evaluating-cell-death-signaling-immunofluorescence-rat-model-ischemic

Evaluating Cell Death Signaling by Immunofluorescence in a Rat Model of Ischemic Stroke

Stroke is a leading cause of death and disability worldwide. Most cases of stroke are ischemic and result from the occlusion of the middle cerebral artery ...

Sichuan University

Although plain radiology is the primary method for assessing joint space width (JSW), it has poor sensitivity to change over time in regards to determining longitudinal progression. We, therefore, developed a new ultrasound (US) measurement method of knee JSW and aimed to provide a monitoring method for the change of JSW in the future.

A measurement method of knee joint space width by ultrasound: a large multicenter study.

Selective serotonin reuptake inhibitors (SSRIs) might theoretically reduce post-stroke disability by direct effects on the brain. This Cochrane Review was first published in 2012 and last updated in 2019.

Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery.

The epidemiology of stroke is evolving in China as the population undergoes demographic, lifestyle, and economic transitions. An updated review is pertinent to providing feedback on current, and in planning future, prevention and management strategies.

Increasing burden of stroke in China: A systematic review and meta-analysis of prevalence, incidence, mortality, and case fatality.

To investigate whether serum calcium and magnesium on the day of symptom onset contribute to prognosis at 1 year after intracerebral hemorrhage (ICH).

Prognostic value of day-of-event serum calcium and magnesium for predicting 1-year prognosis after intracerebral hemorrhage.

Runt-related transcription factor-1 (RUNX1), a key member of the core-binding factor family of transcription factors, has emerged as a novel therapeutic target for cardiovascular disease. There is an urgent need to fully understand the expression pattern of Runx1 in the heart and the mechanisms by which it is controlled under normal conditions and in response to disease. The expression of Runx1 is regulated at the transcriptional level by two promoters designated P1 and P2. Alternative usage of these two promoters creates differential mRNA transcripts diversified in distribution and translational potential. While the significance of P1/P2 promoter-switch in the transcriptional control of Runx1 has been highlighted in the embryogenic process, very little is known about the level of P1- and P2-specific transcripts in adult hearts, and the underlying mechanisms controlling the promoter-switch.

Age-related promoter-switch regulates Runx1 expression in adult rat hearts.

The Ultrasound Physician Branch of the Chinese Medical Doctor Association sought to develop evidence-based recommendations on the operational standards for 2-D shear wave elastography examination of musculoskeletal tissues. A consensus panel of 22 Chinese musculoskeletal ultrasound experts reviewed current scientific evidence and proposed a set of 12 recommendations for 13 key issues, including instruments, operating methods, influencing factors and image interpretation. A final consensus was reached through discussion and voting. On the basis of research evidence and expert opinions, the strength of recommendation for each proposition was assessed using a visual analog scale, while further emphasizing the best available evidence during the question-and-answer session. These expert consensus guidelines encourage facilitation of the standardization of clinical practices for collecting and reporting shear wave elastography data.

Chinese Ultrasound Doctors Association Guideline on Operational Standards for 2-D Shear Wave Elastography Examination of Musculoskeletal Tissues.

Severe ischemic stroke carries a high rate of disability and death. The severity of stroke is often assessed by the degree of neurological deficits or the extent of brain infarct, defined as severe stroke and large infarction, respectively. Critically severe stroke is a life-threatening condition that requires neurocritical care or neurosurgical intervention, which includes stroke with malignant brain edema, a leading cause of death during the acute phase, and stroke with severe complications of other vital systems. Early prediction of high-risk patients with critically severe stroke would inform early prevention and treatment to interrupt the malignant course to fatal status. Selected patients with severe stroke could benefit from intravenous thrombolysis and endovascular treatment in improving functional outcome. There is insufficient evidence to inform dual antiplatelet therapy and the timing of anticoagulation initiation after severe stroke. Decompressive hemicraniectomy (DHC) <48 h improves survival in patients aged <60 years with large hemispheric infarction. Studies are ongoing to provide evidence to inform more precise prediction of malignant brain edema, optimal indications for acute reperfusion therapies and neurosurgery, and the individualized management of complications and secondary prevention. We present an evidence-based review for severe ischemic stroke, with the aims of proposing operational definitions, emphasizing the importance of early prediction and prevention of the evolution to critically severe status, summarizing specialized treatment for severe stroke, and proposing directions for future research.

Definition, prediction, prevention and management of patients with severe ischemic stroke and large infarction.

Myocardial infarction (MI) results in prolonged ischemia and the subsequent cell death leads to heart failure which is linked to increased deaths or hospitalizations. New therapeutic targets are urgently needed to prevent cell death and reduce infarct size among patients with MI. Runt-related transcription factor-1 (RUNX1) is a master-regulator transcription factor intensively studied in the hematopoietic field. Recent evidence showed that RUNX1 has a critical role in cardiomyocytes post-MI. The increased RUNX1 expression in the border zone of the infarct heart contributes to decreased cardiac contractile function and can be therapeutically targeted to protect against adverse cardiac remodelling. This study sought to investigate whether pharmacological inhibition of RUNX1 function has an impact on infarct size following MI. In this work we demonstrate that inhibiting RUNX1 with a small molecule inhibitor (Ro5-3335) reduces infarct size in an in vivo rat model of acute MI. Proteomics study using data-independent acquisition method identified increased cathepsin levels in the border zone myocardium following MI, whereas heart samples treated by RUNX1 inhibitor present decreased cathepsin levels. Cathepsins are lysosomal proteases which have been shown to orchestrate multiple cell death pathways. Our data illustrate that inhibition of RUNX1 leads to reduced infarct size which is associated with the suppression of cathepsin expression. This study demonstrates that pharmacologically antagonizing RUNX1 reduces infarct size in a rat model of acute MI and unveils a link between RUNX1 and cathepsin-mediated cell death, suggesting that RUNX1 is a novel therapeutic target that could be exploited clinically to limit infarct size after an acute MI.

Pharmacological inhibition of RUNX1 reduces infarct size after acute myocardial infarction in rats and underlying mechanism revealed by proteomics implicates repressed cathepsin levels.

Chordoma is a rare bone cancer with variable clinical outcomes. Here, we recruited 184 sporadic chordoma patients from the US and Canada and collected their clinical and treatment data. The average age at diagnosis was 45.5 years (Range 5-78) and the chordoma site distribution was 49.2% clivus, 26.2% spinal, and 24.0% sacral. Most patients (97.5%) received surgery as the primary treatment, among whom 85.3% also received additional treatment. Except for the most prevalent cancers like prostate, lung, breast, and skin cancer, there was no discernible enrichment for any specific cancer type among patients or their family members. Among a subset of patients (N = 70) with tumor materials, we conducted omics analyses and obtained targeted panel sequencing and SNP array genotyping data for 51 and 49 patients, respectively. The most recurrent somatic driver mutations included PIK3CA (12%), followed by chromatin remodeling genes PBRM1 and SETD2. Amplification of the 6q27 region, containing the chordoma susceptibility gene TBXT, was detected in eight patients (16.3%). Clival patients appeared to be less likely to carry driver gene mutations, chromosome arm level deletion events (e.g., 5p, 5p, and 9p), or 6q27 amplification compared to sacral patients. After adjusting for age, sex, tumor site, and additional treatment, patients with somatic deletions of 14q (OR = 13.73, 95% CI 1.96-96.02, P = 0.008) and 18p (OR = 13.68, 95% CI 1.77-105.89, P = 0.012) were more likely to have persistent chordoma. The study highlights genomic heterogeneity in chordoma, potentially linked to location and clinical progression.

Xing Hua

Department of Neurology,
West China Hospital,
Department of Neurology, West China Hospital

Sichuan University

Evaluating Cell Death Signaling by Immunofluorescence in a Rat Model of Ischemic Stroke

Xing Hua

Department of Neurology,West China Hospital,Department of Neurology, West China Hospital

Sichuan University

Evaluating Cell Death Signaling by Immunofluorescence in a Rat Model of Ischemic Stroke

Department of Neurology,
West China Hospital,
Department of Neurology, West China Hospital