Protective effects of Scutellaria baicalensis Georgi against hydrogen peroxide-induced DNA damage and apoptosis in HaCaT human skin keratinocytes

Oxidative stress due to excessive accumulation of reactive oxygen species (ROS) is one of the risk factors for the development of several chronic diseases. In this study, we investigated the protective effects of Scutellaria bai- calensis rhizome ethanol extract (SBRE) against oxidative stress-induced cellular damage and elucidated the un- derlying mechanisms in the HaCaT human skin keratinocyte cell line. Our results revealed that treatment with SBRE prior to hydrogen peroxide (H2O2) exposure significantly increased viability of aCaT cells. SBRE also effectively attenuated H2O2-induced comet tail formation and inhibited the H2O2-induced phosphorylation levels of the histone γH2AX, as well as the number of apoptotic bodies and Annexin V-positive cells. In addition, SBRE exhibited scavenging activity against intracellular ROS generation and restored the mitochondrial membrane po- tential loss by H2O2. Moreover, H2O2 enhanced the cleavage of caspase-3 and degradation of poly (ADP-ribose)- polymerase, a typical substrate protein of activated caspase-3, as well as DNA fragmentation; however, these events were almost totally reversed by pretreatment with SBRE. Furthermore, SBRE increased the levels of heme oxygenase-1 (HO-1), which is a potent antioxidant enzyme, associated with the induction of nuclear fac- tor-erythroid 2-related factor 2 (Nrf2). According to our data, SBRE is able to protect HaCaT cells from H2O2- induced DNA damage and apoptosis through blocking cellular damage related to oxidative stress through a mech-anism that would affect ROS elimination and activating the Nrf2/HO-1 signaling pathway

Sensitization rates of airborne pollen and mold in children

PurposeAeroallergens are important causative factors of allergic diseases. Previous studies on aeroallergen sensitization rates investigated patients groups that had visited pediatric allergy clinics. In contrast, we investigated sensitization rates in a general population group of elementary school to teenage students in Incheon, Jeju, and Ulsan.MethodsAfter obtaining parental consent, skin-prick tests were performed on 5,094 students between March and June 2010. Elementary school students were tested for 18 common aeroallergens, whereas middle and high school students were tested for 25 allergens. The 25 allergens included Dermatophagoides pteronyssinus, Dermatophagoides farinae, pollen (birch, alder, oak, Japanese cedar, pine, willow, elm, maple, Bermuda grass, timothy grass, rye grass, orchard grass, meadow grass, vernal grass, mugwort, Japanese hop, fat hen, ragweed, and plantain), and mold (Penicillatum, Aspergillus, Cladosporium, and Alternaria).ResultsThe sensitization rates in descending order were 25.79% (D. pteronyssinus), 18.66% (D. farinae), 6.20% (mugwort), and 4.07% (willow) in Incheon; 33.35% (D. pteronyssinus), 24.78% (D. farinae), 15.36% (Japanese cedar), and 7.33% (Alternaria) in Jeju; and 32.79% (D. pteronyssinus), 30.27% (D. farinae), 10.13% (alder), and 8.68% (birch) in Ulsan. The dust mite allergen showed the highest sensitization rate among the 3 regions. The sensitization rate of tree pollen was the highest in Ulsan, whereas that of Alternaria was the highest in Jeju. The ragweed sensitization rates were 0.99% in Incheon, 1.07% in Jeju, and 0.81% in Ulsan.ConclusionThe differences in sensitization rates were because of different regional environmental conditions and distinct surrounding biological species. Hence, subsequent nationwide studies are required

Clinical effectiveness and safety of sirolimus in pediatric patients with complex vascular anomalies: necessitating personalized and comprehensive approaches

BackgroundManaging complex vascular anomalies in pediatric care requires comprehensive approaches. Sirolimus, an mTOR inhibitor with immunosuppressive and anti-angiogenic properties, offers promise. We evaluated sirolimus's effectiveness and safety in pediatric patients with complex vascular anomalies at a tertiary children's hospital.MethodsOur study included 20 patients, aged 1 month to 19 years, with diverse vascular anomalies resistant to conventional therapies or located in high-risk areas precluding surgery. The evaluation of response encompassed measuring the reduction in the size of the targeted vascular or lymphatic lesions as observed on radiologic imaging, along with considering improvements reported by the patients.ResultsPatients used sirolimus for a median of 2.1 years, ranging from 0.6–4.3 years. Results indicated that 60% of patients achieved complete or partial response (CR/PR), whereas 40% had stable disease (SD). Notably, no disease progression occurred. Lesion size assessment was complex, yet patients' self-reported improvements were considered. Three patients reinitiated sirolimus after discontinuation due to worsening lesions. Sirolimus treatment demonstrated good tolerability, with minor complications except for one case of Pneumocystis jiroveci pneumonia. Group comparisons based on response highlighted better outcomes in patients with vascular tumors (CR/PR group 58.0% vs. SD group 0.0%, P = 0.015) or localized measurable lesions (83.3% vs. 12.5%, P = 0.005).ConclusionOur study underscores sirolimus's potential for treating complex vascular anomalies in pediatric patients. Challenges associated with optimal treatment duration and concurrent interventions necessitate a comprehensive approach and genetic testing to optimize outcomes

The impact of transferring patients with ST-segment elevation myocardial infarction to percutaneous coronary intervention-capable hospitals on clinical outcomes

Background: Primary percutaneous coronary intervention (PCI) is recommended for ST-segment elevation myocardial infarction (STEMI) patients even when the patient must be transported to a PCI-capable hospital. This study aimed to evaluate the long-term clinical outcomes of STEMI patients who were transferred for primary PCI compared to patients who arrived directly to PCI-capable hospitals. Methods: A total of 3,576 STEMI patients with less than 12 h of symptom onset-to-door time from the Korea Acute Myocardial Infarction Registry were divided into transfer (n = 2,176) and direct-arrival (n = 1,400) groups according to their status. The primary outcome was the composite of major adverse cardiac event (MACE), defined as death, non-fatal myocardial infarction, and revascularization at 1 year. Results: In the transfer vs. the direct-arrival group, the median symptom onset-to-firstmedical contact time was significantly shorter (60 vs. 80 min, p < 0.001), but the median symptom onset-to-door time was significantly longer (194 vs. 90 min, p < 0.001). The median door-to-balloon time was significantly shorter in the transfer group vs. the direct-arrival group (75 vs. 91 min, p < 0.001). Total death and the composite of MACE were not significantly different during hospitalization (5.1 vs. 3.9%, p = 0.980; 5.4 vs. 4.8%, p = 0.435, respectively) and at 1-year (8.2 vs. 6.6%, p = 0.075; 13.7 vs. 13.9%, p = 0.922, respectively). Conclusions: Transferring STEMI patients to PCI-capable hospitals with a time delay did not affect clinical outcomes after 1 year. This study suggests that inter-hospital transfer should be encouraged even with delay for STEMI patients who require primary PCI in areas with a similar geographic accessibility

Duodenal Mucosa-Associated Lymphoid Tissue Lymphoma: A Case Report

Primary duodenal mucosa associated lymphoid tissue (MALT) lymphoma is very rare, and little is known about its clinical course or effective treatment. We describe a case of primary duodenal MALT lymphoma that was resistant to Helicobacter pylori (H. pylori) eradication and regressed after chemotherapy with cyclophosphamide, vincristine, and prednisolone (CVP). A 71-year-old woman was referred to our department because of epigastric pain and dyspepsia. Gastroduodenoscopy revealed an irregular mucosal nodular lesion with ulceration extending from the bulb to the second portion of the duodenum. Histopathological examination of a biopsy specimen disclosed low-grade MALT lymphoma composed of atypical lymphoid cells with lymphoepithelial lesion. Abdominal CT scans revealed 0.5 to 1.5 cm lymph nodes in the peritoneal cavity, suggestive of lymph node metastasis. We successfully eradicated H. pylori but did not see signs of remission. We administered systemic CVP chemotherapy every 3 weeks. After 6 courses of CVP, the patient achieved complete remission and was followed up without recurrence for about a year

Chlorin e6 Prevents ADP-Induced Platelet Aggregation by Decreasing PI3K-Akt Phosphorylation and Promoting cAMP Production

A number of reagents that prevent thrombosis have been developed but were found to have serious side effects. Therefore, we sought to identify complementary and alternative medicinal materials that are safe and have long-term efficacy. In the present studies, we have assessed the ability of chlorine e6 (CE6) to inhibit ADP-induced aggregation of rat platelets and elucidated the underlying mechanism. CE6 inhibited platelet aggregation induced by 10 µM ADP in a concentration-dependent manner and decreased intracellular calcium mobilization and granule secretion (i.e., ATP and serotonin release). Western blotting revealed that CE6 strongly inhibited the phosphorylations of PI3K, Akt, c-Jun N-terminal kinase (JNK), and different mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase 1/2 (ERK1/2) as well as p38-MAPK. Our study also demonstrated that CE6 significantly elevated intracellular cAMP levels and decreased thromboxane A2 formation in a concentration-dependent manner. Furthermore, we determined that CE6 initiated the activation of PKA, an effector of cAMP. Taken together, our findings indicate that CE6 may inhibit ADP-induced platelet activation by elevating cAMP levels and suppressing PI3K/Akt activity. Finally, these results suggest that CE6 could be developed as therapeutic agent that helps prevent thrombosis and ischemia

Recessive C10orf2 mutations in a family with infantile-onset spinocerebellar ataxia, sensorimotor polyneuropathy, and myopathy

Recessive mutations in chromosome 10 open reading frame 2 (C10orf2) are relevant in infantile-onset spinocerebellar ataxia (IOSCA). In this study, we investigated the causative mutation in a Korean family with combined phenotypes of IOSCA, sensorimotor polyneuropathy, and myopathy. We investigated recessive mutations in a Korean family with two individuals affected by IOSCA. Causative mutations were investigated using whole exome sequencing. Electrophysiological analyses and muscle and nerve biopsies were performed, along with magnetic resonance imaging (MRI) of the brain and lower extremities. Compound heterozygous mutations c.1460C>T and c.1485-1G>A in C10orf2 were identified as causative of IOSCA. Skeletal muscle showed mitochondrial DNA (mtDNA) deletions. Both patients showed a period of normal development until 12–15 months, followed by ataxia, athetosis, hearing loss, and intellectual disability. Electrophysiological findings indicated motor and sensory polyneuropathies. Muscle biopsy revealed variations in the size and shape of myofibers with scattered, small, and angulated degenerating myofibers containing abnormal mitochondria; these observations are consistent with myopathy and may be the result of mtDNA deletions. Sural nerve biopsy revealed an axonal neuropathy. High-signal-intensity lesions in the middle cerebellar peduncles were correlated with clinical severity, and MRI of the lower legs was compatible with the hypothesis of length-dependent axonal degeneration. We identified novel compound heterozygous mutations of the C10orf2 gene as the cause of IOSCA with sensorimotor polyneuropathy and myopathy. Signs of motor neuropathy and myopathy were discovered for the first time in IOSCA patients with C10orf2 mutations. These results suggest that the clinical spectrum of IOSCA caused by C10orf2 mutations may be more variable than previously reported. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10048-014-0405-1) contains supplementary material, which is available to authorized users

Guidewire-catheter induced hydrodissection to assist radiofrequency ablation for subcapsular hepatocellular carcinoma with iodized oil retention in patients with failed artificial ascites due to perihepatic adhesion

PURPOSEWe aimed to evaluate the usefulness of guidewire-catheter induced hydrodissection (GIH) to assist radiofrequency ablation (RFA) for subcapsular hepatocellular carcinoma (HCC) with iodized oil retention in patients with failed artificial ascites due to perihepatic adhesion.METHODSThis retrospective study included 17 patients with small subcapsular HCC ineligible for ultrasonography-guided RFA who received RFA under guidance of fluoroscopy and cone-beam computed tomography immediately after iodized oil transarterial chemoembolization (TACE) between April 2011 and January 2016. In the study patients, creation of artificial ascites to protect the perihepatic structures failed due to perihepatic adhesion and GIH was attempted to separate the perihepatic structures from the ablation zone. The technical success rate of GIH, technique efficacy of RFA with GIH, local tumor progression (LTP), peritoneal seeding, and complications were evaluated.RESULTSThe technical success rate of GIH was 88.24% (15 of 17 patients). Technique efficacy was achieved in all 15 patients receiving RFA with GIH. During an average follow-up period of 48.1 months, LTP developed in three patients. Cumulative LTP rates at 1, 2, 3, and 5 years were 13.3%, 20.6%, 20.6%, and 20.6%, respectively. No patient had peritoneal seeding. Two of the 15 patients receiving RFA with GIH had a CIRSE grade 3 liver abscess, but none had complications associated with thermal injury to the diaphragm or abdominal wall near the ablation zone.CONCLUSIONGIH can be a useful method to assist RFA for subcapsular HCC with iodized oil retention in patients with failed artificial ascites due to perihepatic adhesion