다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

Tumor-associated macrophages: from mechanisms to therapy.

We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.

The somatic genomic landscape of glioblastoma

A complex network of chemokines and their receptors influences the development of primary tumours and metastases. New information about the biological role of chemokines in these processes is providing insights into host–tumour interactions, such as the role of the leukocyte infiltrate, and into the mechanisms that determine the metastatic potential and site-specific spread of cancer cells. Chemokine-receptor antagonists are showing promise in animal models of inflammation and autoimmune disease. Could manipulating the local chemokine network have therapeutic benefits in malignant disease?

Cancer and the chemokine network

https://www.cell.com/trends/neurosciences/pdf/S0166-2236(09)00153-2.pdf

Molecular dissection of reactive astrogliosis and glial scar formation.

Biological rhythms regulate physiological activities. Shiftwork disrupts normal circadian rhythms and may increase the risk of cancer through unknown mechanisms. To mimic environmental light/dark changes encountered by shift workers, a protocol called 'chronic jet lag (CJL)' induced by repeatedly shifting light-dark cycles has been used. Here, we subjected mice to CJL by advancing light-dark cycle by 6 h every 2 days, and conducted RNA sequencing to analyze the expression profile and molecular signature in the brain areas of prefrontal cortex and nucleus accumbens. We also performed positron emission tomography (PET) imaging to monitor changes related to glucose metabolism in brain. Our results reveal systematic reprogramming of gene expression associated with cancer-related pathways and metabolic pathways in prefrontal cortex and nucleus accumbens. PET imaging indicates that glucose uptake level was significantly reduced in whole brain as well as the individual brain regions. Moreover, qPCR analysis describes that the expression levels of cancer-related genes were altered in prefrontal cortex and nucleus accumbens. Overall, these results suggest a molecular and metabolic link with CJL-mediated cancer risk, and generate hypotheses on how CJL increases the susceptibility to cancer.

Circadian disruption in mice through chronic jet lag-like conditions modulates molecular profiles of cancer in nucleus accumbens and prefrontal cortex.

Isolation and Culture of Primary Human CNS Neural Cells

Microglia are the immune sentinels of the central nervous system with protective roles such as the removal of neurotoxic oxidized phosphatidylcholines (OxPCs). As aging alters microglial function and elevates neurological disability in diseases such as multiple sclerosis, defining aging-associated factors that cause microglia to lose their custodial properties or even become injurious can help to restore their homeostasis. We used single-cell and spatial RNA sequencing in the spinal cord of young (6-week-old) and middle-aged (52-week-old) mice to determine aging-driven microglial reprogramming at homeostasis or after OxPC injury. We identified numerous aging-associated microglial transcripts including osteopontin elevated in OxPC-treated 52-week-old mice, which correlated with greater neurodegeneration. Osteopontin delivery into the spinal cords of 6-week-old mice worsened OxPC lesions, while its knockdown in 52-week-old lesions attenuated microglial inflammation and axon loss. Thus, elevation of osteopontin and other transcripts in aging disorders including multiple sclerosis perturbs microglial functions contributing to aging-associated neurodegeneration. 

Single-cell and spatial RNA sequencing identify perturbators of microglial functions with aging

The destruction of the blood-brain barrier (BBB) after intracerebral hemorrhage (ICH) is associated with poor prognosis. Modulation of sphingosine 1-phosphate receptor (S1PR) may improve outcomes from ICH. Ozanimod (RPC-1063) is a newly developed S1PR regulator which can selectively modulate type 1/5 sphingosine receptors. Here, we studied the impact of Ozanimod on neuroprotection in an experimental mouse model of ICH, induced by injecting collagenase type VII into the basal ganglia. Ozanimod was administered by gavage 2 h after surgery and once a day thereafter until sacrifice. The results demonstrate that Ozanimod treatment improved neurobehavioral deficits in mice and decreased weight loss after ICH. Ozanimod significantly reduced the density of activated microglia and infiltrated neutrophils in the perihematoma region. Furthermore, Ozanimod reduced hematoma volume and water content of the ICH brain. The results of TUNEL staining indicate that Ozanimod mitigated brain cell death. The quantitative data of Evans blue (EB) staining showed that Ozanimod reduced EB dye leakage. Overall, Ozanimod reduces the destruction of the BBB and exert neuroprotective roles following ICH in mice.

/pdf/neuroprotection-by-ozanimod-following-intracerebral-34jy0j44.pdf

Neuroprotection by Ozanimod Following Intracerebral Hemorrhage in Mice

Objectives: This article aimed to analyze the relationship between obesity and the efficacy of acute ischaemic stroke patients treated with IVT.Background: Stroke causes morbidity and mortality in large numbers of individuals annually. Intravenous thrombolysis (IVT)with recombinant tissue plasminogen activator (r-tPA) is currently the only approved by the FDA for treatment of acute ischaemic stroke. Researchers have focused on studying the mechanisms associated with ischaemic stroke. Obesity is an established vascular risk factor with increasing prevalence and a huge impact on public health worldwide. It is an independent predictor for ischaemic stroke with a 4% risk increase for each unit augmentation in body mass index (BMI). Therefore, obese patients will constitute an increasing subgroup of candidates for IVT. However, its impact on prognosis in acute ischaemic stroke patients with intravenous thrombolysis did not reach a consensus conclusion.Methods: Systematic literature search of PUBMED databases published before August 2020, was performed to identify studies addressing the role of obesity in acute ischaemic stroke patients treated with IVT. Studies included randomized clinical trials, observational studies, guideline statements, and review articles.Conclusions: Obesity may be related to long-term prognosis of large group of AIS patients treated with IVT. It depends on the scale of clinical study samples, follow-up time, and evaluation criteria.

V. Wee Yong

Papers

Circadian disruption in mice through chronic jet lag-like conditions modulates molecular profiles of cancer in nucleus accumbens and prefrontal cortex.

Isolation and Culture of Primary Human CNS Neural Cells

Single-cell and spatial RNA sequencing identify perturbators of microglial functions with aging

Neuroprotection by Ozanimod Following Intracerebral Hemorrhage in Mice

Obesity in acute ischaemic stroke patients treated with intravenous thrombolysis therapy.