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1.
Bioresour Technol ; 406: 131002, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38889869

RESUMO

A continuous chemical-free green approach was investigated for the comprehensive reutilization of all components in herbal extraction residues (HERs), taking Glycyrrhiza uralensis residue (GUR) as an example. The GUR structural changes induced by mechanical extrusion which improve the specific surface area and enzyme accessibility of GUR. With 3 % pretreated GUR loading of high-tolerance Penicillium oxalicum G2. The reducing sugar yield of 11.45 g/L was achieved, along with an 81.06 % in situ enzymatic hydrolysis. Finally, 8.23 g/L bioethanol (0.40 g/g total sugar) was produced from GUR hydrolysates after 24 h fermentation of Pichia stipitis G32. The amount of functional medicinal ingredients extracted from GUR after hydrolysis (39.63 mg/g) was 37.69 % greater than that of un-pretreated GUR. In total, 1.49 g flavonoids, 294.36 U cellulase, and 14.13 g ethanol could be produced from 100 g GUR using this process, illustrating that this green and efficient process has the potential for industrial production.

2.
Opt Express ; 32(7): 12708-12723, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38571086

RESUMO

Based on the theory of the microwave photonic filter (MPF), to our knowledge, a novel fiber Bragg grating (FBG) wavelength demodulation method based on time-domain detection is proposed. The method uses VNA (vector network analyzer) to measure the S21 parameter of the sensor system, and converts them to the time-domain through inverse discrete Fourier transform (IDFT), The wavelength demodulation and positioning of FBG can be realized by measuring the amplitude and position of the time-domain peak. In order to improve the number of FBG multiplexes, a method is proposed to eliminate the effect of spectrum overlap by normalization in the case of two FBGs and three FBGs. The experimental results show that the temperature sensitivity is 0.00503 RAC/°C, the positioning resolution of the system is 1.25 cm, and the limit of the wavelength difference between two FBGs allowed by the system is 0.25 nm. This method has the advantages of high demodulation precision, strong multiplexing ability and high precision positioning, and has broad application prospects.

3.
Biochim Biophys Acta Mol Basis Dis ; 1870(5): 167136, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38531483

RESUMO

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/patologia
4.
BMC Nephrol ; 25(1): 64, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395806

RESUMO

BACKGROUND: Oxidative stress has been implicated in the pathogenesis of chronic kidney disease (CKD), prompting the exploration of antioxidants as a potential therapeutic avenue for mitigating disease progression. This study aims to investigate the beneficial impact of Tempol on the progression of CKD in a rat model utilizing oxidized albumin as a biomarker. METHODS: After four weeks of treatment, metabolic parameters, including body weight, left ventricle residual weight, kidney weight, urine volume, and water and food intake, were measured. Systolic blood pressure, urinary protein, oxidized albumin level, serum creatinine (Scr), blood urea nitrogen (BUN), 8-OHdG, TGF-ß1, and micro-albumin were also assessed. Renal fibrosis was evaluated through histological and biochemical assays. P65-NF-κB was quantified using an immunofluorescence test, while Smad3, P65-NF-κB, and Collagen I were measured using western blot. TNF-α, IL-6, MCP-1, TGF-ß1, Smad3, and P65-NF-κB were analyzed by RT-qPCR. RESULTS: Rats in the high-salt diet group exhibited impaired renal function, characterized by elevated levels of blood urea nitrogen, serum creatinine, 8-OHdG, urine albumin, and tubulointerstitial damage, along with reduced body weight. However, these effects were significantly ameliorated by Tempol administration. In the high-salt diet group, blood pressure, urinary protein, and oxidized albumin levels were notably higher compared to the normal diet group, but Tempol administration in the treatment group reversed these effects. Rats in the high-salt diet group also displayed increased levels of proinflammatory factors (TNF-α, IL-6, MCP1) and profibrotic factors (NF-κB activation, Collagen I), elevated expression of NADPH oxidation-related subunits (P65), and activation of the TGF-ß1/Smad3 signaling pathway. Tempol treatment inhibited NF-κB-mediated inflammation and TGF-ß1/Smad3-induced renal fibrosis signaling pathway activation. CONCLUSION: These findings suggest that Tempol may hold therapeutic potential for preventing and treating rats undergoing 5/6 nephrectomy. Further research is warranted to elucidate the mechanisms underlying Tempol's protective effects and its potential clinical applications. Besides, there is a discernible positive relationship between oxidized albumin and other biomarkers, such as 8-OHG, urinary protein levels, mALB, Scr, BUN, and TGF-ß1 in a High-salt diet combined with 5/6 nephrectomy rat model. These findings suggest the potential utility of oxidized albumin as a sensitive indicator for oxidative stress assessment.


Assuntos
Óxidos N-Cíclicos , Insuficiência Renal Crônica , Marcadores de Spin , Fator de Crescimento Transformador beta1 , Animais , Ratos , Albuminas/química , Albuminas/metabolismo , Peso Corporal , Colágeno/metabolismo , Creatinina , Dieta , Fibrose , Inflamação/tratamento farmacológico , Interleucina-6/metabolismo , Nefrectomia , NF-kappa B/metabolismo , Estresse Oxidativo , Insuficiência Renal Crônica/tratamento farmacológico , Cloreto de Sódio/efeitos adversos , Cloreto de Sódio/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Biomarcadores , Sódio na Dieta/efeitos adversos
5.
Mol Biol Rep ; 51(1): 123, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38227062

RESUMO

BACKGROUND: Roux-en-Y gastric bypass surgery (RYGB) improves glucose-stimulated insulin secretion (GSIS) in type 2 diabetes (T2D) patients. SNAP25 plays an essential role in GSIS. Clinical studies indicate that enhanced GLP-1 signaling is an important contributor to the improved ß-cell function in T2D. We aimed to explore whether GLP-1-regulated SNAP25 is involved in the enhanced secretory function of ß-cells in diabetic Goto-Kakizaki (GK) rats after RYGB. METHODS AND RESULTS: RYGB or sham surgery was conducted in GK rats. mRNA and protein expression of SNAP25 was assessed by qPCR and Western blot, respectively. Occupancy of CREB and acetyltransferase CBP and acetylation of histone H3 (ACH3) at the Snap25 promoter were determined using ChIP assay. RYGB led to increased SNAP25 expression and CREB phosphorylation in islets from GK rats. Increased SNAP25 improved GSIS in ß-cells cultured in high glucose conditions. Consistent with increased plasma GLP-1 after RYGB, GLP-1R agonist exendin4 increased SNAP25 expression and CREB phosphorylation in ß-cells. Mechanistically, exendin4 promoted the recruitment of CREB and CBP, thereby increasing ACH3 at the Snap25 promoter. Consistently, inhibition of CBP attenuated the effect of exendin4 on SNAP25 expression. Furthermore, the knockdown of SNAP25 diminished the increase of GSIS potentiated by chronic GLP-1 culture in INS-1 832/13 cells. CONCLUSIONS: Our findings unravel the novel mechanisms of RYGB-enhanced SNAP25 expression in ß-cells, and SNAP25 may contribute to the improved ß-cell secretory function induced by RYGB.


Assuntos
Diabetes Mellitus Tipo 2 , Derivação Gástrica , Secreção de Insulina , Proteína 25 Associada a Sinaptossoma , Animais , Ratos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/cirurgia , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Glucose , Histonas , Proteína 25 Associada a Sinaptossoma/genética
6.
Am J Transl Res ; 14(11): 8279-8285, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505329

RESUMO

INTRODUCTION: Gastrointestinal stromal tumors (GISTs) rarely occur in the duodenum, and only a few cases have been reported. Its clinical manifestations are not specific, and the imaging examination results are not typical, so a preoperative diagnosis is difficult. Pathologic examinations and genetic testing after surgical resection are the main diagnostic methods. Here, a case of duodenal stromal tumor complicated by gastrointestinal perforation is reported. A 57-year-old man presented with paroxysmal abdominal pain and bloating for 7 days. Contrast-enhanced computed tomography of the abdomen revealed a large mass (10 cm in diameter) in the right upper abdomen, which was considered neoplastic. The mass was anterior and inferior to the head of the pancreas, and medial to the mesenteric vessels. The tumor surrounded the descending and horizontal parts of the duodenum, and it ruptured into the lumen of the descending duodenum. After the patient underwent tumor resection, we found a rupture of the descending duodenal opening. After that, duodenal fistula drainage, gastrostomy, jejunostomy, small intestinal adhesion release and abdominal irrigation drainage were performed. Immunohistochemical staining results were as follows: CD34 (-), desmin (-), S-100 (-), CD117 (9.7) (+), DoG-1 (+), SDHB (+), Ki-67 (+5%). Based on these results, the lesion was finally diagnosed as duodenal GIST. The patient underwent surgical resection without targeted therapy and recovered well. DISCUSSION: Duodenal stromal tumors often present with gastrointestinal bleeding and other clinical symptoms, requiring urgent surgery. Complete resection of the tumor is an effective surgical method. Extended resection does not prolong survival. However, surgical treatment should be determined according to the size and location of the tumor and its relationship to the pancreas. This highly malignant duodenal stromal tumor was >10 cm, accompanied by gastrointestinal perforation and necrosis. Surgical resection was required while protecting the organ function.

7.
Oncogene ; 41(36): 4185-4199, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35882980

RESUMO

HFE (Hemochromatosis) is a conventional iron level regulator and its loss of function due to gene mutations increases the risk of cancers including hepatocellular carcinoma (HCC). Likewise, studies focusing on HFE overexpression in cancers are all limited to linking up these events as a consequence of iron level deregulation. No study has explored any iron unrelated role of HFE in cancers. Here, we first reported HFE as an oncogene in HCC and its undescribed function on promoting abscission in cytokinesis during mitotic cell division, independent of its iron-regulating ability. Clinical analyses revealed HFE upregulation in tumors linking to large tumor size and poor prognosis. Functionally and mechanistically, HFE promoted cytokinetic abscission via facilitating ESCRT abscission machinery recruitment to the abscission site through signaling a novel HFE/ALK3/Smads/LIF/Hippo/YAP/YY1/KIF13A axis. Pharmacological blockage of HFE signaling axis impeded tumor phenotypes in vitro and in vivo. Our data on HFE-driven HCC unveiled a new mechanism utilized by cancer cells to propel rapid cell division. This study also laid the groundwork for tumor intolerable therapeutics development given the high cytokinetic dependency of cancer cells and their vulnerability to cytokinetic blockage.


Assuntos
Carcinoma Hepatocelular , Hemocromatose , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Divisão Celular , Citocinese/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Proteína da Hemocromatose/genética , Humanos , Ferro , Cinesinas , Neoplasias Hepáticas/genética
8.
Microb Biotechnol ; 15(9): 2401-2410, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35730125

RESUMO

The natural flavonoids luteolin and luteoloside have anti-bacterial, anti-inflammatory, anti-oxidant, anti-tumour, hypolipidemic, cholesterol lowering and neuroprotective effects, but their poor water solubility limits their application in industrial production and the pharmaceutical industry. In this study, luteolin-7-O-ß-(6″-O-succinyl)-d-glucoside, a new compound that was prepared by succinyl glycosylation of luteolin by the organic solvent tolerant bacterium Bacillus amyloliquefaciens FJ18 in an 8.0% DMSO (v/v) system, was obtained and identified. Its greater water solubility (2293 times that of luteolin and 12 232 times that of luteoloside) provides the solution to the application problems of luteolin and luteoloside. The conversion rate of luteolin (1.0 g l-1 ) was almost 100% at 24 h, while the yield of luteolin-7-O-ß-(6″-O-succinyl)-d-glucoside reached 76.2%. In experiments involving the oxygen glucose deprivation/reoxygenation injury model of mouse hippocampal neuron cells, the cell viability was significantly improved with luteolin-7-O-ß-(6″-O-succinyl)-d-glucoside dosing, and the expressions of the anti-oxidant enzyme HO-1 in the nucleus increased, providing a neuroprotective effect for ischemic cerebral cells. The availability of biosynthetic luteolin-7-O-ß-(6″-O-succinyl)-d-glucoside, which is expected to replace luteolin and luteoloside, would effectively expand the clinical application value of luteolin derivatives.


Assuntos
Luteolina , Fármacos Neuroprotetores , Animais , Anti-Inflamatórios , Antioxidantes , Glucosídeos , Luteolina/farmacologia , Camundongos , Fármacos Neuroprotetores/farmacologia , Solubilidade , Água
9.
ACS Appl Mater Interfaces ; 14(26): 30192-30204, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35731779

RESUMO

A self-healing coating possesses a broad application prospect in the metal corrosion protection area due to its pleasurable performance. By far, despite a great deal of research studies that have been reported in this field, it is still a challenge to construct an intrinsic self-healing surface that can repair a damaged structure and restore superhydrophobicity simultaneously. Herein, a self-healing superhydrophobic coating was fabricated by combining polydopamine (PDA)-functionalized Cu2+-doped graphene oxide (GO), octadecylamine (ODA), and polydimethylsiloxane (PDMS), which can recover the superhydrophobicity and microstructure of the coating after chemical/physical damage. The as-prepared self-healing coating displayed excellent liquid repellency with a water contact angle of 158.2 ± 2° and a sliding angle of 4 ± 1°, which endowed the Mg alloy with excellent anticorrosion performance. Once the coating is scratched, the local damaged structure will be automatically repaired through the chelation of catechol and Cu2+. Also, the superhydrophobicity of the coating can be rapidly restored under 1-sun irradiation even after being etched by O2 plasma. Furthermore, the as-fabricated self-healing coating still exhibited excellent corrosion protection against a magnesium alloy after immersion in 3.5 wt % NaCl solution for 30 days, which was attributed to the efficient repair of defects in GO by PDA through π-π interactions and the inherent chemical inertia of PDMS. Moreover, the as-fabricated self-healing coating also exhibited favorable mechanical stability, chemical durability, and weather resistance. This study paves a fresh insight into the design of robust self-healing coatings with huge application potential.

10.
Nanomaterials (Basel) ; 12(9)2022 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-35564151

RESUMO

With the fast development of industry and nuclear energy, large amounts of different radionuclides are inevitably released into the environment. The efficient solidification or elimination of radionuclides is thereby crucial to environmental pollution and human health because of the radioactive hazardous of long-lived radionuclides. The properties of negatively or positively charged radionuclides are quite different, which informs the difficulty of simultaneous elimination of the radionuclides. Herein, we summarized recent works about the selective sorption or catalytic reduction of target radionuclides using different kinds of nanomaterials, such as carbon-based nanomaterials, metal-organic frameworks, and covalent organic frameworks, and their interaction mechanisms are discussed in detail on the basis of batch sorption results, spectroscopy analysis and computational calculations. The sorption-photocatalytic/electrocatalytic reduction of radionuclides from high valent to low valent is an efficient strategy for in situ solidification/immobilization of radionuclides. The special functional groups for the high complexation of target radionuclides and the controlled structures of nanomaterials can selectively bind radionuclides from complicated systems. The challenges and future perspective are finally described, summarized, and discussed.

11.
J Hazard Mater ; 426: 127838, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-34844805

RESUMO

Crystallization and immobilization of actinides to form actinide compounds are of significant importance for the extraction and reutilization of nuclear waste in the nuclear industry. In this paper, the state-of-art progress in the crystallization of actinides are summarized, as well as the main functionalization of the actinide compounds, i.e., as adsorbents for heavy metal ions and organic pollutant in waste management, as (photo)catalysts for organic degradation and conversion, including degradation of organic dyes and antibiotics, dehydrogenation of N-heterocycles, CO2 cycloaddition, selective alcohol oxidation and selective oxidation of sulfides. This review will give a comprehensive summary about the synthesis and application exploration of solid actinide crystalline salts and actinide-based metal organic frameworks in the past decades. Finally, the future perspectives and challenges are proposed in the end to give a promising direction for future investigation.


Assuntos
Elementos da Série Actinoide , Estruturas Metalorgânicas , Resíduos Radioativos , Elementos da Série Actinoide/análise , Cristalização , Metais , Resíduos Radioativos/análise
12.
Molecules ; 26(23)2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34885684

RESUMO

The selective elimination of long-lived radioactive actinides from complicated solutions is crucial for pollution management of the environment. Knowledge about the species, structures and interaction mechanism of actinides at solid-water interfaces is helpful to understand and to evaluate physicochemical behavior in the natural environment. In this review, we summarize recent works about the sorption and interaction mechanism of actinides (using U, Np, Pu, Cm and Am as representative actinides) on natural clay minerals and man-made nanomaterials. The species and microstructures of actinides on solid particles were investigated by advanced spectroscopy techniques and computational theoretical calculations. The reduction and solidification of actinides on solid particles is the most effective way to immobilize actinides in the natural environment. The contents of this review may be helpful in evaluating the migration of actinides in near-field nuclear waste repositories and the mobilization properties of radionuclides in the environment.

13.
3 Biotech ; 11(7): 314, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34109099

RESUMO

Glycosylation is a prominent biological mechanism, affecting the structural and functional diversity of many natural products. In this study, a novel thermostable uridine diphosphate-dependent glycosyltransferase gene PpGT1 was cloned from Paenibacillus polymyxa NJPI29 and recombinantly expressed in B. subtilis WB600. The purified PpGT1 had a molecular weight of 45 kDa, as estimated using SDS-PAGE. The PpGT1 could catalyze the glycosylation of vanillic acid, methyl vanillate, caffeic acid, cinnamic alcohol, and ferulic acid. Moreover, PpGT1 possessed good thermostability and retained 80% of its original activity even after 12 h of incubation at 45 °C. In addition, PpGT1 remained stable within a neutral to alkaline pH range as well as in the presence of metal ions. The synthesis of methyl vanillate 4-O-ß-D-glucoside by purified PpGT1 reached a yield 3.58 mM in a system with pH 8.0, 45 °C, 12 mM UDP-Glc, and 4 mM methyl vanillate. 3D-structure-based amino acid sequence alignments revealed that the catalytic residues and C-terminated PSPG motif were conserved. These unusual properties indicated that PpGT1 is a candidate UGT for valuable natural product industrial applications. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02855-z.

14.
J Cell Mol Med ; 2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33611845

RESUMO

In this study, we investigated how Roux-en-Y gastric bypass (RYGB) enhances glucagon-like peptide 1 (GLP-1) response in GK rats and explored the potential link between RYGB-stimulated BAs/FXR signalling and GLP-1R-linked signalling in ß-cells, a key pathway that regulates glucose-stimulated insulin secretion (GSIS). Here we show that RYGB restores GLP-1R expression in GK rat islets. This involves increased total BAs as well as chenodeoxycholic acid (CDCA), leading to FXR activation, increasing FXR binding to the promoter of Glp-1r and enhancing occupancy of histone acetyltransferase steroid receptor coactivator-1 (SRC1), thus increasing histone H3 acetylation at the promoter. These coordinated events bring about increased GLP-1R expression, resulting in greater GLP-1 response in ß-cells. Moreover, ablation of FXR suppressed the stimulatory effects of GLP-1. Thus, this study unravels the crucial role of the BAs/FXR/SRC1 axis-controlled GLP-1R expression in ß-cells, which results in enhanced incretin effect and normalized blood glucose of GK rats after RYGB.

15.
Front Chem ; 9: 635191, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33634077

RESUMO

Upgrading of biomass derived 5-hydroxymethylfurfural (HMF) has attracted considerable interest recently. A new highly HMF-tolerant strain of Burkholderia contaminans NJPI-15 was isolated in this study, and the biocatalytic reduction of HMF into 2,5-bis(hydroxymethyl)furan (BHMF) using whole cells was reported. Co-substrate was applied to improve the BHMF yield and selectivity of this strain as well as HMF-tolerant level. The catalytic capacity of the cells can be substantially improved by Mn2+ ion. The strain exhibited good catalytic performance at a pH range of 6.0-9.0 and a temperature range of 25°C-35°C. In addition, 100 mM HMF could be reduced to BHMF by the B. contaminans NJPI-15 resting cells in presence of 70 mM glutamine and 30 mM sucrose, with a yield of 95%. In the fed-batch strategy, 656 mM BHMF was obtained within 48 h, giving a yield of 93.7%. The reported utilization of HMF to produce BHMF is a promising industrially sound biocatalytic process.

16.
Biotechnol Appl Biochem ; 67(2): 249-256, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31628682

RESUMO

Raspberry ketone is a primary aroma component of the red raspberry. The glycosylation of this compound is a potential approach used to improve its pharmaceutical properties. In this work, raspberry ketone glycosides are produced in bacteria for the first time. Bacillus licheniformis PI15, an organic solvent-tolerant glycosyltransferase-producing strain, was isolated from chemically polluted soil. The cloning and heterologous expression of a glycosyltransferase, which was designated PI-GT1, in Escherichia coli BL21 resulted in the expression of an active and soluble protein that accounted for 15% of the total cell protein content. Purified PI-GT1 was highly active and stable over a broad pH range (6.0-10.0) and showed excellent pH stability. PI-GT1 maintained almost 60% of its maximal activity after 3 H of incubation at 20-40 °C and demonstrated optimal activity at 30 °C. Additionally, PI-GT1 displayed high stability and activity in the presence of hydrophilic solvents with log P ≤ -0.2 and retained more than 80% of its activity after 3 H of treatment. Supplementation with 10% DMSO markedly improved the glycosylation of raspberry ketone, resulting in a value 26 times higher than that in aqueous solution. The organic solvent-tolerant PI-GT1 may have potential uses in industrial chemical and pharmaceutical synthesis applications.


Assuntos
Bacillus licheniformis/enzimologia , Butanonas/metabolismo , Dimetil Sulfóxido/metabolismo , Glicosídeos/biossíntese , Glicosiltransferases/metabolismo , Butanonas/química , Dimetil Sulfóxido/química , Glicosídeos/química , Glicosilação , Concentração de Íons de Hidrogênio , Solventes/química , Solventes/metabolismo
17.
Mol Metab ; 29: 1-11, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31668381

RESUMO

OBJECTIVE: Roux-en-Y gastric bypass surgery (RYGB) improves the first phase of glucose-stimulated insulin secretion (GSIS) in patients with type 2 diabetes. How it does so remains unclear. Farnesoid X receptor (FXR), the nuclear receptor of bile acids (BAs), is implicated in bariatric surgery. Moreover, the transient receptor potential ankyrin 1 (TRPA1) channel is expressed in pancreatic ß-cells and involved in insulin secretion. We aimed to explore the role of BAs/FXR and TRPA1 in improved GSIS in diabetic rats after RYGB. METHODS: RYGB or sham surgery was conducted in spontaneous diabetic Goto-Kakizaki (GK) rats, or FXR or TRPA1 transgenic mice. Gene and protein expression of islets were assessed by qPCR and western blotting. Electrophysiological properties of single ß-cells were studied using patch-clamp technique. Binding of FXR and histone acetyltransferase steroid receptor coactivator-1 (SRC1) to the TRPA1 promoter, acetylated histone H3 (ACH3) levels at the TRPA1 promoter were determined using ChIP assays. GSIS was measured using enzyme-linked immunosorbent assays or intravenous glucose tolerance test (IVGTT). RESULTS: RYGB increases GSIS, particularly the first-phase of GSIS in both intact islets and GK rats in vivo, and ameliorates hyperglycemia of GK rats. Importantly, the effects of RYGB were attenuated in TRPA1-deficient mice. Moreover, GK ß-cells displayed significantly decreased TRPA1 expression and current. Patch-clamp recording revealed that TRPA1-/- ß-cells displayed a marked hyperpolarization and decreased glucose-evoked action potential firing, which was associated with impaired GSIS. RYGB restored TRPA1 expression and current in GK ß-cells. This was accompanied by improved glucose-evoked electrical activity and insulin secretion. Additionally, RYGB-induced TRPA1 expression involved BAs/FXR-mediated recruitment of SRC1, promoting ACH3 at the promoter of TRPA1. CONCLUSIONS: The BAs/FXR/SRC1 axis-mediated restoration of TRPA1 expression plays a critical role in the enhanced GSIS and remission of diabetes in GK rats after RYGB.


Assuntos
Diabetes Mellitus Tipo 2/patologia , Secreção de Insulina , Receptores Citoplasmáticos e Nucleares/metabolismo , Canal de Cátion TRPA1/metabolismo , Animais , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/cirurgia , Diabetes Mellitus Tipo 2/veterinária , Potenciais Evocados , Derivação Gástrica , Histonas/metabolismo , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Coativador 1 de Receptor Nuclear/antagonistas & inibidores , Coativador 1 de Receptor Nuclear/genética , Coativador 1 de Receptor Nuclear/metabolismo , Regiões Promotoras Genéticas , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Wistar , Ratos Zucker , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Receptores Citoplasmáticos e Nucleares/genética , Canal de Cátion TRPA1/genética
18.
J Diabetes Res ; 2019: 8915818, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31485455

RESUMO

Adenylyl cyclase 8 (ADCY8) and Farnesoid X Receptor (FXR) have been identified in pancreatic ß-cells and play important roles in insulin secretion. But the mechanisms underlying with respect to the regulation of ADCY8 expression in ß-cells, particularly whether FXR is involved, remain unexplored. We now show that ADCY8 expression is decreased in Goto-Kakizaki (GK) rat islets compared with healthy Wistar controls. We also found that reduced ADCY8 is associated with decreased expression of FXR. Consistently, ADCY8 expression was suppressed by the knockdown of FXR in INS-1 832/13 cells, as well as the islets from FXR knockout mice. On the contrary, ADCY8 expression was increased in FXR-overexpressed INS-1 832/13 cells or in the case of FXR activation. Mechanistically, FXR directly binds to Adcy8 promoter and recruits the histone acetyltransferase Steroid Receptor Coactivator 1 (SRC1), thereby resulting in the increased acetylation of histone H3 in Adcy8 locus, promoting Adcy8 gene transcription in ß-cells. Thus, this study indicates that FXR is a critical transcription factor that mediates ADCY8 expression in pancreatic ß-cells and has characterized the chromatin modification associated with Adcy8 transcription.


Assuntos
Adenilil Ciclases/genética , Receptores Citoplasmáticos e Nucleares/fisiologia , Adenilil Ciclases/metabolismo , Animais , Células Cultivadas , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Regulação Enzimológica da Expressão Gênica , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ratos , Ratos Wistar , Ratos Zucker , Receptores Citoplasmáticos e Nucleares/genética
19.
Int J Biol Macromol ; 135: 373-378, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31108143

RESUMO

A phenolic-UDP-glycosyltransferase Bs-PUGT from Bacillus subtilis PI18 was cloned and expressed in Escherichia coli BL21 (DE3). The purified Bs-PUGT could catalyze the glycosylation of tyrosol, 4-hydroxybenzyl alcohol, 2-hydroxybenzyl alcohol, caffeic acid, cinnamic alcohol, ferulic acid, and so on. This enzyme showed a high activity and stability over a broad pH range and was sensitive to temperature. Studies on the kinetic parameters indicated that the affinity of Bs-PUGT to UDP-G (Km) and its catalytic efficiency (Kcat) increased by 1.5-fold and 1.7-fold, respectively, with the addition of 10 mM Ca2+. The most effective glycosylation of caffeic acid catalyzed by whole-cell E. coli/Bs-PUGT was achieved with a molar yield of 78.3% in a system with pH 8.0, 30 °C, 25 g/L sucrose, 10 mM Ca2+, and 0.5 g/L substrate concentration. The addition of Ca2+ increased the molar yield of caffeic acid glucosides and shortened the reaction. This work proposes a strategy for the efficient glycosylation of phenolic compounds by microbe-derived glycosyltransferase assisted by metal ions.


Assuntos
Bacillus subtilis/enzimologia , Cálcio/química , Glicosiltransferases/química , Fenóis/química , Ativação Enzimática , Glucosídeos/química , Glicosilação , Glicosiltransferases/genética , Concentração de Íons de Hidrogênio , Íons , Cinética , Metais , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Especificidade por Substrato , Temperatura
20.
ISA Trans ; 93: 137-144, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30926124

RESUMO

This work investigates the stability and H∞ performance of interval time-varying delay systems. The aim is to find new optimal analysis method, which can integrate the constructed Lyapunov-Krasovskii functional (LKF) with estimating technique effectively to reduce the conservatism of the main results. A new augmented vector and LKF with triple integral terms are constructed to establish relationships among different vectors firstly. Then two different integral inequalities are used to show how to integrate constructed LKF with estimating technique effectively to reduce the conservatism of the main criteria. Meanwhile, less conservative criteria are derived compared with some existing results. Numerical examples are also given to show the superiority of the proposed approaches.

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