Par3 regulates the asymmetric division of basal stem cells in psoriasis via the Par3/mInsc/LGN signaling axis.

OBJECTIVE: This research aimed to investigate the mechanism in psoriasis with the involvement of Par3-containing exosomes from macrophages by regulating the asymmetric division of basal stem cells. METHODS: BrdU labeling and double immunofluorescence assays were conducted to detect the proportion of asymmetric division in psoriasis mice. Western blot assay was conducted to examine the expression of Par3/mInsc/LGN signaling pathway-related proteins in psoriasis mice. Next, the asymmetric division of keratinocytes in normal mice treated with macrophages and their secreted exosomes were determined, together with the related protein detection. After establishing a macrophage-specific Par3 knockout mouse model, the asymmetric division of isolated keratinocytes and the related proteins were measured. An epidermal-specific mInsc, LGN, or NuMA knockout mouse model was induced, followed by the determination of the asymmetric division of isolated keratinocytes. RESULTS: The asymmetric division of basal stem cells was increased, and the expression of Par3/mInsc/LGN signaling pathway-related proteins was elevated in psoriasis. Par3-containing macrophage-derived exosomes enhanced asymmetric division of basal stem cells and expression of Par3/mInsc/LGN signaling pathway-related proteins in mice. However, mice with Par3 loss presented opposite trends. There was a decreased asymmetric division of basal stem cells in epidermal-specific mInsc, LGN, and NUMA knockout mice. CONCLUSION: Our study suggests that macrophage-derived exosomes-shuttled Par3 are absorbed by the basal stem cells and regulate the asymmetric division of cells to produce a large number of transit-amplifying cells, thus causing psoriasis-related symptoms in conjunction with various other factors.

Administration of isoliquiritigenin prevents nonalcoholic fatty liver disease through a novel IQGAP2-CREB-SIRT1 axis.

Isoliquiritigenin (ISO) is a flavonoid extracted from the root of licorice, which serves various biological and pharmacological functions including antiinflammatory, antioxidation, liver protection, and heart protection. However, the mechanism of its action remains elusive and the direct target proteins of ISO have not been identified so far. Through cell-based screening, we identified ISO as a potent lipid-lowering compound. ISO treatment successfully ameliorated fatty acid-induced cellular lipid accumulation and improved nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) by increasing PPARα-dependent lipid oxidation and decreasing SREBPs-dependent lipid synthesis. Both these signaling required the activation of SIRT1. Knockdown of SIRT1 resulted in the reversal of ISO beneficiary effects suggesting that the lipid-lowering activity of ISO was regulated by SIRT1 expression. To identify the direct target of ISO, limited proteolysis combined with mass spectrometry (LiP-SMap) strategy was applied and IQGAP2 was identified as the direct target for ISO in regulating lipid homeostasis. In the presence of ISO, both mRNA and protein levels of SIRT1 were increased; however, this effect was abolished by blocking IQGAP2 expression using siRNA. To explore how IQGAP2 regulated the expression level of SIRT1, proteome profiler human phospho-kinase array kit was used to reveal possible phosphorylated kinases and signaling nodes that ISO affected. We found that through phosphorylation of CREB, ISO transduced signals from IQGAP2 to upregulate SIRT1 expression. Thus, we not only demonstrated the molecular basis of ISO in regulating lipid metabolism but also exhibited for the first time a novel IQGAP2-CREB-SIRT1 axis in treating NAFLD/NASH.

Different pattern of risk factors for post-ERCP pancreatitis in patients with biliary stricture.

OBJECTIVE: To identify possible risk factors associated with post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in biliary stricture (BS), common bile duct stone (CBDS) and unselected patients. MATERIALS AND METHODS: Consecutive ERCP patients with native papilla from January 2010 to December 2014 in Xijing Hospital were eligible. Patient-related and procedure-related parameters were collected retrospectively. The primary outcome was PEP. Univariate and multivariate logistic regression were used for data analysis. RESULTS: Totally 3133 unselected patients were included. 695 (22.2%) had BS alone and 1893 (60.4%) had CBDS alone. PEP incidence was higher in BS group compared with CBDS group (6.8% vs. 3.8%, p = .001). Among patient-related factors, duodenal stenosis (OR, 2.74; 95%CI, 1.14-6.59) and hilar stricture (OR, 2.59; 95%CI, 1.41-4.77) were found to be independently associated with PEP in BS group. While female gender (OR, 2.11; 95%CI, 1.20-3.73) and normal total bilirubin (OR, 1.93; 95%CI, 1.13-3.32) were related to PEP in CBDS group. Among procedure-related factors, cannulation time ≥ 5 min (OR, 2.38; 95%CI, 1.06-5.33) and precut (OR, 3.20; 95%CI, 1.35-7.59) was respectively the only independent risk factor for PEP in BS and CBDS group. CONCLUSIONS: Patients with BS and CBDS had different patterns of patient-related and procedure-related risk factors for PEP. The prophylaxis of PEP may need to be individualized based on different indications.

Enhanced instructions improve the quality of bowel preparation for colonoscopy: a meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: The success of a colonoscopy is highly dependent on the quality of bowel preparation (BP). Many patients have poor BP due to non-compliance with regular instructions. Reports concerning the effects of enhanced instructions on BP quality are inconsistent. The aim of this meta-analysis was to compare BP quality between patients receiving enhanced instructions in addition to regular instructions and those who received regular instructions only. METHODS: MEDLINE, EMBASE, Web of Science, and the Cochrane Library were searched to identify relevant studies published for August 2015. The quality of BP (adequate/inadequate), adenoma detection rate, polyp detection rate, willingness to repeat preparation, and adverse events were estimated by using odds ratios (OR) and 95% confidence intervals (CI) with random effects models. RESULTS: Eight randomized controlled trials (n = 3795) were included. Patients who received enhanced instructions showed significantly better BP quality than those receiving only regular instructions (OR, 2.35; 95% CI, 1.65-3.35; P < .001). Subgroup analysis showed that the beneficial effects of enhanced instructions on BP quality were consistent among patients receiving different purgative types, administration methods, or diet restriction (all P < .05). Patients in the enhanced instructions group showed more willingness to repeat the preparation (OR, 1.91; 95% CI, 1.20-3.04; P = .006). CONCLUSIONS: Enhanced instructions significantly improved the quality of BP and willingness to repeat the preparation in patients undergoing colonoscopy. Factors related to patient instructions appear to be as important as the preparation method itself in improving BP quality.

Risk of Stroke in Patients with Herpes Zoster: A Systematic Review and Meta-Analysis.

BACKGROUND: Several observational studies suggest that herpes zoster (HZ) may increase the risk of stroke, but the results are inconsistent. Our study was designed to assess the association between HZ and the risk of stroke through a meta-analysis of cohort studies. METHODS: The electronic databases PubMed and EMBASE were searched from inception to May 31, 2016 to identify relevant cohort studies that assess the risk of stroke in patients with HZ. Reference lists were also reviewed to identify potential studies. The random-effects model and fixed-effects model were used to calculate the summary relative risks (RRs) with 95% confidence intervals (CIs). RESULTS: Six cohort studies (251,076 HZ patients and 8462 cases of stroke) were identified in the study. The result showed that HZ was significantly correlated with increased risk of stroke, and the pooled RR was 1.36 (95% confidence interval [CI]: 1.10, 1.67) (P = .004). In the subgroup analysis, the significant association was observed except for stroke type (hemorrhage group). In the sensitivity analysis, excluding 1 study, the pooled RR was 1.45 (95% CI: 1.17, 1.80) (P = .001) for HZ, and 4.42 (95% CI: 2.75, 7.11) (P = .000) for herpes zoster ophthalmicus. Considerable heterogeneity was observed in our study. CONCLUSION: Our study furnishes evidence of a positive association between HZ and the risk of stroke.

Rhizotomy targeting the intermediate nerve, the glossopharyngeal nerve and the upper 1st to 2nd rootlets of the vagus nerve for the treatment of laryngeal neuralgia combined with intermediate nerve neuralgia--a case report.

BACKGROUND: In neurosurgery, the most common type of facial and pharyngeal pain is trigeminal neuralgia. In contrast, glossopharyngeal neuralgia is relatively rare, and laryngeal neuralgia is the most rarely observed. CASE PRESENTATION: A case of laryngeal neuralgia combined with intermediate nerve neuralgia that was admitted to our hospital in May 2012 was reported here. The patient was a 58-year-old middle-aged female, who experienced 2 years of paroxysmal burning and stabbing pain near the thyroid perichodrium, in the skin covering the right front side of the neck, and deep in inner ear. CONCLUSION: The surgical treatment plan similar to that for glossopharyngeal neuralgia could be applied if laryngeal neuralgia is associated with glossopharyngeal neuralgia and intermediate neuralgia or if no obvious improvement is achieved with the above mentioned treatment approaches.

BubR1 controls starvation-induced lipolysis via IMD signaling pathway in Drosophila.

Lipolysis, the key process releasing fat acids to generate energy in adipose tissues, correlates with starvation resistance. Nevertheless, its detail mechanisms remain elusive. BubR1, an essential mitotic regulator, ensures proper chromosome alignment and segregation during mitosis, but its physiological functions are largely unknown. Here, we use Drosophila adult fat body, the major lipid storage organ, to study the functions of BubR1 in lipolysis. We show that both whole body- and fat body-specific BubR1 depletions increase lipid degradation and shorten the lifespan under fasting but not feeding. Relish, the conserved regulator of IMD signaling pathway, acts as the downstream target of BubR1 to control the expression level of Bmm and modulate the lipolysis upon fasting. Thus, our study reveals new functions of BubR1 in starvation-induced lipolysis and provides new insights into the molecular mechanisms of lipolysis mediated by IMD signaling pathway.

Bub1 and Bub3 regulate metabolic adaptation via macrolipophagy in Drosophila.

Lipophagy, the process of selective catabolism of lipid droplets (LDs) by autophagy, maintains lipid homeostasis and provides cellular energy under metabolic adaptation, yet its underlying mechanism remains largely ambiguous. Here, we show that the Bub1-Bub3 complex, the crucial regulator involved in the whole process of chromosome alignment and separation during mitosis, controls the fasting-induced lipid catabolism in the fat body (FB) of Drosophila. Bidirectional deviations of the Bub1 or Bub3 level affect the consumption of triacylglycerol (TAG) of fat bodies and the survival rate of adult flies under starving. Moreover, Bub1 and Bub3 work together to attenuate lipid degradation via macrolipophagy upon fasting. Thus, we uncover physiological roles of the Bub1-Bub3 complex on metabolic adaptation and lipid metabolism beyond their canonical mitotic functions, providing insights into the in vivo functions and molecular mechanisms of macrolipophagy during nutrient deprivation.

Phase separation of BuGZ regulates gut regeneration and aging through interaction with m6A regulators.

Exploring the role of phase separation in intracellular compartment formation is an active area of research. However, the associations of phase separation with intestinal stem cell (ISC)-dependent regeneration and aging remain unclear. Here, we demonstrate that BuGZ, a coacervating mitotic effector, shows age- and injury-associated condensation in Drosophila ISC nuclei during interphase. BuGZ condensation promotes ISC proliferation, affecting Drosophila gut repair and longevity. Moreover, m6A reader YT521-B acts as the transcriptional and functional downstream of BuGZ. The binding of YT521-B promotor or m6A writer Ime4/ Mettl14 to BuGZ controls its coacervation, indicating that the promotor may accelerate the phase transition of its binding transcription factor. Hence, we propose that phase separation and m6A regulators may be critical for ameliorating ISC-dependent gut regeneration and aging and requires further study.

Focal nodular hyperplasia mimicking hepatocellular adenoma and carcinoma in two cases.

Focal nodular hyperplasia (FNH) is a solid benign tumor of the liver, predominantly in young women. A correct diagnosis of FNH is essential for making appropriate clinical decisions and avoiding unnecessary liver resection. Herein, we reported that two male cases with FNH, who initially presented with persistent abdominal discomfort, were misdiagnosed with hepatocellular adenoma (HCA) and hepatocellular carcinoma (HCC) on contrast-enhanced magnetic resonance imaging and computed tomography scans, respectively. After surgery, a histological diagnosis of FNH was finally established. In this paper, we also reviewed the knowledge regarding diagnosis and differential diagnosis of FNH on imaging examinations, which are helpful for avoiding misdiagnoses and guiding clinical interventions.

Risk Factors for Post-ERCP Pancreatitis in High-Risk Patients Receiving Post-procedure Rectal Indomethacin.

BACKGROUND: Post-ERCP pancreatitis (PEP) is the most common adverse event of ERCP. Rectal indomethacin has been widely administered to decrease the incidence of PEP in high-risk patients. However, it cannot completely prevent the occurrence of PEP. The purpose of the study was to evaluate the risk factors for PEP in high-risk patients receiving post-ERCP indomethacin. METHODS: From June 2012 to July 2015, patients undergoing ERCP and at high risk for PEP in three tertiary hospitals in China were enrolled. All patients received indomethacin after the procedure. Patient-related and procedure-related risk factors for PEP were collected. Logistic regression analysis was used to investigate the risk factors. RESULTS: Seven hundred ninety patients at high risk for PEP received post-ERCP indomethacin. The incidence of overall PEP and moderate-to-severe PEP was 8.0 and 1.5%, respectively. In multivariate analysis, suspected sphincter of Oddi dysfunction (SOD) (OR 2.73; 95%CI 1.38-5.43; p = 0.004), the presence of hilar obstruction (OR 4.53; 95%CI 1.60-12.81; p = 0.004), number of cannulation attempts ≥ 13 (OR 2.00; 95%CI 1.07-3.77; p = 0.030), inadvertent pancreatic duct (PD) cannulation ≥ 1 (OR 2.26; 95%CI 1.04-4.90; p = 0.040), and pancreatic contrast injections ≥ 1 (OR 2.30; 95%CI 1.02-5.23; p = 0.046) were high risk factors for overall PEP. For moderate-to-severe PEP, suspected SOD (OR 4.67; 1.19-18.35; p = 0.027), the presence of hilar obstruction (OR 7.95; 1.39-44.97; p = 0.010), and more cannulation attempts (OR 3.71; 1.09-12.65; p = 0.036) were three independent risk factors. CONCLUSIONS: A substantial number of high-risk patients had PEP even receiving post-ERCP rectal indomethacin. The independent risk factors included suspected SOD, hilar stricture, more cannulation attempts, inadvertent PD cannulation, and PD contrast injections. TRIAL REGISTRATION: NCT02709421.