Exacerbated ischemic brain damage in type 2 diabetes via methylglyoxal-mediated miR-148a-3p decline.

Background: Although microvascular dysfunction is a widespread phenomenon in type 2 diabetes (T2D) and is recognized as a main cause of T2D-aggravated ischemic stroke injury, the underlying mechanisms by which T2D-mediated exacerbation of cerebral damage after ischemic stroke is still largely uncharacterized. Here, we found that methylglyoxal-mediated miR-148a-3p decline can trigger blood-brain barrier dysfunction, thereby exacerbating cerebrovascular injury in diabetic stroke.

Methods: Using T2D models generated with streptozotocin plus a high-fat diet or db/db mice, and then inducing focal ischemic stroke through middle cerebral artery occlusion and reperfusion (MCAO/R), we established a diabetic stroke mouse model.

Rational development of fingolimod nano-embedded microparticles as nose-to-brain neuroprotective therapy for ischemic stroke.

Ischemic stroke is one of the major diseases causing varying degrees of dysfunction and disability worldwide. The current management of ischemic stroke poses significant challenges due to short therapeutic windows and limited efficacy, highlighting the pressing need for novel neuroprotective treatment strategies. Previous studies have shown that fingolimod (FIN) is a promising neuroprotective drug.

How to use the Surveillance, Epidemiology, and End Results (SEER) data: research design and methodology.

In the United States (US), the Surveillance, Epidemiology, and End Results (SEER) program is the only comprehensive source of population-based information that includes stage of cancer at the time of diagnosis and patient survival data. This program aims to provide a database about cancer incidence and survival for studies of surveillance and the development of analytical and methodological tools in the cancer field. Currently, the SEER program covers approximately half of the total cancer patients in the US.

Plasma metabolomic profiling of patients with transient ischemic attack reveals positive role of neutrophils in ischemic tolerance.

Background: Transient ischemic attack (TIA) induces ischemic tolerance that can reduce the subsequent ischemic damage and improve prognosis of patients with stroke. However, the underlying mechanisms remain elusive. Recent advances in plasma metabolomics analysis have made it a powerful tool to investigate human pathophysiological phenotypes and mechanisms of diseases.

Spatial Proteomics Analysis of Soft and Stiff Regions in Human Acute Arterial Thrombus.

Background: The soft regions of a thrombus tend to be more susceptible to r-tPA (recombinant tissue-type plasminogen activator)-mediated thrombolysis and are more easily removed by mechanical thrombectomy than the stiff counterpart. This study aimed to understand the molecular pathological differences between the soft and stiff regions of human arterial thrombus.

Methods: We developed a spatial proteomic workflow combining proteomics with laser-captured microdissection to analyze human arterial thrombi with Masson trichrome staining to identify stiff and soft regions from 2 independent cohorts of patients with acute myocardial or cerebral infarction.

Maf1 is an intrinsic suppressor against spontaneous neural repair and functional recovery after ischemic stroke.

Introduction: Spontaneous recovery after CNS injury is often very limited and incomplete, leaving most stroke patients with permanent disability. Maf1 is known as a key growth suppressor in proliferating cells. However, its role in neuronal cells after stroke remains unclear.

Non-enzymatic role of SOD1 in intestinal stem cell growth.

Superoxide dismutase 1 (SOD1) modulates intestinal barrier integrity and intestinal homeostasis as an antioxidant enzyme. Intestinal homeostasis is maintained by the intestinal stem cells (ISCs). However, whether and how SOD1 regulates ISCs is unknown.

Consensus clustering of gene expression profiles in peripheral blood of acute ischemic stroke patients.

Acute ischemic stroke (AIS) is a primary cause of mortality and morbidity worldwide. Currently, no clinically approved immune intervention is available for AIS treatment, partly due to the lack of relevant patient classification based on the peripheral immunity status of patients with AIS. In this study, we adopted the consensus clustering approach to classify patients with AIS into molecular subgroups based on the transcriptomic profiles of peripheral blood, and we identified three distinct AIS molecular subgroups and 8 modules in each subgroup by the weighted gene co-expression network analysis.

Mediating bio-fate of polymeric cholecalciferol nanoparticles through rational size control.

Whilst 10-200 nm polymeric nanoparticles hold enormous medical potential, successful clinical translation remains scarce. There is an inadequate understanding of how these nanoparticles could be fabricated with consistent particle architecture in this size range, as well as their corresponding biological performance. We seek to fill this important knowledge gap by employing Design of Experiment (DoE) to examine critical formulation and processing parameters of cholecalciferol (VitD3)-loaded nanoparticles by flash nanoprecipitation (FNP).

Brain delivering RNA-based therapeutic strategies by targeting mTOR pathway for axon regeneration after central nervous system injury.

Injuries to the central nervous system (CNS) such as stroke, brain, and spinal cord trauma often result in permanent disabilities because adult CNS neurons only exhibit limited axon regeneration. The brain has a surprising intrinsic capability of recovering itself after injury. However, the hostile extrinsic microenvironment significantly hinders axon regeneration.

CircOGDH Is a Penumbra Biomarker and Therapeutic Target in Acute Ischemic Stroke.

Background: Acute ischemic stroke (AIS) is a leading cause of disability and mortality worldwide. Prediction of penumbra existence after AIS is crucial for making decision on reperfusion therapy. Yet a fast, inexpensive, simple, and noninvasive predictive biomarker for the poststroke penumbra with clinical translational potential is still lacking.

Circular RNA circ-FoxO3 attenuates blood-brain barrier damage by inducing autophagy during ischemia/reperfusion.

Blood-brain barrier (BBB) damage can be a result of central nervous system (CNS) diseases and may be a cause of CNS deterioration. However, there are still many unknowns regarding effective and targeted therapies for maintaining BBB integrity during ischemia/reperfusion (I/R) injury. In this study, we demonstrate that the circular RNA of FoxO3 (circ-FoxO3) promotes autophagy via mTORC1 inhibition to attenuate BBB collapse under I/R.

Pharmacological preconditioning by TERT inhibitor BIBR1532 confers neuronal ischemic tolerance through TERT-mediated transcriptional reprogramming.

After a sublethal ischemic preconditioning (IPC) stimulus, the brain has a remarkable capability of acquiring tolerance to subsequent ischemic insult by establishing precautionary self-protective mechanism. Understanding this endogenous mechanism would reveal novel and effective neuroprotective targets for ischemic brain injury. Our previous study has implied that telomerase reverse transcriptase (TERT) is associated with IPC-induced tolerance.

Inhibition of PDE1-B by Vinpocetine Regulates Microglial Exosomes and Polarization Through Enhancing Autophagic Flux for Neuroprotection Against Ischemic Stroke.

Exosomes contribute to cell-cell communications. Emerging evidence has shown that microglial exosomes may play crucial role in regulation of neuronal functions under ischemic conditions. However, the underlying mechanisms of microglia-derived exosome biosynthesis are largely unknown.

Rifampicin Suppresses Amyloid-β Accumulation Through Enhancing Autophagy in the Hippocampus of a Lipopolysaccharide-Induced Mouse Model of Cognitive Decline.

Background: Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) deposition. The metabolism of Aβ is critically affected by autophagy. Although rifampicin is known to mediate neuroinflammation, the underlying mechanism by which rifampicin regulates the cognitive sequelae remains unknown.

USP8 protects against lipopolysaccharide-induced cognitive and motor deficits by modulating microglia phenotypes through TLR4/MyD88/NF-κB signaling pathway in mice.

Ubiquitin-specific protease 8 (USP8) regulates inflammation in vitro; however, the mechanisms by which USP8 inhibits neuroinflammation and its pathophysiological functions are not completely understood. In this study, we aimed to determine whether USP8 exerts neuroprotective effects in a mouse model of lipopolysaccharide (LPS)-induced cognitive and motor impairment. We commenced intracerebroventricular USP8 administration 7 days prior to i.

Identification of Blood Circular RNAs as Potential Biomarkers for Acute Ischemic Stroke.

Many hospitals lack facilities for accurate diagnosis of acute ischemic stroke (AIS). Circular RNA (circRNA) is highly expressed in the brain and is closely associated with stroke. In this study, we examined whether the blood-borne circRNAs could be promising candidates as adjunctive diagnostic biomarkers and their pathophysiological roles after stroke.

Prostaglandin E1 Alleviates Cognitive Dysfunction in Chronic Cerebral Hypoperfusion Rats by Improving Hemodynamics.

Compensatory vascular mechanisms can restore cerebral blood flow (CBF) but fail to protect against chronic cerebral hypoperfusion (CCH)-mediated neuronal damage and cognitive impairment. Prostaglandin E1 (PGE1) is known as a vasodilator to protect against ischemic injury in animal models, but its protective role in CCH remains unclear. To determine the effect of PGE1 on cerebral hemodynamics and cognitive functions in CCH, bilateral common carotid artery occlusion (BCCAO) was used to mimic CCH in rats, which were subsequently intravenously injected with PGE1 daily for 2 weeks.

HMG-CoA Reductase Inhibitors Attenuate Neuronal Damage by Suppressing Oxygen Glucose Deprivation-Induced Activated Microglial Cells.

Ischemic stroke is usually followed by inflammatory responses mediated by microglia. However, the effect of statins on directly preventing posthypoxia microglia inflammatory factors to prevent injury to surrounding healthy neurons is unclear. Atorvastatin and rosuvastatin, which have different physical properties regarding their lipid and water solubility, are the most common HMG-CoA reductase inhibitors (statins) and might directly block posthypoxia microglia inflammatory factors to prevent injury to surrounding neurons.

A balancing act: mTOR integrates nutrient signals to regulate redox-dependent growth and survival through SOD1.

Maintaining cellular redox is critical for growth, metabolism and survival in response to changing environments. How nutrients regulate this process is a long-standing fundamental question in cell biology. Our recent study revealed a conserved mechanism by which eukaryotes, particularly cancer cells, couple nutrient signaling to dynamically regulate redox homeostasis.

SOD1 Phosphorylation by mTORC1 Couples Nutrient Sensing and Redox Regulation.

Nutrients are not only organic compounds fueling bioenergetics and biosynthesis, but also key chemical signals controlling growth and metabolism. Nutrients enormously impact the production of reactive oxygen species (ROS), which play essential roles in normal physiology and diseases. How nutrient signaling is integrated with redox regulation is an interesting, but not fully understood, question.

Neuroprotective Mechanisms of Polysaccharides Against Ischemic Insults by Regulating NR2B and NR2A Containing NMDA Receptor Signaling Pathways.

Glutamate excitotoxicity plays an important role in neuronal death after ischemia. However, all clinical trials using glutamate receptor inhibitors have failed. This may be related to the evidence that activation of different subunit of NMDA receptor will induce different effects.

Dl-3-n-Butylphthalide Treatment Enhances Hemodynamics and Ameliorates Memory Deficits in Rats with Chronic Cerebral Hypoperfusion.

Our previous study has revealed that chronic cerebral hypoperfusion (CCH) activates a compensatory vascular mechanism attempting to maintain an optimal cerebral blood flow (CBF). However, this compensation fails to prevent neuronal death and cognitive impairment because neurons die prior to the restoration of normal CBF. Therefore, pharmacological invention may be critical to enhance the CBF for reducing neurodegeneration and memory deficit.

Dynamic monitoring of antimicrobial resistance using magnesium zinc oxide nanostructure-modified quartz crystal microbalance.

Antimicrobial resistance (AMR) is becoming a major global-health concern prompting an urgent need for highly-sensitive and rapid diagnostic technology. Traditional assays available for monitoring bacterial cultures are time-consuming and labor-intensive. We present a magnesium zinc oxide (MZO) nanostructure-modified quartz crystal microbalance (MZO-QCM) biosensor to dynamically monitor antimicrobial effects on E.