Growing evidences suggest that stroke is a systemic disease affecting many organ systems beyond the brain. Stroke-related systemic inflammatory response and immune dysregulations may play an ...important role in brain injury, recovery, and stroke outcome. The two main phenomena in stroke-related peripheral immune dysregulations are systemic inflammation and post-stroke immunosuppression. There is emerging evidence suggesting that the spleen contracts following ischemic stroke, activates peripheral immune response and this may further potentiate brain injury. Whether similar brain–immune crosstalk occurs in hemorrhagic strokes such as intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) is not established. In this review, we systematically examined animal and human evidence to date on peripheral immune responses associated with hemorrhagic strokes. Specifically, we reviewed the impact of clinical systemic inflammatory response syndrome (SIRS), inflammation- and immune-associated biomarkers, the brain–spleen interaction, and cellular mediators of peripheral immune responses to ICH and SAH including regulatory T cells (Tregs). While there is growing data suggesting that peripheral immune dysregulation following hemorrhagic strokes may be important in brain injury pathogenesis and outcome, details of this brain-immune system cross-talk remain insufficiently understood. This is an important unmet scientific need that may lead to novel therapeutic strategies in this highly morbid condition.
Background. Seven persons in one family living in eastern China developed fever and thrombocytopenia during May 2007, but the initial investigation failed to identify an infectious etiology. In ...December 2009, a novel bunyavirus (designated severe fever with thrombocytopenia syndrome bunyavirus SFTSV) was identified as the cause of illness in patients with similar clinical manifestations in China. We reexamined this family cluster for SFTSV infection. Methods. We analyzed epidemiological and clinical data for the index patient and 6 secondary patients. We tested stored blood specimens from the 6 secondary patients using real time reverse transcription polymerase chain reaction (RT-PCR), viral culture, genetic sequencing, micro-neutralization assay (MNA), and indirect immunofluorescence assay (IFA). Results. An 80-year-old woman with fever, leucopenia, and thrombocytopenia died on 27 April 2007. Between 3 and 7 May 2007, another 6 patients from her family were admitted to a local county hospital with fever and other similar symptoms. Serum specimens collected in 2007 from these 6 patients were positive for SFTS viral RNA through RT-PCR and for antibody to SFTSV through MNA and IFA. SFTSV was isolated from 1 preserved serum specimen. The only shared characteristic between secondary patients was personal contact with the index patient; none reported exposure to suspected animals or vectors. Conclusions. Clinical and laboratory evidence confirmed that the patients of fever and thrombocytopenia occurring in a family cluster in eastern China in 2007 were caused by a newly recognized bunyavirus, SFTSV. Epidemiological investigation strongly suggests that infection of secondary patients was transmitted to family members by personal contact.
Acute kidney injury (AKI) is increasing in prevalence and causes a global health burden. AKI is associated with significant mortality and can subsequently develop into chronic kidney disease (CKD). ...The kidney is one of the most energy-demanding organs in the human body and has a role in active solute transport, maintenance of electrochemical gradients, and regulation of fluid balance. Renal proximal tubular cells (PTCs) are the primary segment to reabsorb and secrete various solutes and take part in AKI initiation. Mitochondria, which are enriched in PTCs, are the main source of adenosine triphosphate (ATP) in cells as generated through oxidative phosphorylation. Mitochondrial dysfunction may result in reactive oxygen species (ROS) production, impaired biogenesis, oxidative stress multiplication, and ultimately leading to cell death. Even though mitochondrial damage and malfunction have been observed in both human kidney disease and animal models of AKI and CKD, the mechanism of mitochondrial signaling in PTC for AKI-to-CKD transition remains unknown. We review the recent findings of the development of AKI-to-CKD transition with a focus on mitochondrial disorders in PTCs. We propose that mitochondrial signaling is a key mechanism of the progression of AKI to CKD and potential targeting for treatment.
Background
Angiogenesis is a critical biological process essential for solid cancer growth and metastasis. It has been shown that microRNAs (miRNAs) play a vital role in a variety of biological ...processes in cancers. However, whether miR-130b is involved in prostate cancer angiogenesis remains ill-defined.
Methods
We performed the miRNA microarray to analyze miRNA expression in human prostate cancer specimens. In vitro gain-of-function assays and loss-of-function assays were conducted to explore the potential functions of miR-130b in human prostate cancer cells. Correlation analysis and dual-luciferase reporter assay were performed to validate whether tumor necrosis factor-α (TNF-α) was a direct target of miR-130b. The Matrigel plug and tumor vascular imaging assays were performed to confirm the anti-angiogenic activity of miR-130b in nude mice.
Results
We found that miR-130b was one of the miRNAs being most significantly downregulated. Subsequently, we found that miR-130b expression was markedly downregulated in human prostate cancer cell lines. Down-regulation of miR-130b in prostate cancer cells significantly promoted the proliferation, invasion and tubule formation of human umbilical vein endothelial cells (HUVECs), while ectopic expression of miR-130b blocked prostate cancer angiogenesis in vitro and in vivo. Mechanistic analyses indicated that tumor necrosis factor-α (TNF-α) was regulated by miR-130b directly. MiR-130b attenuated nuclear factor-κB (NF-κB) signaling and its downstream gene vascular endothelial growth factor-A (VEGFA) by directly inhibiting TNF-α expression. Additionally, subsequent investigations identified that the ectopic level of VEGFA markedly abrogated the anti-angiogenic effect induced by miR-130b. Interestingly, VEGFA could in turn decrease the expression of miR-130b, thus forming a negative feedback loop that drives the angiogenesis of prostate cancer.
Conclusion
These findings show that miR-130b/TNF-α/NF-κB/VEGFA feedback loop is significantly correlated with angiogenesis in prostate cancer and miR-130b could be regarded as potential therapeutic target for prostate cancer anti-angiogenesis treatment.
Most water and essential soil nutrient uptake is carried out by fine roots in plants. It is therefore important to understand the global geographic patterns of fine-root nitrogen and phosphorus ...cycling. Here, by compiling plant root data from 211 studies in 51 countries, we show that live fine roots have low nitrogen (N) and phosphorus (P), but similar N:P ratios when compared with green leaves. The fine-root N:P ratio differs between biomes and declines exponentially with latitude in roots of all diameter classes. This is in contrast to previous reports of a linear latitudinal decline in green leaf N:P, but consistent with nonlinear declines in leaf litter N:P. Whereas the latitudinal N:P decline in both roots and leaves reflects collective influences of climate, soil age and weathering, differences in the shape of the response function may be a result of their different N and P use strategies.
Background and purpose
Hyperglycemia in acute stroke leads to poor neurological outcomes. The role of microRNA (miRNA) in hyperglycemia‐associated genes can provide new avenues for stroke prognostic ...applications. We aimed to identify novel genes and their regulated miRNAs that are associated with hyperglycemia‐induced unfavorable stroke outcomes and further validated in the plasma exosome. Moreover, we intended to evaluate the prognostic ability of miRNA–messenger RNA (mRNA) biomarkers in addition to using traditional risk factors.
Methods
After the integration analysis of small RNA sequencing and mRNA polymerase chain reaction array, two mRNAs and six miRNAs were selected for validation in middle cerebral artery occlusion animal models and ischaemic stroke patients. Receiver operator characteristic analysis was used to determine the performance of mRNA and miRNA expression.
Results
The increased Fas expression was associated with hyperglycemia after acute stroke onset in animal and human studies. In addition, Fas gene level was significantly higher in patients with an unfavorable outcome when compared with patients with a favorable outcome. The expression of Fas and miRNA hsa‐let‐7b‐5p in addition to traditional risk factors could increase the discrimination and predictive ability for poor prognosis. The higher exosomal Fas was further observed among patients with an unfavorable outcome, suggesting Fas signal transporting through exosome in the circulation system.
Conclusions
Combined analyses of Fas and has‐let‐7b‐5p expression in addition to traditional risk factors are favorable prognostic biomarkers for predicting poor neurological outcomes at 3 months after stroke onset in ischaemic stroke patients. Additional studies are required to address the precise role of the apoptosis pathway in unfavorable hyperglycemia‐induced stroke outcomes.
ABSTRACT
Grids of DOV star models are evolved by wdec with fixed atmospheric constituent to the spectral values of XC/XHe/XO = 50/33/17. The core compositions are from white dwarf models at highest ...Teff evolved by mesa. The eigenfrequencies are calculated and used to fit the observed modes. Based on 264.1 h of photometric observations on PG 1159−035, Winget et al. identified 125 individual frequencies. Costa et al. identified 198 pulsation modes for PG 1159−035 according to the WET photometric data from 1983, 1985, 1989, and 2002. Both of them derived frequency splitting values of δσl = 1 ∼ 4.2 $\mu$Hz and δσl = 2 ∼ 6.9 $\mu$Hz. According to the values of δσl = 1 and δσl = 2, 20 triplets and 9 quintuplets are selected and used to constrain the fitting models. Our optimal model has Teff = 129 000 K, M* = 0.63 M⊙, log g = 7.59, log(Menv/M*) = −5.0, and σRMS = 1.97 s. The values of Teff and log g are consistent with that values of Córsico et al. The calculated modes of minimum rate of period change correspond to modes with maximum kinetic energy distributed in the envelope. The observed rates of period change with positive and negative values can also be partially reproduced. In particular, there are negative rates of period change for the calculated modes from our optimal model, which is not found in previous work.
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