RESUMO
Ferroptosis has been shown to be involved in carbon tetrachloride (CCl4)-induced acute liver injury (ALI). The mitochondrion-targeted antioxidant MitoQ can eliminate the production of mitochondrial reactive oxygen species (mtROS). This study investigated the role of MitoQ in CCl4-induced hepatocytic ferroptosis and ALI. MDA and 4HNE were elevated in CCl4-induced mice. In vitro, CCl4 exposure elevated the levels of oxidized lipids in HepG2 cells. Alterations in the mitochondrial ultrastructure of hepatocytes were observed in the livers of CCl4-evoked mice. Ferrostatin-1 (Fer-1) attenuated CCl4-induced hepatic lipid peroxidation, mitochondrial ultrastructure alterations and ALI. Mechanistically, acyl-CoA synthetase long-chain family member 4 (ACSL4) was upregulated in CCl4-exposed human hepatocytes and mouse livers. The ACSL4 inhibitor rosiglitazone alleviated CCl4-induced hepatic lipid peroxidation and ALI. ACSL4 knockdown inhibited oxidized lipids in CCl4-exposed human hepatocytes. Moreover, CCl4 exposure decreased the mitochondrial membrane potential and OXPHOS subunit levels and increased the mtROS level in HepG2 cells. Correspondingly, MitoQ pretreatment inhibited the upregulation of ACSL4 in CCl4-evoked mouse livers and HepG2 cells. MitoQ attenuated lipid peroxidation in vivo and in vitro after CCl4 exposure. Finally, MitoQ pretreatment alleviated CCl4-induced hepatocytic ferroptosis and ALI. These findings suggest that MitoQ protects against hepatocyte ferroptosis in CCl4-induced ALI via the mtROS-ACSL4 pathway.
Assuntos
Tetracloreto de Carbono , Doença Hepática Induzida por Substâncias e Drogas , Coenzima A Ligases , Ferroptose , Hepatócitos , Camundongos Endogâmicos C57BL , Compostos Organofosforados , Espécies Reativas de Oxigênio , Regulação para Cima , Animais , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Regulação para Cima/efeitos dos fármacos , Células Hep G2 , Coenzima A Ligases/metabolismo , Coenzima A Ligases/genética , Camundongos , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Ferroptose/efeitos dos fármacos , Tetracloreto de Carbono/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Masculino , Compostos Organofosforados/farmacologia , Ubiquinona/análogos & derivados , Ubiquinona/farmacologia , Antioxidantes/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacosRESUMO
The aim of the work was to systematically evaluate the efficacy and safety of Vandetanib in the treatment of advanced medullary thyroid carcinoma (MTC). MeSH entries to search for randomized controlled trials and clinical research literature on the application of Vandetanib in the treatment of medullary thyroid cancer from PubMed, Chinese national knowledge infrastructure (CNKI), and Web of Science databases since their establishment until March 2023 were used. In terms of efficacy, the analysis results showed that Vandetanib had a significantly higher objective response rate compared to the control group using placebo (OR=2.13, 95% CI: 1.38, 3.29). In terms of side effects, Vandetanib significantly increases the incidence of hypertension, rash, and diarrhea, and has statistical significance (p+<+0.05). Vandetanib has a better therapeutic effect on MTC, but it also increases the incidence of hypertension, rash, and diarrhea. Attention should be paid to the relief of side effects when using it.
Assuntos
Carcinoma Neuroendócrino , Piperidinas , Quinazolinas , Neoplasias da Glândula Tireoide , Humanos , Carcinoma Neuroendócrino/tratamento farmacológico , Piperidinas/administração & dosagem , Piperidinas/efeitos adversos , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias da Glândula Tireoide/tratamento farmacológico , Resultado do TratamentoRESUMO
Lithium metal anode (LMA) is puzzled by the serious issues corresponding to infinite volume change and notorious lithium dendrite during long-term stripping/plating process. Herein, the transition metal nitrides array with outstanding lithiophilicity, including CoN, VN, and Ni3 N, are decorated onto carbon framework as "nests" to uniform Li nucleation and guide Li metal deposition. These transition metal nitrides with excellent conductivity can guarantee the fast electron transport, therefore maintain a stable interface for Li reduction. In addition, the designed multi-dimensional structure of metal nitride array decorated carbon framework can effectively regulate the growth of Li metal during the stripping/plating process. Of note, attributing to the lattice-matching between CoN and Li metal, the composite Li/CoN@CF anode exhibits ultra-stable cycling performance in symmetrical cells (over 4000 h@1 mA cm-2 with 1 mAh cm-2 and 1000h@20 mA cm-2 with 20 mAh cm-2 ). The assembled full cells based on Li/CoN@CF composite anode, LiFePO4 or S as cathodes, deliver excellent cycling stability and rate capability. This strategy provides an effective approach to develop a stable lithium metal anode for lithium metal batteries.
RESUMO
In recent years, organic-inorganic hybrid nanoflower technology has become an effective method for enzyme immobilization. Here, seven hierarchical flower-like hemoglobin-phosphate organic-inorganic hybrid nanomaterials (Hb-M3(PO4)2·nH2O HNFs) were synthesized through an improved universal one-pot wet-chemical method, with Ca2+, Mn2+, Fe2+, Co2+, Ni2+, Cu2+ and Zn2+ as inorganic components. In this synthesis process, the metal cations are successively involved in the coordination reaction with Hb and the metathesis reaction to generate phosphate precipitation. The coordination ability of metal cations and the generation rate of phosphate precipitations were evaluated, then the progress of the two chemical reactions was controlled synchronously by adjusting the phosphate buffer (PB) concentration, and finally a flower-like structure conducive to substrate diffusion and transport was obtained. Due to the conformational transformation of hemoglobin and the abundant Cu2+/Fe3+ active sites, the hemoglobin-Cu3(PO4)2·3H2O nanoflowers have extremely high catalytic activity, which is â¼14 times that of Hb. Importantly, this method is suitable for the monometallic-ionic, polymetallic-ionic and polyvalent metal-ion nanoflowers, which broadens the chemical composition and structural diversity of nanoflowers.
Assuntos
Nanoestruturas , Fosfatos , Biocatálise , Fosfatos/química , Metais , Nanoestruturas/química , HemoglobinasRESUMO
BACKGROUND: The risk factors for the recurrent choledocholithiasis after endoscopic retrograde cholangiopancreatography (ERCP) have not been well studied. The aim of this study was to explore the risk factors of recurrent choledocholithiasis. METHODS: We carried out a retrospective analysis of data collected between January 1, 2010 and January 1, 2020. Univariate analysis and multivariate analysis were used to explore the independent risk factors of recurrent choledocholithiasis following therapeutic ERCP. RESULTS: In total, 598 patients were eventually selected for analysis, 299 patients in the recurrent choledocholithiasis group and 299 patients in the control group. The overall rate of recurrent choledocholithiasis was 6.91%. Multivariate analysis showed that diabetes [odds ratio (OR) = 3.677, 95% confidence interval (CI): 1.875-7.209; P < 0.001], fatty liver (OR = 4.741, 95% CI: 1.205-18.653; P = 0.026), liver cirrhosis (OR = 3.900, 95% CI: 1.358-11.201; P = 0.011), history of smoking (OR = 3.773, 95% CI: 2.060-6.908; P < 0.001), intrahepatic bile duct stone (OR = 4.208, 95% CI: 2.220-7.976; P < 0.001), biliary stent (OR = 2.996, 95% CI: 1.870-4.800; P < 0.001), and endoscopic papillary balloon dilation (EPBD) (OR = 3.009, 95% CI: 1.921-4.715; P < 0.001) were independent risk factors of recurrent choledocholithiasis. However, history of drinking (OR = 0.183, 95% CI: 0.099-0.337; P < 0.001), eating light food frequently (OR = 0.511, 95% CI: 0.343-0.760; P = 0.001), and antibiotic use before ERCP (OR = 0.315, 95% CI: 0.200-0.497; P < 0.001) were independent protective factors of recurrent choledocholithiasis. CONCLUSIONS: Patients with the abovementioned risk factors are more likely to have recurrent CBD stones. Patients who eat light food frequently and have a history of drinking are less likely to present with recurrent CBD calculi.
Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Coledocolitíase , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Coledocolitíase/diagnóstico por imagem , Coledocolitíase/cirurgia , Estudos Retrospectivos , Cateterismo , Fatores de Risco , Esfinterotomia EndoscópicaRESUMO
The most promising energy storage devices are lithium-sulfur batteries (LSBs), which offer a high theoretical energy density that is five times greater than that of lithium-ion batteries. However, there are still significant barriers to the commercialization of LSBs, and mesoporous carbon-based materials (MCBMs) have attracted much attention in solving LSBs' problems, due to their large specific surface area (SSA), high electrical conductivity, and other unique advantages. The synthesis of MCBMs and their applications in the anodes, cathodes, separators, and "two-in-one" hosts of LSBs are reviewed in this study. Most interestingly, we establish a systematic correlation between the structural characteristics of MCBMs and their electrochemical properties, offering recommendations for improving performance by altering the characteristics. Finally, the challenges and opportunities of LSBs under current policies are also clarified. This review provides ideas for the design of cathodes, anodes, and separators for LSBs, which could have a positive impact on the performance enhancement and commercialization of LSBs. The commercialization of high energy density secondary batteries is of great importance for the achievement of carbon neutrality and to meet the world's expanding energy demand.
Assuntos
Carbono , Lítio , Condutividade Elétrica , Fontes de Energia Elétrica , EnxofreRESUMO
PURPOSE: The present study aimed to investigate fish oil plus vitamin D3 (FO + D) supplementation on biomarkers of non-alcoholic fatty liver disease (NAFLD). METHODS: In a 3-month randomized controlled trial, 111 subjects with NAFLD, aged 56.0 ± 15.9 y, were randomized into FO + D group (n = 37), fish oil group (FO, n = 37) or corn oil group (CO, n = 37). The subjects consumed the following capsules (3 g/day), which provided 2.34 g/day of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) + 1680 IU vitamin D3 (FO + D group), or 2.34 g/day of EPA + DHA (FO group), or 1.70 g/d linoleic acid (CO group). RESULTS: Using multivariable-adjusted general linear model, there were significant net reductions in serum alanine aminotransferase (ALT), and triacylglycerol (TAG) and TNF-α levels in the FO + D and FO groups, compared with the control group (P < 0.05). The supplemental FO + D also showed significant reductions in insulin (- 1.58 ± 2.00 mU/L vs. - 0.63 ± 1.55 mU/L, P = 0.050) and IL-1ß (- 6.92 ± 7.29 ng/L vs. 1.06 ± 5.83 ng/L, P < 0.001) in comparison with control group. Although there were no significant differences between FO + D and FO groups regarding biochemical parameters, supplemental FO + D showed decreases in ALT (from 26.2 ± 13.5 U/L to 21.4 ± 9.6 U/L, P = 0.007), aspartate aminotransferase (AST, from 22.5 ± 7.0 U/L to 20.2 ± 4.0 U/L, P = 0.029), HOMA-IR (from 3.69 ± 1.22 to 3.38 ± 1.10, P = 0.047), and TNF-α (from 0.43 ± 0.38 ng/L to 0.25 ± 0.42 ng/L, P < 0.001) levels following the intervention. CONCLUSION: The present study demonstrated that groups supplemented with FO + D and FO had similar beneficial effects on biomarkers of hepatocellular damage and plasma TAG levels in subjects with NAFLD, while in the FO + D group, there were some suggestive additional benefits compared with FO group on insulin levels and inflammation. TRIAL REGISTRATION: ChiCTR1900024866.
Assuntos
Colecalciferol , Óleos de Peixe , Hepatopatia Gordurosa não Alcoólica , Biomarcadores , Colecalciferol/administração & dosagem , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácido Eicosapentaenoico/administração & dosagem , Óleos de Peixe/administração & dosagem , Humanos , Insulina , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Triglicerídeos/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Au-CEW-Cu3(PO4)2-GO nanoflowers (HNFs), which were assembled of gold nanoparticals (Au NPs), chicken egg white (CEW), copper phosphate (Cu3(PO4)2) and graphene oxide (GO) together to form a flower-like organic/inorganic hybrid nanocomposite, were synthesized through a simple and gentle one-pot co-precipitation method. The prepared samples were well characterized by scanning electron microscope, transmission electron microscope, energy dispersive x-ray spectrometer, x-ray diffraction and Raman spectrometer. The prepared Au-CEW-Cu3(PO4)2-GO HNFs was used to modify glassy carbon electrode to fabricate an electrochemical sensor for detection of ascorbic acid (AA). The electrochemical test results show that the linear range of the developed sensor is 8-300µM and the detection limit is 2.67µM (S/N = 3). While this sensor displays high sensitivity of 6.01 × 10-3µAµM-1cm-2and low detection potential of 35 mV due to the combination of the high conductivity of Au NPs, the larger specific surface area of GO and the intrinsic electrocatalytic activity of CEW-Cu3(PO4)2HNFs. Moreover, the Au-CEW-Cu3(PO4)2-GO HNFs-based sensor was successfully developed for application in electrochemical detection of AA in vitamin C tablets.
RESUMO
We have built a Fizeau fiber interferometer to investigate the internal cylindrical defects in an aluminum plate based on laser ultrasonic techniques. The ultrasound is excited in the plate by a Q-switched Nd:YAG laser. When the ultrasonic waves interact with the internal defects, the transmitted amplitudes of longitudinal and shear waves are different. The experimental results show that the difference in transmission amplitudes can be attributed to the high frequency damping of internal cylinders. When the scanning point is close to the internal defect, the longitudinal waves attenuate significantly in the whole defect area, and their amplitude is always smaller than that of shear waves. By comparing the transmitted amplitudes of longitudinal and shear waves at different scanning points, we can achieve a C scan image of the sample to realize the visual inspection of internal defects. Our system exhibits outstanding performance in detecting internal cylinders, which could be used not only in evaluating structure cracks but also in exploring ultrasonic transmission characteristics.
RESUMO
The European Space Agency (ESA) Climate Change Initiative (CCI) project combines multi-sensors at different microwave frequencies to derive three harmonized soil moisture products using active, passive and combined approaches. These long-term soil moisture products assist in understanding the global water and carbon cycles. However, extensive validations are a prerequisite before applying the retrieved soil moisture into climatic or hydrological models. To fulfill this objective, we assess the performances of three CCI soil moisture products (active, passive and combined) with respect to in-situ soil moisture networks located in China, Spain and Canada. In order to compensate the scale differences between ground stations and the CCI product's coarse resolution, we adopted two upscaling approaches of Inverse Distance Weighting (IDW) interpolation and simple Arithmetic Mean (AM). The temporal agreements between the satellite retrieved and ground-measured soil moisture were quantified using the unbiased root mean square error (ubRMSE), RMSE, correlation coefficients (R) and bias. Furthermore, the temporal variability of the CCI soil moisture is interpreted and verified with respect to the Tropical Rainfall Measuring Mission (TRMM) precipitation observations. The results show that the temporal variations of CCI soil moisture agreed with the in-situ ground measurements and the precipitation observations over the China and Spain test sites. In contrast, a significant overestimation was observed over the Canada test sites, which may be due to the strong heterogeneity in soil and vegetation characteristics in accordance with the reported poor performance of soil moisture retrieval there. However, despite a retrieval bias, the relatively temporal variation of the CCI soil moisture also followed the ground measurements. For all the three test sites, the soil moisture retrieved from the combined approach outperformed the active-only and passive-only methods, with ubRMSE of 0.034, 0.050, and 0.050-0.054 m3/m3 over the test sites in China, Spain and Canada, respectively. Thus, the CCI combined soil moisture product is suggested to drive the climatic and hydrological studies.
RESUMO
A large number of recent studies are focused on evaluating the mechanism of action of trans fatty acids (TFAs) on the progression of apoptosis. A strong positive association has been reported between TFA and coronary heart disease (CHD), obesity and nonalcoholic steatohepatitis and so on. The present study reviewed the biological effects of trans fatty acids (TFA) and their possible roles in lipid rafts in regulating apoptosis. The following aspects of TFA were included: the research about TFA and diseases affecting serum lipid levels, inducing system inflammation and immune response, and the correlation between TFA and apoptosis. The primary purpose of the review article was to comprehensively evaluate the potential correlation between lipid rafts and apoptosis induced by different structures of TFA and provide some new research progress and future directions about it.
Assuntos
Apoptose , Microdomínios da Membrana/metabolismo , Ácidos Graxos trans/metabolismo , Caspases/metabolismo , Caveolinas/metabolismo , Proteína Ligante Fas/metabolismo , Humanos , Inflamação/patologia , Microdomínios da Membrana/química , Transdução de Sinais , Ácidos Graxos trans/químicaRESUMO
[This corrects the article DOI: 10.1039/D4SC02420F.].
RESUMO
Lithium-sulfur batteries (LSBs) with two typical platforms during discharge are prone to the formation of soluble lithium polysulfides (LiPS), leading to a decrease in the cycling life of the battery. Under practical working conditions, the transformation of S8 into Li2S is cross-executed rather than a stepwise reaction, where the liquid LiPS to solid Li2S conversion can occur at a high state of charge (SOC) to maintain the current requirement. Therefore, advancing Li2S deposition can effectively reduce the accumulation of LiPSs and ultimately improve the reaction kinetics. Herein, a "butterfly material" GeS2-MoS2/rGO is used as a sulfur host. Rich catalytic heterointerfaces can be obtained via the abundant S-S bonds formed between GeS2 and MoS2. MoS2 (left wing) can enhance LiPS adsorption, while the lattice-matching nature of Fdd2 GeS2 (right wing) and Fm3Ìm Li2S can induce multiple nucleation and regulate the 3D growth of Li2S. Li2S deposition can be advanced to occur at 80% SOC, thereby effectively inhibiting the accumulation of soluble LiPSs. Attributed to the synergistic effect of catalytic and lattice-matching properties, robust coin and pouch LSBs can be achieved.
RESUMO
Iodinated X-ray contrast media (ICM) are ubiquitously present in water sources and challenging to eliminate using conventional processes, posing a significant risk to aquatic ecosystems. Ultraviolet light-emitting diodes (UV-LED) emerge as a promising technology for transforming micropollutants in water, boasting advantages such as diverse wavelengths, elimination of chemical additives, and no induction of microorganisms' resistance to disinfectants. The research reveals that iohexol (IOX) degradation escalates as UV wavelength decreases, attributed to enhanced photon utilization efficiency. Pseudo-first-order rate constants (kobs) were determined as 3.70, 2.60, 1.31 and 0.65 cm2 J-1 at UV-LED wavelengths of 255, 265, 275 and 285 nm, respectively. The optical properties of dissolved organic matter (DOM) and anions undeniably influence the UV-LED photolysis process through photon competition and the generation of reactive substances. The influence of Cl- on IOX degradation was insignificant at UV-LED 255, but it promoted IOX degradation at 265, 275 and 285 nm. IOX degradation was accelerated by ClO2-, NO3-and HA due to the formation of various reactive species. In the presence of NO3-, the kobs of IOX followed the order: 265 > 255 > 275 > 285 nm. Photosensitizers altered the spectral dependence of IOX, and the intermediate photoactivity products were detected using electron spin resonance. The transformation pathways of IOX were determined through density functional theory calculations and experiments. Disinfection by-products (DBPs) yields of IOX during UV-LED irradiation decreased as the wavelength increased: 255 > 265 > 275 > 285 nm. The cytotoxicity index value decreased as the UV-LED wavelength increased from 255 to 285 nm. These findings are crucial for selecting the most efficient wavelength for UV-LED degradation of ICM and will benefit future water purification design.
RESUMO
A simple, cheap and rugged method was developed for simultaneous deter mination of 6 neonicotinoid residues in soil, including imidacloprid, acetamiprid, thiamethoxam, thiacloprid, clothianidin and nitenpyram. The soil sample was produced by dispersive liquid-liquid micro-extraction (DLLME) after extracted by the mixed solution of acetonitrile and CH2Cl2 (2:1, phi). The analytes were separated by HPLC with Alltima C18 column (4.6 mm x 250 mm, 5 microm) and detected by PDA at 260 nm. External standard method was used for quantification. The results showed that good linearity was obtained with correlation coefficients between 0.9982 and 0.9999 in the range of 0.5-200 microg x L(-1). The limits of detection (LODs) were in the range between 0.0005 and 0.003 microg x mL(-1) (S/N = 3). The method was validated with five soil samples spiked at three fortification levels (0.05, 0.1, 1.0 mg x kg(-1)) and recoveries were in the range of 55.3%-95.6% with RSD of 1.4%-7.0%. The effect of clean-up was evaluated by UV spectra and demonstrated that the method established is effective. In conclusion, this method is competent for the simultaneous analysis of 6 neonicotinoid residues in soil.
Assuntos
Cromatografia Líquida de Alta Pressão , Resíduos de Praguicidas/análise , Solo/química , Guanidinas , Imidazóis , Limite de Detecção , Neonicotinoides , Nitrocompostos , Oxazinas , Piridinas , Tiametoxam , Tiazinas , TiazóisRESUMO
Introduction: Proteomics technology has been used in various fields in recent years for the Q6 exploration of novel markers and the study of disease pathogenesis, and has become one of the most important tools for researchers to explore unknown areas. However, there are fewer studies related to the construction of clinical models using proteomics markers. Methods: In our previous study we used DIA proteomics to screen for proteins that were significant in 31 PCOS patients compared to women of normal reproductive age. In this study, we used logistic regression among these protein markers to screen out variables with diagnostic value and constructed logistic regression models. Results: We constructed a logistic model using these protein markers, where HIST1H4A (OR=1.037) was an independent risk factor for polycystic ovary syndrome and TREML1 (OR=0.976) were protective factors for the disease. The logistic regression model equation is: Logit (PCOS) =0.036*[HIST1H4A]-0.024*[TREML1]-16.368. The ROC curve analyzing the diagnostic value of the model has an AUC value of 0.977 and a Youden index of0.903, which gives a cutoff value of 0.518 at this point. The model has a sensitivity of 93.5% and a specificity of 96.8%. Calibration curves show fair consistency of the model. Discussion: Our study is the first to use proteomic results with clinical biochemical data to construct a logistic regression model, and the model is consistent. However, our study still needs a more complete sample to confirm our findings.
Assuntos
Síndrome do Ovário Policístico , Humanos , Feminino , Síndrome do Ovário Policístico/diagnóstico , Modelos Logísticos , Proteômica , Curva ROC , Fatores de Risco , Receptores ImunológicosRESUMO
The commercialization of lithium-sulfur batteries (LSBs) is obstructed by several technical challenges, the most severe of which is the irreversible loss of soluble polysulfide intermediates. These soluble polysulfides must be anchored or confined in the cathode side to maintain the long life of the LSBs. Here, 1T MoS2-MnO2/CC heterostructure functional covering layer is designed to regulate the rate-determining step from the liquid-to-solid reaction to solid-to-solid reaction. Rapid and uniform nucleation of solid Li2S2/Li2S is therefore achieved, and the loss of soluble polysulfides is retarded. The Li-S batteries assembled with 1T MoS2-MnO2/CC covering layer therefore deliver outstanding rate capabilities even under high sulfur loads and large current rates. This study paves a novel way to suppress the polysulfides' "farewell effect" from the perspective of the kinetics.
RESUMO
BACKGROUND: Previous study found that supplements with active vitamin D3 alleviated experimental colitis. The objective of this study was to investigate the possible role of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a ketone synthase, on vitamin D3 protecting against experimental colitis. METHODS: HMGCS2 and vitamin D receptor (VDR) were measured in UC patients. The effects of vitamin D deficiency (VDD) and exogenous 1,25(OH)2D3 supplementation on experimental colitis were investigated in dextran sulfate sodium (DSS)-treated mice. DSS-induced oxidative stress and inflammation were analyzed in HT-29 cells. HMGCS2 was detected in 1,25(OH)2D3-pretreated HT-29 cells and mouse intestines. HMGCS2 was silenced to investigate the role of HMGCS2 in 1,25(OH)2D3 protecting against experimental colitis. RESULTS: Intestinal HMGCS2 downregulation was positively correlated with VDR reduction in UC patients. The in vivo experiments showed that VDD exacerbated DSS-induced colitis. By contrast, 1,25(OH)2D3 supplementation ameliorated DSS-induced colon damage, oxidative stress and inflammation. HMGCS2 was up-regulated after 1,25(OH)2D3 supplementation both in vivo and in vitro. Transfection with HMGCS2-siRNA inhibited antioxidant and anti-inflammatory effects of 1,25(OH)2D3 in DSS-treated HT-29 cells. CONCLUSION: 1,25(OH)2D3 supplementation up-regulates HMGCS2, which is responsible for 1,25(OH)2D3-mediated protection against oxidative stress and inflammation in DSS-induced colitis. These findings provide a potential therapeutic strategy for alleviating colitis-associated oxidative stress and inflammation.
Assuntos
Colite , Humanos , Camundongos , Animais , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/prevenção & controle , Inflamação/tratamento farmacológico , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Colecalciferol/uso terapêutico , Estresse Oxidativo , Sulfato de Dextrana/farmacologia , Camundongos Endogâmicos C57BL , Hidroximetilglutaril-CoA SintaseRESUMO
Tropomyosin (TM) is a major shellfish allergen and a minor fish allergen. Different digestion profiles affect potential allergen anaphylaxis of protein. In this study, released peptides of fish-TM, shrimp-TM, and clam-TM by in vitro digestion of simulated gastric fluid (SGF), simulated intestinal fluid (SIF), and gastrointestinal (GI) were analyzed using sequential windowed acquisition of all theoretical fragment ion mass spectra (SWATH-MS) based proteomics. Results showed that digestion products of shrimp-TM yielded a lot of peptides matched T/B cell epitopes while core regions matched epitopes were distributed along the entire chain. Pepsin or trypsin-based digestion products of shrimp-TM presented many more peptides matched T/B cell epitopes compared with those of fish-TM and clam-TM. Besides, a differentiating peptide of VEKDKALSNAEGEVAAL (72-88) overlapped T/B cell epitopes could be used as a candidate peptide marker to identify tropomyosin allergen. These findings would supply new insight into the different allergenicity of tropomyosin.
Assuntos
Bivalves , Hipersensibilidade Alimentar , Penaeidae , Perciformes , Animais , Tropomiosina/metabolismo , Mapeamento de Epitopos , Epitopos de Linfócito B/metabolismo , Imunoglobulina E/metabolismo , Proteômica , Penaeidae/metabolismo , Alérgenos/metabolismo , Bivalves/genética , Bivalves/metabolismo , Perciformes/metabolismo , Peptídeos/metabolismo , DigestãoRESUMO
Polycystic ovary syndrome (PCOS) is a disease in which endocrine metabolic abnormalities coexist with reproductive system abnormalities, with the main clinical manifestations including abnormal menstruation, hirsutism, acne, infertility, and obesity, and it is also a high risk for the development of many pregnancy complications, gynecological malignancies and other diseases. Therefore, timely intervention to prevent the progression of PCOS is of great significance for improving the quality of life of most female patients. Insulin resistance (IR) is one of the most common endocrine disorders in PCOS patients, with approximately 75% of PCOS patients experiencing varying degrees of IR. It is now believed that it is mainly related to the PI3K signaling pathway. The role of autophagy and apoptosis of ovarian granulosa cells (GCs) in the pathogenesis of PCOS has also been gradually verified in recent years. Coincidentally, it also seems to be associated with the PI3K signaling pathway. Our aim is to review these relevant studies, to explore the association between the IR, cellular autophagy and apoptosis in PCOS patients and the PI3K pathway. We summarize some of the drug studies that have improved PCOS as well. We have also found that proteomics holds great promise in exploring the pathogenesis of PCOS, and we have published our views on this.