Changes in Vertebrobasilar Artery Dissection Visible with High-Resolution Vessel Wall Imaging: A Serial Follow-Up Study

Background: High-resolution vessel wall imaging (HR-VWI) can identify vertebrobasilar artery dissections (VBADs) due to its good intramural hematoma and intimal flap visualization. Although the clinical course of VBADs is known to be benign, changes in VBADs visible using HR-VWI at follow-up are unknown. Thus, this study aimed to assess serial changes in VBADs using HR-VWI at follow-up. Materials and methods: Patients with neurological symptoms from VBADs who had undergone both initial and follow-up HR-VWI examinations were retrospectively enrolled. Enrolled patients with VBADs at the initial HR-VWI after acute symptom onset underwent serial follow-up with HR-VWI at 3, 6, 12, and 24 months. Patients were classified into three groups based on the results of follow-up HR-VWI examinations: type 1 = wall thickness of the dissected artery; type 2 = no interval change; and type 3 = occlusion. Results: Fifteen patients (median age: 50 years, nine males) were enrolled in this study. All patients initially showed an intimal flap and a double lumen. Twelve (80%) patients showed strong wall enhancement. Nine (60%) patients had an intramural hematoma. During serial follow-up, nine (60.0%) patients showed type 1 lesions due to attachment of the intimal flap to the vessel wall, five (33.3%) showed type 2, and one showed type 3. Four patients with BA dissection showed type 2 lesions without change in the intimal flap or the double lumen. Conclusions: Changes in VBADs in HR-VWI were observed during the follow-up period. Most patients with VBADs showed the healing process, such as the disappearance of the intimal flap and the double lumen

Acute Distal Vertebral Artery Occlusion in Patients with Asymmetrical Vertebral Artery Geometry: Role of Black-Blood-Enhanced MR Imaging

Background: The purpose of this study was to evaluate the diagnostic value of contrast enhancement in a unilateral distal vertebral artery (VA) using black blood (BB)-enhanced magnetic resonance (MR) imaging in patients with acute neurological symptoms and asymmetrical VA geometry. Methods: From January 2020 to August 2021, we retrospectively analyzed BB-contrast-enhanced MR imaging and MR angiography (MRA) findings in stroke patients visiting the emergency room for an evaluation of acute neurological symptoms. We classified four patterns according to asymmetrical VA geometry using MRA and contrast enhancement using BB-enhanced MR imaging: type 1 = enhanced VA + no visualization of VA, type 2 = enhanced VA + hypoplastic VA, type 3 = non-enhanced VA + hypoplastic VA, or type 4 = non-enhanced VA + no visualization of VA. Results: In total, 288 patients (type 1 = 65, type 2 = 17, type 3 = 130, type 4 = 76) were enrolled in this study. Of these patients, 82 (28.5%) showed contrast enhancement of a unilateral distal VA on BB-enhanced MR imaging, and 51 (17.8%) had positive findings on diffusion-weighted imaging (DWI) in the ipsilateral medulla, pons, or posterior inferior cerebellar artery (PICA) territory. The contrast enhancement of a unilateral distal VA using BB-enhanced MR imaging demonstrated a significantly higher prevalence in patients with acute infarction on DWI (50.0% vs. 4.9%, p < 0.001). Conclusions: The contrast enhancement of a unilateral distal VA on BB-enhanced MR imaging is associated with acute infarction of the medulla, pons, or PICA territory and suggests acute occlusion of a distal VA

Prevalence of Symptomatic Nonstenotic Carotid Disease Using Simultaneous Non-Contrast Angiography and Intraplaque Hemorrhage Imaging for MR Screen Protocol

Background: To determine the prevalence of symptomatic nonstenotic carotid disease (SyNC) using simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) imaging for patients with acute stroke as an MR screen protocol and to assess imaging findings of carotid plaques. Patients and Methods: From May 2020 to October 2021, 2459 patients with suspected acute neurological symptoms were evaluated with brain diffusion-weighted imaging (DWI) and carotid SNAP imaging. We analyzed the degree of stenosis and intraplaque hemorrhage (IPH) using SNAP imaging. Prevalence of SyNC and risk factors for stroke in patients with SyNC were determined. We performed subgroup multivariate analysis between SyNC and other etiologies of stroke (non-SyNC). Results: Of 4608 carotid arteries in 2304 patients enrolled in this study, 454 (9.9%) plaques (both lesions in 128 patients) were found on SNAP imaging. Of these plaques, 353 (77.8%) showed stenosis of <50%. Of plaques with <50% stenosis, 47 (13.3%) patients had a territorial acute focal infarction. Seventeen (36.2%) were classified with embolic stroke of undetermined source (ESUS) and SyNC. High maximal wall thickness and carotid IPH were identified as influencing factors for SyNC. Conclusion: For patients with <50% stenosis and territorial infarction, SyNC is a relatively important source of stroke. Especially, high maximal wall thickness and carotid IPH are important risk factors for SyNC

Effect of diabetes on exosomal miRNA profile in patients with obesity

Introduction Obesity is a risk factor for type 2 diabetes mellitus (T2DM) and cardiovascular disease. T2DM increases the risk of cardiovascular-related death. We investigated changes in circulating exosomal microRNA (miRNA) profiles in patients with DM with obesity compared with patients without DM with obesity.Research design and methods This prospective study involved 29 patients with obesity (patients without DM=16, patients with DM=13) and healthy volunteers (HVs) (n=18). We measured circulating levels of exosomal miRNAs by next-generation sequencing and compared miRNA levels across the three groups.Results The expression levels of 25 miRNAs (upregulated=14, downregulated=11) differed between patients with obesity with DM and patients with obesity without DM. Compared with HV, patients with DM with obesity had 53 dysregulated miRNAs. Additionally, moving stepwise from HV to patients with obesity without DM to patients with obesity with DM, there was a consistent increase in expression levels of miR-23a-5p and miR-6087 and a consistent decrease in expressions levels of miR-6751-3p.Conclusions Our data show that the exosomal miRNAs is altered by dysregulated glucose metabolism in patients with obesity. This circulating exosomal miRNA signature in patients with obesity with or without DM is a potential biomarker and therapeutic target in these patients

Embryonic Stem Cell–Derived mmu-miR-291a-3p Inhibits Cellular Senescence in Human Dermal Fibroblasts Through the TGF-β Receptor 2 Pathway

Abstract Senescent cells accumulate in various tissues over time and contribute to tissue dysfunction and aging-associated phenotypes. Accumulating evidence suggests that cellular senescence can be inhibited through pharmacological intervention, as well as through treatment with soluble factors derived from embryonic stem cells (ESCs). In an attempt to investigate the anti-senescence factors secreted by ESCs, we analyzed mouse ESC-derived extracellular microRNAs in conditioned medium via microRNA array analysis. We selected mmu-miR-291a-3p as a putative anti-senescence factor via bioinformatics analysis. We validated its inhibitory effects on replicative, Adriamycin-induced, and ionizing radiation–induced senescence in human dermal fibroblasts. Treatment of senescent cells with mmu-miR-291a-3p decreased senescence-associated β-galactosidase activity, enhanced proliferative potential, and reduced mRNA and protein expression of TGF-β receptor 2, p53, and p21. mmu-miR-291a-3p in conditioned medium was enclosed in ESC-derived exosomes and exosomes purified from ESC conditioned medium inhibited cellular senescence. The inhibitory effects of mmu-miR-291a-3p were mediated through the TGF-β receptor 2 signaling pathway. Hsa-miR-371a-3p and hsa-miR-520e, the human homologs of mmu-miR-291a-3p, showed similar anti-senescence activity. Furthermore, mmu-miR-291a-3p accelerated the excisional skin wound healing process in aged mice. Our results indicate that the ESC-derived mmu-miR-291a-3p is a novel candidate agent that can be utilized for cell-free therapeutic intervention against aging and aging-related diseases

Effects of Gardeniae Fructus Extract and Geniposide on Promoting Ligament Cell Proliferation and Collagen Synthesis

Korean Government; Korea Research Foundation [KRF-2007-211-E00002]; Korean Government (MOEHRRD) [KRF-2008-331-E00451]Gardeniae Fructus is a traditional medicine used for the treatment of contusion such as ankle sprain. Geniposide is one of the main components of Gardeniae Fructus with diverse biological activities. In order to gain further insight into the therapeutic action of Gardeniae Fructus extract (GFE) and geniposide on ligament injuries, a new in vitro model was developed in the present study. Rat hind ankle ligament fibroblasts (RHALFs) derived from Sprague-Dawley rats were cultured, and the cell proliferation and collagen content were examined by MTT and a Sirius Red-based colorimetric assay after stimulating with each drug. The cell growth of RHALFs was promoted by culturing with 37.5-150 mu g/mL of GFE and 25-200 mu M of geniposide. The content of collagen in the RHALFs was significantly increased up to 131.4% and 124.2% of the control value by culturing with the GFE and geniposide, respectively. By contrast, both cell growth and collagen content were impaired by adding 25-200 mu M of diclofenac, one of the common medications for ligament injuries. The findings suggest that GFE and geniposide may ameliorate the treatment of ligament injuries by proliferating ligament fibroblasts and promoting the synthesis of collagen. However, the use of diclofenac to treat acute ligament injuries should be reassessed although it possesses a potential effect on relieving symptoms. Copyright (C) 2009 John Wiley & Sons, Ltd

Inhibition of Osteoarthritis-Related Molecules by Isomucronulatol 7-<i>O</i>-β-<span style="font-variant: small-caps">d</span>-glucoside and Ecliptasaponin A in IL-1β-Stimulated Chondrosarcoma Cell Model

Osteoarthritis (OA) is the common form of arthritis and is characterized by disability and cartilage degradation. Although natural product extracts have been reported to have anti-osteoarthritic effects, the potential bioactivity of Ryupunghwan (RPH), a traditional Korean medicinal botanical formula that contains Astragalus membranaceus, Turnera diffusa, Achyranthes bidentata, Angelica gigas, Eclipta prostrata, Eucommia ulmoides, and Ilex paraguariensis, is not known well. Therefore, the inhibitory effects of single compounds isolated from RPH on the OA-related molecules were investigated using IL-1&#946;-stimulated chondrosarcoma SW1353 (SW1353) cell model. Two bioactive compounds, isomucronulatol 7-O-&#946;-d-glucoside (IMG) and ecliptasaponin A (ES) were isolated and purified from RPH using column chromatography, and then the structures were analyzed using ESI-MS, 1H-NMR, and 13C-NMR spectrum. The expression or amount of matrix metalloproteinase 13 (MMP13), COX1/2, TNF-&#945;, IL-1&#946; or p65 was determined by RT-PCR, Western blot, and enzyme-linked immunosorbent assay (ELISA). RPH pretreatment reduced the expression and amounts of MMP13, and the expression of collagen II, COX1/2, TNF-&#945;, IL-1&#946; or p65, which were increased in IL-1&#946;-stimulated SW1353 cells. IMG reduced the expression of all OA-related molecules, but the observed inhibitory effect was less than that of RPH extract. The other single compound ES showed the reduced expression of all OA-related molecules, and the effect was stronger than that in IMG (approximately 100 fold). Combination pretreatment of both single components remarkably reduced the expression of MMP13, compared to each single component. These synergic effects may provide potential molecular modes of action for the anti-osteoarthritic effects of RPH observed in clinical and animal studies

A case report of quadruple cancer in a single patient including the breast, rectum, ovary, and endometrium

Multiple primary cancer is defined as the multiple occurrence of malignant neoplasms in the same individual. Due to the development of new diagnostic techniques and the rise in long-term survival of cancer, reports of multiple primary cancers have gradually increased. Herein, we describe the case of a 68-year-old female patient with quadruple primary cancer of the breast, rectum, ovary, and endometrium. For its great rarity, we report this case with a review of the literature

mirRICH, a simple method to enrich the small RNA fraction from over-dried RNA pellets

<p>Techniques to isolate the small RNA fraction (<200nt) by column-based methods are commercially available. However, their use is limited because of the relatively high cost. We found that large RNA molecules, including mRNAs and rRNAs, are aggregated together in the presence of salts when RNA pellets are over-dried. Moreover, once RNA pellets are over-dried, large RNA molecules are barely soluble again during the elution process, whereas small RNA molecules (<100nt) can be eluted. We therefore modified the acid guanidinium thiocyanate-phenol-chloroform (AGPC)-based RNA extraction protocol by skipping the 70% ethanol washing step and over-drying the RNA pellet for 1 hour at room temperature. We named this novel small RNA isolation method “mirRICH.” The quality of the small RNA sequences was validated by electrophoresis, next-generation sequencing, and quantitative PCR, and the findings support that our newly developed column-free method can successfully and efficiently isolate small RNAs from over-dried RNA pellets.</p