismo , Dieta Hiperlipídica/efeitos adversos , Microglia/metabolismo , Camundongos , Masculino , Ansiedade/metabolismo , Ácidos Graxos não Esterificados/sangue , Ácidos Graxos não Esterificados/metabolismo , Depressão/metabolismo , Comportamento Animal , Minociclina/farmacologiaRESUMO
BACKGROUND: Both the traditional loop electrosurgical excision procedure (LEEP) and the newly developed 5-aminolevulinic acid photodynamic therapy (ALA-PDT) are used to treat high-grade squamous intraepithelial lesions. However, the clinical efficacy and safety of these two therapies have rarely been compared. Thus, this study aimed to compare the clinical efficacy and safety of the two treatment regimens. METHODS: One hundred and twenty patients in two groups (60 + 60) with grade 2 cervical intraepithelial neoplasia (CIN2) were voluntary treated with photodynamic therapy or LEEP between June 2020 and December 2022. Follow-up was conducted at 3, 4-6, and 7-12 months after treatment. RESULTS: Although the total effective rate of LEEP was higher during the first 6 months after treatment, both the total effective rate of lesion degradation and the double-negative rate of high-risk HPV16/18 and liquid-based cervical cytology by ALA-PDT treatment increased with time and finally exceeded those of LEEP at 7-12 months. CONCLUSIONS: ALA-PDT may be more promising than LEEP for treating patients with CIN2 because of the better CIN2 degradation and high-risk HPV negativity, less damage, and greater fertility conservation, especially after 6 months.
Assuntos
Ácido Aminolevulínico , Eletrocirurgia , Fotoquimioterapia , Fármacos Fotossensibilizantes , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Humanos , Ácido Aminolevulínico/uso terapêutico , Feminino , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Displasia do Colo do Útero/cirurgia , Displasia do Colo do Útero/tratamento farmacológico , Eletrocirurgia/métodos , Adulto , Pessoa de Meia-Idade , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/cirurgiaRESUMO
Farnesoid X receptor (FXR) improves the function of islets, especially in the setting of Roux-en-Y gastric bypass (RYGB). Here we investigated how FXR activation regulates ß-cell proliferation and explored the potential link between FXR signaling and the menin pathway in controlling E2F3 expression, a key transcription factor for controlling adult ß-cell proliferation. Stimulation with the FXR agonist GW4064 or chenodeoxycholic acid (CDCA) increased E2F3 expression and ß-cell proliferation. Consistently, E2F3 knockdown abolished GW4064-induced proliferation. Treatment with GW4064 increased E2F3 expression in ß-cells via enhancing Steroid receptor coactivator-1 (SRC1) recruitment, increasing the pro-transcriptional acetylation of histone H3 at the E2f3 promoter. GW4064 treatment also decreased the association between FXR and menin, leading to the induction of FXR-mediated SRC1 recruitment. Mimicking the impact of FXR agonists, RYGB also increased E2F3 expression and ß-cell proliferation in GK rats and SD rats. These findings unravel the crucial role of the FXR/menin signaling in epigenetically controlling E2F3 expression and ß-cell proliferation, a mechanism possibly underlying RYGB-induced ß-cell proliferation.
Assuntos
Proliferação de Células , Fator de Transcrição E2F3 , Epigênese Genética , Células Secretoras de Insulina , Receptores Citoplasmáticos e Nucleares , Animais , Ratos , Proliferação de Células/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores Citoplasmáticos e Nucleares/agonistas , Receptores Citoplasmáticos e Nucleares/genética , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Masculino , Fator de Transcrição E2F3/metabolismo , Fator de Transcrição E2F3/genética , Ratos Wistar , Histonas/metabolismo , Isoxazóis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologiaRESUMO
DNA molecules are vital macromolecules that play a fundamental role in many cellular processes and have broad applications in medicine. For example, DNA aptamers have been rapidly developed for diagnosis, biosensors, and clinical therapy. Recently, we proposed a computational method of predicting DNA 3D structures, called 3dDNA. However, it lacks a scoring function to evaluate the predicted DNA 3D structures, and so they are not ranked for users. Here, we report a scoring function, 3dDNAscoreA, for evaluation of DNA 3D structures based on a deep learning model ARES for RNA 3D structure evaluation but using a new strategy for training. 3dDNAscoreA is benchmarked on two test sets to show its ability to rank DNA 3D structures and select the native and near-native structures.
Assuntos
DNA , Conformação de Ácido Nucleico , DNA/química , Modelos Moleculares , Aprendizado ProfundoRESUMO
OBJECTIVE: Aggregating evidence convincingly establishes the predominant genetic basis underlying congenital heart defects (CHD), though the heritable determinants contributing to CHD in the majority of cases remain elusive. In the current investigation, BMP10 was selected as a prime candidate gene for human CHD mainly due to cardiovascular developmental abnormalities in Bmp10-knockout animals. The objective of this retrospective study was to identify a new BMP10 mutation responsible for CHD and characterize the functional effect of the identified CHD-causing BMP10 mutation. METHODS: Sequencing assay of BMP10 was fulfilled in a cohort of 276 probands with various CHD and a total of 288 non-CHD volunteers. The available family members from the proband harboring an identified BMP10 mutation were also BMP10-genotyped. The effect of the identified CHD-causative BMP10 mutation on the transactivation of TBX20 and NKX2.5 by BMP10 was quantitatively analyzed in maintained HeLa cells utilizing a dual-luciferase reporter assay system. RESULTS: A novel heterozygous BMP10 mutation, NM_014482.3:c.247G>T;p.(Glu83*), was identified in one proband with patent ductus arteriosus (PDA), which was confirmed to co-segregate with the PDA phenotype in the mutation carrier's family. The nonsense mutation was not observed in 288 non-CHD volunteers. Functional analysis unveiled that Glu83*-mutant BMP10 had no transactivation on its two representative target genes TBX20 and NKX2.5, which were both reported to cause CHD. CONCLUSION: These findings provide strong evidence indicating that genetically compromised BMP10 predisposes human beings to CHD, which sheds light on the new molecular mechanism that underlies CHD and allows for antenatal genetic counseling and individualized precise management of CHD.
RESUMO
To improve the application potential of pomelo peel insoluble dietary fiber (PIDF) in emulsion systems, acetylation (PIDF-A), cellulase hydrolysis (PIDF-E), and wet ball milling (PIDF-M) were investigated in this paper as methods to change the emulsification properties of PIDF. The impact of the methods on PIDF composition, structure, and physicochemical properties was also assessed. The results demonstrated that both acetylation modification and cellulase hydrolysis could significantly improve the emulsification properties of PIDF. The emulsions stabilized with PIDF-A and PIDF-E could be stably stored at 25 °C for 30 d without phase separation at particle concentrations above 0.8% (w/v) and had higher storage stability: The D4,3 increments of PIDF-A- and PIDF-E-stabilized emulsions were 0.98 µm and 0.49 µm, respectively, at particle concentrations of 1.2% (w/v), while the storage stability of PIDF-M-stabilized emulsion (5.29 µm) significantly decreased compared with that of PIDF (4.00 µm). Moreover, PIDF-A showed the highest water retention capacity (21.84 g/g), water swelling capacity (15.40 mL/g), oil retention capacity (4.67 g/g), and zeta potential absolute (29.0 mV) among the PIDFs. In conclusion, acetylation modification was a promising method to improve the emulsifying properties of insoluble polysaccharides.
RESUMO
The organic modification of montmorillonite was successfully achieved using cetyltrimethyl ammonium bromide under facile conditions. The modified montmorillonite was subsequently used for the fabrication of montmorillonite-induced nanopore-rich cement paste (MNCP), and the shrinkage behavior and fundamental performance of MNCP were also investigated. The results indicate that alkali cations on a montmorillonite layer surface were exchanged by using CTAB under 80 °C, successfully achieving the organic modification of montmorillonite. As a pore-forming agent, the modified montmorillonite caused a reduction in shrinkage: the 28-day autogenous shrinkage at a design density of 400 kg/m3 and 800 kg/m3 was reduced to 2.05 mm/m and 0.24 mm/m, and the highest reduction percentages during the 28-day drying shrinkage were 68.1% and 62.2%, respectively. The enlarged interlamellar pores and hydrophobic effects caused by the organic modification of montmorillonite aided this process. Organic-modified montmorillonite had a minor influence on dry density and thermal conductivity and could contribute to an enhancement of strength in MNCP.