Role of Thrombin in Soluble Thrombomodulin-Induced Suppression of Peripheral HMGB1-Mediated Allodynia in Mice

High mobility group box 1 (HMGB1), a nuclear protein, once released into the extracellular space under pathological conditions, plays a pronociceptive role in redox-dependent distinct active forms, all-thiol HMGB1 (at-HMGB1) and disulfide HMGB1 (ds-HMGB1), that accelerate nociception through the receptor for advanced glycation endproducts (RAGE) and Toll-like receptor 4 (TLR4), respectively. Thrombomodulin (TM), an endothelial membrane protein, and soluble TM, known as TMα, promote thrombin-mediated activation of protein C and also sequester HMGB1, which might facilitate thrombin degradation of HMGB1. The present study aimed at clarifying the role of thrombin in TMα-induced suppression of peripheral HMGB1-dependent allodynia in mice. Thrombin-induced degradation of at-HMGB1 and ds-HMGB1 was accelerated by TMα in vitro. Intraplantar (i.pl.) injection of bovine thymus-derived HMGB1 in an unknown redox state, at-HMGB1, ds-HMGB1 or lipopolysaccharide (LPS), known to cause HMGB1 secretion, produced long-lasting mechanical allodynia in mice, as assessed by von Frey test. TMα, when preadministered i.pl., prevented the allodynia caused by bovine thymus-derived HMGB1, at-HMGB1, ds-HMGB1 or LPS, in a dose-dependent manner. The TMα-induced suppression of the allodynia following i.pl. at-HMGB1, ds-HMGB1 or LPS was abolished by systemic preadministration of argatroban, a thrombin-inhibiting agent, and accelerated by i.pl. co-administered thrombin. Our data clearly indicate that TMα is capable of promoting the thrombin-induced degradation of both at-HMGB1 and ds-HMGB1, and suppresses the allodynia caused by either HMGB1 in a thrombin-dependent manner. Considering the emerging role of HMGB1 in distinct pathological pain models, the present study suggests the therapeutic usefulness of TMα for treatment of intractable and/or persistent pain.     

Adverse Effects of High Temperature On Mammary Alveolar Development In Vitro

Journal of Mammary Gland Biology and Neoplasia - In the mammary glands during pregnancy, the alveolar buds are first branched from the mammary ducts after which they form the alveolar luminal...     

Preoperative change of modified Glasgow prognostic score after stenting predicts the long-term outcomes of obstructive colorectal cancer

Inflammation-based markers predict the long-term outcomes of various malignancies. We investigated the relationship between the modified Glasgow prognostic score (mGPS) and the long-term outcomes of obstructive colorectal cancer in patients who underwent self-expandable metallic colonic stent placement and subsequently received curative surgery. We retrospectively analyzed 63 consecutive patients with pathological stage II and III obstructive colorectal cancer from 2013 to 2018. The mGPS was calculated before stenting and surgery, and the difference of the scores was defined as the d-mGPS. All d-mGPS = 2 patients were > 70 years of age (p = 0.01). Postoperative complications were more common in the preoperative mGPS = 2 group (p = 0.02). The postoperative hospital stay was significantly longer in the mGPS = 2 group (p = 0.007). Multivariate analyses revealed that d-mGPS was an independent prognostic factor for overall survival (OS) (hazard ratio [HR] = 9.18, p = 0.004) and cancer-specific survival (HR = 9.98, p = 0.01). Preoperative mGPS = 2 was significantly associated with poor OS (HR = 5.53, p = 0.04). The results indicated that mGPS might serve as a valuable indicator of the immunonutritional status of preoperative patients, and a preoperative change of the status might affect the long-term outcomes of patients with obstructive colorectal cancer.     

Liposome‐Encapsulated Hemoglobin Accelerates Bronchial Healing After Pneumonectomy in the Rat With or Without Preoperative Radiotherapy

Liposome‐encapsulated hemoglobin (LEH) has been reported to accelerate wound healing in the stomach and skin in an experimental setting. LEH was tested in bronchial anastomotic healing after radiation and pneumonectomy in the rat. Sprague‐Dawley rats (n = 61) received preoperative radiation (20 Gy) to the chest and underwent left pneumonectomy with bronchial stump closure using the Sweet method 4 days later, when they were randomized to receive intravenous infusion of LEH with high O₂ affinity (P₅₀O₂ = 17 mm Hg, 10 mL/kg, n = 32) or saline (n = 29). Additional rats (n = 18) were treated in the same way without preoperative radiation. Bronchial anastomotic healing was evaluated 2 days after surgery by determining the bursting pressure and infiltration of neutrophils, monocytes, and macrophages. Bronchial bursting pressure was elevated in the rats receiving LEH both in the unirradiated group (LEH 212 ± 78 vs. saline 135 ± 63 mm Hg, P < 0.05) and in rats with preoperative radiation (LEH 162 ± 48 vs. saline 116 ± 56 mm Hg, P < 0.01). Moreover, the percentage of rats with bursting pressure <100 mm Hg tended to be smaller in the unirradiated group (LEH 1/9 [11.1%] vs. saline 4/9 [44.4%], NS) and was significantly reduced in irradiated animals (LEH 3/32 [9.4%] vs. saline 11/29 [38%], P < 0.05). There were no morphological differences except for macrophage infiltration to the anastomotic area, which was significantly prominent in the LEH‐treated rats (P < 0.05) regardless of the presence or absence of preoperative irradiation (IR). The results suggest that LEH with high O₂ affinity may improve mechanical strength and morphological findings in bronchial anastomosis in rats regardless of the presence or absence of preoperative IR. The irradiated rats later treated with LEH had equivalent or better bronchial healing than that of saline‐treated naïve animals undergoing pneumonectomy alone.     

Pathology and sensitivity of current clinical criteria in corticobasal syndrome

The aim of this study was to investigate corticobasal syndrome with respect to underlying pathologies, the ability of current clinical criteria to detect early stages of disease, and symptoms and signs predicting background pathologies. We retrospectively analyzed the clinicopathological findings from patients with corticobasal syndrome. We also analyzed whether those findings fulfilled the diagnostic criteria for corticobasal degeneration (CBD). Finally, we investigated characteristic clinical features that are specific to each background pathology. Of 10 consecutive autopsied patients who had corticobasal syndrome (mean age ± standard deviation, 67.9 ± 9.3 years; male:female ratio, 6:4), three had corticobasal degeneration pathology, three had progressive supranuclear palsy, three had Alzheimer's disease, and one had atypical four‐repeat tauopathy. Nine patients fulfilled Mayo criteria, and all 10 patients fulfilled modified Cambridge criteria at the later stage, but only two patients fulfilled either clinical criteria within 2 years of disease onset. Five patients fulfilled the clinical criteria for possible CBD (p‐CBD), and one patient fulfilled the clinical research criteria for probable sporadic CBD (cr‐CBD) at the later stage. Only two patients fulfilled the criteria for either p‐CBD or cr‐CBD within 2 years of disease onset. Although we could not find any predictive characteristic clinical features that were specific to CBD pathology, only patients with progressive supranuclear palsy developed apraxia of eyelid opening and cerebellar ataxia. Myoclonus and memory impairment, especially if they appear at an early stage of the disease, may predict Alzheimer's disease pathology. Sensitivity of the available clinical criteria for corticobasal syndrome was poor within 2 years of disease onset. © 2013 International Parkinson and Movement Disorder Society     

Psychometric evaluation of the Nurse Competence Scale: A cross‐sectional study

Measuring nurses' competence for practice is critical for quality and safety improvement in nursing care and patient outcomes . While the Nurse Competence Scale is a widely used international measure of the generic nursing competence of nurses in various career stages, it has not been used in Thailand. This study involved the forward–backward translation of the scale into Thai and evaluation of its psychometric properties with 571 nurses at one public and one private hospital in Chiang Mai, Thailand. Participants also completed a demographic form. The content validity analysis revealed that the item‐level content validity index (I‐CVI) was .90, and the scale‐level content validity index (S‐CVI/Average) was .91. The principal component analysis with varimax rotation demonstrated that the six factor structure accounted for 58.45% of the total variance. The Mann–Whitney U‐test showed a significant difference between low and high work experience groups for all six factors, providing further support for the scale's construct validity. The reliability analysis showed an acceptable level of Cronbach's alphas in six factors ranging from .82 to .88. In conclusion, the Thai version demonstrated promising psychometric properties, but requires further testing with nurses in different settings before use in practice.     

A comprehensive gene expression analysis of human hepatocellular carcinoma cell lines as components of a bioartificial liver using a radial flow bioreactor.

BACKGROUND/AIMS: The cells constituting a bioartificial liver are crucial for an effective liver support system. We compared global gene expression profiles in a radial flow bioreactor or a monolayer culture of three functional liver cell lines previously established from human hepatocellular carcinoma. METHODS: The expressions of 60,000 genes of the FLC-4, FLC-5, and FLC-7 cell lines were analyzed by the microarray technique with the Affymetrix GeneChip system. Global gene expression profiles were compared with two-way cluster analysis. Several liver function-related genes were compared between the bioreactor and culture conditions. RESULTS: Cluster analysis revealed that gene expression profiles of bioreactor-grown cells resembled those of the normal liver. Genes related to cellular structure were highly expressed in the bioreactor-grown cells, while genes involved in proliferation or carcinogenesis were suppressed. In the bioreactor-grown cells, some genes for liver functions were expressed at a level similar to that in normal liver, although none of the cell lines expressed the complete set of genes encoding ammonium metabolism or cytochrome P450 species. CONCLUSION: The high-density three-dimensional culture in the radial flow bioreactor prompted differentiation of the cells. These data may be useful for improving the cells by genetic or pharmacological reinforcement and for monitoring bioartificial livers.     

Circulating leptin levels are associated with physical activity or physical fitness in Japanese

Objective

The aim of this study was to evaluate the link between circulating leptin levels and physical activity and/or physical fitness in apparently healthy Japanese.

Methods

A total of 85 men and 111 women who were not taking any medication were enrolled in this cross-sectional study. Circulating leptin levels, physical activity measured by tri-axial accelerometers and peak oxygen uptake were evaluated. We also assessed anthropometric data, blood pressure, blood examinations and energy intake.

Results

Circulating leptin levels were 3.2 ± 2.3 ng/mL in men and 5.9 ± 3.8 ng/mL in women. Circulating leptin levels were significantly and positively correlated with body weight, body mass index, abdominal circumference, insulin and the homeostasis model assessment index, and significantly and negatively correlated with peak oxygen uptake in both sexes. Stepwise multiple regression showed that peak oxygen uptake in men and physical activity evaluated by \(\sum {\left[ {{\text{metabolic equivalents }} \times \rm h {\text{ per week}}({\text{METs}}\;\;h/w)} \right]}\) in women were determinant factors for circulating leptin levels after adjusting for confounding factors.