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The development of formaldehyde (HCHO) gas sensors with high sensitivity, good selectivity, and fast response at room temperature is an important research topic. The resonant microcantilever, with high sensitivity, easy batch manufacturing, and integration, generates sensing signals based on the relationship between the frequency and the mass addition of the adsorbed molecules and shows good application potential in HCHO detection. Herein, we report two species of MoS2 nanosheets (NSs) with 1T and 2H phases as sensitive materials to construct high-performance HCHO resonant cantilever sensors. The 2H-MoS2 gas sensors show better sensitivity toward HCHO compared to the 1T-MoS2 gas sensor. Specifically, the 2H-MoS2 sensor displayed a high sensitivity (Hz) of 13.6-1 ppm HCHO at room temperature, with high selectivity, low limit of detection (10 ppb), and good humidity resistance. The effect of phase structures on the sensing performance was studied by in situ characterizations, thermodynamic analysis, and density functional theory calculations. The good sensing ability could be attributed to the abundant active sites induced by the surface defects, suitable adsorption strength, and the outstanding thermodynamic performance of the 2H-MoS2. The combination of two-dimensional (2D) nanosheet and microcantilever sensors provides a new direction for developing a high-performance room-temperature gas sensor in the future.
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Construction of convenient systems for isomer discrimination is of great importance for medical and life sciences. Here, we report a simple and effective chiral sensing device based on a highly ordered self-assembly framework. Cu2+-modified ß-cyclodextrin (Cu-ß-CD) was self-assembled to the ammonia-ethanol cotreated chitosan (ae-CS), and the highly ordered framework was gradually formed during the "re-growth" process of the shrinked ae-CS films. Tryptophan (Trp) isomers were well discriminated with the highly ordered framework by electrochemical approach. This study is the first example showing how an ordered structure influences chiral recognition.
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OBJECTIVE: To investigate differential diagnosis between intrahepatic cholangiocarcinoma (ICC) and arterial phase enhanced hepatic inflammatory lesions in patients without liver cirrhosis using contrast-enhanced ultrasound (CEUS). METHODS: ICC and hepatic inflammatory lesions cases with CEUS and pathological diagnosis between Sep 2013 and Oct 2016 were investigated retrospectively. Imaging features of conventional ultrasound and CEUS were analyzed. The parameters of time intensity curve (TIC), including the arrival time, peak intensity (PI) in the lesions, the starting time for washout, and the intensity difference at 3 min (ΔI3) after contrast agent infection between the lesion and the liver parenchyma, were compared between ICC and hepatic inflammatory lesions. RESULTS: Twenty-five ICC and fifteen inflammatory patients were included in this study. Seventeen ICC (68.0%) and two inflammatory cases (13.3%) showed bile duct dilatation on conventional ultrasound. Using CEUS, three ICC cases (12.0%) were misdiagnosed as inflammatory lesions and three inflammatory lesions (20.0%) as ICC; two ICC (8.0%) and one inflammatory case (6.7%) could not be made definite diagnosis. Washout started at 34.5±3.5 s and 61.5±12.9 s for ICC and inflammatory lesions respectively (P<0.001). The intensity difference between lesion and liver parenchyma at 3 min after contrast agent injection was 10.8±3.1 dB in ICC and 4.2±2.3 dB in inflammatory group (P<0.001). The sensitivity and specificity differentiating ICC and inflammatory lesions were 76% and 87% if the cut-off value of the intensity difference was 7.7 dB. CONCLUSIONS: Combined with TIC analysis, and particularly with the characteristic of the early-starting and obvious washout in ICC, CEUS can be useful in differential diagnosis between hepatic inflammatory lesions and ICC.
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Objective: To study the inhibitory effect of 3' untranslated region (UTR)-targeted artificial microRNA (amiRNA) against porcine reproductive and respiratory syndrome virus (PRRSV) replication in porcine alveolar macrophages (PAM). Methods: Recombinant adenovirus (rAd) expressing the 3' UTR-targeted or control amiRNA and green fluorescent protein (GFP) reporter gene were generated by transfecting AAV-293 cells with the transfer vector. The expression of sequence-specific amiRNA was detected by quantitative RT-PCR. The anti-PRRSV effect of amiRNA was detected by quantitative RT-PCR, Western blotting and viral titration assay. Results: Two rAds, namely rAd-amiR3UTR-GFP and rAd-amiRcon-GFP, were generated. Both primary PAM and 3D4/163 cells could be transduced by rAd with different transduction efficiencies. The amiR3UTR was expressed in dose-and timedependent manners in rAd-transduced PAM cells. The amiR3UTR, but not amiRcon, had significant and stable inhibitory effects against replication of three different PRRSV strains in a dose-dependent manner. Conclusion: The rAd-delivered amiR3UTR had strong anti-PRRSV effect against different PRRSV strains and rAd-amiR3UTR-GFP could be explored further as the alternative strategy against PRRS.
Subject(s)
Macrophages, Alveolar/virology , MicroRNAs/genetics , Porcine Reproductive and Respiratory Syndrome/virology , Porcine respiratory and reproductive syndrome virus/genetics , 3' Untranslated Regions , Animals , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , MicroRNAs/metabolism , Porcine respiratory and reproductive syndrome virus/physiology , RNA, Viral/genetics , RNA, Viral/metabolism , Swine , Transfection , Virus ReplicationABSTRACT
Inspired by the double helix structure of DNA, a simple enantioselective system based on chitosan (CS) was employed for electrochemical enantiorecognition of tryptophan (Trp) isomers. The recognition mechanism was proposed from the supramolecular point of view, which was further verified by the recognition of Trp isomers with sulfonated CS (SCS). The SCS-based chiral system presented the ability of indicating the percentage of d-Trp in racemic mixture, extending future applications of the electrochemical chiral system based on natural polysaccharides.
Subject(s)
Biomimetics/methods , Chitosan/chemistry , DNA/chemistry , Electroplating , Sulfonic Acids/chemistry , Tryptophan/chemistry , Carbon/chemistry , Electrochemistry , Electrodes , Models, Molecular , Nucleic Acid Conformation , Stereoisomerism , TemperatureABSTRACT
Rapid and accurate detection of acute myocardial infarction can improve patients' chances of survival. Cardiac troponin I (cTn I) is an important diagnostic biomarker for acute myocardial infarction. However, current immunoassays are insufficient to accurately measure cTn I, as they have limited detection sensitivity and are time-consuming. Surface-enhanced Raman scattering (SERS) is a brilliant fingerprints diagnostic technique characterised by ultrasensitivity, fast response, and qualitative and quantitative analysis capabilities. In this study, reporter molecules (4-Mercaptobenzoic acid, 4-MBA) embedded Au@Ag core-shell nanospheres as SERS nanotags were prepared for the detection of cTn I. As the Raman reporters were embedded between the core and the shell, they could be protected from the external environment and nanoparticle aggregation. Excellent SERS performances were obtained due to the enhanced local electromagnetic field in the gap of core and shell metals. In a standard phosphate buffered saline (PBS) environment, the limit of detection for cTn I was 0.0086 ng mL-1 (8.6 ppt) with a good linear relationship. The excellent Raman detection performance was attributed to the localized surface plasmon resonance effect and strong electromagnetic field enhancement effect produced by the gap between the Au core and the Ag shell. The SERS nanotags we prepared were facile to synthesize, and the analysis procedure could be completed quickly (15 min), which made the detection of cTn I faster. Therefore, the proposed SERS nanotags have significant potential to be a faster and more accurate tool for acute myocardial infarction diagnostics.
Subject(s)
Metal Nanoparticles , Myocardial Infarction , Nanospheres , Humans , Troponin I , Gold , Silver , Spectrum Analysis, Raman/methods , Myocardial Infarction/diagnosisABSTRACT
OBJECTIVE: Although several studies have identified an association between the rs4784227-cancer susceptibility candidate gene 16 (CASC16) polymorphism and breast cancer, the results remain inconclusive. Therefore, we conducted a meta-analysis to assess the relationship between the rs4784227-CASC16 polymorphism and breast cancer risk. METHODS: Studies were searched in the PubMed, Web of Science, Embase, Google Scholar, and Cochran Library databases until June 10, 2021, to identify all potential literature on rs4784227-CASC16 polymorphism and breast cancer risk association. Fixed-effect or random-effect models were used to calculate odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs). Subgroup analyses, publication bias, and sensitivity analyses were also conducted. RESULTS: Seventeen eligible studies involving 34,719 subjects (18,445 cases and 16,274 healthy controls) from 7 articles were included in the current meta-analysis. The pooled ORs regarding the association between the rs4784227-CASC16 polymorphism and breast cancer risk were statistically significant [T vs C: OR = 1.244, 95% CI = 1.202-1.287; TT vs CT + CC: OR = 1.407, 95% CI = 1.296-1.528; CC vs CT + TT: OR = 0.777, 95% CI = 0.745-0.811; TT vs CC: OR = 1.544, 95% CI = 1.419-1.681; CT vs CC: OR = 1.244, 95% CI = 1.189-1.301]. On subgroup analysis, the rs4784227-CASC16 T/C gene has a certain correlation with breast cancer susceptibility in Asian and North American populations, but no significant risk in the Australian population. CONCLUSION: Our pooled analysis showed a significant association between the rs4784227- (T) allele and breast cancer susceptibility in Asian and North American populations, and intervention with this mutation might be a new therapeutic strategy for breast cancer. However, large-scale and well-designed studies are needed in different populations to further evaluate the role of the rs4784227-CASC16 polymorphism in breast cancer.
Subject(s)
Breast Neoplasms , Genetic Predisposition to Disease , Neoplasm Proteins , Asian People , Australia , Breast Neoplasms/genetics , Female , Humans , Neoplasm Proteins/genetics , North America , Polymorphism, Single NucleotideABSTRACT
Rapid and accurate detection of myocardial infarction (MI) can boost the patient's chance of survival. Surface enhanced Raman scattering (SERS) is an outstanding diagnostic technique because of its strong light stability, high resolution, and qualitative and quantitative analysis based on the characteristic fingerprint. However, its reliability, stability and specificity remain to be improved, especially in the quantitative analysis of serum samples. In this study, we developed in situ silver nanoparticles (Ag NPs) on the surface of polydopamine (PDA) as a SERS substrate and found that PDA could act as a reducing agent to support the nucleation and growth of Ag NPs and control the distance and aggregation of Ag NPs to stabilize the Raman signal. In a standard phosphate buffered saline (PBS) environment, PDA@Ag could reach a low detection limit of 0.01 ng mL-1 cardiac troponin I (cTn I) with a good linear relationship. At the same time, the PDA@Ag substrate also possessed excellent stability, specificity and biocompatibility for cTn I detection. In addition, we verified the application potentiality of PDA@Ag in real serum samples and found that the performance of SERS was almost the same as that in PBS. This excellent detection performance of PDA@Ag could be attributed to both the enhanced electromagnetic field and the increased Raman cross-section, dominated by the gap distance between Ag NPs, reaction force between the antigen and the antibody and excellent biocompatibility and reducibility of PDA. In conclusion, this work may provide a new perspective for the in situ synthesis and growth of a uniform SERS substrate on the carrier to achieve the stability and specificity of SERS-based biological detection of MI.
Subject(s)
Metal Nanoparticles , Myocardial Infarction , Humans , Indoles , Myocardial Infarction/diagnosis , Polymers , Reproducibility of Results , Silver , Spectrum Analysis, Raman/methods , Troponin IABSTRACT
Two-dimensional (2D) ZnSnO3 is a promising candidate for future gas sensors due to its high chemical response and excellent electronic properties. However, the preparation of 2D ZnSnO3 nanosheets by utilizing soluble inorganic salts and nonorganic solvents remains a challenge. In this work, 2D ZnSnO3 was synthesized via a facile graphene oxide (GO)-assisted co-precipitation method, in which inorganic salts in the aqueous phase replaced metal organic salts in a non-aqueous system. Meanwhile, a "dissolution and recrystallization" mechanism was proposed to explain the transformation from 3D nanocubes to 2D nanosheets. In comparison, the 2D ZnSnO3 nanosheets showed a higher response to formaldehyde (HCHO) at low operating temperature (100 °C). The response (Ra/Rg) of the 2D ZnSnO3 sensor to 10 ppm HCHO was as high as 57, which was approximately 5 times the response of the ZnSnO3 nanocubes sensor. However, the ZnSnO3 nanocubes sensor showed better gas sensing performance to ethanol at high temperature (200 °C). Different gas-sensitive properties were attributed to the different gas diffusion and adsorption processes caused by the morphology and nanostructure. Moreover, both sensors could detect either 0.1 ppm HCHO or ethanol at their optimum operating temperature. This work presents a relatively economical method to prepare 2D compound metal oxides, provides a novel "dissolution and recrystallization" mechanism for 2D multi-metal oxide preparation, and sheds light on the great potential of high-efficiency HCHO and/or ethanol gas sensors.
Subject(s)
Nanostructures , Formaldehyde , Metals , Oxides , TemperatureABSTRACT
BACKGROUND: Trastuzumab is a generally safe agent prescribed in the systemic treatment of breast cancer. Tinnitus is not a currently known adverse event related to trastuzumab. Here, we describe a rare case of severe tinnitus and a migraine headache induced by trastuzumab used for adjuvant therapy. CASE SUMMARY: A 37-year-old woman was diagnosed with hormone receptor-positive and human epidermal growth factor receptor 2-positive breast cancer. After surgery, she was treated with four cycles of epirubicin and cyclophosphamide; she then received docetaxel and a loading dose of trastuzumab plus pertuzumab. Less than half an hour after trastuzumab infusion, the patient complained of severe tinnitus and left-sided migraine headache. Trastuzumab monotherapy was discontinued immediately, and symptoms disappeared after 10 min. Trastuzumab was readministered, and severe tinnitus and migraine headache recurred. Trastuzumab was stopped, and severe tinnitus diminished after 10 min. Pertuzumab and docetaxel therapy was then administered, and no adverse events were observed. Subsequent infusions of trastuzumab every three weeks did not show the same symptoms. CONCLUSION: Although trastuzumab is well-tolerated in most patients, we should pay attention to the risk of severe tinnitus and migraine.
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OBJECTIVE: To explore the impact of humanized nursing care on negative emotions and quality of life (QOL) of patients with mental disorders. METHODS: Among the 112 patients with mental disorders treated in our hospital from July, 2017 to November, 2019, 53 who received routine care served as the control group and 59 who received humanized nursing care were in the observation group. Changes in self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores were compared for mental status assessment, and the generic quality of life inventory-74 (GQOL-74) was used to evaluate their QOL. Besides, patient satisfaction, scores of activity of daily living (ADL) scale and mini-mental state examination (MMSE) were compared after intervention. RESULTS: After intervention, patients in the observation group had higher scores in the self-rating anxiety scale, self-rating depression scale, the generic quality of life inventory-74, and mini-mental state examination, and lower scores in the activities of daily living scale; they also presented a higher overall satisfaction than those in control group. CONCLUSION: Humanized nursing care contributes to the relief of negative emotions and the enhancement of quality of life of patients with mental disorders, which is worth popularizing in clinical nursing services.
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Hydrogen (H2) molecules are easy to leak during production, storage, transportation and usage. Because of their flammability and explosive nature, quick and reliable dectection of H2 molecule is of great significance. Herein, an excellent H2 gas sensor has been realized based on Pd nanocrystal sensitized two-dimensional (2D) porous TiO2 (Pd/TiO2). The formation of 2D porous TiO2 with the removal of graphene oxide template has been monitored by an in-situ transmission electron microscope. It is found that the size of the GO template can be almost completely replicated by 2D TiO2. The Pd/TiO2 sensor exhibited an instantaneous response and a satisfactory low detection limit for H2 detection. These excellent gas-sensing performances (good selectivity, unique linearity response and high stability) can be attributed to the unique 2D porous structure and the synergistic effect between oxidized Pd and TiO2, including the unique adsorption properties of O2 or/and H2 on Pd/TiO2, the reaction between PdO and H2 gas, and the regulated depletion layer arising from p-type PdO to n-type TiO2. This work demonstrates a rational design and synthesis of highly efficient H2 sensitive materials for energy and manufacturing security.
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OBJECTIVE: Macrophage apoptosis plays important roles in atherosclerosis. Bcl-2 is a key cell survival molecule, but its role in macrophage apoptosis in atherosclerosis is not known. The goal herein was to determine the effect of macrophage-targeted deletion of Bcl-2 on macrophage apoptosis in atherosclerotic lesions of Apoe(-/-) mice. METHODS AND RESULTS: Bcl2(flox)-LysMCre mice were created as a model of macrophage Bcl-2 deficiency. Macrophages from these mice were more susceptible to apoptosis than those from control Bcl2(WT)-LysMCre mice. The mice were bred onto the Apoe(-/-) background and fed a Western-type diet for 4 or 10 weeks. Apoptotic cells were equally very rare in the lesions of both groups of the 4-week-diet mice, and there was no difference in lesion area. However, Bcl2(flox)-LysMCre;Apoe(-/-) plaques from the 10-week-diet protocol had a 40% to 45% increase in apoptotic cells and, in female mice, a approximately 25% increase in plaque necrosis (P<0.05) compared with Bcl2(WT)-LysMCre lesions. CONCLUSIONS: Macrophage Bcl-2 plays a protective role against macrophage apoptosis specifically in advanced atherosclerotic lesions of Apoe(-/-) mice.
Subject(s)
Apolipoproteins E/deficiency , Apoptosis , Atherosclerosis/pathology , Macrophages, Peritoneal/pathology , Proto-Oncogene Proteins/deficiency , Animals , Apolipoproteins E/genetics , Atherosclerosis/etiology , Atherosclerosis/metabolism , Cells, Cultured , Diet, Atherogenic , Disease Models, Animal , Female , Macrophages, Peritoneal/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Necrosis , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-bcl-2ABSTRACT
As a foodborne bacterium, Listeria monocytogenes (LM) can cause serious diseases and even death to weak people. 3-Hydroxy-2-butanone (3H-2B) has been proven to be a biomarker for exhalation of LM. Detection of 3H-2B is a fast and effective method for determining whether the food is infected. Herein, we present an excellent 3H-2B gas sensor based on bimetallic PtCu nanocrystal modified WO3 hollow spheres. The structure and morphology of the PtCu/WO3 were characterized, and their gas sensitivities were measured by a static testing method. The results showed that the sensor response of WO3 hollow spheres was enhanced by about 15 times after modification with bimetallic PtCu nanocrystal. The maximum response value of the PtCu/WO3 sensor to 10 ppm 3H-2B is as high as 221.2 at 110 °C. In addition, the PtCu/WO3 sensor also exhibited good selectivity to 3H-2B, fast response/recovery time (9 s/28 s), and low limit of detection (LOD < 0.5 ppm). Furthermore, the sensitivity mechanism was studied by monitoring the reaction products by gas chromatography-mass spectrometry. The excellent gas-sensing performance can be attributed to the synergy between PtCu and WO3, including the unique spillover effect of O2 on PtCu nanoparticles, the regulated depletion layer by p-type CuxO to n-type WO3, and their selective catalysis to 3H-2B. Hence, this work offers the rational design and synthesis of highly efficient sensitive materials for the detection of LM for food security.
Subject(s)
Acetoin/analysis , Metals, Heavy/chemistry , Nanoparticles/chemistry , Biomarkers/analysis , Limit of Detection , Listeria monocytogenes/metabolism , Nanocomposites/chemistry , Oxygen/chemistryABSTRACT
AIMS: The heterodimerization of angiotensin II receptors (AT1R and AT2R) with adiponectin receptor AdipoR1 and AdipoR2 may instigate high glucose (HG)-induced renal tubulointerstitial injury. This study examined the effect of telmisartan on diabetic nephropathy (DN) and its underlying mechanism. MAIN METHODS: Diabetes was induced in rats through a single intraperitoneal injection of streptozotocin. Diabetic rats treated with or without the intravenous injection of AdipoR1 siRNA were intragastrically administered with 5â¯mg/kg/d telmisartan or a vehicle for 12â¯weeks. The rat proximal tubular epithelial cell line NRK-52E was treated with HG (30â¯mmol/L) with or without telmisartan (10⯵M) for 48â¯h. KEY FINDINGS: In streptozotocin-induced diabetic rats, telmisartan treatment could decrease the inulin clearance rate, restore the glomerular surface area and mesangial area, alleviate renal fibrosis, and decrease urinary albumin excretion. Furthermore, diabetic rats exhibited increased AT1R-AdipoR1 heterodimers in the renal tubular compartment, which could be attenuated by telmisartan treatment, accompanied by a decrease in the expression level of cytokines MIP-1α, ICAM-1 and MCP-1. In vitro, HG promoted the dimerization formation of AT1R-AdipoR1 in cultured NRK-52E cells, but this effect was not found in NRK-52E cells transfected with the AdipoR1-G269E,G273E mutant. Telmisartan could inhibit HG-induced AT1R-AdipoR1 dimerization, downregulate the expression levels of inflammatory cytokines, and alleviate cell apoptosis in NRK-52E cells. Furthermore, AdipoR1 knockdown could abate the renoprotective benefits of telmisartan. SIGNIFICANCE: The heterodimerization of AT1R-AdipoR1 probably contributes to the renal injury of DN, and provides an additional mechanistic insight into how telmisartan prevents the development and progression of DN.
Subject(s)
Diabetic Nephropathies/drug therapy , Diabetic Nephropathies/metabolism , Telmisartan/metabolism , Animals , Cell Line , Diabetes Mellitus, Experimental , Dimerization , Disease Models, Animal , Fibrosis , Kidney/physiopathology , Male , RNA, Small Interfering , Rats , Rats, Wistar , Receptor, Angiotensin, Type 1/drug effects , Receptors, Adiponectin/drug effects , Streptozocin/pharmacology , Telmisartan/pharmacologyABSTRACT
OBJECTIVE: Numerous studies have evaluated the association between the rs2187668 polymorphism in the human leucocyte antigen (HLA) complex class II HLA-DQ a-chain 1 (HLA-DQA1) gene and idiopathic membranous nephropathy (iMN) risk, which provided new insight into potential new targets for the treatment of iMN. However, this relationship remains inconclusive. Our aim was to evaluate the relationship between this polymorphism and iMN susceptibility by performing a meta-analysis. METHODS: Articles were identified in the PubMed, Google Scholar, EMBASE, Cochran Library databases. Meta-analyses were performed for rs2187668 allele frequency, genotypes, and the association with iMN susceptibility. Subgroup analyses, publication bias and sensitivity analyses were also conducted. RESULTS: 11 eligible studies (3209 cases and 7358 controls) from 7 articles were included. Statistical analyses were carried out using Stata 12.0, combining data from all the relevant studies. The pooled odds ratios (ORs) regarding the association between the HLA-DQA1 rs2187668 polymorphism and iMN risk were statistically significant [A vs G: ORâ=â3.34, 95% confidence interval (CI)â=â2.70-4.13; AA vs GAâ+âGG: ORâ=â8.69, 95% CIâ=â6.64-11.36; GG vs GAâ+âAA: ORâ=â0.25, 95% CIâ=â0.19-0.33;AA vs GG: ORâ=â12.61, 95% CIâ=â8.02-19.81; GA vs GG: ORâ=â3.45, 95% CIâ=â2.79-4.25]. CONCLUSIONS: Our pooled analysis showed a significant association between rs2187668-(A) allele and iMN susceptibility, and the intervention of this mutation might bring new therapeutic strategy for iMN. However, further studies should be performed to confirm this finding.
Subject(s)
Glomerulonephritis, Membranous/genetics , HLA-DQ alpha-Chains/genetics , Genetic Predisposition to Disease , Genotype , Humans , Polymorphism, Genetic , Risk FactorsABSTRACT
Oxidative and inflammatory damage have been suggested to play important roles in the pathogenesis of diabetic nephropathy (DN). Chlorogenic acid (CGA) is one of the most abundant polyphenols and has known immunoprotective, antioxidant and anti-inflammatory properties. In the present study, animal experiments were designed to examine the protective effects of CGA in DN, and cellular experiments were designed to explore the underlying mechanisms. CGA significantly attenuated diabetic renal damage based on histological pathology and molecular biological methods. Pre-treatment with CGA increased the nuclear translocation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1) and reduced the phosphorylation of IĸB and subsequent nuclear translocation of nuclear factor kappa beta (NF-ĸB). Nrf2 small interfering RNA (siRNA) and the HO-1 inhibitor zinc protoporphyrin (ZnPPIX) significantly increased the nuclear translocation of NF-ĸB and the production of pro-inflammatory cytokines in HBZY-1 cells. The NF-ĸB inhibitor pyrrolidine dithiocarbamate (PDTC) increased Nrf2 nuclear translocation and HO-1 expression and antioxidant levels. Thus, these results suggest that CGA is a potential therapeutic agent in the treatment of DN due to its antioxidant and anti-inflammatory effects which are mediated via the modulation of the Nrf2/HO-1 and NF-ĸB pathways. Moreover, CGA-induced the activation of Nrf2/HO-1,which interacts with the inhibition of NF-ĸB, as each begets and amplifies the other.
Subject(s)
Chlorogenic Acid/therapeutic use , Diabetic Nephropathies/drug therapy , Inflammation/drug therapy , Kidney/pathology , NF-E2-Related Factor 2/metabolism , Animals , Cell Line , Heme Oxygenase (Decyclizing)/metabolism , Humans , Kidney/drug effects , Male , NF-E2-Related Factor 2/genetics , NF-kappa B/metabolism , Oxidative Stress/drug effects , Rats , Rats, Sprague-Dawley , Signal TransductionABSTRACT
Inflammation plays a pivotal role in the development and progression of diabetic nephropathy (DN). Oridonin (Ori), a component isolated from Rabdosia rubescens, possesses remarkable anti-inflammatory, immunoregulatory and antitumor properties. However, the renoprotective effects of Ori and the underlying molecular mechanisms have not been explored in DN. In this study, we aimed to investigate the protective effects and potential mechanisms responsible for the anti-inflammatory effects of Ori in diabetes-induced renal injury in vivo and in vitro. Our results showed that Ori significantly attenuated diabetes-induced renal injury and markedly decreased urinary protein excretion levels, serum creatinine concentrations and blood urea nitrogen concentrations in rats. Ori also significantly alleviated infiltration of inflammatory cells (cluster of differentiation (CD)68) in kidney tissues and reduced the levels of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1ß and monocyte chemotactic protein 1 (MCP-1), both in vivo and in vitro. TLR4 is a principal mediator of innate immune and inflammatory responses and participates in the development of DN. Our molecular studies indicated that Ori administration significantly down-regulated TLR4 overexpression in DN. Additional studies were conducted to investigate the effect of Ori on the p38-mitogen-activated protein kinase (p38-MAPK) and nuclear factor (NF)-κB pathways. The results showed that Ori inhibited IκBα, p65, and p38 phosphorylation, as well as NF-κB DNA-binding activity. In conclusion, these results demonstrated that Ori exerts protective effects in diabetes-induced renal injury in vivo and in vitro. These effects may be ascribed to its anti-inflammatory and modulatory effects on the TLR4/p38-MAPK and TLR4/NF-κB signaling pathways.
Subject(s)
Anti-Inflammatory Agents/therapeutic use , Diabetes Mellitus, Experimental/drug therapy , Diabetic Nephropathies/drug therapy , Diterpenes, Kaurane/therapeutic use , Kidney/drug effects , Animals , Cells, Cultured , Creatinine/blood , Cytokines/metabolism , Disease Models, Animal , Humans , Inflammation Mediators/metabolism , Isodon/immunology , Kidney/metabolism , Kidney/pathology , Male , NF-kappa B/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction , Toll-Like Receptor 4/metabolism , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
AIM: We have previously proved that oxidized low-density lipoprotein (oxLDL), a proatherogenic lipoprotein, plays a pivotal role in the development of atherosclerotic calcification (AC). The present study was performed to investigate whether tanshinone II A (TS II A), an anti-oxidant which has been shown to inhibit in vitro oxidation of LDL, has the effects to inhibit AC in rat model and by which, if any, mechanisms. METHODS: Rat AC model was induced by excessive vitamin D(2) (VD) and high cholesterol diet (HCD), which was proven to be successful histopathologically and biochemically. RESULTS: Administration of AC rats with TS II A (35, 70 mg/kg) dose-dependently attenuated the AC pathological changes, meanwhile reduced the vessel contents of lipid and calcium. However, TS II A had no effects on serum levels of lipids, calcium and 25-OH VD. Further studies revealed that TS II A decreased serum concentration of oxLDL, reduced the superoxide anion production and malondialdehyde (MDA) in vessel. In addition, TS II A increased vessel Cu/Zn SOD activity, upregulated vessel mRNA and protein expression of Cu/Zn SOD. CONCLUSION: The results suggested that TS II A significantly attenuated the AC in rat model, which might be attributed to its inhibition of oxLDL production independent of the serum levels of lipids, calcium and 25-OH VD, and that increasing of Cu/Zn SOD activity as well as mRNA and protein expression by TS II A might protect LDL against oxidation induced by superoxide anion in vessel.