In the present study, we aimed to determine whether ethanol extracts of Fructus Schisandrae (FS), the dried fruit of Schizandra chinensis Baillon, mitigates the development of dexamethasone-induced muscle atrophy. Adult SPF/VAT outbred CrljOri:CD1 (ICR) mice were either treated with dexamethasone to induce muscle atrophy. Some mice were treated with various concentrations of FS or oxymetholone, a 17α-alkylated anabolic-androgenic steroid. Muscle thickness and weight, calf muscle strength, and serum creatine and creatine kinase (CK) levels were then measured. The administration of FS attenuated the decrease in calf thickness, gastrocnemius muscle thickness, muscle strength and weight, fiber diameter and serum lactate dehydrogenase levels in the gastrocnemius muscle bundles which was induced by dexamethasone in a dose-dependent manner. Treatment with FS also prevented the dexamethasone-induced increase in serum creatine and creatine kinase levels, histopathological muscle fiber microvacuolation and fibrosis, and the immunoreactivity of muscle fibers for nitrotyrosine, 4-hydroxynonenal, inducible nitric oxide synthase and myostatin. In addition, the destruction of the gastrocnemius antioxidant defense system was also inhibited by the administration of FS in a dose-dependent manner. FS downregulated the mRNA expression of atrogin-1 and muscle RING-finger protein-1 (involved in muscle protein degradation), myostatin (a potent negative regulator of muscle growth) and sirtuin 1 (a representative inhibitor of muscle regeneration), but upregulated the mRNA expression of phosphatidylinositol 3-kinase, Akt1, adenosine A1 receptor and transient receptor potential cation channel subfamily V member 4, involved in muscle growth and the activation of protein synthesis. The overall effects of treatment with 500 mg/kg FS were comparable to those observed following treatment with 50 mg/kg oxymetholone. The results from the present study support the hypothesis that FS has a favorable ameliorating effect on muscle atrophy induced by dexamethasone, by exerting anti-inflammatory and antioxidant effects on muscle fibers, which may be due to an increase in protein synthesis and a decrease in protein degradation.
OBJECTIVES This study tested the diagnostic and prognostic utility of a rapid, visual T1 assessment method for identification of cardiac amyloidosis (CA) in a “real-life” referral population undergoing cardiac magnetic resonance for suspected CA. BACKGROUND In patients with confirmed CA, delayed-enhancement cardiac magnetic resonance (DE-CMR) frequently shows a diffuse, global hyperenhancement (HE) pattern. However, imaging is often technically challenging, and the prognostic significance of diffuse HE is unclear. METHODS Ninety consecutive patients referred for suspected CA and 64 hypertensive patients with left ventricular hypertrophy (LVH) were prospectively enrolled and underwent a modified DE-CMR protocol. After gadolinium administration a method for rapid, visual T1 assessment was used to identify the presence of diffuse HE during the scan, allowing immediate optimization of settings for the conventional DE-CMR that followed. The primary endpoint was all-cause mortality. RESULTS Among patients with suspected CA, 66% (59 of 90) demonstrated HE, with 81% (48 of 59) of these meeting pre-specified visual T1 assessment criteria for diffuse HE. Among hypertensive LVH patients, 6% (4 of 64) had HE, with none having diffuse HE. During 29 months of follow-up (interquartile range: 12 to 44 months), there were 50 (56%) deaths in patients with suspected CA and 4 (6%) in patients with hypertensive LVH. Multivariable analysis demonstrated that the presence of diffuse HE was the most important predictor of death in the group with suspected CA (hazard ratio: 5.5, 95% confidence interval: 2.7 to 11.0; p < 0.0001) and in the population as a whole (hazard ratio: 6.0, 95% confidence interval 3.0 to 12.1; p < 0.0001). Among 25 patients with myocardial histology obtained during follow-up, the sensitivity, specificity, and accuracy of diffuse HE in the diagnosis of CA were 93%, 70%, and 84%, respectively. CONCLUSIONS Among patients suspected of CA, the presence of diffuse HE by visual T1 assessment accurately identifies patients with histologically-proven CA and is a strong predictor of mortality.
This paper focuses on how to optimally route transfer cranes in a container yard during loading operations of export containers at port terminals. Decision variables are the number of containers that a transfer crane picks up at each yard-bay and the sequence of yard-bays that a transfer crane visits during a loading operation. This routing problem is formulated as a mixed integer program. The objective function of the formulation is to minimize the total container handling time of a transfer crane, which includes setup time at each yard-bay and travel time between yard-bays. Based on the mixed integer program, an optimizing algorithm is developed.
R esults: O f the total of 99,025 malignancies, 55,398 (55.9% ) cases were males and 43,627 (44.1% ) were fem ales. M ore than one third of cases were from the elderly (65 years old and more). The six leading primary cancer sites in the order of their relative frequency, were stomach (24.0% ), followed by the lung (16.0% ), the liver (15.4% ), the colorectum (11.6% ), the bladder (3.2% ), and the prostate (3.0% ) among males. In females, the breast (16.8% ) was the common cancer site, followed by the stomach (15.3% ), the colorectum (10.7% ), the thyroid gland (9.5% ), the cervix uteri (9.1% ), and the lung (6.6% ).C onclusion: W ith the continued increase in cancer cases especially prostate cancer among males and thyroid cancer among females, the total number of registered cancer cases in Korea continues to rapidly increase.
Abstract. In the present study, the beneficial and synergistic effects of Polycalcium, a mixture of Polycan and calcium (Ca) lactate-gluconate in a 1:9 weight ratio, on a rat model of osteoarthritis (OA) were explored. Polycalcium (50, 100 and 200 mg/kg) was administered orally once per day for 28 days from 1 week after the OA-modeling surgery. Diclofenac sodium (2 mg/kg) was administered as a reference drug. Following the OA surgery, increases in the maximum extension angles, edematous changes in knee and capsule thickness, reductions in chondrocyte proliferation and cartilage glycosaminoglycan (GAG) levels, as well as changes in cartilage degeneration were observed. However, these OA-related symptoms were inhibited after 28 days of continuous oral treatment with Polycalcium. Anti-OA effects, including the induction of chondrocyte proliferation, were detected in the Polycalcium-treated rats and were more favorable compared with those in rats treated with Polycan or Ca lactate-gluconate alone (100 mg). Therefore, a mixture of Polycan and Ca lactate-gluconate was demonstrated to have beneficial synergistic effects on OA.
Cytosolic NADP+-dependent isocitrate dehydrogenase (IDPc) synthesizes reduced NADP (NADPH), which is an essential cofactor for the generation of reduced glutathione (GSH), the most abundant and important antioxidant in mammalian cells. We investigated the role of IDPc in kidney ischemia-reperfusion (I/R) in mice. The activity and expression of IDPc were highest in the cortex, modest in the outer medulla, and lowest in the inner medulla. NADPH levels were greatest in the cortex. IDPc expression in the S1 and S2 segments of proximal tubules was higher than in the S3 segment, which is much more susceptible to I/R. IDPc protein was also highly expressed in the mitochondrion-rich intercalated cells of the collecting duct. IDPc activity was 10- to 30-fold higher than the activity of glucose-6-phosphate dehydrogenase, another producer of cytosolic NADPH, in various kidney regions. This study identifies that IDPc may be the primary source of NADPH in the kidney. I/R significantly reduced IDPc expression and activity and NADPH production and increased the ratio of oxidized glutathione to total glutathione [GSSG/(GSH+GSSG)], resulting in kidney dysfunction, tubular cell damage, and lipid peroxidation. In LLC-PK(1) cells, upregulation of IDPc by IDPc gene transfer protected the cells against hydrogen peroxide, enhancing NADPH production, inhibiting the increase of GSSG/(GSH+GSSG), and reducing lipid peroxidation. IDPc downregulation by small interference RNA treatment presented results contrasting with the upregulation. In conclusion, these results demonstrate that IDPc is expressed differentially along tubules in patterns that may contribute to differences in susceptibility to injury, is a major enzyme in cytosolic NADPH generation in kidney, and is downregulated with I/R.
Peroxisome proliferator-activated receptor (PPAR)-␥ ligands have been shown to inhibit human lung cancers by inducing apoptosis and differentiation. In the present study, we elucidated the apoptotic mechanism of PPAR␥ activation in human lung cancers by using a novel PPAR␥ agonist, 1-(trans-methylimino-N-oxy)-6-(2-morpholinoethoxy)-3-phenyl-(1H-indene-2-carboxylic acid ethyl ester (KR-62980), and rosiglitazone. PPAR␥ activation selectively inhibited cell viability of nonsmall-cell lung cancer with little effect on small-cell lung cancer and normal lung cells. The cell death induced by PPAR␥ activation presented apoptotic features of oligonucleosomal DNA fragmentation in A549 human non-small-cell lung cancer cell line. Reactive oxygen species (ROS) production was accompanied by increased expression of proline oxidase (POX), a redox enzyme expressed in mitochondria, upon incubation with the agonists. POX RNA interference treatment blocked PPAR␥-induced ROS formation and cytotoxicity, suggesting that POX plays a functional role in apoptosis through ROS formation. The apoptotic effects by the agonists were antagonized by bisphenol A diglycidyl ether, a PPAR␥ antagonist, and by knockdown of PPAR␥ expression, indicating the involvement of PPAR␥ in these actions. The results of the present study suggest that PPAR␥ activation induces apoptotic cell death in non-smallcell lung carcinoma mainly through ROS formation via POX induction.Lung cancer is the most common cause of cancer death in the world for men and women, and its epidemic is closely associated with smoking. The cancer can be divided into two groups as small-cell lung cancer and non-small-cell lung cancer (NSCLC), of which NSCLC constitutes major populations (Ginsber et al., 1993). NSCLC are subdivided into squamous, adenocarcinoma, and large cell carcinoma phenotypes, and they are frequently associated with Ras mutation. Various approaches for lung cancer treatment, including induction of differentiation and apoptosis, have been attempted, but conventional chemotherapy and radiotherapy of lung cancer are still of limited effectiveness, necessitating the development of new treatment strategies.Peroxisome proliferator-activated receptors (PPARs) are members of the family of ligand-activated transcription factors that include receptors for steroids, thyroid hormone, retinoic acid, and vitamin D. Of subtypes of PPAR (PPAR␣, PPAR, and PPAR␥), each encoded by a separate gene, the role of PPAR␥, in particular, in the proliferation and differentiation of various cancers has been extensively investigated. PPAR␥ expression has been identified in various cancer cell lines and in human tumors, including breast, colon, gastric, prostate, and lung cancers. Furthermore, various PPAR␥ ligands, including thiazolidinediones, exhibited anticancer effects in many types of cancer cells, and their actions were associated with the induction of differentiation and apoptosis. With regard to the role of Article, publication date, and citation information can be found at http:/...
The first crustal‐scale controlled source seismic refraction experiment in the southern Korean Peninsula, KCRUST2002, was carried out along a 300‐km long profile across this peninsula in December 2002. Iterative processing and modeling produced a laterally varying layered crustal velocity model. The crust is thickest (34 km) below the Okcheon fold belt in the middle of the transect and thinnest (28 km) at the eastern end where the Cretaceous Gyeongsang basin is characterized by 5 km of low velocity material that constitutes the upper crust. The P velocities in upper and lower crust range from 5.4 to 6.0 km/s and from 6.4 to 6.7 km/s, respectively. The average crustal Poisson's ratio is found to be 0.25–0.27 (Vp/Vs = 1.73−1.78) along the profile. A mid‐crustal velocity discontinuity is recognized in the northwestern part of the transect. The underlying mantle has velocities in the range of 7.9–8.1 km/s.
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