Background and objectives: Carvedilol is a cardiovascular drug, beta- and alpha1-adrenoceptor antagonist, currently approved for the treatment of hypertension, angina, congestive heart failure by FDA. Carvedilol has been shown to attenuate oxygen free radical-initiated lipid peroxidation and to inhibit neointimal formation of aorta following vascular injury by balloon angioplasty. We have investigated the effect of carvedilol on DNA synthesis of vascular smooth muscle cells (VSMC) stimulated by platelet-derived growth factor (PDGF)-BB. MATERIALS AND METHOD: Rat aortic smooth muscle cells were obtained by the combined collagenase and elastase methods. Cells between the 4th and 8th passages were used for the experiments. Incorporated radioactivity of [3H]-thymidine was measured by liquid scintillation spectrometry. RESULTS: PDGF-BB (1 nM) increased [3H]-thymidine incorporation about 70-100% over basal value in cultured VSMC. PDGF-stimulated increase in DNA synthesis was significantly suppressed by simultaneous administration of carvedilol. In contrast, propranolol did not significantly affect 3[H]-thymidine uptake in rat aortic VSMC. CONCLUSION: The present study demonstrate that carvedilol significantly inhibits the proliferation of vascular smooth muscle cell in our condition. These results indicate that carvedilol may be effective in the treatment of cardiovascular diseases principally associated with abnormal vascular smooth muscle growth.
Angioplasty, Balloon ; Animals ; Aorta ; Cardiovascular Diseases ; Cell Proliferation ; Collagenases ; DNA ; Heart Failure ; Hypertension ; Lipid Peroxidation ; Muscle, Smooth, Vascular* ; Myocytes, Smooth Muscle ; Oxygen ; Pancreatic Elastase ; Platelet-Derived Growth Factor ; Propranolol ; Radioactivity ; Rats ; Spectrum Analysis ; Vascular System Injuries

Hepatic dysregulation of lipid metabolism exacerbates inflammation and enhances the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). STAT3 has been linked to lipid metabolism and inflammation. Jolkinolide B (JB), derived from Euphorbia fischeriana, is known for its pharmacological anti-inflammatory and anti-tumor properties. Therefore, this study investigated whether JB affects MASLD prevention by regulating STAT3 signaling. JB attenuated steatosis and inflammatory responses in palmitic acid (PA)-treated hepatocytes. Additionally, JB treatment reduced the mRNA expression of de-novo lipogenic genes, such as acetyl-CoA carboxylase and stearoyl-CoA desaturase 1. Interestingly, JB-mediated reduction in inflammation and lipogenesis was dependent on STAT3 signaling. JB consistently modulated mitochondrial dysfunction and the mRNA expression of inflammatory cytokines by inhibiting PA-induced JAK/STAT3 activation. This study suggests that JB is a potential therapeutic agent to prevent major stages of MASLD through inhibition of JAK/STAT3 signaling in hepatocytes.

Hepatic dysregulation of lipid metabolism exacerbates inflammation and enhances the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). STAT3 has been linked to lipid metabolism and inflammation. Jolkinolide B (JB), derived from Euphorbia fischeriana, is known for its pharmacological anti-inflammatory and anti-tumor properties. Therefore, this study investigated whether JB affects MASLD prevention by regulating STAT3 signaling. JB attenuated steatosis and inflammatory responses in palmitic acid (PA)-treated hepatocytes. Additionally, JB treatment reduced the mRNA expression of de-novo lipogenic genes, such as acetyl-CoA carboxylase and stearoyl-CoA desaturase 1. Interestingly, JB-mediated reduction in inflammation and lipogenesis was dependent on STAT3 signaling. JB consistently modulated mitochondrial dysfunction and the mRNA expression of inflammatory cytokines by inhibiting PA-induced JAK/STAT3 activation. This study suggests that JB is a potential therapeutic agent to prevent major stages of MASLD through inhibition of JAK/STAT3 signaling in hepatocytes.

Hepatic dysregulation of lipid metabolism exacerbates inflammation and enhances the progression of metabolic dysfunction-associated steatotic liver disease (MASLD). STAT3 has been linked to lipid metabolism and inflammation. Jolkinolide B (JB), derived from Euphorbia fischeriana, is known for its pharmacological anti-inflammatory and anti-tumor properties. Therefore, this study investigated whether JB affects MASLD prevention by regulating STAT3 signaling. JB attenuated steatosis and inflammatory responses in palmitic acid (PA)-treated hepatocytes. Additionally, JB treatment reduced the mRNA expression of de-novo lipogenic genes, such as acetyl-CoA carboxylase and stearoyl-CoA desaturase 1. Interestingly, JB-mediated reduction in inflammation and lipogenesis was dependent on STAT3 signaling. JB consistently modulated mitochondrial dysfunction and the mRNA expression of inflammatory cytokines by inhibiting PA-induced JAK/STAT3 activation. This study suggests that JB is a potential therapeutic agent to prevent major stages of MASLD through inhibition of JAK/STAT3 signaling in hepatocytes.

BACKGROUND AND OBJECTIVES: The octapeptide hormone of the renin-angiotensin system, angiotensin ii, regulates a wide variety of physiological responses including salt and water balance, blood pressure, and vascular tone. Contradictory results have been reported regarding the effects of angiotensin ii on vascular smooth mu-scle cell (VSMC) proliferation. The aim of the present study was to investigate the direct effect of angiotensin ii on the growth of VSMC. MATERIALS AND METHOD: Rat aortic smooth muscle cells were obtained by the combined collagenase and elastase methods. Cells between the 4th and 8th passages were used for the experiments. Cultures were treated daily for 3 days with either angiotensin ii alone or angiotensin ii with equimolar concentrations of saralasin. Incorporated radioactivity of [3H]thymidine and [14C]phenylalanine was measured by liquid scintillation spectrometry. RESULTS: Angiotensin ii increased [14C]phenyalanine incor-poration about 20-30%, and saralasin completely blocked the stimulation by angiotensin ii. However, there was no significant increase in [3H]thymidine incorporation by angiotensin ii stimulation in this study. CONCLUSION: These results suggest that angiotensin ii alone induces cellular hypertrophy but has no detectable mitogenic activity in cultured rat aortic VSMC.
Angiotensin II* ; Angiotensins* ; Animals ; Blood Pressure ; Collagenases ; Hypertrophy ; Muscle, Smooth, Vascular* ; Myocytes, Smooth Muscle ; Pancreatic Elastase ; Radioactivity ; Rats ; Renin-Angiotensin System ; Saralasin ; Spectrum Analysis

OBJECTIVE: Our aim was to evaluate the changes in blood glucose control and lipid profiles after 2-months of smoking cessation in healthy males. METHODS: Smoking abstinence was evaluated through self-report and urine cotinine levels. 12 individuals who succeeded in quitting smoking were analyzed. Fasting values of glucose and insulin were used to estimate the beta-cell activity and insulin resistance was evaluated using the Homeostasis Model Assessment (HOMA) and Quantitative Insulin Sensitivity Check Index (QUICKI). RESULTS: The data showed that the subjects had a significant increase in weight, body mass index and fasting plasma glucose levels after smoking cessation. The HOMA-Insulin Resistance and the HOMA beta-cell function increased significantly (p=0.005, p=0.047 respectively). The QUICKI showed a significant decrease (p=0.005). In addition, the low-density lipoprotein cholesterol levels decreased significantly (p=0.028); however, changes in the high-density lipoprotein cholesterol, the triglyceride and total cholesterol levels were not significant (p=0.284, p=0.445 respectively). CONCLUSION: During the initial stage of smoking abstinence, insulin resistance increased and insulin sensitivity decreased due to elevated body weight and fat composition. Therefore, it is important to educate individuals that stop smoking about the necessity of weight control during smoking cessation programs.
Blood Glucose ; Body Weight ; Cholesterol ; Cotinine ; Fasting ; Glucose ; Homeostasis ; Humans ; Insulin ; Insulin Resistance ; Lipoproteins ; Male ; Plasma ; Smoke ; Smoking ; Smoking Cessation

BACKGROUND: Atherosclerosis is a diffuse disease process that produce thickening of the vascular wall because of intimal deposition of lipid, fibrous tissue, and calcific material. Nowadays it is possible to evaluate atherosclerotic changes of carotid arteries accurately by developed noninvasive techniques such as ultrasonography. Left ventricular hypertrophy (LVH) is known to be an important risk factor for cardiovascular events in hypertension. The purpose of this study was to establish whether the carotid intimal - medial thickness (IMT) correlates with the severity of LVH. METHOD: We measured intimal-medial thickness (IMT) for 12 sites in carotid arteries (near and far walls in common carotid, bifurcation, and internal carotid arteries of both sides) by B-mode ultrasonography in both 38 normotensive and 72 hypertensive patients. Left ventricular measurements were made according to the recommendations of the American Society of Echocardiography. Left ventricular mass was derived from the formula described by Devereux et al. and each left ventricular mass value was indexed to body surface area. And then we have investigated whether hypertensive patients have significant changes of carotid IMT and IMT correlates with left ventricular mass index (LVMI). RESULTS: (1) Most hypertensive patients had diffuse thickening of the carotid artery and some had focal or multiple plaques. (2) In general, mean IMT was widest in the carotid bifurcation. (3) The mean IMT of all 12 segments increased about 40% in hypertensive patients compared with normal control group. (4) LVMI significantly correlates with IMT of carotid artery, especially bifurcation site and mean all 12 segments. CONCLUSION: The mean IMT may serve as a useful marker of the severity of atherosclerosis in hypertensive patients. The significant association between carotid IMT and LVMI suggests a simultaneous correlation of carotid atherosclerosis with left ventricular hypertrophy in hypertension.
Atherosclerosis ; Body Surface Area ; Carotid Arteries* ; Carotid Artery Diseases ; Carotid Artery, Internal ; Echocardiography ; Humans ; Hypertension ; Hypertrophy, Left Ventricular* ; Risk Factors ; Ultrasonography

OBJECTIVE: The purpose of our study was to evaluate the overall prevalence and clinical significance of interposition of the posterior cruciate ligament (PCL) into the medial compartment of the knee joint in coronal magnetic resonance imaging (MRI). MATERIALS AND METHODS: We retrospectively reviewed 317 consecutive patients referred for knee MRI at our institution between October 2009 and December 2009. Interposition of the PCL into the medial compartment of the knee joint on proton coronal MRI was evaluated dichotomously (i.e., present or absent). We analyzed the interposition according to its prevalence as well as its relationship with right-left sidedness, gender, age, and disease categories (osteoarthritis, anterior cruciate ligament tear, and medial meniscus tear). RESULTS: Prevalence of interposition of PCL into the medial compartment of the knee joint was 47.0% (149/317). There was no right (50.0%, 83/166) to left (43.7%, 66/151) or male (50.3%, 87/173) to female (43.1%, 62/144) differences in the prevalence. There was no significant association between the prevalence and age, or the disease categories. CONCLUSION: Interposition of the PCL into the medial compartment of the knee joint is observed in almost half of patients on proton coronal MRI of the knee. Its presence is not associated with any particular factors including knee pathology and may be regarded as a normal MR finding.
Adolescent ; Adult ; Aged ; Child ; Female ; Humans ; Image Processing, Computer-Assisted ; Knee Joint/*radiography ; *Magnetic Resonance Imaging ; Male ; Menisci, Tibial/radiography ; Middle Aged ; Osteoarthritis/diagnosis/epidemiology/radiography ; Posterior Cruciate Ligament/*radiography ; Prevalence ; Retrospective Studies ; Young Adult

BACKGROUND: Vascular lesions are the major cause of morbidity and mortality in hypertensive patients. However, the pathologic characteristics of gradually evolving, chronic hypertension have not been adequately studied and the mechanism by which hypertension accelerates atherosclerosis is still uncertain. This study was undertaken to invertigate the ultrastructural changes of the aorta and the effect of high cholesterol diet in spontaneously hypertensive rats(SHR). METHODS: Spontaneously hypertensive rats (n=80, male, 5 weeks old) and Wistar rats (n=40, male, 5 week old) were used. Forty SHR were fed with 2% cholestrol diete, while the remainder with control diet. Systolic blood pressure was measured weekly until 16 weeks after birth, and then biweekly until 40 weeks after birth. Transmission and scanning electron microscopy were used to evaluate ultrastrucural changes of the aorta. RESULTS: 1) The blood pressure of SHR rose stedily and progressively from the 5 weeks after birth and reached nearly 190mmHG at the 16 weeks after birth. 2) In SHR, the subendothelial component contained finely granular substances, abundant fibrillar collagen and elastin. Infiltration of the mononuclear blood leukocytes into the intima was frequently seen. 3) Endothelium from cholestrol-fed SHR did exhibit numerous pinocytotic vesicles and contained many cytoplasmic filaments. There were a number of large mononuclear lipid-filled cells in the intimal lesions. Blistering of the endothelial plasma membrane was also observed in high cholesterol diet-fed SHR. Later on, adhesion of platelets, febrin, and white blood cells as well as damage of intima shown as multiple small holes were more marked. 4) There was no significant difference in systoloic blood pressure between high cholesterol diet-fed and control diet-fed SHR. CONCLUSION: In the aorta of SHR, the most prominent change was an expansion of the subendothelial space and infiltration of the mononuclear leukocytes into the intima. The present study showed that the SHR was indeed a reliable model for the essential hypertension. In some SHR, high cholesterol diet could induce more pronounced vascular lesions, which were enhanced by hypertension.
Aorta* ; Atherosclerosis ; Blister ; Blood Pressure ; Cell Membrane ; Cholesterol* ; Cytoskeleton ; Diet* ; Elastin ; Endothelium ; Fibrillar Collagens ; Humans ; Hypertension ; Leukocytes ; Leukocytes, Mononuclear ; Male ; Microscopy, Electron ; Microscopy, Electron, Scanning ; Mortality ; Parturition ; Rats, Inbred SHR* ; Rats, Wistar

BACKGROUND: The use of mouse bone marrow mesenchymal stem cells (mBMSCs) represents a promising strategy for performing preclinical studies in the field of cell-based regenerative medicine; however, mBMSCs obtained via conventional isolation methods have two drawbacks, i.e., (i) they are heterogeneous due to frequent macrophage contamination, and (ii) they require long-term culturing for expansion. METHODS: In the present study, we report a novel strategy to generate highly pure mBMSCs using liposomal clodronate.This approach is based on the properties of the two cell populations, i.e., BMSCs (to adhere to the plasticware in culture dishes) and macrophages (to phagocytose liposomes). RESULTS: Liposomal clodronate added during the first passage of whole bone marrow culture was selectively engulfed by macrophages in the heterogeneous cell population, resulting in their effective elimination without affecting the MSCs.This method allowed the generation of numerous high-purity Sca-1 ＋ CD44 ＋ F4/80 - mBMSCs ([ 95%) with just one passaging. Comparative studies with mBMSCs obtained using conventional methods revealed that the mBMSCs obtained in the present study had remarkably improved experimental utilities, as demonstrated by in vitro multilineage differentiation and in vivo ectopic bone formation assays. CONCLUSION Our newly developed method, which enables the isolation of mBMSCs using simple and convenient protocol, will aid preclinical studies based on the use of MSCs.