Chemokine receptors are implicated in inflammation and immune responses. Neuro-inflammation is associated with activation of astrocyte and amyloid-beta (Aβ) generations that lead to pathogenesis of Alzheimer disease (AD). Previous our study showed that deficiency of CC chemokine receptor 5 (CCR5) results in activation of astrocytes and Aβ deposit, and thus memory dysfunction through increase of CC chemokine receptor 2 (CCR2) expression. CCR5 knockout mice were used as an animal model with memory dysfunction. For the purpose LPS was injected i.p. daily (0.25 mg/kg/day). The memory dysfunctions were much higher in LPS-injected CCR5 knockout mice compared to CCR5 wild type mice as well as non-injected CCR5 knockout mice. Associated with severe memory dysfuction in LPS injected CCR5 knockout mice, LPS injection significant increase expression of inflammatory proteins, astrocyte activation, expressions of β-secretase as well as Aβ deposition in the brain of CCR5 knockout mice as compared with that of CCR5 wild type mice. In CCR5 knockout mice, CCR2 expressions were high and co-localized with GFAP which was significantly elevated by LPS. Expression of monocyte chemoattractant protein-1 (MCP-1) which ligands of CCR2 also increased by LPS injection, and increment of MCP-1 expression is much higher in CCR5 knockout mice. BV-2 cells treated with CCR5 antagonist, D-ala-peptide T-amide (DAPTA) and cultured astrocytes isolated from CCR5 knockout mice treated with LPS (1 μg/ml) and CCR2 antagonist, decreased the NF-ĸB activation and Aβ level. These findings suggest that the deficiency of CCR5 enhances response of LPS, which accelerates to neuro-inflammation and memory impairment.
Although substrate composition can influence the chemical reactivity of graphene, substrate lattice orientation provides a valuable alternative. The effect of Cu surface orientation on the reactivity of graphene was explored through a reductive transformation. Among the substrates tested, only Cu(111) led to the efficient, fast and uniform functionalization of graphene, as demonstrated by Raman mapping, and this arose from compressive strain induced by Cu(111). Functionalization effectively relaxes the strain, which can be subsequently reintroduced after thermal treatment. Theoretical calculations showed how compression facilitates the reduction and hybridization of carbon atoms, while coupling experiments revealed how kinetics may be used to control the reaction. The number of graphene layers and their stacking modes were also found to be important factors. In a broader context, a description of how graphene undergoes chemical modification when positioned on certain metal substrates is provided.
Osteoporosis is an age-related disease caused by imbalanced bone remodeling resulting from excessive bone resorption. Osteoporosis is tightly linked with induction of chronic inflammation, which activates osteoclasts and impairs osteoprogenitor in bone marrow. T helper 17 (Th17) cells have been recently recognized as one of major inducers in the pathophysiology of bone loss by secreting IL-17. Thus, modulation of Th17 development is anticipated to affect the progression of osteoporosis. Substance P (SP) is reported to provide anti-inflammatory effects by controlling immune cell profile and also, promote restoration of damaged stem cell niches-the bone marrow-by repopulating BMSCs or potentiating its paracrine ability. This study aimed to explore the therapeutic effects of systemically injected SP on ovariectomy (OVX)-induced osteoporosis. Resultantly, SP injection obviously blocked OVX-induced impairment of bone microarchitecture and reduction of the mineral density. In osteoporotic condition, SP could ameliorate chronic inflammation by promoting Treg cell polarization and inhibiting the development of osteoclastogenic Th17 cells. Moreover, SP could rejuvenate stem cell and enable stem cells to repopulate and differentiate into osteoblast. Collectively, our study strongly suggests that SP treatment can block osteoporosis and furthermore, SP treatment provides therapeutic effect on chronic disease with inflammation and stem cell dysfunction.
To determine whether dietary fatty acids affect pancreatic β-cell function, the INS-1 β-cells and the pancreatic islets isolated from Zucker obese (fa/fa) rats were cultured with stearic acid and conjugated linoleic acid (CLA).As a result, DNA fragmentation laddering was substantially decreased in the INS-1 β-cells and the isolated pancreatic islets cultured with 2 mM CLA compared to those cultured with stearic acid.To investigate the mechanism by which CLA alleviates cell apoptosis under DNA fragmentation assay, we examined mRNA expressions of apoptosis-related proteins including Bax and Bcl-2 associated with cell death agonist and antagonist, respectively, in both INS-1 cells and islets cultured with 2 mM fatty acids.Bax mRNA expression was not altered by either stearic acid or CLA, whereas Bcl-2 mRNA expression was enhanced by CLA when compared to the stearic acid cultures.However, there were no changes in cell apoptosis and apoptotic-regulating gene products in either INS-1 cells or isolated islets treated with or without 2 mM CLA.It is concluded that CLA maintains β-cell viability via increased Bcl-2 expression compared to the stearic acid cultures, which may help to alleviate, at least somewhat, the onset of NIDDM in the physiological status.More detailed study is still needed to elucidate the effect of CLA on the prevention of fatty acid-induced β-cell apoptosis.(
Background Dense breast reduced the sensitivity of mammography in breast cancer screening and known as an independent risk factor of breast cancer. The relationship between breast density and age, body mass index has studied. However, there are few studies on the relationship between breast density and lifestyle related disease. In this study, we investigated the relationship between mammographic breast density and lifestyle related disease. Methods Retrospective cross sectional research was carried out from people who visited a single health screening center in Busan from January 2015 to December 2015. We investigated age, past history of the subjects and measured their height, weight, blood pressure and waist circumference. The biochemical test was carried out using their blood. All patients underwent mammography. The breast density on mammography determined by the basis of American College of Radiology Breast Imaging Reporting and Data System (ACR BI-RADS) breast composition and 996 people was recruited. Results In the distribution of breast density, 16.3% of women (n=160) had dense breast. Age (under 49), body mass index (BMI) (underweight) were positively correlated with the BI-RADS composition category 3, 4 but the number of lifestyle related disease were negatively correlated (age ρ=0.17, BMI ρ=0.39, the number of lifestyle related disease ρ=-0.21). The odds ratio (OR) of dense breast increased with decreasing lifestyle related disease severity (OR=3.06, 95% confidence interval: 1.13-8.22, P=0.027). Conclusions This study showed that the number of lifestyle related disease was negatively correlated with mammographic density. The OR of dense breast increased with decreasing lifestyle related disease severity. Therefore, primary physicians should consider negative correlation between breast density and lifestyle related disease in breast cancer screening.
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