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1.
Cell Death Dis ; 13(4): 318, 2022 04 07.
Article in English | MEDLINE | ID: mdl-35393391

ABSTRACT

Neuroinflammation occurs early in Alzheimer's disease (AD). The initial stage of AD is related to glial dysfunction, which contributes to impairment of Aß clearance and disruption of synaptic connection. CEBPß, a member of the CCAAT-enhancer-binding protein (CEBP) family, modulates the expression of inflammation-associated genes, and its expression is elevated in brains undergoing degeneration and injured brains. However, the mechanism underlying CEBPß-mediated chronic inflammation in AD is unclear. In this study, we observed that increases in the levels of nuclear CEBPß facilitated the interaction of CEBPß with the NFκB p65 subunit, increasing the transcription of proinflammatory cytokines in the APP/PS1 mouse brain. Oral administration of nanocarrier-packaged carnosic acid (CA) reduced the aberrant activation of microglia and astrocytes and diminished mature IL-1ß, TNFα and IL-6 production in the APP/PS1 mouse brain. CA administration reduced ß-amyloid (Aß) deposition and ameliorated cognitive impairment in APP/PS1 mice. We observed that CA blocked the interaction of CEBPß with NFκB p65, and chromatin immunoprecipitation revealed that CA reduced the transcription of the NFκB target genes TNFα and IL-6. We confirmed that CA alleviated inflammatory mediator-induced neuronal degeneration and reduced Aß secretion by inhibiting the CEBPß-NFκB signalling pathway in vitro. Sulfobutyl ether-beta-cyclodextrin (SBEßCD) was used as the encapsulation agent for the CA-loaded nanocarrier to overcome the poor water solubility and enhance the brain bioavailability of CA. The CA nanoparticles (NPs) had no obvious toxicity. We demonstrated a feasible SBEßCD-based nanodelivery system targeting the brain. Our data provide experimental evidence that CA-loaded NPs are potential therapeutic agents for AD treatment.


Subject(s)
Alzheimer Disease , Abietanes , Alzheimer Disease/metabolism , Amyloid beta-Peptides/metabolism , Amyloid beta-Protein Precursor/metabolism , Animals , Cognition , Disease Models, Animal , Inflammation/drug therapy , Interleukin-6 , Mice , Mice, Transgenic , Microglia/metabolism , Neuroinflammatory Diseases , Presenilin-1 , Tumor Necrosis Factor-alpha/metabolism
2.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-676125

ABSTRACT

Objective To report the outcome of emergency repair traumatized limbs by vascularized free tissue transplantation.Methods From April 1988 to August 2004,86 patients,58 men and 28 women,had undergone emergency vascularized free tissue transplantation to have their injured limbs repaired in 54 cases and the missing thumbs reconstructed in 32.The patients aged from 5 to 55 (mean 27.9) years. The transplants included latissimus dorsi myocutaneons flap,anterolateral femoral skin flap,medial crural skin flaps,dorsal pedal flaps,medial plantar flap,composite tissue mass of the discarded limbs and big toe skin- nail flap.The operations were performed 1 to 5 days after injuries.Results Postoperative vascular crises occurred in 8 cases and were all followed by exploration with successes in 5 cases while failure in 3.The total survival rate of the transplants was 96.5% (83/86).In this series all the patients were followed up for 1 to 16 years with a mean of 7.5 years only to reveal satisfying functional recovery in all the repaired limbs and an ex- cellent and good rate of 87.5% in the reconstructed thumbs.Conclusion Emergency vascularized free tis- sue transplantation is an effective way to repair a traumatized limb and to reconstruct a traumatically missing thumb.

3.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-278178

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the availability of serum level of macrophage clony stimulating factor (M-CSF) as a marker for early diagnosis of Alzheimer's disease (AD).</p><p><b>METHODS</b>The serum levels of M-CSF in 70 patients with AD, 52 healthy controls, 22 patients with VAD (vascular dementia) were measured and the serum levels of IL-1 beta, IL-6, TNF-alpha in 32 patients with AD and 20 controls were measured as well.</p><p><b>RESULTS</b>Serum levels of M-CSF were significantly elevated in patients with AD when compared with healthy controls (P < 0.01) and VAD controls (P < 0.05) respectively. At the early stage of mild dementia and middle dementia, serum levels of M-CSF were significantly elevated, but at the later stage of severe dementia, they returned to normal level. Serum levels of IL-1 beta were significantly elevated in AD patients compared with controls (P < 0.05), and serum levels of TNF-alpha and IL-6 were within the normal range in patients with AD.</p><p><b>CONCLUSIONS</b>The results suggest that serum M-CSF level may provide a convenient and sensitive means for the early diagnosis of Alzheimer's disease.</p>


Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Alzheimer Disease , Blood , Biomarkers , Blood , Interleukin-1 , Blood , Interleukin-6 , Blood , Macrophage Colony-Stimulating Factor , Blood , Tumor Necrosis Factor-alpha , Metabolism
4.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-675410

ABSTRACT

Objective To measure the width of space in front of the femoral neck at different age of normal children for diagnosis such as hip disease in children as bilateral transient synovitis of the hip. Methods Four hundred and twenty normal children below 14 years old were divided into 14 groups according to their age. Every group contained 30 children. They underwent bilateral ultrasonographic assessment. The width of space in front of the femoral neck was measured and collected. The mean width value in each group was compared mutually by statistical analysis (t test). Results The mean width of space in front of the femoral neck of normal children below 14 years old was 2.0 - 5.9 mm, the range was 1.2 - 7.8 mm. Conclusions The width of space in front of the femoral neck is different at different age of normal children, the mean value below 14 years old

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