Regulatory effect of caveolin-1 in liver diseases / 临床肝胆病杂志

Caveolin-1 （CAV1） is a structural protein of caveolae on the plasma membrane and is an important regulatory factor for liver function. CAV1 regulates hepatic lipid deposition， lipid and glucose metabolism， mitochondrial function， and hepatocyte proliferation through various molecular pathways. Therefore， CAV1 plays a crucial role in maintaining liver physiology during the metabolic regulatory processes such as hepatic steatosis and hepatocyte proliferation. Furthermore， CAV1 is also involved in the development and progression of different types of liver injury， hepatitis， and liver cirrhosis. This article reviews the role of CAV1 in liver-related diseases and its mechanism in the regulation of liver macrophages， so as to provide a theoretical basis for targeting CAV1 in the treatment of liver-related diseases.

Caveolin-1 mediated fluid shear stress regulates proliferation and apoptosis of MC3T3-E1 osteoblasts / 中国组织工程研究

BACKGROUND:Fluid shear stress plays an important role in osteoblast proliferation and apoptosis.However,whether Caveolin-1 is involved in the process of fluid shear stress-induced proliferation and apoptosis in osteoblasts is unknown. OBJECTIVE:To explore the role of Caveolin-1 in fluid shear stress-regulated osteoblast proliferation and apoptosis. METHODS:The MC3T3-E1 osteoblasts in good growth status were selected and loaded with fluid shear stress at an intensity of 1.2 Pa for different times(0,30,60,90 minutes).The expression of Caveolin-1 protein was observed and conditions with a time of 60 minutes were screened for the experiment.MC3T3-E1 cells were divided into control group,fluid shear stress group,fluid shear stress+pcDNA 3.1 group(control),fluid shear stress+pcDNA Cav-1 group(plasmid overexpression),and intervened with fluid shear stress and overexpression of Cav-1,respectively.The expression of molecules related to proliferation and apoptosis in MC3T3-E1 cells was detected by qRT-PCR and western blot.In addition,the proliferative activity of MC3T3-E1 cells was detected by cell counting kit-8 and EdU assay;and cell apoptosis was detected by Hoechst 33258 and flow cytometry. RESULTS AND CONCLUSION:The expression of Caveolin-1 in MC3T3-E1 cells was significantly down-regulated after loading fluid shear stress,and the expression level was lowest after 60 minutes.Overexpression of Caveolin-1 attenuated the proliferation-promoting and apoptosis-suppressing effects of fluid shear stress in MC3T3-E1 cells.In conclusion,Caveolin-1 has a vital role in fluid shear stress-regulated osteoblast proliferation and apoptosis,which may offer a potential therapeutic strategy for osteoporosis.

Chemical characterization and effects of volatile oil of Alpinia zerumbet on the quality of collagen deposition and caveolin-1 expression in a muscular fibrosis murine model

Abstract This study evaluated the effect of the volatile oil of Alpinia zerumbet (VOAz) on caveolin-1 gene expression and muscular fibrosis. The rats were immobilized to induce fibrosis of the gastrocnemius muscle, and they were treated with VOAz. Collagen quality was assessed by histology and the expression of the caveolin-1 (CAV-1) gene was evaluated using qPCR. Histomorphological analysis indicated a significant reduction in the perimeter, width, and intensity of collagen in the treated groups, thus showing that the oil was effective in regulating the quality of collagen at the three concentrations. The results of expression levels suggested a decrease in the lesioned group and in two treatment groups (0.0115 µg/g and 0.009 µg/g). However, with the lowest concentration (0.0065 µg/g), no significant difference was observed, with levels similar to those found in healthy tissue. Therefore, the results showed that VOAz has the potential to be a non-invasive and low-cost alternative to aid in the treatment of muscular fibrosis.

Resumo Este estudo avaliou o efeito do óleo volátil de Alpinia zerumbet (OVAz) na expressão do gene da caveolina-1 e na fibrose muscular. Os ratos foram imobilizados para induzir a fibrose do músculo gastrocnêmio, e foram tratados com OVAz. A qualidade do colágeno foi avaliada com histologia e à expressão do gene caveolina-1 (CAV-1) foi avaliada usando qPCR. A análise histomorfológica indicou uma redução significativa no perímetro, largura e intensidade do colágeno nos grupos tratados. Os resultados dos níveis de expressão sugeriram diminuição nos grupos de lesão e em dois grupos de tratamento (0,0115 µg/g e 0,009 µg/g). No entanto, com a menor concentração (0,0065 µg/g), não foi observada diferença significativa, apresentando níveis semelhantes aos encontrados em tecido saudável. O uso do OVAz foi eficaz para reverter as alterações do colágeno causadas pela fibrose, e sua menor concentração apresentou uma possível tendência de aumento na expressão do CAV-1. Portanto, os resultados mostraram que o OVAz tem potencial para ser uma alternativa não invasiva e de baixo custo para auxiliar no tratamento da fibrose muscular.

Chemical characterization and effects of volatile oil of Alpinia zerumbet on the quality of collagen deposition and caveolin-1 expression in a muscular fibrosis murine model / Caracterização química e efeitos do óleo volátil de Alpinia zerumbet na qualidade da deposição do colágeno e expressão da caveolina-1 em modelo murino de fibrose muscular

Abstract This study evaluated the effect of the volatile oil of Alpinia zerumbet (VOAz) on caveolin-1 gene expression and muscular fibrosis. The rats were immobilized to induce fibrosis of the gastrocnemius muscle, and they were treated with VOAz. Collagen quality was assessed by histology and the expression of the caveolin-1 (CAV-1) gene was evaluated using qPCR. Histomorphological analysis indicated a significant reduction in the perimeter, width, and intensity of collagen in the treated groups, thus showing that the oil was effective in regulating the quality of collagen at the three concentrations. The results of expression levels suggested a decrease in the lesioned group and in two treatment groups (0.0115 µg/g and 0.009 µg/g). However, with the lowest concentration (0.0065 µg/g), no significant difference was observed, with levels similar to those found in healthy tissue. Therefore, the results showed that VOAz has the potential to be a non-invasive and low-cost alternative to aid in the treatment of muscular fibrosis.

Resumo Este estudo avaliou o efeito do óleo volátil de Alpinia zerumbet (OVAz) na expressão do gene da caveolina-1 e na fibrose muscular. Os ratos foram imobilizados para induzir a fibrose do músculo gastrocnêmio, e foram tratados com OVAz. A qualidade do colágeno foi avaliada com histologia e à expressão do gene caveolina-1 (CAV-1) foi avaliada usando qPCR. A análise histomorfológica indicou uma redução significativa no perímetro, largura e intensidade do colágeno nos grupos tratados. Os resultados dos níveis de expressão sugeriram diminuição nos grupos de lesão e em dois grupos de tratamento (0,0115 µg/g e 0,009 µg/g). No entanto, com a menor concentração (0,0065 µg/g), não foi observada diferença significativa, apresentando níveis semelhantes aos encontrados em tecido saudável. O uso do OVAz foi eficaz para reverter as alterações do colágeno causadas pela fibrose, e sua menor concentração apresentou uma possível tendência de aumento na expressão do CAV-1. Portanto, os resultados mostraram que o OVAz tem potencial para ser uma alternativa não invasiva e de baixo custo para auxiliar no tratamento da fibrose muscular.

Changes of serum VILIP-1 and Cav-1 levels in cases with severe craniocerebral injury undergoing decompression and their effects on the prognosis of the disease / 临床外科杂志

Objective To explore the serum levels of VILIP-1 and Cav-1 in cases with severe craniocerebral injury undergoing decompression and their effects on the prognosis.Methods 108 patients with severe craniocerebral injury who were treated in our hospital from July 2019 to July 2022 were selected as the study group,and 120 healthy people who came to our hospital for physical examination were selected as the health group.All cases were followed up for 6 months,and were divided into good prognosis group(GOS=4-5 points,n=82)and poor prognosis group(GOS=1-3 points,n=26)according to GOS.The levels of serum VILIP-1 and Cav-1 were detected by ELISA.The diagnostic value of serum VILIP-1 and Cav-1 on the prognosis of patients was evaluated by the ROC curve.Multivariate logistic regression analysis was used to explore the prognostic factors of patients.Results The levels of serum VILIP-1 and Cav-1 in study group were higher than those in healthy group(P＜0.05).The levels of serum VILIP-1 and Cav-1 in case with poor prognosis were higher than those in cases with good prognosis(P＜0.05).The AUC(95％CI)of serum VILIP-1 and Cav-1 to predict the prognosis of patients was 0.848(0.797～0.899)and 0.817(0.766～0.868).The AUC(95％CI)of the combined detection was 0.905(0.854～0.956).The time from injury to admission,admission GCS score,history of diabetes,admission pupillary reaction,preoperative brain midline displacement and postoperative complications in good prognosis group were different from those in poor prognosis group(P＜0.05).Preoperative midline displacement≥5 mm(OR=2.467,95％CI:1.619～3.760),postoperative complications≥ 2(OR=2.321,95％CI:1.544～3.489),VILIP-1≥10.37 ng/ml(OR=3.367,95％CI:2.087～5.432),and Cav-1≥32.28 μg/L(OR=2.770,95％CI:1.786～4.298)were risk factors for prognosis in patients(P＜0.05).Conclusion Serum VILIP-1 and Cav-1 can be used as biological indicators to predict the prognosis of patients with severe brain injury after decompression,and the increase of serum VILIP-1 and Cav-1 levels are risk factors for prognosis.

Miriplatin-loaded liposome, as a novel mitophagy inducer, suppresses pancreatic cancer proliferation through blocking POLG and TFAM-mediated mtDNA replication

Pancreatic cancer is a more aggressive and refractory malignancy. Resistance and toxicity limit drug efficacy. Herein, we report a lower toxic and higher effective miriplatin (MPt)-loaded liposome, LMPt, exhibiting totally different anti-cancer mechanism from previously reported platinum agents. Both in gemcitabine (GEM)-resistant/sensitive (GEM-R/S) pancreatic cancer cells, LMPt exhibits prominent anti-cancer activity, led by faster cellular entry-induced larger accumulation of MPt. The level of caveolin-1 (Cav-1) determines entry rate and switch of entry pathways of LMPt, indicating a novel role of Cav-1 in nanoparticle entry. After endosome-lysosome processing, in unchanged metabolite, MPt is released and targets mitochondria to enhance binding of mitochondria protease LONP1 with POLG and TFAM, to degrade POLG and TFAM. Then, via PINK1-Parkin axis, mitophagy is induced by POLG and TFAM degradation-initiated mitochondrial DNA (mtDNA) replication blocking. Additionally, POLG and TFAM are identified as novel prognostic markers of pancreatic cancer, and mtDNA replication-induced mitophagy blocking mediates their pro-cancer activity. Our findings reveal that the target of this liposomal platinum agent is mitochondria but not DNA (target of most platinum agents), and totally distinct mechanism of MPt and other formulations of MPt. Self-assembly offers LMPt special efficacy and mechanisms. Prominent action and characteristic mechanism make LMPt a promising cancer candidate.

Role of caveolin-eNOS platform and mitochondrial ATP-sensitive potassium channel in abrogated cardioprotective effect of ischemic preconditioning in postmenopausal women

Abstract Caveolin, the protein of the caveolar membrane, interacts and binds with endothelial nitric oxide synthase (eNOS), forming a caveolin-eNOS complex leading to suppression of the eNOS activity. Caveolin, therefore, maintains eNOS in the inactivated state leading to reduced nitric oxide (NO) production. Ischemic preconditioning disrupts the caveolin-eNOS complex leading to activation of the eNOS and thus results in cardioprotection. During ischemic preconditioning, NO produces cardioprotection by the opening of the KATP channel, and the caveolin forms a suitable signalling platform facilitating the interaction of NO with the KATP channel. Estrogen deficiency has been reported to upregulate caveolin-1 expression. The article aims to review the various mechanisms that placed the women at the risk of coronary artery diseases after postmenopausal estrogen deficiency and their role in the cardioprotective effect of ischemic preconditioning.

Exploration and insights into the cellular internalization and intracellular fate of amphiphilic polymeric nanocarriers

The beneficial or deleterious effects of nanomedicines emerge from their complex interactions with intracellular pathways and their subcellular fate. Moreover, the dynamic nature of plasma membrane accounts for the movement of these nanocarriers within the cell towards different organelles thereby not only influencing their pharmacokinetic and pharmacodynamic properties but also bioavailability, therapeutic efficacy and toxicity. Therefore, an in-depth understanding of underlying parameters controlling nanocarrier endocytosis and intracellular fate is essential. In order to direct nanoparticles towards specific sub-cellular organelles the physicochemical attributes of nanocarriers can be manipulated. These include particle size, shape and surface charge/chemistry. Restricting the particle size of nanocarriers below 200 nm contributes to internalization

Synthesis, bioactivity evaluation of dibenzoyl methane halophenols and their interactions with CAV-1 / 药学学报

Caveolin-1 (CAV-1) is related to inflammation, oxidative damage, and immunity. In order to obtain a series of dibenzoylmethane halophenols with strong anti-inflammatory and antioxidant effects targeting CAV-1, twenty-nine target compounds were therefore synthesized by Baker-Ventaraman rearrangement and demethylation reaction, starting from the substituted benzoyl chloride and o-hydroxyacetophenone, and their interactions with CAV-1 were investigated by BLI technique. Their in vitro anti-inflammatory and antioxidant properties were also evaluated. The results showed that compounds A6, A17, A18, and A29 not only specifically bind to CAV-1, but also present strong anti-inflammatory and antioxidant effects. These results suggest that this class of compounds can affect the signaling pathways related to inflammation and oxidative stress by directly acting on CAV-1. In particular, these compounds exhibit the most significantly inhibitory effects on IL-1β and COX-2 release. IL-1β plays a key regulatory role in the development of arthritis. Therefore, it is worth expecting for the application of such compounds in the prevention and treatment of arthritis.

Low-intensity pulsed ultrasound ameliorates angiotensin II-induced cardiac fibrosis by alleviating inflammation via a caveolin-1-dependent pathway / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

OBJECTIVES@#Cardiac hypertrophy and fibrosis are major pathological manifestations observed in left ventricular remodeling induced by angiotensin II (AngII). Low-intensity pulsed ultrasound (LIPUS) has been reported to ameliorate cardiac dysfunction and myocardial fibrosis in myocardial infarction (MI) through mechano-transduction and its downstream pathways. In this study, we aimed to investigate whether LIPUS could exert a protective effect by ameliorating AngII-induced cardiac hypertrophy and fibrosis and if so, to further elucidate the underlying molecular mechanisms.@*METHODS@#We used AngII to mimic animal and cell culture models of cardiac hypertrophy and fibrosis. LIPUS irradiation was applied in vivo for 20 min every 2 d from one week before mini-pump implantation to four weeks after mini-pump implantation, and in vitro for 20 min on each of two occasions 6 h apart. Cardiac hypertrophy and fibrosis levels were then evaluated by echocardiographic, histopathological, and molecular biological methods.@*RESULTS@#Our results showed that LIPUS could ameliorate left ventricular remodeling in vivo and cardiac fibrosis in vitro by reducing AngII-induced release of inflammatory cytokines, but the protective effects on cardiac hypertrophy were limited in vitro. Given that LIPUS increased the expression of caveolin-1 in response to mechanical stimulation, we inhibited caveolin-1 activity with pyrazolopyrimidine 2 (pp2) in vivo and in vitro. LIPUS-induced downregulation of inflammation was reversed and the anti-fibrotic effects of LIPUS were absent.@*CONCLUSIONS@#These results indicated that LIPUS could ameliorate AngII-induced cardiac fibrosis by alleviating inflammation via a caveolin-1-dependent pathway, providing new insights for the development of novel therapeutic apparatus in clinical practice.

Upregulation of OGT by Caveolin-1 Promotes Mouse Hepatocellular Carcinoma Cells Migration and Invasion / 中国生物化学与分子生物学报

Caveolin-1 (Cav-1), a major structural protein of caveolae, is implicated in the vesicular uptake processes of transcytosis and cell signaling. However, its role in modulating protein glycosylation and tumor metastasis remains to be further elucidated. In the present study, it was shown that Cav-1 promotes the expression of O-GlcNAcylation and O-GlcNAc transferase (OGT), and triggers the invasion and metastasis of hepatocellular carcinoma (HCC) cells. The results of RT-qPCR, Western blot and dual lucif-erase reporter assay showed that Cav-1 negatively regulated the expression of transcription factor RUNX2 in HCC. Subsequently, this results in attenuate RUNX2-induced transcription of miR24. miR24 suppresses mouse HCC cells invasion and metastasis via directly targeting Ogt mRNA 3′UTR. This research provides evidence of Cav-1-mediated OGT expression and O-GlcNAc (O-linked N-acetylglucosamine) elevation. These data give insight into a novel mechanism of HCC occurrence and development.

Caveolin-1 promotes tumor cell proliferation and vasculogenic mimicry formation in human glioma

Vasculogenic mimicry (VM) plays an important role in human glioma progression and resistance to antiangiogenic therapy as a compensatory neovascularization mechanism in malignant tumors. Caveolin-1 (Cav-1) has been found to contribute to VM formation. However, it remains largely unknown whether Cav-1 expression correlates with VM in glioma. In this study, we examined CAV-1 expression levels and VM in human glioma cell lines and in 94 human gliomas with different grades of malignancy, and present Cox proportional hazards regression. The molecular role of Cav-1 in glioma cells was investigated using quantitative polymerase chain reaction (qRT-PCR) assays, western blotting, CCK-8 assays, and tubule formation assays. Cav-1 expression and VM formation were positively correlated with each other and both were closely associated with glioma development and progression as evidenced by the presence of cystic tumor, shortened survival time, and advanced-stage glioma in glioma patients with Cav-1 overexpression/increased VM formation. Cav-1 promoted U251 glioma cell proliferation and VM formation in a Matrigel-based 3D culture model. VM-associated factors including hypoxia-inducible factor 1α (HIF-1α) and p-Akt was significantly elevated by Cav-1 overexpression but suppressed by siCav-1 in U251 cells. Collectively, our study identified Cav-1 as an important regulator of glioma cell proliferation and VM formation, contributing to glioma development and progression.

Inhibitory effect of paeonol on aortic endothelial inflammation in atherosclerotic rats by up-regulation of caveolin-1 expression and suppression of NF-κB pathway / 中国中药杂志

To explore whether paeonol can play an anti-atherosclerotic role by regulating the expression of aortic caveolin-1 and affecting NF-κB pathway, so as to inhibit the inflammatory response of vascular endothelium in atherosclerotic rats. The atherosclerotic model of rats was induced by high-fat diet and vitamin D_2. The primary culture of vascular endothelial cells(VECs) was carried out by tissue block pre-digestion and adherent method. The injury model of VECs was induced by lipopolysaccharide(LPS), and filipin, a small concave protein inhibitor, was added for control. HE staining was used to observe pathological changes of aorta. TNF-α, IL-6 and VCAM-1 were detected by ELISA. Western blot assay was used to detect the protein expression levels of caveolin-1 and p65 in aorta and VECs. The results showed that as compared with model group, paeonol significantly reduced aortic plaque area and lesion degree in rats, decreased the level of serum TNF-α, IL-6 and VCAM-1 in the rats and enhanced the relative expression level of caveolin-1, decreased p65 expression conversely(P<0.05 or P<0.01). In vitro, as compared to model group, paeonol obviously improved cell morphology, decreased the secretion of TNF-α, IL-6 and VCAM-1 in VECs, increased caveolin-1 expression, and decreased p65 protein expression(P<0.05 or P<0.01). Furthermore, filipin could reverse the effect of paeonol on expression of inflammatory factors and proteins(P<0.05 or P<0.01). According to the results, it was found that paeonol could play the role of anti-atherosclerosis by up-regulating the expression of caveolin-1 and inhibiting the activation of NF-κB pathway to reduce vascular inflammation in atherosclerotic rats.

MicroRNA-124 mediates hepatocellular carcinoma malignancy by targeting caveolin-1 / 中国肿瘤临床

Objective: To explore the effect of microRNA-124 (miR-124)/caveolin-1 in the progression of hepatocellular carcinoma (HCC). Methods: The expression levels of miR-124 and caveolin-1 were evaluated in HCC tissues, adjacent tissues, and cell lines by qRT-PCR. A dual-luciferase reporter gene assay was used to confirm the relationship between microRNA-124 and caveolin-1. MicroRNA-124 mediated caveolin-1 levels, which was determined by qRT-PCR and Western blot analyses. CCK-8, colony formation, and transwell assays were used to evaluate the proliferation and invasion of HCC cells. Results: A low level of miR-124 together with a high level of caveolin-1 was found in HCC tissues and MHCC97H cells compared with control cells. Caveolin-1 was determined to be the target gene of miR-124, and alterations of miR-124 could modulate caveolin-1. Cells transfected with a miR-124 mimic in MHCC97H cells inhibited proliferation and invasion, whereas upregulation of caveolin-1 promoted proliferation and invasion. MHCC97L cells transfected with a miR-124 inhibitor showed increased proliferation and invasion, whereas cells transfected with siCaveolin-1 showed decreased proliferation and invasion. Patients with HCC with higher miR-124 and lower caveolin-1 levels lived longer than patients with lower miR-124 and higher caveolin-1 levels. Conclusions: MiR-124 mediated the proliferation and invasion of HCC by targeting caveolin-1.

Involvement of lipid microdomains in human endothelial cells infected by Streptococcus agalactiae type III belonging to the hypervirulent ST-17

BACKGROUND Streptococcus agalactiae capsular type III strains are a leading cause of invasive neonatal infections. Many pathogens have developed mechanisms to escape from host defense response using the host membrane microdomain machinery. Lipid rafts play an important role in a variety of cellular functions and the benefit provided by interaction with lipid rafts can vary from one pathogen to another. OBJECTIVES This study aims to evaluate the involvement of membrane microdomains during infection of human endothelial cell by S. agalactiae. METHODS The effects of cholesterol depletion and PI3K/AKT signaling pathway activation during S. agalactiae-human umbilical vein endothelial cells (HUVEC) interaction were analysed by pre-treatment with methyl-β-cyclodextrin (MβCD) or LY294002 inhibitors, immunofluorescence and immunoblot analysis. The involvement of lipid rafts was analysed by colocalisation of bacteria with flotillin-1 and caveolin-1 using fluorescence confocal microscopy. FINDINGS In this work, we demonstrated the importance of the integrity of lipid rafts microdomains and activation of PI3K/Akt pathway during invasion of S. agalactiae strain to HUVEC cells. Our results suggest the involvement of flotillin-1 and caveolin-1 during the invasion of S. agalactiae strain in HUVEC cells. CONCLUSIONS The collection of our results suggests that lipid microdomain affects the interaction of S. agalactiae type III belonging to the hypervirulent ST-17 with HUVEC cells through PI3K/Akt signaling pathway.

Analysis the methylation of caveolin-2 gene in peripheral blood of uygur pigeon feeders / 中国医师进修杂志

study the methylation status of caveolin-2(CAV2) gene in peripheral blood of uygur pigeon breeder lung patients, and discuss the significance of methylation of CAV2. Methods Twenty cases of uygur people who suffered from diseases after raising pigeons were enrolled into case group; 20 Urgur pigeons without disease were enrolled into case control group; and 20 uygur healthy subjects without pigeon were enrolled into healthy control group. General data of 60 subjects were collected and peripheral blood samples were collected. DNA was extracted from the retained peripheral blood samples, followed by hydrogen sulfite transformation, PCR amplification, in vitro transcription and RNase A-specific enzyme digestion, and finally, matrix-assisted laser desorption ionization time-of-flight mass spectrometry was used to detect the methylation of CAV2. Results CpG site of CAV2 fragment(CpG_1, CpG_2-4, CpG_5, CpG_6-8, CpG_9, CpG_10, CpG_11), actually detected 9 sites (CpG_1, CpG_2-4, CpG_5, CpG_6-8, CpG_11), the methylation rate distribution of each site in the three groups showed no statistical differences (P>0.05). The methylation rates of each site between the three groups were compared in pairs, and showed no statistical differences (P > 0.05). Conclusions Whether CAV2 gene methylation has any effect on the pulmonary pathogenesis and pulmonary fibrosis process of uygur pigeon feeders remains to be further studied.

Effects of ezetimibe and rosuvastatin on the expression of Caveolin-1 mRNA in smooth muscle derived foam cells / 中国医师杂志

Objective To investigate the influence of ezetimibe combined with rosuvastatin on expression of Caveolin-1 in smooth muscle derived foam cells induced by oxidized low density lipoprotein (oxLDL).Methods The rat thoracic aortic smooth muscle cells (VSMCs) were selected from generations 3-5 in logarithmic growth cycle.The rat vascular smooth cells were induced using oxidized low density lipoprotein(ox-LDL 50 μg/ml for 48 h) to establish foam cell model.The normal cultured rat thoracic aortic smooth muscle cells were used as blank control group.Foam cells were divided into foam cell group,different concentrations of ezetimibe group,different concentrations of rosuvastatin group,combination group.The foam cells were incubated with different doses of ezetimibe (3.0,10.0,30.0 μmol/L) or rosuvastatin (0.1,1.0,5.0 μmol/L) for 24 h,or cultured with rosuvastatin 5.0 μmol/L + ezetimibe 30.0 μmol/L in combination groups.Oil red O staining was used to identify foam cell models.The expression of Caveolin-1 mRNA was detected by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR).Results Compared with blank control group,the mRNA expression of Caveolin-1 in foam cell group were decreased significantly [(0.248 7 ± 0.042 0) vs (1.004 1 ± 0.017 1),P ＜ 0.05].Compared with foam cell group,the mRNA expression of Caveolin-1 was increased in a dose-dependent manner in ezetimibe group and rosuvastatin group [(0.371 3 ±0.025 2),(0.489 8 ±0.027 9),(0.726 1 ±0.029 1) vs (0.248 7 ±0.042 0);(0.460 2±0.022 8),(0.623 7 ±0.028 8),(0.751 8 ±0.043 1) vs (0.248 7 ±0.042 0),P ＜0.05].Compared with the ezetimibe (30.0 μmol/L) and the rosuvastatin (5.0 μmol/L),the mRNA expression of Caveolin-1 in combined group were increased,the difference was statistically significant [(0.726 1 ±0.029 1),(0.751 8 ± 0.043 1) vs (0.937 6 ± 0.029 7),P ＜ 0.05].Conclusions Ezetimibe and rosuvastatin can promote the reverse transport of cholesterol (RCT) in smooth muscle derived foam cells by upregulating expression of Caveolin-1 mRNA.And the combination of ezetimibe (30.0 μmol/L) and rosuvastatin (5.0 μmol/L) has more significant effect.

Effect of penehyclidine hydrochloride on expression of caveolin-1 during LPS-induced lung injury in rats / 中华麻醉学杂志

Objective To evaluate the effect of penehyclidine hydrochloride (PHC) on the expression of caveolin-1 (Cav-1) with lipopolysaccharide (LPS)-induced lung injury (LI) in rats.Methods Thirty SPF healthy male Sprague-Dawley rats,weighing 170-190 g,were divided into 3 groups (n =10each) using a random number table method:control group (group C),LPS-induced LI group (group LI)and PHCD group.LI was produced by injecting LPS 0.2 ml (5 mg/kg) via the trachea in anesthetized rats.PHCD 0.5 ml (2 mg/kg) was intraperitoneally injected at 1 h before establishing the model in group PHCD.Arterial blood samples were collected at 24 h after establishing the model for blood gas analysis and for determination of serum tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) concentrations by enzyme-linked immunosorbent assay.Rats were then sacrificed,and the lungs were removed.The main bronchus was lavaged,and the broncho-alveolar lavage fluid (BALF) was collected for calculation of the percentage of polymorphonuclear neutrophils (PMNs).Lung tissues were obtained for examination of pathological changes and for determination of myeloperoxidase (MPO) activity (by colorimetric assay),wet/dry weight ratio (W/D ratio),and expression of Cav-1 and nuclear factor kappa B (NF-sB) in nucleoprotein (by Western blot).Results Compared with group C,pH value and PaO2 were significantly decreased,the PaCO2,percentage of PMNs in BALF,W/D ratio and MPO activity were increased,the Car-1 expression was down-regulated,the expression of NF-κB in nucleoprotein was up-regulated,and the serum TNF-α and IL-1β concentrations were increased in group LI (P＜0.05).Compared with group LI,pH value and PaO2 were significantly increased,the PaCO2,percentage of PMNs in BALF,W/D ratio and MPO activity were decreased,the Cav-1 expression was up-regulated,the expression of NF-κB in nucleoprotein was down-regulated,and the serum TNF-α and IL-1β concentrations were decreased (P＜0.05),and the path ological changes of lung tissues were significantly attenuated in group PHCD (P＞0.05).Conclusion The mechanism by which PHC reduces LPS-induced LI may be related to up-regulating the expression of Cav-1 and mitigating inflammatory responses in lung tissues of rats.

Changes of Caveolin-1, matrix metalloproteinase-9 and interleukin-1β in cerebrospinal fluid of children with bacterial meningitis or viral encephalitis / 中华实用儿科临床杂志

Objective@#To investigate the changes and clinical significance of Caveolin-1, matrix metalloproteinase-9(MMP-9) and interleukin-1β(IL-1β)in cerebrospinal fluid of children with bacterial meningitis or viral encephalitis.@*Methods@#Thirty-six cases of children with bacterial meningitis, 42 cases of children with viral encephalitis, and 20 cases of children with non-nervous system infection were selected from September 2016 to June 2018 at the Third Affiliated Hospital of Zhengzhou University.The levels of Caveolin-1, MMP-9 and IL-1β in cerebrospinal fluid were detected by using enzyme linked immunosorbent assay(ELISA).@*Results@#Cerebrospinal fluid Caveolin-1, MMP-9 , IL-1β levels in the acute phase of bacterial meningitis were(49.06±8.96) ng/L, (134.79±18.88) μg/L, (100.02±14.67) μg/L, respectively, and (29.13±7.25) ng/L, (18.69±7.23) μg/L, (47.57±8.95) μg/L in recovery phase, which were higher than those of the controls[(11.18±2.24) ng/L, (11.53±3.54) μg/L, (39.75±7.08) μg/L)], and the differences were significant (all P<0.05). Cerebrospinal fluid Caveolin-1, MMP-9, IL-1β levels in the acute phase of viral encephalitis were (42.71±10.48) ng/L, (62.78±17.39) μg/L, (57.97±11.28) μg/L, respectively, and (29.13±7.25) ng/L, (18.69±7.23) μg/L, (47.57±8.95) μg/L in recovery phase, which were higher than those of controls, and the differences were significant (all P<0.05). The levels of Caveolin-1, MMP-9 and IL-1β in cerebrospinal fluid of bacterial meningitis group and viral encephalitis group were significantly higher than those of convalescent group (all P<0.05). The levels of Caveolin-1, MMP-9, IL-1β in cerebrospinal fluid of bacterial meningitis group were significantly higher than those in viral encephalitis group (all P<0.05) in the acute phase, and no significant difference was found in the recovery phase(all P>0.05). Cerebrospinal fluid Caveolin-1, MMP-9, IL-1β showed no significant difference among children with different severity of intracranial infection.Correlation analysis showed that there was a positive correlation between Caveolin-1, MMP-9 and IL-1 β levels in cerebrospinal fluid of acute in bacterial meningitis group and viral encephalitis group(Caveolin-1 and MMP-9: R2=0.239, P<0.05; MMP-9 and IL-1β: R2=0.766, P<0.01; Caveolin-1 and IL-1β: R2=0.245, P<0.05).@*Conclusions@#Caveolin-1, MMP-9 and IL-1 β involved in the pathogenesis of intracranial infection in children, and the effects of different pathogens on intracranial infection were different.

Analysis the methylation of caveolin-2 gene in peripheral blood of uygur pigeon feeders / 中国医师进修杂志

Objective@#To study the methylation status of caveolin-2(CAV2) gene in peripheral blood of uygur pigeon breeder lung patients, and discuss the significance of methylation of CAV2.@*Methods@#Twenty cases of uygur people who suffered from diseases after raising pigeons were enrolled into case group; 20 Urgur pigeons without disease were enrolled into case control group; and 20 uygur healthy subjects without pigeon were enrolled into healthy control group. General data of 60 subjects were collected and peripheral blood samples were collected. DNA was extracted from the retained peripheral blood samples, followed by hydrogen sulfite transformation, PCR amplification, in vitro transcription and RNase A-specific enzyme digestion, and finally, matrix-assisted laser desorption ionization time-of-flight mass spectrometry was used to detect the methylation of CAV2.@*Results@#CpG site of CAV2 fragment(CpG_1, CpG_2-4, CpG_5, CpG_6-8, CpG_9, CpG_10, CpG_11), actually detected 9 sites (CpG_1, CpG_2-4, CpG_5, CpG_6-8, CpG_11), the methylation rate distribution of each site in the three groups showed no statistical differences (P > 0.05). The methylation rates of each site between the three groups were compared in pairs, and showed no statistical differences (P > 0.05).@*Conclusions@#Whether CAV2 gene methylation has any effect on the pulmonary pathogenesis and pulmonary fibrosis process of uygur pigeon feeders remains to be further studied.