Evaluation of Carotid Stiffness in Metabolic Syndrome by Real-Time Shear Wave Elasticity Imaging and Ultrafast Pulse Wave Velocity.

OBJECTIVE: This study utilized real-time shear wave elasticity imaging (SWE) and ultrafast pulse wave velocity (ufPWV) to assess carotid arterial stiffness, aiming to predict atherosclerosis risk in patients with metabolic syndrome (MS). METHODS: In this study, 181 patients with metabolic syndrome (MS group) were compared with 73 healthy adults. The MS group was divided into three groups: MS I group: CIMT was normal (CIMT < 1.0 mm, no plaque, n = 61); MS II group: CIMT thickening (1.0 mm ≤ CIMT<1.5 mm, no plaque, n = 39); MS III group: plaque group (CIMT ≥ 1.5 mm, plaque, n = 81). Concurrently, the group of 73 healthy individuals was designated as the control set (NC). Parameters assessed include carotid intima-media thickness (CIMT), elastic modulus values of the carotid artery's anterior and posterior walls (Mean, Max, Min), pulse wave velocity at systole's commencement (PWV-BS), and pulse wave velocity at systole's termination (PWV-ES). Differences, distribution characteristics, and correlations across these groups were analyzed. RESULTS: A significant association was found between PWV-BS, PWV-ES, and arteriosclerosis severity, with these factors gaining importance as arteriosclerosis progressed. Notably, PWV-ES differences were significant across the four groups (p < 0.05). Both MS III and MS II groups exhibited higher PWV-ES values compared to the MS I group and controls. Statistically significant differences were observed between MS III, MS II, and MS I groups relative to the control group (p < 0.05). Additionally, the Mean, Max, and Min values of the anterior and posterior carotid walls in the MS III group surpassed those of the other groups. CONCLUSION: Real-time shear wave elasticity imaging and ultrafast pulse wave velocity are valuable tools for assessing atherosclerosis risk in MS patients. These non-invasive, safe, and reproducible imaging techniques can quantitatively evaluate the stiffness of the common carotid artery's wall, offering important insights into cardiovascular risk assessment.

Combination of mild therapeutic hypothermia and adipose-derived stem cells for ischemic brain injury.

Mild therapeutic hypothermia has been shown to mitigate cerebral ischemia, reduce cerebral edema, and improve the prognosis of patients with cerebral ischemia. Adipose-derived stem cell-based therapy can decrease neuronal death and infiltration of inflammatory cells, exerting a neuroprotective effect. We hypothesized that the combination of mild therapeutic hypothermia and adipose-derived stem cells would be neuroprotective for treatment of stroke. A rat model of transient middle cerebral artery occlusion was established using the nylon monofilament method. Mild therapeutic hypothermia (33°C) was induced after 2 hours of ischemia. Adipose-derived stem cells were administered through the femoral vein during reperfusion. The severity of neurological dysfunction was measured by a modified Neurological Severity Score Scaling System. The area of the infarct lesion was determined by 2,3,5-triphenyltetrazolium chloride staining. Apoptotic neurons were detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining. The regeneration of microvessels and changes in the glial scar were detected by immunofluorescence staining. The inflammatory responses after ischemic brain injury were evaluated by in situ staining using markers of inflammatory cells. The expression of inflammatory cytokines was measured by reverse transcription-polymerase chain reaction. Compared with mild therapeutic hypothermia or adipose-derived stem cell treatment alone, their combination substantially improved neurological deficits and decreased infarct size. They synergistically reduced the number of TUNEL-positive cells and glial fibrillary acidic protein expression, increased vascular endothelial growth factor levels, effectively reduced inflammatory cell infiltration and down-regulated the mRNA expression of the proinflammatory cytokines interleukin-1ß, tumor necrosis factor-α and interleukin-6. Our findings indicate that combined treatment is a better approach for treating stroke compared with mild therapeutic hypothermia or adipose-derived stem cells alone.

Intravenous Administration of Adipose-Derived Stem Cell Protein Extracts Improves Neurological Deficits in a Rat Model of Stroke.

Treatment of adipose-derived stem cell (ADSC) substantially improves the neurological deficits during stroke by reducing neuronal injury, limiting proinflammatory immune responses, and promoting neuronal repair, which makes ADSC-based therapy an attractive approach for treating stroke. However, the potential risk of tumorigenicity and low survival rate of the implanted cells limit the clinical use of ADSC. Cell-free extracts from ADSC (ADSC-E) may be a feasible approach that could overcome these limitations. Here, we aim to explore the potential usage of ADSC-E in treating rat transient middle cerebral artery occlusion (tMCAO). We demonstrated that intravenous (IV) injection of ADSC-E remarkably reduces the ischemic lesion and number of apoptotic neurons as compared to other control groups. Although ADSC and ADSC-E treatment results in a similar degree of a long-term clinical beneficial outcome, the dynamics between two ADSC-based therapies are different. While the injection of ADSC leads to a relatively mild but prolonged therapeutic effect, the administration of ADSC-E results in a fast and pronounced clinical improvement which was associated with a unique change in the molecular signature suggesting that potential mechanisms underlying different therapeutic approach may be different. Together these data provide translational evidence for using protein extracts from ADSC for treating stroke.

IRGM1 enhances B16 melanoma cell metastasis through PI3K-Rac1 mediated epithelial mesenchymal transition.

Melanoma is one of the most aggressive skin cancers and is well known for its high metastatic rate. Studies have shown that epithelial mesenchymal transition (EMT) is essential for melanoma cell metastasis. However, the molecular mechanisms underlying EMT are still not fully understood. We have shown that IRGM1, a member of immunity-related GTPase family that regulates immune cell motility, is highly expressed by melanoma cells. The current study aimed to explore whether and how IRGM1 may regulate melanoma cell metastasis. To test this, we modified IRGM1 expression in B16 melanoma cells. We found that over-expression of IRGM1 substantially enhanced pulmonary metastasis in vivo. In keeping with that, knocking-in IRGM1 strongly enhanced while knocking-down IRGM1 impaired B16 cell migration and invasion ability in vitro. Interestingly, we observed that IRGM1 enhanced F-actin polymerization and triggers epithelial mesenchymal transition (EMT) through a mechanism involved in PIK3CA mediated Rac1 activation. Together, these data reveals a novel molecular mechanism that involved in melanoma metastasis.