Treatment outcome comparison of Invisalign vs fixed appliance treatment in first premolar extraction patients.

INTRODUCTION: In this study, we compared the dentitional changes after Invisalign and conventional orthodontic treatment with 4 first premolar extractions. METHODS: This retrospective study included 57 patients whose orthodontic treatment involved the extraction of 4 first premolars because of bialveolar protrusion. A total of 27 patients were treated with Invisalign (mean age, 25.5 ± 5.2 years) and 30 patients with the fixed appliance (mean age, 24.4 ± 5.8 years). The angular and linear changes of the maxillary and mandibular central incisors, second premolars, first molars, and second molars were measured from the recordings on the basis of the lateral cephalograms taken before and after treatment. The angular changes of the canines and second premolars were measured using panoramic radiographs. RESULTS: The overbite and interincisal angle increased significantly in the Invisalign group compared with in the conventional fixed appliance group (P <0.05). The maxillary central incisors showed increased lingual tipping in the Invisalign group (P <0.05), whereas there was no statistically significant difference in the angular change of the mandibular incisors between groups (P >0.05). The maxillary first and second molars showed mesial tipping in the Invisalign group (P <0.05). The maxillary second premolars, first and second molars, and the mandibular second molars showed mesial movement in the Invisalign group (P <0.05). CONCLUSIONS: The Invisalign group showed more statistically significant lingual tipping of the maxillary central incisors, distal tipping of the maxillary canines, and mesial tipping of the maxillary first and second molars after maximum retraction of the anterior teeth compared with the fixed appliance group.

Regulation of Dihydropyrimidinase-like 3 Gene Expression by MicroRNAs in PC12 Cells with Induced Ischaemia and Hypothermia.

Although hypothermic treatment has been reported to have some beneficial effects on ischaemia at the clinical level, the mechanism of ischaemia suppression by hypothermia remains unclear due to a lack of mechanism understanding and insufficient data. The aim of this study was to isolate and characterize microRNAs specifically expressed in ischaemia-hypothermia for the dihydropyrimidinase-like 3 (Dpysl3) gene. PC12 cells were induced with CoCl2 for chemical ischaemia and incubated at 32 ℃ for hypothermia. In ischaemia-hypothermia, four types of microRNAs (miR-106b-5p, miR-194-5p, miR-326-5p, and miR-497-5p) were highly related to the Dpysl3 gene based on exosomal microRNA analysis. Dpysl3 gene expression was up-regulated by miR-497-5p but down-regulated by miR-106b-5p, miR-194-5p and miR-326-5p. Our results suggest that these four microRNAs are involved in the regulation of Dpysl3 gene expression. These findings provide valuable clues that exosomal microRNAs could be used as therapeutic targets for effective treatment of ischaemia.

Depression or Anxiety According to Management Modalities in Patients With Unruptured Intracranial Aneurysms.

BACKGROUND: In the treatment of unruptured intracranial aneurysms, the risk was usually estimated by objective neurological sequelae. However, their effects on depression and anxiety are rare and remain controversial. We aimed to evaluate the risk of depression and anxiety in patients with unruptured intracranial aneurysm stratified by management strategies in a population-based, longitudinal cohort study. METHODS: Using the Korean National Health Insurance Research Database, 71 750 patients with unruptured intracranial aneurysms between 2008 and 2011 were identified and followed up until the end of 2020. The risk of depression and anxiety was compared among management strategies with respect to age, sex, and medical comorbidities. RESULTS: The Kaplan-Meier survival curves indicated that the treatment (clipping and endovascular treatment) group developed depression more frequently than the observation group (P<0.001). The adjusted hazard ratio was 1.11 (95% CI, 1.07-1.15) in the treatment group. According to the management modality, the Kaplan-Meier survival curves indicated that clipping and endovascular treatment groups developed depression more frequently than the observation group (P<0.0001). The adjusted hazard ratio was 1.15 (95% CI, 1.10-1.21) for clipping and 1.07 (95% CI, 1.02-1.12) for endovascular treatment. The depression risk was higher with advanced age (hazard ratio for 45-64 years, 1.37 [95% CI, 1.29-1.45] and hazard ratio for ≥65 years, 2.04 [95% CI, 1.92-2.17]). The risk for anxiety did not differ among the management modalities. CONCLUSIONS: In this study, the risk of depression was slightly greater after clipping surgery than endovascular treatment. Data on treatment-related, long-term psychological outcomes, such as depression, may aid decision-making for preventive treatment of asymptomatic unruptured intracranial aneurysm patients.

Lipidomics reveals that acupuncture modulates the lipid metabolism and inflammatory interaction in a mouse model of depression.

Depression is a serious disease that has considerable impact on lipid metabolism and inflammatory responses. Recent studies have shown that leptin, which is well known as a mediator of energy homeostasis and is a cytokine in inflammatory response, plays an important role in depression. Acupuncture is widely used to treat depression; however, the underlying mechanisms and the effect of acupuncture on depression remain poorly understood. In this study, we utilized the chronic restraint stress (CRS) induced depression model and acupuncture treatment was performed at KI10, LR8, LU8, LR4 (AP) or non-acupoint (NP). Then, lipidomics was applied to investigate the effects of acupuncture on lipid metabolism and analyze leptin signals in the brain and changes of immune markers. Acupuncture treatment at AP improved depression-like behavior in an open-field test, forced swimming test, and marble burying test. Concurrently, CRS mice treated with AP acupuncture (CRS + AP) had significantly lower levels of aspartate aminotransaminase (AST, liver injury markers) and exhibited different lipid patterns in liver lipidomic profiles. In particular, triglycerides (TGs) contributed the change of lipid patterns. Compared to the CRS mice, TGs with relatively high degrees of unsaturated fatty acids increased in the CRS + AP mice, but did not change in CRS mice treated with NP acupuncture (CRS + NP). The levels of leptin in plasma and leptin receptor positive cells in the brain (hypothalamus and hippocampus) decreased and increased, respectively, in the CRS + AP mice, while opposite patterns were exhibited in the CRS and CRS + NP mice. These results indicated that acupuncture treatment at AP attenuated leptin insensitivity in CRS mice. Additionally, expression of pro-inflammatory cytokines such as interleukin-1 beta and tumor necrosis factor-alpha were decreased in the spleen, plasma, and liver of CRS + AP mice, which was one of results of alleviation of leptin resistance. In conclusion, these results show that AP acupuncture treatment effectively alleviated the depression-like behavior, affected immune responses, and altered hepatic lipid metabolism through the attenuation of leptin insensitivity.

3,4-dihydroxytoluene, a metabolite of rutin, suppresses the progression of nonalcoholic fatty liver disease in mice by inhibiting p300 histone acetyltransferase activity.

3,3',4',5,7-Pentahydroxyflavone-3-rhamnoglucoside (rutin) is a flavonoid with a wide range of pharmacological activities. Dietary rutin is hardly absorbed because the microflora in the large intestine metabolize rutin into a variety of compounds including quercetin and phenol derivatives such as 3,4-dihydroxyphenolacetic acid (DHPAA), 3,4-dihydroxytoluene (DHT), 3,4-hydroxyphenylacetic acid (HPAA) and homovanillic acid (HVA). We examined the potential of rutin and its metabolites as novel histone acetyltransferase (HAT) inhibitors. DHPAA, HPAA and DHT at the concentration of 25 µM significantly inhibited in vitro HAT activity with DHT having the strongest inhibitory activity. Furthermore, DHT was shown to be a highly efficient inhibitor of p300 HAT activity, which corresponded with its high degree of inhibition on intracellular lipid accumulation in HepG2 cells. Docking simulation revealed that DHT was bound to the p300 catalytic pocket, bromodomain. Drug affinity responsive target stability (DARTS) analysis further supported the possibility of direct binding between DHT and p300. In HepG2 cells, DHT concentration-dependently abrogated p300-histone binding and induced hypoacetylation of histone subunits H3K9, H3K36, H4K8 and H4K16, eventually leading to the downregulation of lipogenesis-related genes and attenuating lipid accumulation. In ob/ob mice, administration of DHT (10, 20 mg/kg, iv, every other day for 6 weeks) dose-dependently improved the NAFLD pathogenic features including body weight, liver mass, fat mass, lipid accumulation in the liver, and biochemical blood parameters, accompanied by the decreased mRNA expression of lipogenic genes in the liver. Our results demonstrate that DHT, a novel p300 histone acetyltransferase inhibitor, may be a potential preventive or therapeutic agent for NAFLD.

Association between Air Pollutants and Initial Hospital Admission for Ischemic Stroke in Korea from 2002 to 2013.

OBJECTIVES: There is limited information regarding the association between air pollution exposure and stroke incidence. Therefore, this study aimed to assess the associations between short-term exposure to ambient air pollutants and initial hospital admission for ischemic stroke. MATERIALS AND METHODS: From the Korea National Health Insurance Service-National Sample Cohort 2002-2013 database in South Korea, 55,852 first hospital admissions for ischemic stroke were identified. A generalized additive Poisson model was used to explore the association between air pollutants, including particulate matter, sulfur dioxide, nitrogen dioxide, and carbon monoxide and admissions for ischemic stroke. RESULTS: All air pollutant models showed significant associations with ischemic stroke in the single lag model. In all air pollutant models excluding particulate matter 10 µm, a significant association was found between nitrogen dioxide exposure and initial admission for ischemic stroke after adjusting for other pollutants. An increment of 10 µg/m3 in nitrogen dioxide concentration at lag 0 and 14 days corresponded to a 0.259% (95% confidence interval, 0.231-0.287%) and 0.110% (95% confidence interval, 0.097-0.124) increase in initial admission for ischemic stroke, respectively. CONCLUSIONS: The exposure-response relationship between nitrogen dioxide and initial admissions for ischemic stroke was approximately linear, with a sharper response at higher concentrations. Short-term exposure to nitrogen dioxide was positively associated with initial hospital admission for ischemic stroke.

Improvement Effects of Myelophil on Symptoms of Chronic Fatigue Syndrome in a Reserpine-Induced Mouse Model.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is associated with various symptoms, such as depression, pain, and fatigue. To date, the pathological mechanisms and therapeutics remain uncertain. The purpose of this study was to investigate the effect of myelophil (MYP), composed of Astragali Radix and Salviaemiltiorrhizae Radix, on depression, pain, and fatigue behaviors and its underlying mechanisms. Reserpine (2 mg/kg for 10 days, intraperitoneally) induced depression, pain, and fatigue behaviors in mice. MYP treatment (100 mg/kg for 10 days, intragastrically) significantly improved depression behaviors, mechanical and thermal hypersensitivity, and fatigue behavior. MYP treatment regulated the expression of c-Fos, 5-HT1A/B receptors, and transforming growth factor ß (TGF-ß) in the brain, especially in the motor cortex, hippocampus, and nucleus of the solitary tract. MYP treatment decreased ionized calcium binding adapter molecule 1 (Iba1) expression in the hippocampus and increased tyrosine hydroxylase (TH) expression and the levels of dopamine and serotonin in the striatum. MYP treatment altered inflammatory and anti-oxidative-related mRNA expression in the spleen and liver. In conclusion, MYP was effective in recovering major symptoms of ME/CFS and was associated with the regulation of dopaminergic and serotonergic pathways and TGF-ß expression in the brain, as well as anti-inflammatory and anti-oxidant mechanisms in internal organs.

Prevalence of Intracranial Aneurysms in Patients With Systemic Vessel Aneurysms: A Nationwide Cohort Study.

Background and Purpose- Most aneurysms are a focal manifestation of a systemic condition. Some reports have suggested genetic and environmental factors may play a role in pathogenesis. The aim of the present study was to evaluate the prevalence of intracranial aneurysms (IA) in a large cohort of patients with other systemic vessel aneurysms and dissections (OVAD) and identify potential risk factors for IA in this population. Methods- We defined OVAD as systemic vessel aneurysms, excluding aortic dissections and aneurysms. A cohort of 1.1 million patients was extracted from the population-based cohort from the Korea National Health Insurance Service, which holds almost all medical data including diagnostic codes, procedures, and personal information. Using χ2 or Fisher exact test, the prevalence of the IA concerning OVAD status was analyzed. Results- In OVAD individuals, 25.7% (261/1017) of patients had been concurrently diagnosed with IA. The odds ratios for having concurrent IA in patients with OVAD were 56.31 (95% CI, 48.821-64.949; P=0.000). OVAD patients with dyslipidemia were >7× likely to be affected by IA (adjusted odds ratio, 7.7 [95% CI, 6.59-9.01]; P=0.000). Hypertension, diabetes mellitus, old age (>60 years), and male sex had increased odds for having concurrent IA by 5.89, 3.48, 1.83, and 1.35, respectively. Subgroup analysis with socioeconomic or disability revealed that the prevalence of IA was significantly higher in all groups. Uncertainty regarding the temporal sequence of onset and lack of detail on disease severity and subtype prevented more conclusive results. Conclusions- Patients with OVAD have a higher prevalence of IA than control groups. Therefore, we may approach aneurysms as systemic disease, and further investigations about their pathophysiology must follow.

Novel TGF-ß1 inhibitor antagonizes TGF-ß1-induced epithelial-mesenchymal transition in human A549 lung cancer cells.

Transforming growth factor ß1 (TGF-ß1), a multifunctional cytokine, is known to promote tumor invasion and metastasis and induce epithelial-mesenchymal transition (EMT) in various cancer cells. Inhibition of TGF-ß1 signaling is a new strategy for cancer therapy. Most cancer cells display altered or nonfunctional TGF-ß1 signaling; hence, TGF-ß1 inhibitors exert limited effects on these cells. Recent studies have suggested that developing a TGF-ß1 inhibitor from natural compounds is a key step to create novel therapeutic agents. This study aimed to develop a new anti-TGF-ß1 therapy for cancer. We found an improved analog of chalcones, compound 67, and investigated its effects in vitro. We demonstrated the inhibitory role of compound 67 through migration and invasion assays on TGF-ß1-induced EMT of human A549 lung cancer cells. Compound 67 inhibited TGF-ß1-induced smad2 phosphorylation, suppressed TGF-ß1-induced EMT markers, matrix metalloproteinase-2 (MMP-2) and MMP-9, and inhibited migration and invasion of A549 cells. The study results showed that compound 67 is useful to prevent tumor growth and metastasis.

Inhibition of TFEB oligomerization by co-treatment of melatonin with vorinostat promotes the therapeutic sensitivity in glioblastoma and glioma stem cells.

Glioblastoma (GBM) is the most aggressive malignant glioma and most lethal form of human brain cancer (Clin J Oncol Nurs. 2016;20:S2). GBM is also one of the most expensive and difficult cancers to treat by the surgical resection, local radiotherapy, and temozolomide (TMZ) and still remains an incurable disease. Oncomine platform analysis and Gene Expression Profiling Interactive Analysis (GEPIA) show that the expression of transcription factor EB (TFEB) was significantly increased in GBMs and in GBM patients above stage IV. TFEB requires the oligomerization and localization to regulate transcription in the nucleus. Also, the expression and oligomerization of TFEB proteins contribute to the resistance of GBM cells to conventional chemotherapeutic agents such as TMZ. Thus, we investigated whether the combination of vorinostat and melatonin could overcome the effects of TFEB and induce apoptosis in GBM cells and glioma cancer stem cells (GSCs). The downregulation of TFEB and oligomerization by vorinostat and melatonin increased the expression of apoptosis-related genes and activated the apoptotic cell death process. Significantly, the inhibition of TFEB expression dramatically decreased GSC tumor-sphere formation and size. The inhibitory effect of co-treatment resulted in decreased proliferation of GSCs and induced the expression of cleaved PARP and p-γH2AX. Taken together, our results definitely demonstrate that TFEB expression contributes to enhanced resistance of GBMs to chemotherapy and that vorinostat- and melatonin-activated apoptosis signaling in GBM cells by inhibiting TFEB expression and oligomerization, suggesting that co-treatment of vorinostat and melatonin may be an effective therapeutic strategy for human brain cancers.

Initial misdiagnosis of aneurysmal subarachnoid hemorrhage: associating factors and its prognosis.

BACKGROUND: Predicting the fate of patients who are given a misdiagnosis of aneurysmal subarachnoid hemorrhage (aSAH) remains unclear. The purpose was to examine factors associated with initial misdiagnosis of aSAH and to investigate the impact of initial misdiagnosis of aSAH on clinical outcomes. METHODS: Between January 2007 and December 2015, medical records and radiographic data for 3118 consecutive patients with aSAH were reviewed. There were 33 patients who had been documented with an initial misdiagnosis of aSAH, and all met the following criteria: (1) failure to correctly identify aSAH upon initial presentation to health care professionals; and 2) subsequently documented aSAH after the initial misdiagnosis. After applying exclusion criteria, remaining 2898 patients were included in the control group. RESULTS: The most common cause of the misdiagnosis is failure to detect aSAH on the initial radiographic imaging. Misdiagnosis group showed lower initial Glasgow Coma Scale, better Hunt-Hess grade, and lower Fisher's grade. Logistic regression analysis showed that initial HH grade (OR, 0.216; p = 0.014), initial Fisher's grade (OR, 0.732; p = 0.036), and hospital type during initial contact (OR, 2.266; p = 0.042) were independently associated with misdiagnosis of aSAH. CONCLUSIONS: Patients with initially good HH grade, lower Fisher's grade, and visiting non-teaching hospital for initial contact were at risk of being misdiagnosed. Misdiagnosis of aSAH in patients with initial good HH grade did affect clinical outcomes negatively. The rebleeding rate was not significantly different between two groups. However, the mortality rate due to rebleeding was higher in MisDx group than in non-MisDx group.

Brassinosteroid-Induced Transcriptional Repression and Dephosphorylation-Dependent Protein Degradation Negatively Regulate BIN2-Interacting AIF2 (a BR Signaling-Negative Regulator) bHLH Transcription Factor.

Brassinosteroids (BRs) are plant polyhydroxy-steroids that play important roles in plant growth and development via extensive signal integration through direct interactions between regulatory components of different signaling pathways. Recent studies have shown that diverse helix-loop-helix/basic helix-loop-helix (HLH/bHLH) family proteins are actively involved in control of BR signaling pathways and interact with other signaling pathways. In this study, we show that ATBS1-INTERACTING FACTOR 2 (AIF2), a nuclear-localized atypical bHLH transcription factor, specifically interacts with BRASSINOSTEROID-INSENSITIVE 2 (BIN2) among other BR signaling molecules. Overexpression of AIF2 down-regulated transcript expression of growth-promoting genes, thus resulting in retardation of growth. AIF2 renders plants hyposensitive to BR-induced root growth inhibition, but shows little effects on BR-promoted hypocotyl elongation. Notably, AIF2 was dephosphorylated by BR, and the dephosphorylated AIF2 was subject to proteasome-mediated degradation. AIF2 degradation was greatly induced by BR and ABA, but relatively slightly by other hormones such as auxin, gibberellin, cytokinin and ethylene. Moreover, AIF2 transcription was significantly suppressed by a BRI1/BZR1-mediated BR signaling pathway through a direct binding of BRASSINAZOLE RESISTANT 1 (BZR1) to the BR response element (BRRE) region of the AIF2 promoter. In conclusion, our study suggests that BIN2-driven AIF2 phosphorylation could augment the BIN2/AIF2-mediated negative circuit of BR signaling pathways, and the BR-induced transcriptional repression and protein degradation negatively regulate AIF2 transcription factor, reinforcing the BZR1/BES1-mediated positive BR signaling pathway.

Delphinidin inhibits BDNF-induced migration and invasion in SKOV3 ovarian cancer cells.

Brain-derived neurotrophic factor (BDNF), the TrkB ligand, is associated with aggressive malignant behavior, including migration and invasion, in tumor cells and a poor prognosis in patients with various types of cancer. Delphinidin is a diphenylpropane-based polyphenolic ring structure-harboring compound, which exhibits a wide range of pharmacological activities, anti-tumor, anti-oxidant, anti-inflammatory, anti-angiogenic and anti-mutagenic activity. However, the possible role of delphinidin in the cancer migration and invasion is unclear. We investigated the suppressive effect of delphinidin on the cancer migration and invasion. Thus, we found that BDNF enhanced cancer migration and invasion in SKOV3 ovarian cancer cell. To exam the inhibitory role of delphinidin in SKOV3 ovarian cancer migration and invasion, we investigated the use of delphinidin as inhibitors of BDNF-induced motility and invasiveness in SKOV3 ovarian cancer cells in vitro. Here, we found that delphinidin prominently inhibited the BDNF-induced increase in cell migration and invasion of SKOV3 ovarian cancer cells. Furthermore, delphinidin remarkably inhibited BDNF-stimulated expression of MMP-2 and MMP-9. Also, delphinidin antagonized the phosphorylation of Akt and nuclear translocation of NF-κB permitted by the BDNF in SKOV3 ovarian cancer cells. Taken together, our findings provide new evidence that delphinidin suppressed the BDNF-induced ovarian cancer migration and invasion through decreasing of Akt activation.

Antiplatelet drug resistance did not increase the thromboembolic events after stent-assisted coiling of unruptured intracranial aneurysm: a single center experience of 99 cases.

We aimed to evaluate the correlation between aspirin or clopidogrel resistance and the risk of thromboembolic events (TEs). Between June 2011 and April 2015, we reviewed clinical and angiographic characteristics, and TEs in the patients undergoing stent-assisted coil embolization (SAC) of unruptured intracranial aneurysms (UIA) at our institution. We did not modify antiplatelet medication in patients with resistance. The relationships between antiplatelet resistance and the occurrence of acute symptomatic TEs, any diffusion-positive lesions, multiple diffusion-positive lesions, or delayed TEs were investigated. Ninety-nine endovascular treatments with stent-assisted technique were performed on 99 patients. The prevalence of aspirin resistance was 12% and clopidogrel resistance was 62.6%. Acute symptomatic TEs were demonstrated in 4 patients (4%). Diffusion-positive lesions were found in 82 patients [82.1%; 36 patients were group I (≤5) and 46 patients were group II (>5)]. Delayed TEs were demonstrated in 10 patients (10.1%). Neither aspirin resistance nor clopidogrel resistance was relevant to the development of acute symptomatic TEs, any diffusion-positive lesions, multiple diffusion-positive lesions, and delayed TEs (P logistic = not available, 0.448, 0.362, and 0.829 for aspirin resistance and P logistic = 0.607, 0.367, 0.278, and 0.245 for clopidogrel resistance). Without modification of antiplatelet medication, we demonstrated 4% of acute symptomatic TEs and 10% of delayed TEs. Aspirin or clopidogrel resistance did not show significant relationships with acute and delayed TEs in the SAC of UIA.

Preventive Suboccipital Decompressive Craniectomy for Cerebellar Infarction: A Retrospective-Matched Case-Control Study.

BACKGROUND AND PURPOSE: No evidence is available on the benefits of preventive suboccipital decompressive craniectomy (SDC) for patients with cerebellar infarction. The purpose of this matched case-control study was to investigate whether preventive SDC was associated with good clinical outcomes in patients with cerebellar infarction and to evaluate its predisposing factors. METHODS: Between March 2007 and September 2015, 28 patients underwent preventive SDC. We performed propensity score matching to establish a proper control group among 721 patients with cerebellar infarction during the same period. Group A (n=28) consists of those who underwent preventive SDC, and group B (n=56) consists of those who did not undergo preventive SDC. We analyzed and compared clinical outcomes between groups. RESULTS: Clinical outcomes were better in group A than in group B at discharge (P=0.048) and 12-month follow-up (P=0.030). Group B had more deaths within 12 months than group A (log-rank, P<0.05). Logistic regression analysis showed that preventive SDC (odds ratio, 4.815; P=0.009) and the absence of brain stem infarction (odds ratio, 2.862; P=0.033) were independently associated with favorable outcomes (modified Rankin Scale score of 0-2) at 12-month follow-up. CONCLUSIONS: Favorable clinical outcomes including overall survival can be expected after preventive SDC in patients with a volume ratio between 0.25 and 0.33 and the absence of brain stem infarction. Among these patients, preventive SDC might be better than the best medical treatment alone.

Activation of anthocyanin biosynthesis by expression of the radish R2R3-MYB transcription factor gene RsMYB1.

KEY MESSAGE: RsMYB1, a MYB TF of red radish origin, was characterized as a positive regulator to transcriptionally activate the anthocyanin biosynthetic machinery by itself in Arabidopsis and tobacco plants. Anthocyanins, providing the bright red-orange to blue-violet colors, are flavonoid-derived pigments with strong antioxidant activity that have benefits for human health. We isolated RsMYB1, which encodes an R2R3-MYB transcription factor (TF), from red radish plants (Raphanus sativus L.) that accumulate high levels of anthocyanins. RsMYB1 shows higher expression in red radish than in common white radish, in both leaves and roots, at different growth stages. Consistent with RsMYB1 function as an anthocyanin-promoting TF, red radishes showed higher expression of all six anthocyanin biosynthetic and two anthocyanin regulatory genes. Transient expression of RsMYB1 in tobacco showed that RsMYB1 is a positive regulator of anthocyanin production with better efficiency than the basic helix-loop-helix (bHLH) TF gene B-Peru. Also, the synergistic effect of RsMYB1 with B-Peru was larger than the effect of the MYB TF gene mPAP1D with B-peru. Arabidopsis plants stably expressing RsMYB1 produced red pigmentation throughout the plant, accompanied by up-regulation of the six structural and two regulatory genes for anthocyanin production. This broad transcriptional activation of anthocyanin biosynthetic machinery in Arabidopsis included up-regulation of TRANSPARENT TESTA8, which encodes a bHLH TF. These results suggest that overexpression of RsMYB1 promotes anthocyanin production by triggering the expression of endogenous bHLH genes as potential binding partners for RsMYB1. In addition, RsMYB1-overexpressing Arabidopsis plants had a higher antioxidant capacity than did non-transgenic control plants. Taken together, RsMYB1 is an actively positive regulator for anthocyanins biosynthesis in radish plants and it might be one of the best targets for anthocyanin production by single gene manipulation being applicable in diverse plant species.

Endovascular treatment of ruptured blood blister-like aneurysms with multiple (≥3) overlapping Enterprise stents and coiling.

BACKGROUND: Blood blister-like aneurysms (BBAs) are difficult to treat both surgically and endovascularly, and the optimal treatment remains controversial. The aim of this study was to evaluate the clinical and angiographic feasibility of multiple overlapping stents (≥3) with coiling for treating BBA. METHODS: A retrospective review from four institutions identified ten patients with ruptured BBAs who were treated with multiple overlapping stents (≥3). We included both the patients who were initially treated with more than three stents and those who eventually had more than three stents as a consequence of retreatment. Angiographic results (Raymond scale), clinical outcomes (mRS) and treatment courses were evaluated. RESULTS: Initially, seven patients were treated with triple stents and three with double stents. Immediate angiographic results revealed that six aneurysms were Raymond grade 1, three were grade 2, and one was grade 3. Complementary treatment was required in four patients. All three patients who were initially treated with double stents required complementary treatment (100 %). One patient required complementary treatment among the seven patients who were initially treated with three stents (14.3 %). The last follow-up angiography (mean, 12.2 ± 14.7 months; range, 1-44 months) revealed grade 1 in all ten patients. Clinical data (mean follow-up period, 18.2 ± 20.1 months; range, 1-62 months) revealed eight patients with a mRS score of 0-2 and two with mRS 3-5. CONCLUSIONS: Even in the era of flow diverter stents, multiple overlapping stents (≥3) with coiling could be a feasible alternative for treating ruptured BBAs. Additional experience and follow-up are needed in a larger series to state the long-term efficacy of this treatment.

Brassinazole resistant 1 (BZR1)-dependent brassinosteroid signalling pathway leads to ectopic activation of quiescent cell division and suppresses columella stem cell differentiation.

Previous publications have shown that BRI1 EMS suppressor 1 (BES1), a positive regulator of the brassinosteroid (BR) signalling pathway, enhances cell divisions in the quiescent centre (QC) and stimulates columella stem cell differentiation. Here, it is demonstrated that BZR1, a BES1 homologue, also promotes cell divisions in the QC, but it suppresses columella stem cell differentiation, opposite to the action of BES1. In addition, BR and its BZR1-mediated signalling pathway are shown to alter the expression/subcellular distribution of pin-formed (PINs), which may result in changes in auxin movement. BR promotes intense nuclear accumulation of BZR1 in the root tip area, and the binding of BZR1 to the promoters of several root development-regulating genes, modulating their expression in the root stem cell niche area. These BZR1-mediated signalling cascades may account for both the ectopic activation of QC cell divisions as well as the suppression of the columella stem cell differentiation. They could also inhibit auxin-dependent distal stem cell differentiation by antagonizing the auxin/WOX5-dependent pathway. In conclusion, BZR1-/BES1-mediated BR signalling pathways show differential effects on the maintenance of root apical meristem activities: they stimulate ectopic QC division while they show opposite effects on the differentiation of distal columella stem cells in a BR concentration- and BZR1-/BES1-dependent manner.

Observation of cerebral aneurysm wall thickness using intraoperative microscopy: clinical and morphological analysis of translucent aneurysm.

Intracranial aneurysms suffer various interactions between hemodynamics and pathobiology, and rupture when this balance disrupted. Aneurysm wall morphology is a result of these interactions and reflects the quality of the maturation. However, it is a poorly documented in previous studies. The purpose of this study is to observe aneurysm wall thickness and describe the characteristics of translucent aneurysm by analyzing clinical and morphological parameters. 253 consecutive patients who underwent clipping surgery in a single institute were retrospectively analyzed. Only middle cerebral artery aneurysms (MCA) which exposed most part of the dome during surgery were included. Aneurysms were categorized based on intraoperative video findings. Aneurysms more than 90 % of super-thin dome and any aneurysms with entirely super-thin-walled daughter sac were defined as translucent aneurysm. A total of 110 consecutive patients with 116 unruptured MCA aneurysms were included. Ninety-two aneurysms (79.3 %) were assigned to the not-translucent group and 24 (20.7 %) to the translucent group. The relative proportion of translucent aneurysm in each age group was highest at ages 50-59 years and absent at ages 30-39 and 70-79 years. There was a trend that translucent aneurysms were smaller in size (p = 0.019). Multivariate logistic analysis showed that translucent aneurysm was strongly correlated with height <3 mm (p = 0.003). We demonstrated that the translucent aneurysms were smaller in size and the aneurysm height <3 mm was related. These results may provide information in determining treatment strategies in patients with small size aneurysm.