In this study, we examined the effect of progesterone on histopathologic and functional outcomes of intracerebral hemorrhage (ICH) in 10–12-month-old mice. Progesterone or vehicle was administered by intraperitoneal injection 1 hour after collagenase-induced ICH and then by subcutaneous injections at 6, 24, and 48 hours. Oxidative and nitrosative stress were assayed at 12 hours post-ICH. Injury markers were examined on day 1, and lesion was examined on day 3. Neurologic deficits were examined for 28 days. Progesterone posttreatment reduced lesion volume, brain swelling, edema, and cell degeneration and improved long-term neurologic function. These protective effects were associated with reductions in protein carbonyl formation, protein nitrosylation, and MMP-9 activity and attenuated cellular and molecular inflammatory responses. Progesterone also reduced VEGF expression, increased neuronal-specific Na+/K+ ATPase α3 subunit expression, and reduced PKC-dependent Na+/K+ ATPase phosphorylation. Furthermore, progesterone reduced glial scar thickness, myelin loss, brain atrophy, and residual injury volume on day 28 after ICH. With multiple brain targets, progesterone warrants further investigation for its potential use in ICH therapy.
A very brief, proactive and low-cost smoking-reduction intervention without medications for Chinese male smokers with no intention to quit appears to increase smoking abstinence.
AMP-activated protein kinase (AMPK) is essential for maintaining energy balance and has a crucial role in various inflammatory pathways. In this study, AMPK levels positively correlated with many inflammatory indexes in rheumatoid arthritis (RA) patients, especially in the affected synovium. In RA sera, a positive correlation between phosphorylated (p-)AMPK-a1 levels and DAS28 (disease activity score 28) activity (r = 0.270, p < 0.0001) was found. Similarly, a positive correlation was observed between AMPK-a1 and tumor necrosis factor a (TNF-a) levels (r = 0.460, p = 0.0002). Differentially expressed genes between osteoarthritis (OA) and RA synovium from NCBI GEO profiles and our RNA sequencing data suggested activation of metabolic pathways specific to RA-fibroblast-like synoviocytes (FLSs). AMPK-a1 was highly expressed in the synovium of RA but not OA patients. An AMPK activator, metformin, inhibited FLS proliferation at higher but not lower concentrations, whereas the inhibitor dorsomorphin promoted the proliferation of RA-FLSs. Interestingly, both metformin and dorsomorphin inhibited the migration of RA-FLSs. After metformin treatment, expression of interleukin 6 (IL-6), TNF-a, and IL-1b were significantly downregulated in RA-FLSs; however, increased expression of p-AMPK-a1, protein kinase A (PKA)-a1, and HAPLN1 (hyaluronan and proteoglycan link protein 1) was observed. Increased levels of HAPLN1 in RA-FLSs by an AMPK activator could potentially be beneficial in protecting the joints. Hence, our results demonstrate the potential of an AMPK activator as a therapeutic for RA.
Immunologic changes in the hematoma of patients with intracerebral hemorrhage (ICH) and the contribution of these changes to prognosis are unknown. We collected the blood samples and hematoma fluid from 35 patients with acute ICH (<30 hours from symptom onset) and 55 age-matched healthy controls. Using flow cytometry and ELISA, we found that the percentages of granulocytes, regulatory T cells, helper T (Th) 17 cells, and dendritic cells were higher in the peripheral blood of patients with ICH than in healthy controls, whereas the percentages of lymphocytes, M1-like macrophages, and M2-like macrophages were lower. Levels of IL-6, IL-17, IL-23, TNF-α, IL-4, IL-10, and TGF-β were higher in the peripheral blood of patients with ICH. The absolute counts of white blood cells, lymphocytes, monocytes, and granulocytes in the hematoma tended to be greater at 12-30 hours than they were within 12 hours after ICH, but the percentage of Th cells decreased in peripheral blood.Increased levels of IL-10 in the serum and hematoma, and a reduction in M1-like macrophages in hematoma were independently associated with favorable outcome on day 90. These results indicate that immunocytes present in the hematoma may participate in the acute-phase inflammatory response after ICH.
K E Y W O R D Shematoma, immune changes, intracerebral hemorrhage, outcome, patients | 2775 JIANG et Al.
This study characterized confocal images of gastric hyperplastic polyps and adenomas as well as the high accuracy of differentiating hyperplastic polyps and adenomas using CLE.
This study was designed to investigate dynamic changes in the cellular immune system and circulating inflammatory markers after ischemic stroke. Blood was collected from 96 patients and 99 age-matched control subjects for detection of lymphocyte subpopulations and inflammatory markers. We observed decreases in B cells, Th cells, cytotoxic T cells, and NK cells and an increase in regulatory T (Treg) cells in stroke patients on days 1, 3, and 7. Serum levels of TNF-a, C-reactive protein (CRP), IL-4, IL-6, IL-10, IL-17, IL-23, and TGF-β increased, whereas serum level of IFN-? decreased at all time points after stroke. Stroke patients with infection exhibited a similar tendency toward changes in some lymphocyte subpopulations and inflammatory markers as stroke patients without infection. After controlling for NIH Stroke Scale (NIHSS), we observed no differences in lymphocyte subpopulations between patients with anterior circulation stroke and those with posterior circulation stroke at any time point. The splenic volume correlated positively with the percentages of B cells, Th cells, and cytotoxic T cells, but negatively with Treg cells on day 3 after stroke. Infections were associated with splenic volume, leukocyte counts, percentage of Treg cells, and serum levels of CRP, IL-10, and IFN-? on day 3. Lesion volume correlated positively with CRP, IL-6, and IL-23, but negatively with IFN-? on day 3. The NIHSS showed a positive relation with IL-6 and IL-10 on day 3. Ischemic stroke has a profound effect on the systemic immune system that might explain the increased susceptibility of stroke patients to infection.
Positron emission tomography (PET) is used to observe the cerebral
function widely and is a good method to explore the mechanism of
acupuncture treatment on the central nervous system. By using this
method, we observed the cerebral function of 6 patients suffering
from ischemic stroke after receiving EA treatment at Baihui(GV20)
and right Qubin(GB7). The results were: (1) the glucose metabolism
changed significantly on primary motor area (M1), premotor cortex
(PMC), and superior parietal louble (LPs) bilaterally, as well as
the Supplementary Motor Area (SMA) on the unaffected hemisphere
right after the first EA treatment. (2) The glucose metabolism on
bilateral M1 and LPs changed significantly after three weeks of
daily EA treatments. (3) The glucose metabolism on other areas
such as insula, putamen, and cerebellum changed significantly. It
demonstrated that EA at Qubin and Baihui couldactivate the
cerebral structures related to motor function on the bilateral
hemispheres.We concluded that EA was very helpful for the cerebral
motor plasticity after the ischemic stroke. Also based on this
study we assumed that the brain plasticity should be a network and
that acupuncture participated in some sections of this course.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.