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Elucidation of the molecular mechanism underlying the metabolic adaptation is critical to understand homeostasis of life. This review provides the concept, experimental and computational methods, to deal with this issue using "trans-omics" approaches.Recent developments in the computational study of energy transport in proteins are reviewed, including advances in both methodology and applications. The concept of energy exchange network (EEN) is discussed, and a recent calculation of EENs for the allosteric protein FixL is reviewed, which illustrates how residues and protein regions involved in the allosteric transition can be identified. Recent work has examined relations between EENs and protein dynamics as well as structure. We review some of the computational studies carried out on several proteins that explore connections between energy conductivity across polar contacts in proteins and between proteins and water and equilibrium dynamics of the contacts, and we discuss some of the recent experimental work that addresses this topic.The anticancer drug dasatinib (Sprycel) is a BCR-ABL1-targeted tyrosine kinase inhibitor used in treating chronic myelogenous leukemia that has been shown in clinical trials to display cardiovascular toxicities. While dasatinib potently inhibits BCR-ABL1, it is not a highly selective kinase inhibitor and may have off-target effects. A neonatal rat cardiac myocyte model was used to investigate potential mechanisms by which dasatinib damaged myocytes. The anthracycline cardioprotective drug dexrazoxane was shown to be ineffective in preventing dasatinib-induced myocyte damage. Dasatinib treatment increased doxorubicin accumulation in myocytes and doxorubicin-induced myocyte damage, likely through its ability to bind to one or more ABC-type efflux transporters. Dasatinib induced myocyte damage either after a brief treatment that mimicked the clinical situation, or more potently after continuous treatment. Dasatinib slightly induced apoptosis in myocytes as evidenced by increases in caspase-3/7 activity. Dasatinib treatment reduced pERK levels in myocytes most likely through inhibition of RAF, which dasatinib strongly inhibits. Thus, inhibition of the RAF/MEK/ERK pro-survival pathway in the heart may be, in part, a mechanism by which dasatinib induces cardiovascular toxicity.Obsessive-compulsive disorder (OCD) is an important neuropsychiatric disorder worldwide. Common treatments of OCD include serotonergic antidepressants, which can cause potentially serious side effects. We assessed the effects of Lactobacillus casei (L. casei) Shirota consumption in an animal model of OCD. OCD-like symptoms were induced in rats by the chronic injection of the D2/D3 dopamine agonist quinpirole hydrochloride. Rats were classified into five groups of 6 rats. Four groups were injected chronically with quinpirole (0.5 mg/kg, twice weekly for 5 weeks). They were fed with L. casei Shirota (109 CF/g, daily for 4 weeks) (group 1), fluoxetine (10 mg/kg, daily for 4 weeks) (group 2), combination of L. casei Shirota and fluoxetine (group 3), and normal saline (positive control group). The last group did not receive dopamine agonist and was only injected with saline (negative control group). Expression levels of brain-derived neurotrophic factor (Bdnf), solute carrier family 6 member 4 (Slc6a4), and 5-hydroxytryptamine receptor type 2A (Htr2a) were assessed in orbitofrontal cortex tissues of all rats. Behavioral tests showed improvement of OCD signs in rats treated with L. casei Shirota, fluoxetine, and a combination of drugs. Quantitative PCR analysis showed a remarkable decrease in the expression of Bdnf and an increase in the expression of Htr2a in quinpirole-treated rats. After treatment with L. casei Shirota and fluoxetine, the expression level of Bdnf was increased remarkably, whereas Htr2a expression was decreased. The current study showed the effectiveness of L. casei Shirota in the treatment of OCD in a rat model. The beneficial effects of this probiotic are possibly exerted through the modulation of serotonin-related genes expression.PURPOSE Sleep disturbances have a negative impact on the prognosis of chronic kidney disease (CKD). However, information on the prevalence and predictors is limited. This study aimed to evaluate the prevalence and explore clinical factors affecting the quality of sleep in patients with non-dialysis CKD. METHODS Participants included 152 adult non-dialysis patients with stage 3-5 CKD. Demographic and clinical data were collected. Sleep quality and depression were assessed using the Pittsburgh Sleep Quality Index (PSQI) and Beck Depression Inventory (BDI), respectively. Sleep disturbances were defined as a PSQI score ≥ 5. Logistic regression was conducted to explore the independent factors of sleep disturbances. Clinical parameters were correlated with BDI scores using linear regression models. RESULTS The total prevalence of patients with sleep disturbances was 66.4%. Older age, higher BDI scores, lower estimated glomerular filtration rate (eGFR) changes per month (△eGFR/m) before the study, and lower serum magnesium levels were found in patients with sleep disturbances. BDI scores (odds ratio [OR] 1.224, 95% confidence interval [CI] 1.091-1.373, p = 0.001) and age (OR 1.041, 95% CI 1.013-1.069, p = 0.003) were independent predictors of sleep disturbances. Serum uric acid levels (β - 0.629, 95% CI - 1.244 to - 0.013, p = 0.046), △eGFR/m before the study (β - 0.454, 95% CI - 0.885 to - 0.024, p = 0.039), and daily protein intake (β - 0.052, 95% CI - 0.102 to - 0.002, p = 0.043) were negatively associated with BDI scores. CONCLUSION A high overall prevalence of sleep disturbances was found in patients with non-dialysis stage 3-5 CKD. Depression, as a manageable predictor, should be managed, especially in elderly patients.OBJECTIVES We evaluated the clinical manifestations and outcomes of nocardiosis, a rare opportunistic infection that occurs in patients with nephrotic syndrome. METHODS The records of NS patients with nocardiosis in a single hospital during 2000-2019 were retrieved and studied in detail. Luzindole solubility dmso RESULTS Eleven patients were included. The mean time to develop nocardiosis after glucocorticoid therapy was 11.5 ± 14.8 months. Most patients had fever, elevated white blood cell counts and C-reactive protein, whereas procalcitonin levels were normal or slightly elevated in 91% (10/11) patients, except one patient suffered from septic shock. Nine patients were tested for CD4+ T-cell counts; of these, four patients had counts less then 200 cells/μL. The most common site of nocardiosis involvement was lung (100%), followed by subcutaneous tissue (72.7%). Radiological findings for lungs in seven cases were characterized by isolated or scattered nodules and masses, usually located subpleural or close to the hilum. Positive smears of Nocardia were detected in 100% of samples of subcutaneous abscess and pleural fluid.
Website: https://www.selleckchem.com/products/luzindole.html
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