Search

Identifying the cerebral arterial branches is essential for undertaking a computational approach to cerebrovascular imaging. However, the complexity and inter-individual differences involved in this process have not been thoroughly studied. We used machine learning to examine the anatomical profile of the cerebral arterial tree. The method is less sensitive to inter-subject and cohort-wise anatomical variations and exhibits robust performance with an unprecedented in-depth vessel range. We applied machine learning algorithms to disease-free healthy control subjects (n = 42), patients with stroke with intracranial atherosclerosis (ICAS) (n = 46), and patients with stroke mixed with the existing controls (n = 69). We trained and tested 70% and 30% of each study cohort, respectively, incorporating spatial coordinates and geometric vessel feature vectors. Cerebral arterial images were analyzed based on the ‘segmentation-stacking’ method using magnetic resonance angiography. We precisely classified the cerebral arteries across the exhaustive scope of vessel components using advanced geometric characterization, redefinition of vessel unit conception, and post-processing algorithms. We verified that the neural network ensemble, with multiple joint models as the combined predictor, classified all vessel component types independent of inter-subject variations in cerebral arterial anatomy. The validity of the categorization performance of the model was tested, considering the control, ICAS, and control-blended stroke cohorts, using the area under the receiver operating characteristic (ROC) curve and precision-recall curve. The classification accuracy rarely fell outside each image’s 90–99% scope, independent of cohort-dependent cerebrovascular structural variations. The classification ensemble was calibrated with high overall area rates under the ROC curve of 0.99–1.00 [0.97–1.00] in the test set across various study cohorts. Identifying an all-inclusive range of vessel components across controls, ICAS, and stroke patients, the accuracy rates of the prediction were: internal carotid arteries, 91–100%; middle cerebral arteries, 82–98%; anterior cerebral arteries, 88–100%; posterior cerebral arteries, 87–100%; and collections of superior, anterior inferior, and posterior inferior cerebellar arteries, 90–99% in the chunk-level classification. Using a voting algorithm on the queued classified vessel factors and anatomically post-processing the automatically classified results intensified quantitative prediction performance. We employed stochastic clustering and deep neural network ensembles. Ma-chine intelligence-assisted prediction of vessel structure allowed us to personalize quantitative predictions of various types of cerebral arterial structures, contributing to precise and efficient decisions regarding the cerebrovascular disease.

Introduction: Postpartum depression is common; however, little is known about its relationship to social support and postpartum depression. This study examined the association between them among South Korean women within one year of childbirth. Methods This study was based on the 2016 Korean Study of Women’s Health-Related Issues (K-Stori), a cross-sectional survey employing nationally-representative random sampling. Participants were 1,654 postpartum women within a year of giving birth. Chi-square test and logistic regression analysis were conducted to analyze the associations between social support (and other covariates) and postpartum depression. Results Among participants, 266 (16.1%) had postpartum depression. Depending on the level of social support, 6.0%, 53.9%, and 40.1% of them had low, moderate, and high social support, respectively. Women with moderate or low social support were more likely to have postpartum depression (OR = 1.78, 95% CI = 1.26–2.53; OR = 2.76, 95% CI = 1.56–4.89). This trend was observed in participants with multiparity, pregnancy loss, obese body image, and employed women. Conclusion Social support was associated with a decreased likelihood of postpartum depression, indicating the importance of social support, especially for women with multiparity, pregnancy loss experience, negative body image, and employed women for preventing postpartum depression.

Helicobacter pylori (H. pylori) infection is considered as one of the principal risk factors of gastric cancer. Constitutive activation of the signal transducer and activator of transcription 3 (STAT3) plays an important role in inflammation-associated gastric carcinogenesis. In the canonical STAT3 pathway, phosphorylation of STAT3 on Tyr705 is a major event of STAT3 activation. However, recent studies have demonstrated that STAT3 phosphorylated on Ser727 has an independent function in mitochondria. In the present study, we found that human gastric epithelial AGS cells infected with H. pylori resulted in localization of STAT3 phosphorylated on Ser727 (P-STAT3Ser727), predominantly in the mitochondria. Notably, H. pylori-infected AGS cells exhibited the loss of mitochondrial integrity and increased expression of the microtubule-associated protein light chain 3 (LC3), the autophagosomal membrane-associated protein. Treatment of AGS cells with a mitophagy inducer, carbonyl cyanide 3-chlorophenylhydrazone (CCCP), resulted in accumulation of P-STAT3Ser727 in mitochondria. In addition, the elevated expression and mitochondrial localization of LC3 induced by H. pylori infection were attenuated in AGS cells harboring STAT3 mutation defective in Ser727 phosphorylation (S727A). We also observed that both P-STAT3Ser727 expression and LC3 accumulation were increased in the mitochondria of H. pylori-inoculated mouse stomach.

The composition of the gut microbiota is influenced by sex hormones and colorectal cancer (CRC). Previously, we reported that 17β-estradiol (E2) inhibits azoxymethane/dextran sulfate sodium (AOM/DSS)-induced tumorigenesis in male mice. Here, we investigated whether the composition of the gut microbiota is different between male and female, and is regulated by estrogen as a secondary outcome of previous studies. We established four groups of mice based on the sex and estrogen status [ovariectomized (OVX) female and E2-treated male]. Additionally, three groups of males were established by treating them with AOM/DSS, and E2, after subjecting them to AOM/DSS treatment. The mice were sacrificed at 21 weeks old. The composition of the gut microbiota was analyzed using 16S rRNA metagenomics sequencing. We observed a significant increase in the microbial diversity (Chao1 index) in females, males supplemented with E2, and males treated with AOM/DSS/E2 compared with normal males. In normal physiological condition, sex difference and E2 treatment did not affect the ratio of Firmicutes/Bacteroidetes (F/B). However, in AOM/DSS-treated male mice, E2 supplementation showed significantly lower level of the F/B ratio. The ratio of commensal bacteria to opportunistic pathogens was higher in females and E2-treated males compared to normal males and females subjected to OVX. Unexpectedly, this ratio was higher in the AOM/DSS group than that determined in other males and the AOM/DSS/E2 group. Our findings suggest that estrogen alters the gut microbiota in ICR (CrljOri:CD1) mice, particularly AOM/DSS-treated males, by decreasing the F/B ratio and changing Shannon and Simpson index by supply of estrogen. This highlights another possibility that estrogen could cause changes in the gut microbiota, thereby reducing the risk of developing CRC.

Cilostazol, a phosphodiesterase 3 inhibitor, reduces the amyloid-beta (Aβ) burden in mouse models of Alzheimer disease by as yet unidentified mechanisms. In the present study, we examined the possibility that cilostazol ameliorates lysosomal dysfunction. Astrocytes treated with bafilomycin A1 (BafA1) exhibited markedly reduced DND-189 and acridine orange (AO) fluorescence, indicating reduced lysosomal acidity. In both cases, BafA1-induced alkalization was reversed by addition of cilostazol, dibutyryl cAMP or forskolin. All three agents significantly increased free zinc levels in lysosomes, and addition of the zinc chelator TPEN abrogated lysosomal reacidification. These treatments did not raise free zinc levels or reverse BafA1-mediated lysosomal alkalization in metallothionein 3 (Mt3)-null astrocytes, indicating that the increases in zinc in astrocytes were derived mainly from Mt3. Lastly, in FITC-Aβ-treated astrocytes, cilostazol reversed lysosomal alkalization, increased cathepsin D activity, and reduced Aβ accumulation in astrocytes. Cilostazol also reduced mHtt aggregate formation in GFP-mHttQ74–expressing astrocytes. Collectively, our results present the novel finding that cAMP/PKA can overcome the v-ATPase blocking effect of BafA1 in a zinc- and Mt3-dependent manner.

Although metallothionein-3 (MT3), a brain-enriched form of metallothioneins, has been linked to Alzheimer’s disease, little is known regarding the role of MT3 in glioma. As MT3 plays a role in autophagy in astrocytes, here, we investigated its role in irradiated glioma cells. Irradiation increased autophagy flux in GL261 glioma cells as evidenced by increased levels of LC3-II but decreased levels of p62 (SQSTM1). Indicating that autophagy plays a cytoprotective role in glioma cell survival following irradiation, measures inhibiting autophagy flux at various steps decreased their clonogenic survival of irradiated GL261 as well as SF295 and U251 glioma cells. Knockdown of MT3 with siRNA in irradiated glioma cells induced arrested autophagy, and decreased cell survival. At the same time, the accumulation of labile zinc in lysosomes was markedly attenuated by MT3 knockdown. Indicating that such zinc accumulation was important in autophagy flux, chelation of zinc with tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN), induced arrested autophagy in and reduced survival of GL261 cells following irradiation. Suggesting a possible mechanism for arrested autophagy, MT3 knockdown and zinc chelation were found to impair lysosomal acidification. Since autophagy flux plays a cytoprotective role in irradiated glioma cells, present results suggest that MT3 and zinc may be regarded as possible therapeutic targets to sensitize glioma cells to ionizing radiation therapy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Psoriasis is a chronic inflammatory skin disorder mediated by the T-cell–related immune response. Psoriatic patients may have a variety of comorbidities, but their risk of end-stage renal disease (ESRD), particularly according to the subtype of psoriasis, is unclear. We investigated the risk of ESRD in patients with psoriasis according to the subtype of psoriasis and history of systemic therapy for psoriasis. A total of 2,121,228 adults (1,590,921 in the control group and 530,307 in the psoriasis group) were enrolled in this nationwide population-based cohort study until 2015. During follow-up, 1,434 of the subjects in the psoriasis group developed ESRD. After adjusting for confounding factors, psoriasis was associated with the risk of ESRD (hazard ratio (HR) 1.58, 95% confidence interval [95% CI] 1.47–1.68). The psoriatic arthritis group (HR 7.60, 95% CI 1.90–30.41) had a higher risk of ESRD than the control group. Interestingly, no such association was detected in the systemically treated group (HR 1.07, 95% CI 0.80–1.41). Moreover, the acitretin-treated group had a lower risk of ESRD (HR 0.658, 95% CI, 0.494–0.875) than the non-systemically treated group. In conclusion, the risk of developing ESRD in patients with psoriasis differed according to the type of treatment and the presence of arthritis.

Ionic liquids (ILs) which have electrical stability are attractive materials to enhance the potential window of electrolyte. According to the potential window is extended, available voltage for supercapacitor is broaden. In this study, the addition of ILs which is 1-ethyl-3-methylimidazolium tetrafluoroborate (EMIBF4) and 1-ethyl-3-methylimidazolium bis(trifluoromethylesulfonyl) imide (EMITFSI) as co-salts, to a supercapacitor electrolyte increases the ionic conductivity and stability of it due to inhibition of electrolyte decomposition. As a result, the electrochemical stability potential windows (ESPWs) of supercapacitor is improved and the supercapacitor exhibited increased cycling stability. The loss of specific capacitance upon addition of 7 wt% EMIBF4 or EMITFSI to the electrolyte was 2.5% and 8.7%, respectively, after 10,000 cycles at 3.5 V, compared to the specific capacitance of the initial discharge.

This study aimed to identify associations among self-perceived weight status, accuracy of weight perceptions, and weight control behaviors, including both healthy and unhealthy behaviors, in a large, nationally representative sample from an East Asian country. Data were collected from the 2016 Korean Study of Women’s Health Related Issues, a population-based, nationwide survey. Accurate weight perceptions were investigated by comparing body mass index (BMI) categories, based on self-reported height and weight, and weight perceptions. Weight control behaviors over the previous 12 months were additionally surveyed. Odds ratios (ORs) and 95% confidence intervals (CIs) are presented as an index of associations. Among normal weight, overweight, and obese women, 12.8%, 44.3%, and 17.4% under-assessed their weight; 17.9% of normal weight women over-assessed their weight. Both weight status according to BMI category and weight perceptions were strongly associated with having tried to lose weight. Exercise and diet (ate less) were the most commonly applied weight control behaviors. Misperception of weight was related to more unhealthy weight control behaviors and less healthy behaviors: Women who under-assessed their weight showed a lower tendency to engage in dieting (OR = 0.57, 95% CI = 0.43–0.75) and a greater tendency to fast/skip meals (OR = 1.47, 95% CI = 1.07–1.99). Meanwhile, normal weight or overweight women who over-assessed their weight were more likely to have engaged in fasting/skipping meals or using diet pills (OR = 5.72, 95% CI = 2.45–13.56 for fasting/skipping meal in overweight women; OR = 1.62, 95% CI = 1.15–2.29 and OR = 3.16, 95% CI = 1.15–8.23 for using diet pills in normal and overweight women). Inaccuracy of weight perceptions in any direction (over/under) were related to more unhealthy weight control behaviors and less healthy weight control behaviors, especially in normal and overweight women.

The juice of Ageratum houstonianum is used in folk medicine as an external wound healing aid for skin injuries. However, the active component of A. houstonianum and its mode of action in skin wound healing has not been investigated. This study was conducted to investigate the effect of A. houstonianum ethanolnolic extract (AHE) on the expression of aquaporin-3 (AQP3), an integral membrane protein for water and glycerol transport in keratinocytes, and to identify the structure of the A. houstonianum bioactive compound. Here, we show that AHE increased AQP3 gene expression at the transcriptional level through the p38 MAPK pathway in HaCaT cells. Furthermore, AHE ameliorated suppression of AQP3 expression caused by ultraviolet B (UVB) irradiation. Agerarin (6,7-dimethoxy-2,2-dimethyl-2H-chromene) was identified as the bioactive compound responsible for the up-regulation of AQP3 expression by enhancing the expression of the transcription factor circadian locomotor output cycles kaput (CLOCK). In conclusion, agerarin is a bioactive compound in AHE responsible for CLOCK-mediated AQP3 expression in keratinocytes.

Pathogenic T helper cells (TH) and macrophages have been implicated in the development of rheumatoid arthritis (RA), which can lead to severe synovial inflammation and bone destruction. A range of therapies have been widely used for RA, including specific monoclonal antibodies and chemical inhibitors against inflammatory cytokines produced by these cells. However, these have not been sufficient to meet the medical need. Here, we show that in transgenic mice expressing truncated IK (tIK) cytokine, inflammatory arthritis symptoms were ameliorated as the result of suppression of the differentiation of TH1 and TH17 cells and of macrophage activation. During inflammatory responses, tIK cytokine systemically regulated macrophage functions and TH17 cell differentiation through inactivation of the MAPK and NF-κB pathways. Interestingly, the level of tIK cytokine was higher in synovial fluid of RA patients compared with that in osteoarthritis (OA) patients. Our observations suggest that tIK cytokine can counterbalance the induction of inflammatory cells related to RA and thus could be a new therapeutic agent for the treatment of RA.

Pathogenic T helper cells (TH) and macrophages have been implicated in the development of rheumatoid arthritis (RA), which can lead to severe synovial inflammation and bone destruction. A range of therapies have been widely used for RA, including specific monoclonal antibodies and chemical inhibitors against inflammatory cytokines produced by these cells. However, these have not been sufficient to meet the medical need. Here, we show that in transgenic mice expressing truncated IK (tIK) cytokine, inflammatory arthritis symptoms were ameliorated as the result of suppression of the differentiation of TH1 and TH17 cells and of macrophage activation. During inflammatory responses, tIK cytokine systemically regulated macrophage functions and TH17 cell differentiation through inactivation of the MAPK and NF-κB pathways. Interestingly, the level of tIK cytokine was higher in synovial fluid of RA patients compared with that in osteoarthritis (OA) patients. Our observations suggest that tIK cytokine can counterbalance the induction of inflammatory cells related to RA and thus could be a new therapeutic agent for the treatment of RA.

Many mitotic kinases have been targeted for the development of anti-cancer drugs, and inhibitors of these kinases have been expected to perform well for cancer therapy. Efforts focused on selecting good targets and finding specific drugs to target are especially needed, largely due to the increased frequency of anti-cancer drugs used in the treatment of lung cancer. Vaccinia-related kinase 1 (VRK1) is a master regulator in lung adenocarcinoma and is considered a key molecule in the adaptive pathway, which mainly controls cell survival. We found that ursolic acid (UA) inhibits the catalytic activity of VRK1 via direct binding to the catalytic domain of VRK1. UA weakens surveillance mechanisms by blocking 53BP1 foci formation induced by VRK1 in lung cancer cells, and possesses synergistic anti-cancer effects with DNA damaging drugs. Taken together, UA can be a good anti-cancer agent for targeted therapy or combination therapy with DNA damaging drugs for lung cancer patients.

Many mitotic kinases have been targeted for the development of anti-cancer drugs and inhibitors of these kinases have been expected to perform well for cancer therapy. Efforts focused on selecting good targets and finding specific drugs to target are especially needed, largely due to the increased frequency of anti-cancer drugs used in the treatment of lung cancer. Vaccinia-related kinase 1 (VRK1) is a master regulator in lung adenocarcinoma and is considered a key molecule in the adaptive pathway, which mainly controls cell survival. We found that ursolic acid (UA) inhibits the catalytic activity of VRK1 via direct binding to the catalytic domain of VRK1. UA weakens surveillance mechanisms by blocking 53BP1 foci formation induced by VRK1 in lung cancer cells and possesses synergistic anti-cancer effects with DNA damaging drugs. Taken together, UA can be a good anti-cancer agent for targeted therapy or combination therapy with DNA damaging drugs for lung cancer patients.