Artemisia argyi ethanol extract ameliorates nonalcoholic steatohepatitis-induced liver fibrosis by modulating gut microbiota and hepatic signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia argyi (AA), a herbal medicine traditionally used in Asian countries, to treat inflammatory conditions such as eczema, dermatitis, arthritis, allergic asthma and colitis. However, the mechanism of action of this plant with regard to hepatitis and other liver-related diseases is still unclear. AIM: This study aimed to investigate the effects of AA ethanol extract on NASH-related fibrosis and gut microbiota in a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-induced mouse model. METHODS: Male C57BL/6J mice were fed CDAHFD, with or without AA ethanol extract treatment. Biochemical markers, lipid profiles, hepatic mRNA expression levels of key genes, and the fibrosis area were assessed. In vitro, TGF-ß-stimulated human hepatic stellate LX-2 cells and mouse primary hepatic stellate cells (mHSCs) were used to elucidate the effects of AA ethanol extract on fibrosis and steatosis. 16S rRNA sequencing, QIIME2, and PICRUST2 were employed to analyze gut microbial diversity, composition, and functional pathways. RESULTS: Treatment with the AA ethanol extract improved plasma and liver lipid profiles, modulated hepatic mRNA expression levels of antioxidant, lipolytic, and fibrosis-related genes, and significantly reduced CDAHFD-induced hepatic fibrosis. Gut microbiota analysis revealed a marked decrease in Acetivibrio ethanolgignens abundance upon treatment with the AA ethanol extract, and its functional pathways were significantly correlated with NASH/fibrosis markers. The AA ethanol extract and its active components (jaceosidin, eupatilin, and chlorogenic acid) inhibited fibrosis-related markers in LX-2 and mHSC. CONCLUSION: The AA ethanol extract exerted therapeutic effects on CDAHFD-induced liver disease by modulating NASH/fibrosis-related factors and gut microbiota composition. Notably, AA treatment reduced the abundance of the potentially profibrotic bacterium (A. ethanolgignens). These findings suggest that AA is a promising candidate for treating NASH-induced fibrosis.

Long-term effects of local radiotherapy on growth and vertebral features in children with high-risk neuroblastoma.

BACKGROUND: To evaluate the effects of local radiotherapy (RT) on growth, we evaluated the chronological growth profiles and vertebral features of children with high-risk neuroblastoma. METHODS: Thirty-eight children who received local photon or proton beam therapy to the abdomen or retroperitoneum between January 2014 and September 2019 were included. Simple radiography of the thoracolumbar spine was performed before and every year after RT. The height and vertical length of the irradiated vertebral bodies (VBs) compared with the unirradiated VBs (vertebral body ratio, VBR) were analyzed using the linear mixed model. Shape feature analysis was performed to compare the irradiated and unirradiated vertebrae. RESULTS: The follow-up was a median of 53.5 months (range, 21-81 months) after RT. A decline in height z-scores was mainly found in the early phase after treatment. In the linear mixed model with height, the initial height (fixed, p < 0.001), sex (time interaction, p = 0.008), endocrine dysfunction (time interaction, 0.019), and age at diagnosis (fixed and time interaction, both p = 0.002) were significant. Unlike the trend in height, the change in VBR (ΔVBR) decreased gradually (p < 0.001). The ΔVBR in the group that received more than 30 Gy decreased more than in the group that received smaller doses. In the shape feature analysis, the irradiated VBs changed to a more irregular surface that were neither round nor rectangular. CONCLUSION: The irradiated VBs in children were gradually restricted compared to the unirradiated VBs in long-term follow-up, and higher RT doses were significantly affected. Radiation-induced irregular features of VBs were observed.

Cornflower Extract and Its Active Components Alleviate Dexamethasone-Induced Muscle Wasting by Targeting Cannabinoid Receptors and Modulating Gut Microbiota.

Sarcopenia, a decline in muscle mass and strength, can be triggered by aging or medications like glucocorticoids. This study investigated cornflower (Centaurea cyanus) water extract (CC) as a potential protective agent against DEX-induced muscle wasting in vitro and in vivo. CC and its isolated compounds mitigated oxidative stress, promoted myofiber growth, and boosted ATP production in C2C12 myotubes. Mechanistically, CC reduced protein degradation markers, increased mitochondrial content, and activated protein synthesis signaling. Docking analysis suggested cannabinoid receptors (CB) 1 and 2 as potential targets of CC compounds. Specifically, graveobioside A from CC inhibited CB1 and upregulated CB2, subsequently stimulating protein synthesis and suppressing degradation. In vivo, CC treatment attenuated DEX-induced muscle wasting, as evidenced by enhanced grip strength, exercise performance, and modulation of muscle gene expression related to differentiation, protein turnover, and exercise performance. Moreover, CC enriched gut microbial diversity, and the abundance of Clostridium sensu stricto 1 positively correlated with muscle mass. These findings suggest a multifaceted mode of action for CC: (1) direct modulation of the muscle cannabinoid receptor system favoring anabolic processes and (2) indirect modulation of muscle health through the gut microbiome. Overall, CC presents a promising therapeutic strategy for preventing and treating muscle atrophy.

Forsythia velutina Nakai extract: A promising therapeutic option for atopic dermatitis through multiple cell type modulation.

BACKGROUND: Atopic dermatitis (AD) is a complex condition characterized by impaired epithelial barriers and dysregulated immune cells. In this study, we demonstrated Forsythia velutina Nakai extract (FVE) simultaneously inhibits basophils, macrophages, keratinocytes, and T cells that are closely interrelated in AD development. METHODS: We analyzed the effect of FVE on nitric oxide and reactive oxygen species (ROS) production in macrophages, basophil degranulation, T cell activation, and tight junctions in damaged keratinocytes. Expression of cell-type-specific inflammatory mediators was analyzed, and the underlying signaling pathways for anti-inflammatory effects of FVE were investigated. The anti-inflammatory effects of FVE were validated using a DNCB-induced mouse model of AD. Anti-inflammatory activity of compounds isolated from FVE was validated in each immune cell type. RESULTS: FVE downregulated the expression of inflammatory mediators and ROS production in macrophages through TLR4 and NRF2 pathways modulation. It significantly reduced basophil degranulation and expression of type 2 (T2) and pro-inflammatory cytokines by perturbing FcεRI signaling. Forsythia velutina Nakai extract also robustly inhibited the expression of T2 cytokines in activated T cells. Furthermore, FVE upregulated the expression of tight junction molecules in damaged keratinocytes and downregulated leukocyte attractants, as well as IL-33, an inducer of T2 inflammation. In the AD mouse model, FVE showed superior improvement in inflammatory cell infiltration and skin structure integrity compared to dexamethasone. Dimatairesinol, a lignan dimer, was identified as the most potent anti-inflammatory FVE compound. CONCLUSION: Forsythia velutina Nakai extract and its constituent compounds demonstrate promising efficacy as a therapeutic option for prolonged AD treatment by independently inhibiting various cell types associated with AD and disrupting the deleterious link between them.

Insampaedok-San Extract Exerts an Immune-Enhancing Effect through NF-κB p65 Pathway Activation.

Insampaedok-san (IS) has traditionally been prescribed as a medication for cold-related symptoms in Northeast Asia, including Korea and China. In this study, we focused on elucidating the molecular mechanism underlying the immunomodulatory activity of IS water extract (ISE) in macrophages. ISE significantly enhanced the levels of nitric oxide (NO) and prostaglandin E2 (PGE2) by increasing the expression of inducible NO synthase and cyclooxygenase-2 (COX-2) in a dose-dependent manner. ISE, which consists of many herbs, contains a large number of active compounds whose pharmacological targets and mechanisms are complicated. Therefore, network pharmacology analysis was used to predict the potential key components, targets, and mechanisms of ISE as immunomodulators. Subsequently, the network pharmacology results were validated experimentally. Seven key components were identified through HPLC-QTOF-MS. As predicted by the network pharmacology analysis, ISE increased the mRNA expression of Tnf and Il6. Furthermore, ISE increased the phosphorylation, nuclear translocation, and transcriptional activity of the p65 subunit of the nuclear factor-κB (NF-κB) signaling pathway. In contrast, rapamycin, an NF-κB inhibitor, suppressed the ISE-induced mRNA expression of Tnf and Il6. In conclusion, ISE is an immune activator that can elevate the production of NO, PGE2, and proinflammatory cytokines mediated by NF-κB signaling.

Lithospermum erythrorhizon Siebold & Zucc. extract reduces the severity of endotoxin-induced uveitis.

BACKGROUND: Uveitis is an inflammatory eye condition that threatens vision, and effective anti-inflammatory treatments with minimal side effects are necessary to treat uveitis. PURPOSE: This study aimed to investigate the effects of Lithospermum erythrorhizon Siebold & Zucc. against endotoxin-induced uveitis in rat and mouse models. METHODS: Endotoxin-induced uveitis models of rats and mice were used to evaluate the effects of l. erythrorhizon treatment. Clinical inflammation scores and retinal thickness were assessed in the extract of l. erythrorhizon-treated rats. Histopathological examination revealed inflammatory cell infiltration into the ciliary body. Protein concentration, cellular infiltration, and prostaglandin-E2 levels were measured in the aqueous humor of the extract of l. erythrorhizon-treated rats. Protective effects of l. erythrorhizon on the anterior segment of the eye were examined in mice with endotoxin-induced uveitis. Additionally, we investigated the effect of l. erythrorhizon on the expression of pro-inflammatory cytokines [tumor necrosis factor alpha, interleukin-6, and interleukin-8] in lipopolysaccharide-stimulated THP1 human macrophages and examined the involvement of nuclear factor kappaB/activator protein 1 and interferon regulatory factor signaling pathways. Furthermore, three components of l. erythrorhizon were identified and assessed for their inhibitory effects on LPS-induced inflammation in RAW264.7 macrophage cells. RESULTS: Treatment of the extract of l. erythrorhizon significantly reduced clinical inflammation scores and retinal thickening in rats with endotoxin-induced uveitis. Histopathological examination revealed decreased inflammatory cell infiltration into the ciliary body. The extract of l. erythrorhizon effectively reduced the protein concentration, cellular infiltration, and PG-E2 levels in the aqueous humor of rats with endotoxin-induced uveitis. In mice with endotoxin-induced uveitis, the extract of l. erythrorhizon demonstrated a protective effect on the anterior segment of the eye by reducing inflammation and retinal thickening. The extract of l. erythrorhizon suppressed the expression of pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin-6, and interleukin-8) in lipopolysaccharide-induced inflammation in THP1 human macrophages, by modulating nuclear factor kappaB/activator protein 1 and interferon regulatory factor signaling pathways. Moreover, shikonin, acetylshikonin, and ß, ß-dimethylacryloylshikonin showed dose-dependent inhibition of nitric oxide, tumor necrosis factor alpha and interleukin-6 production in RAW264.7 macrophage cells. CONCLUSION: The extract of l. erythrorhizon is a potential therapeutic agent for uveitis management. Administration of the extract of l. erythrorhizon led to reduced inflammation, retinal thickening, and inflammatory cell infiltration in rat and mouse models of uveitis. The compounds (shikonin, acetylshikonin, and ß, ß-dimethylacryloylshikonin) identified in this study played crucial roles in mediating the anti-inflammatory effects of l. erythrorhizon. These findings indicate that the extract of l. erythrorhizon and its constituent compounds are promising candidates for further research and development of novel treatment modalities for uveitis.

Gene Signatures and Associated Transcription Factors of Allergic Rhinitis: KLF4 Expression Is Associated with Immune Response.

This study is aimed at investigating the potential molecular features of allergic rhinitis (AR) and identifying gene signatures and related transcription factors using transcriptome analysis and in silico datasets. Transcriptome profiles were obtained using three independent cohorts (GSE101720, GSE19190, and GSE46171) comprising healthy controls (HC) and patients with AR. The pooled dataset (n = 82) was used to identify the critical signatures of AR compared with HC. Subsequently, key transcription factors were identified by a combined analysis using transcriptome and in silico datasets. Gene ontology: bioprocess (GO: BP) analysis using differentially expressed genes (DEGs) revealed that immune response-related genes were significantly enriched in AR compared with HC. Among them, IL1RL1, CD274, and CD44 were significantly higher in AR patients. We also identified key transcription factors between HC and AR using the in silico dataset and found that AR samples frequently express KLF transcription factor 4 (KLF4), which regulates immune response-related genes including IL1RL1, CD274, and CD44 in human nasal epithelial cells. Our integrative analysis of transcriptomic regulation provides new insights into AR, which may help in developing precision management for patients with AR.

Neuroprotective Effects of Ethanol Extract of Polyscias fruticosa (EEPF) against Glutamate-Mediated Neuronal Toxicity in HT22 Cells.

In traditional herbal medicine, the Polyscias fruticosa has been frequently used for the treatment of ischemia and inflammation. Oxidative stress mediated by elevated glutamate levels cause neuronal cell death in ischemia and various neurodegenerative diseases. However, so far, the neuroprotective effects of this plant extract against glutamate-mediated cell death have not been investigated in cell models. The current study investigates the neuroprotective effects of ethanol extracts of Polyscias fruticosa (EEPF) and elucidates the underlying molecular mechanisms of EEPFs relevant to neuroprotection against glutamate-mediated cell death. The oxidative stress-mediated cell death was induced by 5 mM glutamate treatment in HT22 cells. The cell viability was measured by a tetrazolium-based EZ-Cytox reagent and Calcein-AM fluorescent dye. Intracellular Ca2+ and ROS levels were measured by fluorescent dyes, fluo-3 AM and 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA), respectively. Protein expressions of p-AKT, BDNF, p-CREB, Bax, Bcl-2, and apoptosis-inducing factor (AIF) were determined by western blot analysis. The apoptotic cell death was measured by flow cytometry. The in vivo efficacy of EEPF was evaluated using the Mongolian gerbil mouse by surgery-induced brain ischemia. EEPF treatment showed a neuroprotective effect against glutamate-induced cell death. The EEPF co-treatment reduced the intracellular Ca2+ and ROS and apoptotic cell death. Furthermore, it recovered the p-AKT, p-CREB, BDNF, and Bcl-2 levels decreased by glutamate. The EEPF co-treatment suppressed the activation of apoptotic Bax, the nuclear translocation of AIF, and mitogen-activated protein kinase (MAPK) pathway proteins (ERK1/2, p38, JNK). Further, EEPF treatment significantly rescued the degenerative neurons in the ischemia-induced Mongolian gerbil in vivo model. EEPF exhibited neuroprotective properties that suppress glutamate-mediated neurotoxicity. The underlying mechanism of EEPF is increasing the level of p-AKT, p-CREB, BDNF, and Bcl-2 associated with cell survival. It has therapeutic potential for the treatment of glutamate-mediated neuropathology.

Procaine Abrogates the Epithelial-Mesenchymal Transition Process through Modulating c-Met Phosphorylation in Hepatocellular Carcinoma.

EMT is a critical cellular phenomenon that promotes tumor invasion and metastasis. Procaine is a local anesthetic agent used in oral surgeries and as an inhibitor of DNA methylation in some types of cancers. In this study, we have investigated whether procaine can inhibit the EMT process in HCC cells and the preclinical model. Procaine suppressed the expression of diverse mesenchymal markers but induced the levels of epithelial markers such as E-cadherin and occludin in HGF-stimulated cells. Procaine also significantly reduced the invasion and migration of HCC cells. Moreover, procaine inhibited HGF-induced c-Met and its downstream oncogenic pathways, such as PI3K/Akt/mTOR and MEK/ERK. Additionally, procaine decreased the tumor burden in the HCC mouse model and abrogated lung metastasis. Overall, our study suggests that procaine may inhibit the EMT process through the modulation of a c-Met signaling pathway.

Antiallergic Effects of N,N-dicoumaroylspermidine Isolated from Lithospermum erythrorhizon on Mast Cells and Ovalbumin-Induced Allergic Rhinitis.

In East Asia, the dried root of Lithospermum erythrorhizon has been utilized as an anti-inflammatory, antipyretic, detoxifying, and anti-inflammatory agent. Recently, we reported that L. erythrorhizon protects against allergic rhinitis; however, the component within L. erythrorhizon that exerts antiallergic activity remains unknown. The purpose of the current study was to isolate and characterize the antiallergic active components in an ethanolic extract of L. erythrorhizon roots. We examined the antiallergic effects of L. erythrorhizon reflux ethanol extracts in an ovalbumin (OVA)-induced allergic rhinitis mouse model, and compared the chemical compounds extracted using the hot reflux and cold extraction methods. Chromatographic separation identified two novel anthraquinones, erythrin A and B, one newly discovered compound from the Lithospermum genus, N1″,N3″-dicoumaroylspermidine, and nineteen other recognized compounds. Their chemical structures were elucidated by single (1D) and 2D analysis of nuclear magnetic resonance (NMR) spectroscopic data, as well as high resolution mass spectrometry. Among the identified compounds, N,N'-dicoumaroylspermidine strongly inhibited the release of ß-hexosaminidase, as well as the production of IL-3, IL-4, and IL-13 by IgE-sensitized and BSA-stimulated RBL-2H3 cells. Using the OVA-induced allergic rhinitis mouse model, we showed that N,N'-dicoumaroylspermidine reduced the production of serum OVA-specific IgE and the number of inflammatory cells in nasal lavage fluid. N,N'-dicoumaroylspermidine isolated from L. erythrorhizon exhibits antiallergic properties, making it potentially effective for allergic rhinitis.

Daidzin targets epithelial-to-mesenchymal transition process by attenuating manganese superoxide dismutase expression and PI3K/Akt/mTOR activation in tumor cells.

AIMS: Epithelial-mesenchymal transition (EMT) is a process during which epithelial cells lose their polarity and gain invasive properties to transform into mesenchymal cells. A few recent studies have reported that manganese superoxide dismutase (MnSOD) can effectively modulate EMT phenotype by influencing cellular redox environment via altering the intracellular ratio between O2- and H2O2. Daidzin (DDZ), a naturally occurring isoflavone isolated from Pueraria lobate (Fabaceae), has numerous pharmacologic effects including anti-cholesterol, anti-angiocardiopathy, anti-cancer. However, the potential inhibitory impact of DDZ on cancer metastasis and specifically on the EMT process has not been evaluated. We aimed to evaluate the possible relationship between MnSOD and EMT as well as influence of DDZ on these two processes in colon and prostate carcinoma cells. MAIN METHODS: Cell viability was measured by MTT and real time cell analysis (RTCA) assay. Protein expression level of EMT markers and Akt/mTOR/PI3K signaling pathway were evaluated by Western blot analysis. Expression of EMT markers in cells was observed by immunocytochemistry. Cell invasion and migrations were evaluated by wound healing assay and Boyden chamber assay. KEY FINDINGS: DDZ can block EMT accompanied with down-regulation of MnSOD, fibronectin, vimentin, MMP-9, MMP-2, N-cadherin, twist, and Snail, and up-regulation of occludin and E-cadherin in both unstimulated and TGFß-induced cells. In addition, DDZ exposure also attenuated cell proliferation, invasion, and metastasis by reversing the EMT process in SNU-C2A, DU145, and PC-3 cells. DDZ treatment also modulated activation of PI3K/Akt/mTOR signaling cascades in DU145 cells. Moreover, an overexpression of MnSOD or silencing of MnSOD expression modulated EMT-related proteins, PI3K/Akt/mTOR activation and invasive activity. SIGNIFICANCE: This is first finding on the DDZ in regulating MnSOD and EMT process by targeting PI3K/Akt/mTOR pathway in both colorectal and prostate cancer cell lines. Our data indicated that DDZ might act as a potent suppressor of EMT by affecting MnSOD expression in tumor cells.

Chemical Constituents of the Leaves of Diospyros kaki (Persimmon).

Diospyros kaki (persimmon) leaves have long been utilized as traditional medicine for the treatment of ischemic stroke, angina, and hypertension and as a healthy beverage and cosmetic for anti-aging. This study aimed to isolate as many compounds as possible from an ethanol extract of the persimmon leaves to identify the biologically active compounds. The antioxidative effect of the ethyl acetate layer from the ethanol extract of the persimmon leaves was demonstrated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and online high-performance liquid chromatography-2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (HPLC-ABTS) analysis. A new flavonoid, kaempferol-3-O-ß-d-2″-coumaroylgalactoside (1), and a new natural compound, kaempferol-3-O-ß-d-2″-feruloylglucoside (3) were isolated from the ethyl acetate layer, along with 25 previously known compounds, including fourteen flavonoids, one ionone, two coumarins, seven triterpenoids, and one acetophenone. Their structures were determined by the interpretation of spectrometric and spectroscopic data. All isolated compounds were rapidly evaluated using an online HPLC-ABTS assay, and of these, compounds 4-8, 11, 13, 15, and 16 clearly showed antioxidative effects. The amount of these compounds was 0.3-0.65% of the extract.

Clinical and dosimetric risk factors for vertebral compression fracture after single-fraction stereotactic body radiation therapy for spine metastases.

OBJECTIVES: This analysis was performed to evaluate the incidence of vertebral compression fracture (VCF) and determine the contributing factors for VCF in patients undergoing single-fraction stereotactic body radiotherapy (SBRT) for spinal bone metastases (SBM). METHODS: A retrospective review of medical records was conducted for patients undergoing SBRT for SBM at our institution between January 2010 and December 2018. Patients who had undergone neither pre-SBRT surgical excision nor post-SBRT prophylactic fixation were included. The effects of clinical and dosimetric parameters were analyzed with respect to VCF risk. The following dosimietric parameters of the planning target volume (PTV) were calculated: mean/minimum/maximum dose, radiation dose to 10-90% volume, and irradiated volume receiving more than 10-25 Gy (PTV_V10 - 25 Gy). RESULTS: Among 163 patients (179 vertebrae), 21 (12.8%) experienced VCF. The 1-year and 2-year VCF rates were 12.1% and 13.2%, respectively. Among dosimetric parameters, PTV_V15 Gy was the most significant for VCF prediction. In a univariate analysis, breast or prostate primary, no vertebral body collapse, and PTV_V15 Gy ≤42 cm3 were significantly associated with a lower incidence rate of VCF. In a multivariate analysis, PTV_V15 Gy was the only significant factor for VCF risk. The 1-year VCF rate was 3.8% in patients with PTV_V15 Gy ≤42 cm3, while it was 22.1% in those with PTV_V15 Gy > 42 cm3 (p < 0.01). CONCLUSIONS: SBRT-related VCF was found in 12% of patients in our institution. The PTV_V15 Gy is a significant factor for VCF prediction.

Roots of Lithospermum erythrorhizon promotes retinal cell survival in optic nerve crush-induced retinal degeneration.

Lithospermum erythrorhizon (L. erythrorhizon), used in traditional medicine, is a potent wound healing, anti-inflammatory and antioxidant plant. However, the effects of L. erythrorhizon on retinal degenerative diseases remain unknown. Here, we explored the protective effects of L. erythrorhizon in in vitro and in vivo retinal degeneration. We found that ethanol extract of L. erythrorhizon (EELE) and the dichloromethane fraction of L. erythrorhizon (MCLE) significantly increased cell viability under glutamate/BSO-induced excitotoxicity/oxidative stress in R28 cells. Treatment with EELE and MCLE reduced the intracellular reactive oxygen species (ROS) and the levels of apoptotic proteins, such as cleaved PARP and cleaved caspase-3. Furthermore, oral administration of EELE and MCLE in an in vivo optic nerve crush mouse model decreased RGC cell death and increased retinal thickness. The major compound between EELE and MCLE was found to be lithospermic acid A (LAA), which has been shown to prevent the elevation of ROS in R28. Therefore, EELE and MCLE have protective effects against the death of retinal cells in vitro and in vivo, and the major compound, LAA, has an antioxidant effect on retinal cells, suggesting that EELE and MCLE could be beneficial agents for retinal degenerative diseases, including glaucoma.

Trans-jugular AngioJet rheolytic thrombectomy for acute deep vein thrombosis: Alternative to overcome the limitation of patient's position.

BACKGROUND: To introduce a transjugular retrograde approach for AngioJet rheolytic thrombectomy (RT) just after transjugular placement of inferior vena cava filter (IVCF) to treat acute deep vein thrombosis (DVT). METHODS: From September 2018 to April 2019, transjugular Angiojet RT using pulse spray method was performed just after transjugular placement of IVCF in five patients (M:F = 3:2, mean age 70 years). Patients less than 165 cm in height with acute (<14 days) iliofemoral DVT were unable to assume a prone position. All patients underwent pre- and postprocedural venography to estimate thrombus reduction grade. Computed tomography angiograms at 3 and 6 months postoperative were compared with baseline scans. Post-thrombotic syndrome (PTS) symptoms were evaluated according to Villalta score during 12-month follow-up. RESULTS: Mean procedure time for all procedures was 1.4 h. Thrombus was completely reduced in three patients and 50% to 99% reduction was noted in the other two. No patients had major complications during the hospital stay and follow-up period. Distal migration of IVCF occurred in one patient during the procedure and immediate IVCF repositioning was performed. No DVT remained in follow-up computed tomography scans of all patients. PTS did not develop in any patients during the follow-up period. CONCLUSION: In patients who are unable to assume a prone position, a transjugular retrograde approach with AngioJet RT just after transjugular placement of IVCF to treat acute lower extremity DVT was a time-saving and easy alternative. During the procedure, attention to the guiding catheter position and AngioJet device movement was required to avoid affecting the IVCF.

Co-occurrence of Marchiafava-Bignami Disease and Alcoholic Polyneuropathy in Chronic Alcoholic Patient Who Had Past History of Wernicke Encephalopathy: a Case Report.

Marchiafava-Bignami disease (MBD), Wernicke encephalopathy (WE) and alcoholic polyneuropathy (AP) are distinct diseases and all have strong relationship with chronic alcoholism. A 70-year-old male who had altered mentality and ataxia of both lower limbs and had past history of WE 3 years previously admitted with 6 months history of impaired walking. He also had a symptom of altered sensorium by impaired consciousness for 2 days. In brain magnetic resonance imaging, the body, splenium of corpus callosum and bilateral frontal cortex were involved. The patient was diagnosed with MBD on the basis of the clinical features and the brain imaging findings. The electrodiagnostic findings implied demyelinating neuropathy in all extremities. He failed to recover his mentality and the function of the limbs remained poor finishing several treatment options including medications and physical therapy. The poor prognosis of this patient is thought to be associated with cortical involvement of MBD. We reported this very rare case who was affected by 3 distinct diseases of MBD, AP, and WE as complications of chronic alcohol abuse. Moreover, the case was relevant to a rare clinical presentation of MBD with cortical involvement which was associated with poor prognosis.

Gymnaster Koraiensis Extract Alleviated Metabolic Syndrome Symptoms and Stimulated UCP1-Independent Energy Consumption via AMPK Activation in White Adipose Tissue.

SCOPE: Metabolic syndrome and obesity are rising worldwide concerns that are accompanied by adverse health consequences. Here, it is hypothesized that the ethanol extract from Gymnaster koraiensis (GK), an edible Korean plant known for its anti-cancer and hepatoprotective properties, could attenuate metabolic syndrome-related symptoms in high-fat dietary-induced obese (DIO) mice. METHODS AND RESULTS: Administration of 100 mg kg-1 GK extract to DIO mice effectively reduces body and white adipose tissue (WAT) weight. It also reduces cardiovascular disease risk and improves insulin resistance by lowering the fasting blood glucose levels and mitigating oxidative stress and inflammation. Moreover, supplementation with GK causes elevated energy expenditure in WAT by increasing the mitochondrial oxidative capacity and lipid catabolism through upregulated adenosine monophosphate-activated protein kinase (AMPK) signaling. Orlistat is used as a positive control drug due to its widespread use in previous studies. It is found that GK extract causes weight loss, similar to Orlistat, and it additionally shows unique functions, such as upregulation of energy consumption in WAT. CONCLUSION: GK extract treatment prominently reduces obesity and its associated metabolic complications, such as hyperlipidemia, hyperglycemia, and insulin resistance. Hence, It can be used as a promising multi-target functional food that can improve metabolic syndrome-related symptoms.

In Vivo Anti-Inflammation Potential of Aster koraiensis Extract for Dry Eye Syndrome by the Protection of Ocular Surface.

Dry eye syndrome (DES) is a corneal disease often characterized by an irritating, itching feeling in the eyes and light sensitivity. Inflammation and endoplasmic reticulum (ER) stress may play a crucial role in the pathogenesis of DES, although the underlying mechanism remains elusive. Aster koraiensis has been used traditionally as an edible herb in Korea. It has been reported to have wound-healing and inhibitory effects against insulin resistance and inflammation. Here, we examined the inhibitory effects of inflammation and ER stress by A. koraiensis extract (AKE) in animal model and human retinal pigmented epithelial (ARPE-19) cells. Oral administration of AKE mitigated DE symptoms, including reduced corneal epithelial thickness, increased the gap between lacrimal gland tissues in experimental animals and decreased tear production. It also inhibited inflammatory responses in the corneal epithelium and lacrimal gland. Consequently, the activation of NF-κB was attenuated by the suppression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). Moreover, AKE treatment ameliorated TNF-α-inducible ocular inflammation and thapsigargin (Tg)-inducible ER stress in animal model and human retinal pigmented epithelial (ARPE-19) cells. These results prove that AKE prevents detrimental functional and histological remodeling on the ocular surface and in the lacrimal gland through inhibition of inflammation and ER stress, suggesting its potential as functional food material for improvement of DES.

Anti-cancer potential of persimmon (Diospyros kaki) leaves via the PDGFR-Rac-JNK pathway.

Persimmon leaves are known to have some beneficial effects, including ROS elimination, lipid circulation, and neuronal protection. However, their anti-cancer properties and the underlying mechanisms remain unclear. Herein, we show that treatment with the ethanol extract of persimmon, Diospyros kaki, leaves (EEDK) induces cancer cell death and inhibits cell proliferation. Using fluorescence resonance energy transfer (FRET) technology with genetically-encoded biosensors, we first found that EEDK stimulates a PDGFR-Rac signaling cascade in live cells. Moreover, we found that downstream of the PDGFR-Rac pathway, JNKs are activated by EEDK. In contrast, JNK-downstream inhibitors, such as CoCl2, T-5224, and pepstatin A, attenuated EEDK-induced cell death. Thus, we illustrate that the PDGFR-Rac-JNK signaling axis is triggered by EEDK, leading to cancer cell death, suggesting the extract of persimmon leaves may be a promising anti-cancer agent.

Ultrasound Imaging of the Trunk Muscles in Acute Stroke Patients and Relations With Balance Scales.

OBJECTIVE: To examine the correlation between ultrasonographic trunk muscle parameters and balance scales in mild acute stroke patients. METHODS: A total of 55 stroke patients with hemiparesis and motor power grade ≥4 in the manual motor test were included. The Scale for the Assessment and Rating of Ataxia (SARA), Berg Balance Scale (BBS), Timed Up and Go Test (TUG), and Trunk Control Test (TCT) were used to evaluate patient balance function. Ultrasonographic parameters were measured on both non-paretic and paretic sides of the rectus abdominis, external oblique, internal oblique, transversus abdominis, and erector spinae muscles. Resting thickness and contraction thickness were measured in all muscles, and contractility and contractility ratio were calculated based on measured thicknesses. The differences between paretic and non-paretic muscle parameters, and the correlation between ultrasonographic parameters and balance scales were analyzed. Stroke patients were divided into two groups according to their fall risk. Ultrasonographic measurements between the two groups were compared. RESULTS: All muscles' contraction thickness and contractility were significantly different between paretic and non-paretic sides (p<0.001). Contractility ratios of all trunk muscles showed a significant correlation with SARA, BBS, TUG, and TCT (p<0.05). Contractility ratios of all muscles were significantly different between high- and low-risk fall groups (p<0.05). CONCLUSION: The contractility ratio in stroke patients reflects their balance disturbance and fall risk and it may serve as a new parameter for ultrasound imaging of trunk muscles.