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Furthermore, our findings supported the idea that a reduced volume in the thalamus and an increased volume in pallidum may be related to the decline in motor skills. These structural modifications are in accordance with the functional model of the basal ganglia-thalamocortical circuits controlling movements. Moreover, VBM and volumetry provided partially overlapping results, suggesting that these methods might capture complementary aspects of brain degeneration in PD.

To determine if radiological evidence of blood brain barrier (BBB) dysfunction, measured using Dynamic Contrast Enhanced MRI (DCE-MRI), correlates with serum matrix metalloproteinase (MMP) levels in traumatic brain injury (TBI) patients, and thereby, identify a potential biomarker for BBB dysfunction.

20 patients with a mild, moderate, or severe TBI underwent a DCE-MRI scan and BBB dysfunction was interpreted from K

. K

is a measure of capillary permeability that reflects the efflux of gadolinium contrast into the extra-cellar space. The serum samples were concurrently collected and later analysed for MMP-1, -2, -7, -9, and -10 levels using an ELISA assay. Statistical correlations between MMP levels and the K

value were calculated. Multiple testing was corrected using the Benjamin-Hochberg method to control the false-discovery rate (FDR).

Serum MMP-1 values ranged from 1.5 to 49.6ng/ml (12±12.7), MMP-2 values from 58.3 to 174.1ng/ml (109.5±26.7), MMP-7 from 1.5 to 31.5ng/mL (10±7.4), MMP-9 from 128.6 to 1917.5ng/ml (647.7±749.6) and MMP-10 from 0.1 to 0.6ng/mL (0.3±0.2). Non-parametric Spearman correlation analysis on the data showed significant positive relationship between K

and MMP-7 (r=0.55, p<0.01). Correlations were also found between K

and MMP-1 (r=0.74, p<0.0002) and MMP-2 (r=0.5, p<0.025) but the actual MMP values were not above reference ranges, limiting the interpretation of results. Statistically significant correlations between K

and either MMP-9 or -10 were not found.

This is the first study to show a correlation between DCE measures and MMP values in patients with a TBI. Our results support the suggestion that serum MMP-7 may be considered as a peripheral biomarker quantifying BBB dysfunction in TBI patients.

This is the first study to show a correlation between DCE measures and MMP values in patients with a TBI. Our results support the suggestion that serum MMP-7 may be considered as a peripheral biomarker quantifying BBB dysfunction in TBI patients.In this study, untargeted lipidomics based on UPLC-Q/TOF-MS, network pharmacology and atomic force microscopy were used to explore the common biomarkers of hyperlipidemia and coronary heart disease, the therapeutic mechanism of the main components of Salvia miltiorrhiza as well as the action mechanism of key lipids. Firstly, the serum samples of 30 healthy people, 30 patients with coronary heart disease and 30 patients with hyperlipidemia were analyzed by using lipidomics technology to obtain biomarkers which can be used to link hyperlipidemia and coronary heart disease and to find potential targets; then, the key components and core targets of Salvia miltiorrhiza intervention in hyperlipidemia and coronary heart disease were analyzed by network pharmacology, the results were verified by atomic force microscopy. It showed that SMS2 might be the key target. And through network pharmacology and atomic force microscope analysis, it can be inferred that salvianolic acid A can combine with SMS2 to play a therapeutic role.Selective estrogen receptor modulators (SERMs) are nonsteroidal drugs that display an estrogen-agonist or estrogen-antagonist effect depending on the tissue targeted. SERMs have attracted great clinical interest for the treatment of several pathologies, most notably breast cancer and osteoporosis. There is strong evidence that SERMs secondarily affect cholesterol metabolism, although the mechanism has not been fully elucidated. In this study, we analysed the effect of the SERMs tamoxifen, raloxifene, and toremifene on the expression of lipid metabolism genes by microarrays and quantitative PCR in different cell types, and ascertained the main mechanisms involved. The three SERMs increased the expression of sterol regulatory element-binding protein (SREBP) target genes, especially those targeted by SREBP-2. In consonance, SERMs increased SREBP-2 processing. These effects were associated to the interference with intracellular LDL-derived cholesterol trafficking. When the cells were exposed to LDL, but not to cholesterol/methyl-cyclodextrin complexes, the SERM-induced increases in gene expression were synergistic with those induced by lovastatin. Furthermore, the SERMs reduced the stimulation of the transcriptional activity of the liver X receptor (LXR) by exogenous cholesterol. However, their impact on the expression of the LXR canonical target ABCA1 in the presence of LDL was cell-type dependent. These actions of SERMs were independent of estrogen receptors. We conclude that, by inhibiting the intracellular trafficking of LDL-derived cholesterol, SERMs promote the activation of SREBP-2 and prevent the activation of LXR, two master regulators of cellular cholesterol metabolism. This study highlights the impact of SERMs on lipid homeostasis regulation beyond their actions as estrogen receptor modulators.Oxidative stress and inflammation arising from hyperglycaemia have been identified as important targets in mitigating hyperglycaemia-induced organ dysfunction in diabetics. Chrysophyllum albidum fruit is commonly consumed as fruit snacks because of its beneficial effects in diabetes management. This study aim to evaluate the protective mechanisms of Chrysophyllum albidum fruit extract (CAFE) in streptozotocin-induced rats involving attenuation of oxidative stress, nuclear factor-kappa B (NF-κB) and peroxisome proliferator-activated receptor-gamma (PPAR-γ). CAFE was investigated for in vitro antioxidant and alpha amylase inhibitory activity. Male Wistar rats were made diabetic by single intraperitoneal injection of streptozotocin (60 mg/kg). The rats were then treated with CAFE (100 and 200 mg/kg) and pioglitazone (10 mg/kg) for two weeks. Fasting blood sugar (FBS), blood pressure parameters, lipid profile, oxidative stress parameters, NF-κB and PPAR-γ were determined. The extract showed antioxidant and alpha amylase inhibitory activities. CAFE significantly reduced STZ-induced hyperglycaemia after 7 and 14 days of treatment. CAFE also reduced STZ-induced elevation of diastolic blood pressure and mean arterial pressure and as well reduced atherogenic index in diabetic rats. It significantly decreased lipid peroxidation but increased the enzymatic and non-enzymatic antioxidant markers in the plasma, liver, kidney and pancreas. The immunohistochemical analysis revealed that CAFE significantly decreased hepatic and renal tissues NF-κB while increasing PPAR-γ gene expressions. The results of this study collectively showed the protective effect of Chrysophyllum albidum fruit extract in streptozotocin-induced diabetic rats via modulation of oxidative stress and NF-κB/ PPAR-γ expressions.Major depressive disorder (MDD) is a serious psychiatric disorder that associated with high rate of disability and increasing suicide rate, and the pathogenesis is still unclear. Many researches showed that the energy metabolism of patients with depression is impaired, which may be the direction of depression treatment. In this review, we focus on the "omics" technologies such as genomics, proteomics, transcriptomics and metabolomics, as well as imaging, and the progress on energy metabolism of MDD. selleck chemicals llc These findings indicate that abnormal energy metabolism is one of the important mechanisms for the occurrence and development of depression. Although the research on various mechanisms of depression is still ongoing, the rapid development of new technologies and the joint use of various technologies will help to clarify the pathogenesis of depression and explore efficient diagnosis and treatment methods.Inhalational lung injury often leads to morbidity and mortality during fire disasters. In this study, we aimed to evaluate the protective effects of edaravone combined with dexamethasone on smoke-induced inhalational lung injury. Sprague-Dawley rats were divided into five groups, namely, the control, model (inhalation), and three treatment groups (edaravone, dexamethasone, and edaravone combined with dexamethasone). After drug intervention in the acute lung injury model, arterial blood gas, wetdry weight ratio of the lung tissue, bronchoalveolar lavage fluid, and pulmonary histopathology were determined. The production of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), inflammatory cytokines, peroxidase and apoptosis were further analyzed to explore the underlying mechanisms. The results of blood gas and inflammatory cytokine analysis and the histopathological data demonstrated that edaravone combined with dexamethasone had obvious protective effects on smoke infiltration and tissue injury. Moreover, after the co-administration of edaravone and dexamethasone, malondialdehyde and myeloperoxidase levels in the lung tissue decreased, whereas those of glutathione peroxidase and superoxide dismutase were elevated. In addition, this drug combination could inhibit smoke-induced apoptosis in lung tissues by reducing the cleavage of caspase-3, caspase-9, and poly ADP-ribose polymerase (PARP), and also reverse smoke-mediated mitochondrial dysfunction, including ROS generation, loss of MMP, early release of cytochrome C, second mitochondrial activator of caspases, and apoptosis-inducing factor. In conclusion, edaravone combined with dexamethasone had a protective effect on smoke-induced inhalational lung injury in rats and can be further explored as an attractive therapeutic option for the treatment of smoke inhalation-induced pulmonary dysfunction.Depressive disorder is a kind of emotional disorder that is mainly manifested with spontaneous and persistent low mood. Its etiology is complex and still not fully understood. Metabolomics, an important part of system biology characterized by its integrity and systematicness, analyzes endogenous metabolites of small molecules in vivo and examines the metabolic status of the organism. It is widely used in the field of disease research for its unique advantage in the disease molecular marker discovering Due to fewer adverse reactions and high safety, Chinese herbal medicine (CHM) has great advantages in the treatment of chronic diseases including depression. Metabolomics has been gradually applied to the efficacy evaluation of CHM in treatment of depression and the metabolomics analysis exhibits a systemic metabolic shift in amino acids (such as alanine, glutamic acid, valine, etc.), organic acids (lactic acid, citric acid, stearic acid, palmitic acid, etc.), and sugars, amines, etc. These differential metabolites are mainly involved in energy metabolism, amino acid metabolism, lipid metabolism, etc. In this review, we have exemplified the study of CHM in animals or clinics on the depression, and revealed that CHM treatment has significantly changed the metabolic disorders associated with depression, promoting metabolic network reorganization through restoring of key metabolites, and metabolic pathways, which may be the main mechanism basis of CHM's treatment on depression. Besides, we further envisioned the future application of metabolomics in the study of CHM treatment of depression.