Long-Term Culture Captures Injury-Repair Cycles of Colonic Stem Cells.

The colonic epithelium can undergo multiple rounds of damage and repair, often in response to excessive inflammation. The responsive stem cell that mediates this process is unclear, in part because of a lack of in vitro models that recapitulate key epithelial changes that occur in vivo during damage and repair. Here, we identify a Hopx+ colitis-associated regenerative stem cell (CARSC) population that functionally contributes to mucosal repair in mouse models of colitis. Hopx+ CARSCs, enriched for fetal-like markers, transiently arose from hypertrophic crypts known to facilitate regeneration. Importantly, we established a long-term, self-organizing two-dimensional (2D) epithelial monolayer system to model the regenerative properties and responses of Hopx+ CARSCs. This system can reenact the "homeostasis-injury-regeneration" cycles of epithelial alterations that occur in vivo. Using this system, we found that hypoxia and endoplasmic reticulum stress, insults commonly present in inflammatory bowel diseases, mediated the cyclic switch of cellular status in this process.

Longitudinal evaluation of adverse events due to steroid use in primary immune thrombocytopenia: A population-based study.

This study aimed to investigate the association between the steroid use patterns and the risk of AEs in patients with primary immune thrombocytopenia (ITP). A total of 2691 newly diagnosed adults with ITP between 2011 and 2018 were identified from the National Health Insurance Research Database in Taiwan, and the date of first steroid use was defined as the index date. Post-index steroid use was calculated on a 90-day basis as a time-dependent variable and categorized by the average prednisolone-equivalent daily dose (<10 mg vs. ≥10 mg) and intensity (medication possession ratio <80% vs. ≥80%). Patients were followed up for 1 year from the index date for acute AE events, while chronic AEs were assessed until death, or end of 2019. Compared to patients with low-dose+low-intensity steroid use, those with high-dose+high-intensity steroid use were associated with a higher risk of acute AE (adjusted incident rate ratio [aIRR]: 1.57, 95% confidence interval [CI]: 1.38-1.78, p < 0.01) and chronic AE (aIRR: 1.26, 95% CI: 1.08-1.47, p < 0.01). Metabolic/endocrine and ophthalmologic disorders demonstrated the strongest correlation with a high dose and intensity. The joint effect of steroid dose and intensity was observed in patients with ITP, and the findings suggest that steroids should be used carefully.

TERRA regulates DNA G-quadruplex formation and ATRX recruitment to chromatin.

The genome consists of non-B-DNA structures such as G-quadruplexes (G4) that are involved in the regulation of genome stability and transcription. Telomeric-repeat containing RNA (TERRA) is capable of folding into G-quadruplex and interacting with chromatin remodeler ATRX. Here we show that TERRA modulates ATRX occupancy on repetitive sequences and over genes, and maintains DNA G-quadruplex structures at TERRA target and non-target sites in mouse embryonic stem cells. TERRA prevents ATRX from binding to subtelomeric regions and represses H3K9me3 formation. G4 ChIP-seq reveals that G4 abundance decreases at accessible chromatin regions, particularly at transcription start sites (TSS) after TERRA depletion; such G4 reduction at TSS is associated with elevated ATRX occupancy and differentially expressed genes. Loss of ATRX alleviates the effect of gene repression caused by TERRA depletion. Immunostaining analyses demonstrate that knockdown of TERRA diminishes DNA G4 signals, whereas silencing ATRX elevates G4 formation. Our results uncover an epigenetic regulation by TERRA that sequesters ATRX and preserves DNA G4 structures.

DUSP6 Deficiency Attenuates Neurodegeneration after Global Cerebral Ischemia.

Transient global cerebral ischemia (tGCI) resulting from cardiac arrest causes selective neurodegeneration in hippocampal CA1 neurons. Although the effect is clear, the underlying mechanisms directing this process remain unclear. Previous studies have shown that phosphorylation of Erk1/2 promotes cell survival in response to tGCI. DUSP6 (also named MKP3) serves as a cytosolic phosphatase that dephosphorylates Erk1/2, but the role of DUSP6 in tGCI has not been characterized. We found that DUSP6 was specifically induced in the cytoplasm of hippocampal CA1 neurons 4 to 24 h after tGCI. DUSP6-deficient mice showed normal spatial memory acquisition and retention in the Barnes maze. Impairment of spatial memory acquisition and retention after tGCI was attenuated in DUSP6-deficient mice. Neurodegeneration after tGCI, revealed by Fluoro-Jade C and H&E staining, was reduced in the hippocampus of DUSP6-deficient mice and DUSP6 deficiency enhanced the phosphorylation and nuclear translocation of Erk1/2 in the hippocampal CA1 region. These data support the role of DUSP6 as a negative regulator of Erk1/2 signaling and indicate the potential of DUSP6 inhibition as a novel therapeutic strategy to treat neurodegeneration after tGCI.

Synergistic effect of Abraxane that combines human IL15 fused with an albumin-binding domain on murine models of pancreatic ductal adenocarcinoma.

Nab-paclitaxel (Abraxane), which is a nanoparticle form of albumin-bound paclitaxel, is one of the standard chemotherapies for pancreatic ductal adenocarcinoma (PDAC). This study determined the effect of Abraxane in combination with a fusion protein, hIL15-ABD, on subcutaneous Panc02 and orthotopic KPC C57BL/6 murine PDAC models. Abraxane combined with hIL15-ABD best suppressed tumour growth and produced a 40%-60% reduction in the tumour size for Panc02 and KPC, compared to the vehicle group. In the combination group, the active form of interferon-γ (IFN-γ)-secreting CD8+ T cells and CD11b+ CD86+ M1 macrophages in tumour infiltrating lymphocytes (TILs) were increased. In the tumour drainage lymph nodes (TDLNs) of the combination group, there was a 18% reduction in CD8+ IFN-γ+ T cells and a 0.47% reduction in CD4+ CD25+ FOXP3+ regulatory T cells, as opposed to 5.0% and 5.1% reductions, respectively, for the control group. Superior suppression of CD11b+ GR-1+ myeloid-derived suppressor cells (MDSCs) and the induction of M1 macrophages in the spleen and bone marrow of mice were found in the combination group. Abraxane and hIL15-ABD effectively suppressed NF-κB-mediated immune suppressive markers, including indoleamine 2,3-dioxygenase (IDO), Foxp3 and VEGF. In conclusion, Abraxane combined with hIL15-ABD stimulates the anticancer activity of effector cells, inhibits immunosuppressive cells within the tumour microenvironment (TME) of PDAC, and produces a greater inhibitory effect than individual monotherapies.

Lipocalin-2 mediates the rejection of neural transplants.

Lipocalin-2 (LCN2) has been implicated in promoting apoptosis and neuroinflammation in neurological disorders; however, its role in neural transplantation remains unknown. In this study, we cultured and differentiated Lund human mesencephalic (LUHMES) cells into human dopaminergic-like neurons and found that LCN2 mRNA was progressively induced in mouse brain after the intrastriatal transplantation of human dopaminergic-like neurons. The induction of LCN2 protein was detected in a subset of astrocytes and neutrophils infiltrating the core of the engrafted sites, but not in neurons and microglia. LCN2-immunoreactive astrocytes within the engrafted sites expressed lower levels of A1 and A2 astrocytic markers. Recruitment of microglia, neutrophils, and monocytes after transplantation was attenuated in LCN2 deficiency mice. The expression of M2 microglial markers was significantly elevated and survival of engrafted neurons was markedly improved after transplantation in LCN2 deficiency mice. Brain type organic cation transporter (BOCT), the cell surface receptor for LCN2, was induced in dopaminergic-like neurons after differentiation, and treatment with recombinant LCN2 protein directly induced apoptosis in dopaminergic-like neurons in a dose-dependent manner. Our results, therefore, suggested that LCN2 is a neurotoxic factor for the engrafted neurons and a modulator of neuroinflammation. LCN2 inhibition may be useful in reducing rejection after neural transplantation.

Comparison of long-term effects of exergaming (Xbox one kinet) and companionship programs on attitude towards dementia and the older adults among adolescents: a quasi-experimental longitudinal study.

BACKGROUND: Many studies have been performed on the use of intergenerational programs to improve the negative attitudes and misunderstandings of adolescents toward older people with dementia. However, the findings of these studies are inconclusive. The aim of this study was to compare the long-term effects of exergaming (Kinect) and companionship programs on attitudes toward dementia and the elderly among adolescents. METHODS: A quasi-experimental longitudinal design was used. A total of 200 adolescents aged 12-18 years old were recruited from nine schools in northern Taiwan. The adolescents were assigned to five different groups, namely, a 5-week exergaming group, a 5-week companion group, an 8-week exergaming group, an 8-week companion group, and a control group, using a single blinding procedure. Data collection was performed pretest, post-test and at 1, 3 and 6 months after the post-test. The long-term effects of the two programs (i.e., exergaming and companionship) were analyzed using a generalized estimating equation. RESULTS: Regarding attitudes toward dementia, the 8-week exergaming group had a significantly better attitude than the control group at the 6-month follow-up (p < 0.001). Similarly, the results of the 8-week companion group also showed a significantly improved attitude compared with the control group at the 6-month follow-up (p = 0.041). Regarding attitudes toward the elderly, the 8-week exergaming group had a significantly better attitude than the control group at the 6-month follow-up (p < 0.001). The 8-week companion group had a similar effect on better attitude compared with the control group at the 6-month follow-up (p = 0.016). Furthermore, the 5-week companion group showed a significant improvement compared with the control group at the 6-month follow-up (p = 0.004). CONCLUSIONS: Spending companionship time with older adults is beneficial for improving the attitudes of adolescents toward the elderly. Furthermore, exergaming improves the attitudes of adolescents toward both dementia and older adults. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2100053003 . Retrospectively registered on 07/11/2021.

Anti-Excitotoxic Effects of N-Butylidenephthalide Revealed by Chemically Insulted Purkinje Progenitor Cells Derived from SCA3 iPSCs.

Spinocerebellar ataxia type 3 (SCA3) is characterized by the over-repetitive CAG codon in the ataxin-3 gene (ATXN3), which encodes the mutant ATXN3 protein. The pathological defects of SCA3 such as the impaired aggresomes, autophagy, and the proteasome have been reported previously. To date, no effective treatment is available for SCA3 disease. This study aimed to study anti-excitotoxic effects of n-butylidenephthalide by chemically insulted Purkinje progenitor cells derived from SCA3 iPSCs. We successfully generated Purkinje progenitor cells (PPs) from SCA3 patient-derived iPSCs. The PPs, expressing both neural and Purkinje progenitor's markers, were acquired after 35 days of differentiation. In comparison with the PPs derived from control iPSCs, SCA3 iPSCs-derived PPs were more sensitive to the excitotoxicity induced by quinolinic acid (QA). The observations of QA-treated SCA3 PPs showing neural degeneration including neurite shrinkage and cell number decrease could be used to quickly and efficiently identify drug candidates. Given that the QA-induced neural cell death of SCA3 PPs was established, the activity of calpain in SCA3 PPs was revealed. Furthermore, the expression of cleaved poly (ADP-ribose) polymerase 1 (PARP1), a marker of apoptotic pathway, and the accumulation of ATXN3 proteolytic fragments were observed. When SCA3 PPs were treated with n-butylidenephthalide (n-BP), upregulated expression of calpain 2 and concurrent decreased level of calpastatin could be reversed, and the overall calpain activity was accordingly suppressed. Such findings reveal that n-BP could not only inhibit the cleavage of ATXN3 but also protect the QA-induced excitotoxicity from the Purkinje progenitor loss.

Clinicopathologic Features of Lymphoproliferative Neoplasms Involving the Liver.

Background and Objectives: Primary hepatic lymphoproliferative neoplasms (PHL) are uncommon. This retrospective study is aimed to present the clinicopathological characteristics of PHL and compare to secondary hepatic lymphoproliferative neoplasms (SHL). Materials and Methods: Patients who were diagnosed with lymphoproliferative neoplasms involving the liver between January 2004 and December 2018 at a tertiary medical center in central Taiwan were included. The demographic and clinical data, radiological results and histopathological findings were reviewed and summarized. Results: We analyzed 36 patients comprising 6 PHL patients and 30 SHL patients. The median age at diagnosis tended to be younger in PHL than in SHL (59 vs. 63 years old, p = 0.349). Both entities had a small male predominance. The PHL patients tended to have higher levels of aspartate aminotransferase, alanine transaminase and serum albumin and lower levels of alkaline phosphatase, total bilirubin, γ-glutamyl transferase and lactate dehydrogenase compared with SHL, but there was no significant difference. Multiple mass lesions were the most common radiological finding in both groups. Diffuse large B-cell lymphoma was the predominant subtype in both groups (67% in PHL and 40% in SHL). The PHL patients had a longer median survival than the SHL patients (not reached vs. 3 months, p = 0.003). Conclusions: Although there was no significant difference between PHL and SHL in clinical, laboratory and radiological features, the SHL patients had very poor outcomes with a median survival time of 3 months. Effective therapies are urgently required for these patients.

Efficacy and safety of cervicothoracic epidural blood patch for patients with spontaneous intracranial hypotension.

BACKGROUND: Epidural blood patch (EBP) is a generally effective treatment for spontaneous intracranial hypotension (SIH) caused by cerebrospinal fluid (CSF) leakage through the spinal dura mater. It is still unclear; however, whether application near the leakage site (targeted EBP) is more effective than distal application (untargeted EBP). Further, EBP targeted to high thoracic or cervical spine levels is infrequent due to greater technical requirements and potential complications. Here, we examined the safety and efficacy of EBP applied to high thoracic or cervical spine levels. METHODS: We retrospectively reviewed the clinical and outcome data of 13 patients receiving cervical or high thoracic EBP for SIH. All patients were referred by neurologists following poor response to conservative treatment and presented with persistent headache aggravated by orthostatic changes. RESULTS: Neuroimaging confirmed CSF leakage and targeted EBP resulted in immediate pain improvement. Repeated injections provided additional improvement for patients with recurrent headache. No serious adverse events were documented during follow-up. CONCLUSION: Based on recent studies and our clinical experience, we conclude that EBP targeted to the high thoracic and cervical spine is safe and effective for early-stage SIH.

Biofilm Formation and Virulence of Shigella flexneri Are Modulated by pH of Gastrointestinal Tract.

Shigella infection remains a public health problem in much of the world. Classic models of Shigella pathogenesis suggest that microfold epithelial cells in the small intestine are the preferred initial site of invasion. However, recent evidence supports an alternative model in which Shigella primarily infects a much wider range of epithelial cells that reside primarily in the colon. Here, we investigated whether the luminal pH difference between the small intestine and the colon could provide evidence in support of either model of Shigella flexneri pathogenesis. Because virulence factors culminating in cellular invasion are linked to biofilms in S. flexneri, we examined the effect of pH on the ability of S. flexneri to form and maintain adherent biofilms induced by deoxycholate. We showed that a basic pH (as expected in the small intestine) inhibited formation of biofilms and dispersed preassembled mature biofilms, while an acidic pH (similar to the colonic environment) did not permit either of these effects. To further elucidate this phenomenon at the molecular level, we probed the transcriptomes of biofilms and S. flexneri grown under different pH conditions. We identified specific amino acid (cysteine and arginine) metabolic pathways that were enriched in the bacteria that formed the biofilms but decreased when the pH increased. We then utilized a type III secretion system reporter strain to show that increasing pH reduced deoxycholate-induced virulence of S. flexneri in a dose-dependent manner. Taken together, these experiments support a model in which Shigella infection is favored in the colon because of the local pH differences in these organs.

Neonatal Intrahepatic Cholestasis Caused by Citrin Deficiency with SLC25A13 Mutation Presenting Hepatic Steatosis and Prolonged Jaundice. A Rare Case Report.

Background: Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a rare autosomal recessive disease. The incidence of citrin deficiency is estimated between 1/10,000 and 1/20,000 in Taiwan. Case report: This report describes a case of a 42 day old female infant who suffered from prolonged jaundice, poor weight gain, and anemia. The initial total/direct bilirubin levels were 8.1/3.11 mg/dL. Liver biopsy was performed at 47 days old. The pathology revealed lobules marked with macrovesicular and microvesicular fatty metamorphosis. The serum amino acid profile showed elevated levels of threonine, methionine, citrulline, and arginine. Newborn screening disclosed normal results, but the genetic study revealed SLC25A13 mutation 851-854 del and 615 + 5G > A. The genetic study of her parents showed that the father carried the SLC25A13 mutation 851-854 del and the mother carried the SLC25A13 mutation 615 + 5G > A. Treatment with ursodeoxycholic acid decreased the bilirubin levels to a normal range at the age of 5 months. Conclusion: This report illustrates that hepatic steatosis is a feature of NICCD. For every young infant patient who develops cholestasis, the pediatrician must consider NICCD as a differential diagnosis even if newborn screening shows normal findings.

Induction of apoptosis through extrinsic/intrinsic pathways and suppression of ERK/NF-κB signalling participate in anti-glioblastoma of imipramine.

Glioblastomas are the most aggressive type of brain tumour, with poor prognosis even after standard treatment such as surgical resection, temozolomide and radiation therapy. The overexpression of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in glioblastomas is recognized as an important treatment target. Thus, an urgent need regarding glioblastomas is the development of a new, suitable agent that may show potential for the inhibition of extracellular signal-regulated kinase (ERK)/NF-κB-mediated glioblastoma progression. Imipramine, a tricyclic antidepressant, has anti-inflammatory actions against inflamed glial cells; additionally, imipramine can induce glioblastoma toxicity via the activation of autophagy. However, whether imipramine can suppress glioblastoma progression via the induction of apoptosis and blockage of ERK/NF-κB signalling remains unclear. The main purpose of this study was to investigate the effects of imipramine on apoptotic signalling and ERK/NF-κB-mediated glioblastoma progression by using cell proliferation (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide [MTT] assay), flow cytometry, Western blotting, and cell invasion/migration assay analysis in vitro. The ERK and NF-κB inhibitory capacity of imipramine is detected by NF-κB reporter gene assay and Western blotting. Additionally, a glioblastoma-bearing animal model was used to validate the therapeutic efficacy and general toxicity of imipramine. Our results demonstrated that imipramine successfully triggered apoptosis through extrinsic/intrinsic pathways and suppressed the invasion/migration ability of glioblastoma cells. Furthermore, imipramine effectively suppressed glioblastoma progression in vivo via the inhibition of the ERK/NF-κB pathway. In summary, imipramine is a potential anti-glioblastoma drug which induces apoptosis and has the capacity to inhibit ERK/NF-κB signalling.

Performance of Acoustic Radiation Force Impulse Elastography for Staging Liver Fibrosis in Patients With Chronic Hepatitis C After Viral Eradication.

BACKGROUND: Data on noninvasive liver fibrosis staging after viral eradication are unclear. This histology-based study validated the performance of liver stiffness (LS) measurements after viral eradication. METHODS: Consecutive participants with chronic hepatitis C (CHC) who received concomitant LS measurements through acoustic radiation force impulse (ARFI) elastography and percutaneous liver biopsy were prospectively screened and analyzed. RESULTS: Of the 644 patients, 521 (80.9%) underwent a biopsy at treatment baseline, and the remaining 123 (19.1%) underwent a biopsy at 3 years (median; interquartile range, 0.1) after the sustained virological response (SVR) to pegylated interferon-based and direct-acting antiviral treatments. The proportions of histological fibrosis stages did not differ significantly between the pretreatment and post-SVR groups (P = .0615). However, the LS values differed significantly (P < .0001). The median LS values (presented as shear wave velocities in meters per second) were 1.51 (0.92) for the pretreatment group and 1.22 (0.77) for the post-SVR group. The cutoffs (areas under the receiver operating characteristic curve, obtained using the bootstrap method) to dichotomize between METAVIR fibrosis stage F1 versus stages F2-F4, F1-F2 versus F3-F4, and F1-F3 versus F4 were 1.47 (0.8333, 95% confidence interval [CI] 0.7981-0.8663), 1.81 (0.8763, 95% CI 0.8376-0.9107), and 1.86 (0.8811, 95% CI 0.8378-0.9179) in the pretreatment group, respectively, and 1.22 (0.7872, 95% CI 0.7001-0.8624), 1.59 (0.8808, 95% CI 0.8034-0.9422), and 1.75 (0.9018, 95% CI 0.8201-0.9644) in the post-SVR group, respectively. CONCLUSIONS: The performance of LS measurements through ARFI elastography is promising to determine the liver fibrosis stage on necroinflammation-resolved histology in CHC after viral eradication.

Fat-Water Swaps in Iterative Decomposition of Water and Fat With Echo Asymmetry and Least-Squares Estimation Magnetic Resonance Imaging for Postinstrumentation Spine.

OBJECTIVE: To determine the frequencies of fat-water swaps in iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) water-only images of the postinstrumentation spine and discuss the efficiency of in-phase imaging in improving visibility of the thecal sac. MATERIALS AND METHODS: A total of 276 patients (167 women; mean age, 62.3 years; range, 23-89 years) with metallic devices on the lumbar spine who received complete routine 1.5 T MR imaging, including axial and sagittal images of T1-weighted, T2-weighted, and T2-weighted IDEAL sequences, were included. The exclusion criteria were significant motion artifacts and severe metallic artifacts in any one of the sequences. The images were reviewed by two radiologists to identify fat-water swaps that were divided into 3 groups: extraspinal swaps, intraspinal swaps in sagittal images, and intraspinal swaps in axial images. The qualitative evaluations for the spinal canal in axial images were performed by rating on a five-point scale. Side-by-side comparisons of T2-weighted images and IDEAL in-phase images were also performed. RESULTS: In patient-based data of 276 patients, extraspinal fat-water swaps were noted in 10 patients (3.6%) and intraspinal swaps were noted in 160 patients (58.0%). The intraspinal swaps had a higher incidence in the patients with more levels of metallic devices with screws and the trend was not noted in the extraspinal swaps. A total of 928 axial levels were evaluated in the level-based data of axial images. T1-weighted, T2-weighted, and IDEAL in-phase images had significantly better imaging quality than the IDEAL water-only images (3.9 ± 0.4, 3.9 ± 0.3, 3.8 ± 0.4 vs 3.0 ± 1.3, all P < 0.001). Compared with T2-weighted images, most of the IDEAL in-phase images (reader 1, 90.9%; reader 2, 86.7%) present similar quality. CONCLUSION: Iterative decomposition of water and fat with echo asymmetry and least-squares estimation sequence can provide good fat suppression in most spine MRI with metallic devices but the loss of cerebrospinal fluid signal intensities due to fat-water swaps are noted in more than half of postinstrumentation spine. Routine reconstruction of in-phase images is recommended to improve evaluation of the thecal sac by avoiding pitfall caused by fat-water swaps.

Factors associated with low health literacy among community-dwelling women in Taiwan.

The present study investigated factors associated with health literacy in community-dwelling Taiwanese women, particularly focusing on those associated with prevalent unhealthy behaviors. This cross-sectional study recruited 353 community-dwelling women aged 39-89 years from February to October 2015 in urban, suburban, and rural areas. Variables investigated included physical activity, community activity, tobacco usage, alcohol consumption, and betel-nut chewing. Degree of health literacy was evaluated using the Chinese-language version of the European Health Literacy Survey Questionnaire. Most respondents had inadequate (17.6%), or problematic (49.3%), general health literacy. Multiple logistic regression analyses showed that low educational attainment was closely associated with inadequate or problematic general health literacy. Women who did not engage in regular physical activity or direct community activity were more likely to have inadequate and problematic general health literacy, respectively. Selected unhealthy behaviors (tobacco usage, alcohol consumption, betel-nut chewing) were not associated with health literacy. Low health literacy was prevalent among participants. Lower educational attainment and a lack of physical or community activity were associated with low health literacy. Health literacy should be considered during the process of delivering health information, and health education programs must enhance health literacy tailored to address individuals' lifestyles.

Neutralization of Lipocalin-2 Diminishes Stroke-Reperfusion Injury.

Oxidative stress is a key contributor to the pathogenesis of stroke-reperfusion injury. Neuroinflammatory peptides released after ischemic stroke mediate reperfusion injury. Previous studies, including ours, have shown that lipocalin-2 (LCN2) is secreted in response to cerebral ischemia to promote reperfusion injury. Genetic deletion of LCN2 significantly reduces brain injury after stroke, suggesting that LCN2 is a mediator of reperfusion injury and a potential therapeutic target. Immunotherapy has the potential to harness neuroinflammatory responses and provides neuroprotection against stroke. Here we report that LCN2 was induced on the inner surface of cerebral endothelial cells, neutrophils, and astrocytes that gatekeep the blood-brain barrier (BBB) after stroke. LCN2 monoclonal antibody (mAb) specifically targeted LCN2 in vitro and in vivo, attenuating the induction of LCN2 and pro-inflammatory mediators (iNOS, IL-6, CCL2, and CCL9) after stroke. Administration of LCN2 mAb at 4 h after stroke significantly reduced neurological deficits, cerebral infarction, edema, BBB leakage, and infiltration of neutrophils. The binding epitope of LCN2 mAb was mapped to the ß3 and ß4 strands, which are responsible for maintaining the integrity of LCN2 cup-shaped structure. These data indicate that LCN2 can be pharmacologically targeted using a specific mAb to reduce reperfusion injury after stroke.

Trifecta outcome of ureteral reconstruction in iatrogenic injury and non-iatrogenic ureteral lesions: a 10-year experience at a tertiary referral center.

PURPOSE: To analyze the trifecta outcome (functional, anatomical, and surgical aspects) of surgical reconstruction for ureteral lesions and investigate the factors affecting the success rate of such reconstruction. METHODS: We retrospectively reviewed the data of patients who underwent ureteral reconstruction at our institute between March 2007 and November 2016. Patient profiles, surgical methods, complications, ureteral stenting, laboratory data, and image studies were collected. The trifecta outcome was defined as preserved renal function, no progression of hydronephrosis, and no long-term stenting. The primary endpoint was the percentage of patients who achieved the trifecta outcome. The secondary endpoint was risk factors for trifecta outcome failure. RESULTS: We retrospectively reviewed 178 adult patients who had undergone ureteral reconstruction. The median follow-up period was 37.4 months. In total, 70 (39.3%) patients had iatrogenic ureteral injuries and 108 (60.7%) patients had non-iatrogenic ureteral lesions. Overall, 70% of the patients achieved the trifecta outcome after ureteral reconstruction. A multivariate analysis revealed that risk factors for trifecta failure were malignant diseases [odds ratio (OR) 2.93, p = 0.005], a history of pelvic radiation (OR 3.08, p = 0.032), preoperative estimated glomerular filtration rate < 60 (OR 2.52, p = 0.039), and a type of reconstruction ureteroureterostomy (OR 2.99, p = 0.014). CONCLUSIONS: Trifecta outcome could be used to evaluate the ureteral reconstruction in iatrogenic injury and non-iatrogenic ureteral lesions. This study revealed several risk factors that affected the trifecta outcome.

Benefits and pitfalls of iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) imaging in clinical application of the cervical spine MR.

AIM: To evaluate efficacy of T2-weighted (T2W) iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL)-fast spin echo (FSE) imaging of the cervical spine. MATERIALS AND METHODS: The cervical spine of 100 symptomatic patients was imaged using routine magnetic resonance imaging (MRI) versus IDEAL-FSE imaging. The signal-to-noise ratios (SNRs), contrast-to-noise ratios (CNRs), and image quality were analysed. To compare the diagnostic efficiency of degenerative spondylopathy, evaluations of spondylolisthesis, retrolisthesis, disc herniation, myelopathy, disc degeneration, and bone marrow oedema were also performed. RESULTS: IDEAL-FSE showed significantly higher SNRs and CNRs (all p<0.001) than fat-suppressed (FS) T2W-FSE. Sixteen of 100 patients had cervical spine instrumentation; in those patients, IDEAL-FSE provided significantly better uniformity of fat suppression (p<0.001) and fewer metallic artefacts (p<0.001). For patients without instrumentation, FS T2W-FSE showed significantly better overall image quality (p<0.001) and homogeneity of the cerebrospinal fluid (CSF; p<0.001) with fewer motion artefacts (p<0.001). IDEAL-FSE, however, provided significantly better uniformity of fat suppression (p<0.001). There were no significant differences in the diagnoses of spondylolisthesis, retrolisthesis, disc herniation, or myelopathy between IDEAL and FS T2W images. The only significant differences between the IDEAL and FS T2W images were noted when diagnosing degenerative disc disease at the C2-3 and C5-6 disc levels (p=0.019, p=0.002, respectively) and bone marrow oedema at C3 vertebral body (p=0.029). CONCLUSION: T2W IDEAL-FSE imaging should only be considered as an additional sequence to conventional FS T2W images in patients with poor fat suppression or severe metallic artefacts.

Quantitative Proteomics Analysis Reveals the Min System of Escherichia coli Modulates Reversible Protein Association with the Inner Membrane.

The Min system of Escherichia coli mediates placement of the division septum at the midcell. It oscillates from pole to pole to establish a concentration gradient of the division inhibition that is high at the poles but low at the midcell; the cell middle thereby becomes the most favorable site for division. Although Min oscillation is well studied from molecular and biophysical perspectives, it is still an enigma as to whether such a continuous, energy-consuming, and organized movement of the Min proteins would affect cellular processes other than the division site selection. To tackle this question, we compared the inner membrane proteome of the wild-type and Δmin strains using a quantitative approach. Forty proteins that showed differential abundance on the inner membrane of the mutant cells were identified and defined as proteins of interest (POIs). More than half of the POIs were peripheral membrane proteins, suggesting that the Min system affects mainly reversible protein association with the inner membrane. In addition, 6 out of 10 selected POIs directly interacted with at least one of the Min proteins, confirming the correlation between POIs and the Min system.Further analysis revealed a functional relationship between metabolism and the Min system. Metabolic enzymes accounted for 45% of the POIs, and there was a change of metabolites in the related reactions. We hypothesize that the Min system could alter the membrane location of proteins to modulate their enzymatic activity. Thus, the metabolic modulation in the Δmin mutant is likely an adaptive phenotype in cells of abnormal size and chromosome number due to an imbalanced abundance of proteins on the inner membrane. Taken together, the current work reports novel interactions of the Min system and reveals a global physiological impact of the Min system in addition to the division site placement.