Gustavsenfarley5311

Objectives To investigate the effect and mechanism of sacubitril/valsartan on myocardial fibrosis in rats following experimental myocardial infarction and in TGF-β1-treated myocardial fibroblasts. Methods Male Sprague-Dawley (SD) rats were subjected to coronary artery ligation to establish myocardial infarction and intragastrically fed vehicle, valsartan (Val, 32 mg/kg, once-daily) or sacubitril/valsartan (Sac/Val, 68 mg/kg, once-daily) for 4 weeks. In parallel, myocardial fibroblasts (MFs) isolated from neonatal SD rats were exposed to hypoxia and treated with TGF-β1 (5 ng/ml) plus vehicle, Val (107-10-5 M) or Sac/Val (107-105 M). Rat cardiac function and fibrosis were measured by echocardiography and histological method, respectively. MFs viability and collagen synthesis were determined by cell counting kit-8 and enzyme-linked immunosorbent assay, respectively. Protein expressions of TGF-β1, Smad3, phosphorylated Smad3 (p-Smad3), and p-Smad3 subcellular localization were detected by immunoblotting and immunyocardial fibroblasts by inhibiting the TGF/Smads signaling pathway.Cajanolactone A (CLA) is a stilbenoid isolated from Cajanus canjan (L.) Millsp with the potential to prevent postmenopausal obesity. In this study, the effect of CLA on high-fat diet (HFD)-induced obesity in female C57BL/6 mice was investigated. It was found that, treatment with CLA reduced the energy intake and effectively protected the mice from HFD-induced body weight gain, fat accumulation within the adipose tissues and liver, and impairment in energy metabolism. Further investigation revealed that CLA significantly down-regulated the expression of ORX, ORXR2, pMCH, and Gal in the hypothalamus and antagonized HFD-induced changes in the expression of UCP1, Pgc-1α, Tfam, and Mfn1 in the inguinal white adipose tissue (iWAT); Caveolin-1, MT and UCP3 in the perigonadal white adipose tissue (pWAT); and Pdhb, IRS2, Mttp, Hadhb, and Cpt1b in the liver. CLA also protected the pWAT and liver from HFD-induced mitochondrial damage. However, neither HFD nor CLA showed an effect on the mass of brown adipose tissue (BAT) or the expression of UCP1 in the BAT. In summary, our findings suggest that CLA is a potential drug candidate for preventing diet-induced obesity, at least in females. CLA works most likely by suppressing the hypothalamic expression of orexigenic genes, which leads to reduced energy intake, and subsequently, reduced fat accumulation, thereby protecting the adipose tissues and the liver from lipid-induced mitochondrial dysfunction.Dementias are neurodegenerative and progressive diseases of the central nervous system. The objective of this study was to determine the frequency of potentially inappropriate prescriptions of antipsychotics in a group of patients diagnosed with dementia in Colombia. This was a cross-sectional study based on a population database for drug dispensing that identified prescriptions of antidementia drugs, antipsychotics, and other drugs for patients with a diagnosis of dementia. Descriptive statistics and bivariate and multivariate analyses were performed. A total of 11,372 patients with dementia were identified; 66.6% were women, and the mean age was 80.5 ± 9.6 years. Alzheimer's disease was the most frequent diagnosis (76.6%). A total of 69.0% of patients received antidementia drugs. A total of 37.1% of patients received some antipsychotic, especially atypical antipsychotics (31.0%). Increased age, being treated with memantine, simultaneously presenting with anxiety, depression, and psychotic disorders, and concomitantly receiving anticonvulsants, bronchodilators and benzodiazepines were associated with a greater probability of being prescribed antipsychotics. More than one-third of patients with dementia received antipsychotic prescriptions, which are considered potentially inappropriate because they can worsen cognitive decline and favor the occurrence of adverse events.Parkinson's disease is a neurodegenerative disorder in which activated microglia may appear prior to motor symptoms, but the specific therapeutic mechanisms remain unclear. This study investigated the potential effects of Edaravone (EDA) on M1/M2 polarization of microglia in rats with dopaminergic neurons damage induced by lipopolysaccharide (LPS) and its mechanism. Rats were randomly grouped as the following (n = 10) Control, EDA alone (10 mg/kg), LPS-model (LPS 5 μg), LPS + EDA (5 mg/kg) and LPS + EDA (10 mg/kg). After intragastric administration of EDA once a day for seven consecutive days, LPS was injected into SN pars unilaterally. Rotarod test, pole test, and traction test were used to analyze the intervention effect of EDA on neurobehavioral function in rats. click here Protein expression levels of TH, TNF-α, Arg-1, Iba-1, NLRP3 and caspase-1 were measured by immunofluorescence staining and western blot. In vitro, BV-2 cells were treated with LPS (100 ng/ml) before adding different doses of EDA. Levels of inflamm microglia M1/M2 polarization.Background Despite policies to manage prescription drug spending and ensure accessibility, prescription drug spending has continued to increase in South Korea. Using nationwide claims data, this study analyzed trends in total pharmaceutical expenditures and pharmaceutical expenditures by drug classification. Methods We conducted a retrospective population-based study using the Korean National Health Insurance claims database from January 2010 through December 2019. Pharmaceuticals were categorized as new drugs, continued drugs, and abandoned drugs. Prescription drug spending was calculated using the components of price and quantity for individual products in successive two-year periods, to obviate the need to consider changes over time. Results Total pharmaceutical expenditures increased by 54.2% from 2010 to 2019 (from USD 11.3 billion to USD 17.4 billion). The average annual growth rate was 4.9% overall (the 4% rate for continued drugs was decomposed into -3.5% for the price of drugs, 8.0% for the quantity of drugs, and -0.5% for mixed effects, a measure of changes in drug treatment patterns). The trends were generally consistent. Particularly sharp increases in expenditures were found for groups L (antineoplastic and immunomodulating agents), C (cardiovascular system drugs), and A (alimentary tract and metabolism drugs). Conclusions Since increased prescription drug spending was primarily driven by an increase in the quantity of drugs used, consumer-focused policies to reduce drug use are necessary.Background ET-26 hydrochloride (ET-26HCl), a class 1 new drug, was developed to reserve the advantages of etomidate with a mild adrenocortical inhibition. Purpose this study was to evaluate the potential adverse effects on the cardiovascular system of beagle dogs and the respiratory and central nervous systems of rats. Methods three established methods, the whole-body plethysmography for respiratory function, the prototype telemetry transmitter for cardiovascular function, and the standardized functional observational battery for central nervous system function, were accomplished with Good Laboratory Practice standards. Results no significant difference in the tidal volume, but the respiratory rate and minute ventilation were reduced. The degree of inhibition was the most serious in the first 15 min after dosing and function fully recovered after 1 h. For male rats, the respiratory rate of male rats was reduced significantly at 15 min after injection with ET-26HCl (4 mg/kg, 28.6%, p ≤ 0.01; 8 mg/kg, 24.5%, p 4.84, 66.52 ± 8.50, 73.64 ± 8.51, and 74.24 ± 8.68 mmHg, respectively. For female beagle dogs, the systolic blood pressure after 24 h following administration of vehicle control or 8, 12, or 16 mg/kg ET-26HCl was 128.28 ± 5.22, 124.76 ± 7.29, 134.88 ± 5.56, and 135.36 ± 8.72 mmHg, respectively. The diastolic blood pressure was 67.00 ± 4.10, 62.12 ± 7.87, 69.44 ± 6.40, and 70.20 ± 8.42 mmHg, respectively. In central nervous system function experiment, all the changes observed in the functional observational battery tests, including motor activity, behavior, coordination, and sensory and motor reflex responses, and reduced body temperature, were resulted in general anesthesia effect of ET-26HCl. Conclusion ET-26HCl exerts mild, reversible effects on respiratory, cardiovascular, and central nervous system function as verified by standard in vivo animal models.Cisplatin is one of the first line anti-cancer drugs prescribed for treatment of solid tumors; however, the chemotherapeutic drug resistance is still a major obstacle of cisplatin in treating cancers. Yu Ping Feng San (YPFS), a well-known ancient Chinese herbal combination formula consisting of Astragali Radix, Atractylodis Macrocephalae Rhizoma and Saposhnikoviae Radix, is prescribed as a herbal decoction to treat immune disorders in clinic. To understand the fast-onset action of YPFS as an anti-cancer drug to fight against the drug resistance of cisplatin, we provided detailed analyses of intracellular cisplatin accumulation, cell viability, and expressions and activities of ATP-binding cassette transporters and glutathione S-transferases (GSTs) in YPFS-treated lung cancer cell lines. In cultured A549 or its cisplatin-resistance A549/DDP cells, application of YPFS increased accumulation of intracellular cisplatin, resulting in lower cell viability. In parallel, the activities and expressions of ATP-binding cassette transporters and GSTs were down-regulated in the presence of YPFS. The expression of p65 subunit of NF-κB complex was reduced by treating the cultures with YPFS, leading to a high ratio of Bax/Bcl-2, i.e. increasing the rate of cell death. Prim-O-glucosylcimifugin, one of the abundant ingredients in YPFS, modulated the activity of GSTs, and then elevated cisplatin accumulation, resulting in increased cell apoptosis. The present result supports the notion of YPFS in reversing drug resistance of cisplatin in lung cancer cells by elevating of intracellular cisplatin, and the underlying mechanism may be down regulating the activities and expressions of ATP-binding cassette transporters and GSTs.The gasotransmitter H2S is involved in various physiological and pathophysiological processes. The aim of this study was to investigate the physiological functions of H2S in the lungs. In the model of mouse with genetic deficiency in a H2S natural synthesis enzyme cystathionine-γ-lyase (CSE), we found that arterial oxygen saturation (SaO2) was decreased compared with wild type mice. Hypoxyprobe test showed that mild hypoxia occurred in the tissues of heart, lungs and kidneys in Cse -/- mice. H2S donor GYY4137 treatment increased SaO2 and ameliorated hypoxia state in cardiac and renal tissues. Further, we revealed that lung blood perfusion and airway responsiveness were not linked to reduced SaO2 level. Lung injury was found in Cse -/- mice as evidenced by alveolar wall thickening, diffuse interstitial edema and leukocyte infiltration in pulmonary tissues. IL-8, IL-1β, and TNF-α levels were markedly increased and oxidative stress levels were also significantly higher with increased levels of the pro-oxidative biomarker, MDA, decreased levels of the anti-oxidative biomarkers, T-AOC and GSH/GSSG, and reduced superoxide dismutase (SOD) activity in lung tissues of Cse -/- mice compared with those of wild type mice. GYY4137 treatment ameliorated lung injury and suppressed inflammatory state and oxidative stress in lung tissues of Cse -/- mice. A decrease in SaO2 was found in normal mice under hypoxia. These mice displayed lung injury as evidenced by alveolar wall thickening, interstitial edema and leukocyte infiltration. Increased levels of inflammatory cytokines and oxidative stress were also found in lung tissues of the mice with hypoxia insult. GYY4137 treatment increased SaO2 and ameliorated lung injury, inflammation and oxidative stress. Our data indicate that endogenous H2S is an important factor in maintaining normal SaO2 by preventing oxidative stress and inflammation in the lungs.