Publications by authors named "Dongmei Jia"

26 Publications

  • Page 1 of 1

Low-dose rituximab treatment for new-onset generalized myasthenia gravis.

J Neuroimmunol 2021 May 24;354:577528. Epub 2021 Feb 24.

Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China. Electronic address:

The aim of this retrospective case series study was to evaluate the response and durability of rituximab in patients with new-onset acetylcholine receptor positive (AChR +) generalized myasthenia gravis (MG). Patients were initiated with low-dose rituximab treatment within 3.5 months of onset without concomitant oral immunosuppressants. Seventeen patients (89%) remained relapse-free with a mean follow-up of 51.3 months. Clinical improvement was observed in parallel with the maintenance of low-dose corticosteroids or the complete discontinuation of corticosteroids. Long-term depletion of B cells with low-dose rituximab treatment has shown favorable efficacy and tolerance in reducing disease activity for AChR+ generalized MG.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jneuroim.2021.577528DOI Listing
May 2021

Influencing Factors of Psychological Well-Being of the Non-designated Hospital Staff in China During the COVID-19 Pandemic.

Front Psychiatry 2021 4;12:591026. Epub 2021 Feb 4.

Center for Cognitive Disorders, Beijing Geriatric Hospital, Beijing, China.

Recent studies report that hospital staff at the forefront of caring for COVID-19 patients experience increased psychological distress. To effectively manage the outbreak of COVID-19, China established COVID-19 designated and non-designated hospitals. To date, few studies have examined the impacts of COVID-19 on psychological health of staff working at non-designated hospitals. This study is to explore factors affecting psychological health of non-designated hospital staff in China during the COVID-19 pandemic. Data were collected through an online questionnaire between February and March 2020. The questionnaire consists of General Health Questionnaire (GHQ-20), Social Support Rating Scale (SSRS), Simplified Coping Style Questionnaire (SCSQ), sociodemographic characteristics, employment history, health status, and contact history of COVID-19. The questionnaire was distributed through hospital WeChat groups and work colleague referrals. A total of 470 non-designated hospital staff members completed the questionnaire. Multiple Linear Regression analysis was used to interpret the associations among social support, coping styles, sociodemographic factors, job roles, and psychological status. Data were analyzed using SPSS version 21.0. The non-designated hospital staff differed significantly in anxiety and depression subscores of the GHQ-20 by their job roles, levels of social support, and history of mental disorders. Staff with medical job roles, good self-reported health status, no previous mental disorders, adequate social support, and positive coping styles scored lower in GHQ-20 total score, which indicated healthier psychological status. The results indicate that history of mental health disorders, non-medical job roles, and inadequate social support are associated with greater psychological distress. Personalized support should be provided to those who are vulnerable and in need of social and psychological support.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyt.2021.591026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889587PMC
February 2021

Built-in electric field for photocatalytic overall water splitting through a TiO/BiOBr P-N heterojunction.

Nanoscale 2021 Mar;13(8):4496-4504

College of Material, Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou, Zhejiang 311121, P. R. China.

Photocatalytic overall water splitting to simultaneously obtain abundant hydrogen and oxygen is still the mountain that stands in the way for the practical applications of hydrogen energy, in which composite semiconductor photocatalysts are critical for providing both electrons and holes to promote the following redox reaction. However, the interface between different components forms a deplete layer to hinder the charge transfer to a large extent. In order to enhance the charger transfer from an interface to the surface and promote the spatial separation of electron-hole pairs, a built-in electric field induced by a p-n heterojunction emerges as the best choice. As a touchstone, a p-n heterojunction of TiO2/BiOBr with a strong built-in electric field has been constructed, which presents a wide spectrum response owing to its interleaved band gaps after composition. The built-in electric field greatly enhances the separation and transportation of photogenerated carriers, resulting in fluorescence quenching due to the carrier recombination. The sample also displayed exceptional photoelectron responses: its photocurrent density (43.3 μA cm-2) was over 10 times that of TiO2 (3.5 μA cm-2) or BiOBr (4.2 μA cm-2). In addition, the sample with a molar ratio of 3 : 1 between TiO2 and BiOBr showed the best photocatalytic overall water splitting performance under visible light (λ > 420 nm): the hydrogen and oxygen production rate were 472.7 μmol gcat.-1 h-1 and 95.7 μmol gcat.-1 h-1, respectively, which are the highest values under visible light without other cocatalysts to have been reported in literature for the photocatalyst.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0nr08928aDOI Listing
March 2021

Preparation and Evaluation of a Xanthan Gum-Containing Linezolid Ophthalmic Solution for Topical Treatment of Experimental Bacterial Keratitis.

Pharm Res 2021 Feb 19;38(2):347-359. Epub 2021 Jan 19.

Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, 266042, China.

Purpose: To formulate a xanthan gum-containing linezolid ophthalmic solution (LZD-XG) as a new antibiotic treatment against ocular bacterial infection.

Methods: LZD-XG was prepared and evaluated for its in vitro/in vivo ocular tolerance, in vitro/in vivo antibacterial activity, and in vivo ocular penetration.

Results: The optimized LZD-XG exhibited good in vitro/in vivo eye tolerance. A prolonged ocular surface residence time of LZD-XG was observed after topical instillation, and the ocular permeation was significantly better for LZD-XG than fora linezolid (LZD) ophthalmic solution. The in vitro antimicrobial activity was significantly better with LZD-XG than with LZD. In vivo evaluation also confirmed a strong therapeutic treatment effect of LZD-XG, as it significantly improved the clinical symptoms, ameliorated the damage of Staphylococcus aureus to ocular tissues, lowered the colony forming unit counts in the cornea, and decreased the myeloperoxidase activity in the cornea.

Conclusion: LZD-XG was deemed a viable ophthalmic solution against ocular bacterial infection due to its excellent in vitro and in vivo characterizations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11095-020-02982-xDOI Listing
February 2021

Highly Thermally Stable, Green Solvent Disintegrable, and Recyclable Polymer Substrates for Flexible Electronics.

Macromol Rapid Commun 2020 Oct 24;41(19):e2000292. Epub 2020 Aug 24.

State Key Lab of Pulp and Paper Engineering, South China University of Technology, Guangzhou, 510640, China.

Flexible electronics require its substrate to have adequate thermal stability, but current thermally stable polymer substrates are difficult to be disintegrated and recycled; hence, generate enormous electronic solid waste. Here, a thermally stable and green solvent-disintegrable polymer substrate is developed for flexible electronics to promote their recyclability and reduce solid waste generation. Thanks to the proper design of rigid backbones and rational adjustments of polar and bulky side groups, the polymer substrate exhibits excellent thermal and mechanical properties with thermal decomposition temperature (T ) of 430 °C, upper operating temperature of over 300 °C, coefficient of thermal expansion of 48 ppm K , tensile strength of 103 MPa, and elastic modulus of 2.49 GPa. Furthermore, the substrate illustrates outstanding optical and dielectric properties with high transmittance of 91% and a low dielectric constant of 2.30. Additionally, it demonstrates remarkable chemical and flame resistance. A proof-of-concept flexible printed circuit device is fabricated with this substrate, which demonstrates outstanding mechanical-electrical stability. Most importantly, the substrate can be quickly disintegrated and recycled with alcohol. With outstanding thermally stable properties, accompanied by excellent recyclability, the substrate is particularly attractive for a wide range of electronics to reduce solid waste generation, and head toward flexible and "green" electronics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/marc.202000292DOI Listing
October 2020

Intravenous immunoglobulin for acute attacks in neuromyelitis optica spectrum disorders (NMOSD).

Mult Scler Relat Disord 2020 Sep 26;44:102325. Epub 2020 Jun 26.

China National Clinical Research Center for Neurological Disease, Jing-Jin Center for Neuroinflammation, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China. Electronic address:

Background: During acute attacks of neuromyelitis optica spectrum disorder (NMOSD), intravenous immunoglobulin (IVIG) maybe useful building on experience treating autoimmune disorders.

Methods: We conducted a retrospective study of several treatment modes for NMOSD attacks at Beijing Tiantan Hospital and Tianjin Medical University General Hospital. Clinical outcomes were defined as the short-term remission status. The good (GR), moderate (MR) or poor remission (PR) was respectively defined to triple-grade based on percentage change of initial and follow-up Expanded Disability Status Scale (EDSS) scores.

Results: A total of 243 attacks was analyzed in 198 patients from 2014 to 2019. Treatment groups included 153 attacks given high-dose intravenous steroids (HD-S), 14 given IVIG, 69 episodes of IVIG plus HD-S and 7 treated with plasma exchange. The proportion of patients with better outcomes were significantly lower in IVIG alone group than HD-S alone group (p = 0.004). However, sequential treatments for IVIG and HD-S yielded a higher likelihood of clinical improvement in severe attacks with EDSS ≥ 6.5 (OR = 5.85, p = 0.007).

Conclusion: These results did not support IVIG-alone therapy as a first-line option for acute NMOSD. However, adding HD-S to IVIG therapy was superior to HD-S alone for patients with high-onset EDSS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.msard.2020.102325DOI Listing
September 2020

Safety and efficacy of tocilizumab versus azathioprine in highly relapsing neuromyelitis optica spectrum disorder (TANGO): an open-label, multicentre, randomised, phase 2 trial.

Lancet Neurol 2020 05;19(5):391-401

Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China; China National Clinical Research Center for Neurological Diseases, Advanced Innovation Center for Human Brain Protection, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. Electronic address:

Background: Azathioprine is used as a first-line treatment to prevent relapses of neuromyelitis optica spectrum disorder (NMOSD). Tocilizumab has been reported to reduce NMOSD disease activity in retrospective case reports. We aimed to compare the safety and efficacy of tocilizumab and azathioprine in patients with highly relapsing NMOSD.

Methods: We did an open-label, multicentre, randomised, phase 2 trial at six hospitals in China. We recruited adult patients (aged ≥18 years) with highly relapsing NMOSD diagnosed according to 2015 International Panel for Neuromyelitis Optica Diagnosis criteria, who had an Expanded Disability Status Scale (EDSS) score of 7·5 or lower, and had a history of at least two clinical relapses during the previous 12 months or three relapses during the previous 24 months with at least one relapse within the previous 12 months. Patients were randomly assigned (1:1) to intravenous tocilizumab (8 mg/kg every 4 weeks) or oral azathioprine (2-3 mg/kg per day) by an independent statistician using computer-generated randomisation software with permuted blocks of four. The central review committee, EDSS raters, laboratory personnel, and radiologists were masked to the treatment assignment, but investigators and patients were aware of treatment allocation. The minimum planned duration of treatment was 60 weeks following randomisation. The primary outcome was time to first relapse in the full analysis set, which included all randomly assigned patients who received at least one dose of study drug, and the per-protocol population, which included all patients who used azathioprine or tocilizumab as monotherapy. For the analyses of the primary outcome, the patients were prespecified into two subgroups according to concomitant autoimmune disease status. Safety was assessed in the full analysis set. This study is registered with ClinicalTrials.gov, NCT03350633.

Findings: Between Nov 1, 2017, and Aug 3, 2018, we enrolled 118 patients, of whom 59 were randomly assigned to tocilizumab and 59 were randomly assigned to azathioprine. All 118 patients received one dose of study drug and were included in the full analysis set. 108 participants were included in the per-protocol analysis (56 in the tocilizumab group and 52 in the azathioprine group). In the full analysis set, median time to the first relapse was longer in the tocilizumab group than the azathioprine group (78·9 weeks [IQR 58·3-90·6] vs 56·7 [32·9-81·7] weeks; p=0·0026). Eight (14%) of 59 patients in the tocilizumab group and 28 (47%) of 59 patients in the azathioprine group had a relapse at the end of the study (hazard ratio [HR] 0·236 [95% CI 0·107-0·518]; p<0·0001). In the per-protocol analysis, 50 (89%) of 56 patients in the tocilizumab group were relapse-free compared with 29 (56%) of 52 patients in the azathioprine group at the end of the study (HR 0·188 [95% CI 0·076-0·463]; p<0·0001); the median time to first relapse was also longer in the tocilizumab group than the azathioprine group (67·2 weeks [IQR 47·9-77·9] vs 38·0 [23·6-64·9]; p<0·0001). In the prespecified subgroup analysis of the full analysis set stratified by concomitant autoimmune diseases, among patients without concomitant autoimmune diseases, three (9%) of 34 patients in the tocilizumab group and 13 (35%) of 37 patients in the azathioprine group had relapsed by the end of the study. Among patients with concomitant autoimmune diseases, a lower proportion of patients in the tocilizumab group had a relapse than in the azathioprine group (five [20%] of 25 patients vs 15 [68%] of 22 patients; HR 0·192 [95% CI 0·070-0·531]; p=0·0004). 57 (97%) of 59 patients in the tocilizumab group and 56 (95%) of 59 patients in the azathioprine group had adverse events. Treatment-associated adverse events occurred in 36 (61%) of 59 tocilizumab-treated patients and 49 (83%) of 59 azathioprine-treated patients. One death (2%) occurred in the tocilizumab group and one (2%) in the azathioprine group, but neither of the deaths were treatment-related.

Interpretation: Tocilizumab significantly reduced the risk of a subsequent NMOSD relapse compared with azathioprine. Tocilizumab might therefore be another safe and effective treatment to prevent relapses in patients with NMOSD.

Funding: Tianjin Medical University, Advanced Innovation Center for Human Brain Protection, National Key Research and Development Program of China, National Science Foundation of China.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1474-4422(20)30070-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935423PMC
May 2020

Highly Transparent, Highly Thermally Stable Nanocellulose/Polymer Hybrid Substrates for Flexible OLED Devices.

ACS Appl Mater Interfaces 2020 Feb 14;12(8):9701-9709. Epub 2020 Feb 14.

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience , National Center for Nanoscience and Technology , Beijing 100190 , China.

Flexible organic light-emitting diode (OLED) devices based on polymer substrates have attracted worldwide attention. However, the current OLED polymer substrates are limited due to weak thermal stability, which is not compatible with the high temperature in OLED fabrication. Here, we developed a novel nanocellulose/polyarylate (PAR) hybrid polymer substrate with both high transparency and excellent thermal properties. Benefiting from the nanometer scale of the cellulose nanofibrils (CNFs) and the efficient interfacial interaction with PAR, the substrate exhibited greatly improved thermal stability, with a glass transition temperature of 192 °C, the thermal decomposition temperature of 501 °C, and upper operating temperature up to over 220 °C. Meanwhile, the hybrid substrate exhibits outstanding mechanical properties. Notably, no apparent transparency loss was observed after the CNF addition, and the hybrid substrate maintains a high transmittance of 85% and a low haze of 1.75%@600 nm. Moreover, OLED devices fabricated on the hybrid substrates exhibit a much improved optoelectrical performance than that of the devices fabricated on the conventional poly(ethylene terephthalate) (PET) substrates. We anticipate this research will open up a new route for fabricating flexible high-performance OLEDs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.0c01048DOI Listing
February 2020

A facile one-pot preparation of BiOCO/g-CN composites with enhanced photocatalytic activity.

Water Sci Technol 2019 Apr;79(8):1494-1502

Department of Chemical Engineering and Safety, Binzhou University, Binzhou 256603, China and Engineering Research Center for Wastewater Resource of Shandong Province, Binzhou 256603, China E-mail:

BiOCO modified graphitic carbon nitride (g-CN) nanosheets were prepared by a simple one-pot synthetic strategy. In the presence of ammonium nitrate, different mass ratios of bismuth nitrate/melamine were used to fabricate these catalysts, which were characterized by X-ray diffraction (XRD), N-physisorption, Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), UV-vis analysis, and photoluminescence (PL). The catalytic properties of composites were evaluated by photodegrading tetracycline hydrochloride (TC) under visible light irradiation. Among these catalysts, BiOCO(1.5)/g-CN showed the highest catalytic activity, which was more than 16 times greater than the pristine g-CN material. The improved photocatalytic properties of BiOCO/g-CN may be due to the formation of a heterojunction between BiOCO and g-CN, leading to the effective separation of photo-induced carriers and the enhanced absorption of visible light. Furthermore, the BiOCO/g-CN composites had considerable catalytic stability, which was a key element for their potential applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2166/wst.2019.146DOI Listing
April 2019

Infiltration and persistence of lymphocytes during late-stage cerebral ischemia in middle cerebral artery occlusion and photothrombotic stroke models.

J Neuroinflammation 2017 Dec 15;14(1):248. Epub 2017 Dec 15.

Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, 300052, China.

Background: Evidence suggests that brain infiltration of lymphocytes contributes to acute neural injury after cerebral ischemia. However, the spatio-temporal dynamics of brain-infiltrating lymphocytes during the late stage after cerebral ischemia remains unclear.

Methods: C57BL/6 (B6) mice were subjected to sham, photothrombosis, or 60-min transient middle cerebral artery occlusion (MCAO) procedures. Infarct volume, neurodeficits, production of reactive oxygen species (ROS) and inflammatory factors, brain-infiltrating lymphocytes, and their activation as well as pro-inflammatory cytokine IFN-γ production were assessed. Brain-infiltrating lymphocytes were also measured in tissue sections from post-mortem patients after ischemic stroke by immunostaining.

Results: In mice subjected to transient MCAO or photothrombotic stroke, we found that lymphocyte infiltration persists in the ischemic brain until at least day 14 after surgery, during which brain infarct volume significantly diminished. These brain-infiltrating lymphocytes express activation marker CD69 and produce proinflammatory cytokines such as IFN-γ, accompanied with a sustained increase of reactive oxygen species (ROS) and inflammatory cytokines release in the brain. In addition, brain-infiltrating lymphocytes were observed in post-mortem brain sections from patients during the late stage of ischemic stroke.

Conclusion: Our results demonstrate that brain-infiltration of lymphocytes persists after the acute stage of cerebral ischemia, facilitating future advanced studies to reveal the precise role of lymphocytes during late stage of stroke.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12974-017-1017-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5732427PMC
December 2017

Potential Metabolic Biomarkers to Identify Interstitial Lung Abnormalities.

Int J Mol Sci 2016 Jul 16;17(7). Epub 2016 Jul 16.

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.

Determining sensitive biomarkers in the peripheral blood to identify interstitial lung abnormalities (ILAs) is essential for the simple early diagnosis of ILAs. This study aimed to determine serum metabolic biomarkers of ILAs and the corresponding pathogenesis. Three groups of subjects undergoing health screening, including healthy subjects, subjects with ILAs, and subjects who were healthy initially and with ILAs one year later (Healthy→ILAs), were recruited for this study. The metabolic profiles of all of the subjects' serum were analyzed by liquid chromatography quadruple time-of-flight mass spectrometry. The metabolic characteristics of the ILAs subjects were discovered, and the corresponding biomarkers were predicted. The metabolomic data from the Healthy→ILAs subjects were collected for further verification. The results indicated that five serum metabolite alterations (up-regulated phosphatidylcholine, phosphatidic acid, betaine aldehyde and phosphatidylethanolamine, as well as down-regulated 1-acylglycerophosphocholine) were sensitive and reliable biomarkers for identifying ILAs. Perturbation of the corresponding biological pathways (RhoA signaling, mTOR/P70S6K signaling and phospholipase C signaling) might be at least partially responsible for the pathogenesis of ILAs. This study may provide a good template for determining the early diagnostic markers of subclinical disease status and for obtaining a better understanding of their pathogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms17071148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964521PMC
July 2016

Survey and analysis of simple sequence repeats (SSRs) in three genomes of Candida species.

Authors:
Dongmei Jia

Gene 2016 Jun 13;584(2):129-35. Epub 2016 Feb 13.

Department of Dermatology, Qingpu Branch of Zhongshan Hospital, Fudan University, 1158 East Gongyuan Road, 201700, Shanghai, PR China. Electronic address:

Simple sequence repeats (SSRs) or microsatellites, which composed of tandem repeated short units of 1-6 bp, have been paying attention continuously. Here, the distribution, composition and polymorphism of microsatellites and compound microsatellites were analyzed in three available genomes of Candida species (Candida dubliniensis, Candida glabrata and Candida orthopsilosis). The results show that there were 118,047, 66,259 and 61,119 microsatellites in genomes of C. dubliniensis, C. glabrata and C. orthopsilosis, respectively. The SSRs covered more than 1/3 length of genomes in the three species. The microsatellites, which just consist of bases A and (or) T, such as (A)n, (T)n, (AT)n, (TA)n, (AAT)n, (TAA)n, (TTA)n, (ATA)n, (ATT)n and (TAT)n, were predominant in the three genomes. The length of microsatellites was focused on 6 bp and 9 bp either in the three genomes or in its coding sequences. What's more, the relative abundance (19.89/kbp) and relative density (167.87 bp/kbp) of SSRs in sequence of mitochondrion of C. glabrata were significantly great than that in any one of genomes or chromosomes of the three species. In addition, the distance between any two adjacent microsatellites was an important factor to influence the formation of compound microsatellites. The analysis may be helpful for further studying the roles of microsatellites in genomes' origination, organization and evolution of Candida species.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gene.2016.02.018DOI Listing
June 2016

Effect of endogenous cholecystokinin on the course of acute pancreatitis in rats.

World J Gastroenterol 2015 Jul;21(25):7742-53

Dongmei Jia, Department of Gastroenterology and Metabolism, University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu 807-8555, Japan.

Aim: To examine the effects of pancreatic rest, stimulation and rest/stimulation on the natural course of recovery after acute pancreatitis.

Methods: Acute hemorrhagic pancreatitis (AP) was induced in male rats by intraductal infusion of 40 μL/100 g body weight of 3% sodium taurocholate. All rats took food ad libitum. At 24 h after induction of AP, rats were divided into four groups: control (AP-C), pancreas rest (AP-R), stimulation (AP-S), and rest/stimulation (AP-R/S). Rats in the AP-C, AP-R and AP-S groups received oral administration of 2 mL/kg body weight saline, cholecystokinin (CCK)-1 receptor antagonist, and endogenous CCK release stimulant, respectively, twice daily for 10 d, while those in the AP-R/S group received twice daily CCK-1 receptor antagonist for the first 5 d followed by twice daily CCK release stimulant for 5 d. Rats without any treatment were used as control group (Control). Biochemical and histological changes in the pancreas, and secretory function were evaluated on day 12 at 24 h after the last treatment.

Results: Feeding ad libitum (AP-C) delayed biochemical, histological and functional recovery from AP. In AP-C rats, bombesin-stimulated pancreatic secretory function and HOMA-β-cell score were significantly lower than those in other groups of rats. In AP-R rats, protein per DNA ratio and pancreatic exocrine secretory function were significantly low compared with those in Control rats. In AP-S and AP-R/S rats, the above parameters recovered to the Control levels. Bombesin-stimulated pancreatic exocrine response in AP-R/S rats was higher than in AP-S rats and almost returned to control levels. In the pancreas of AP-C rats, destruction of pancreatic acini, marked infiltration of inflammatory cells, and strong expression of α-smooth muscle actin, tumor necrosis factor-α and interleukin-1β were seen. Pancreatic rest reversed these histological alterations, but not atrophy of pancreatic acini and mild infiltration of inflammatory cells. In AP-S and AP-R/S rats, the pancreas showed almost normal architecture.

Conclusion: The favorable treatment strategy for AP is to keep the pancreas at rest during an early stage followed by pancreatic stimulation by promoting endogenous CCK release.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3748/wjg.v21.i25.7742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4491961PMC
July 2015

Adenosine 5'-monophosphate-induced hypothermia inhibits the activation of ERK1/2, JNK, p38 and NF-κB in endotoxemic rats.

Int Immunopharmacol 2014 Nov 13;23(1):205-10. Epub 2014 Sep 13.

ICU, The Affiliated Hospital of Medical College, 16 Jiangsu Road, Qingdao, China. Electronic address:

Many studies have shown that LPS mainly activates four signal transduction pathways to induce inflammation, namely the p38, ERK1/2, JNK and IKK/NF-κB pathways. Studies have demonstrated that 5'-AMP-induced hypothermia (AIH) exhibits high anti-inflammatory capabilities. In this study, we explore that how AIH inhibits the inflammatory response. Wistar rats were divided into five groups: a control group, an LPS group, a 5'-AMP pre-treatment group, a 5'-AMP post-treatment group and a 5'-AMP group. For each group, plasma and lung were collected from the rats at 6h and 12h after LPS injection. ELISA assays were used to detect plasma levels of CD14, CRP and MCP-1. Inflammatory pathway activation and TLR4 expression were assayed separately by Western blot analysis and immunohistochemistry. Our results showed that rats treated with AIH either before or after an LPS-challenge had a significant decrease in plasma levels of CD14, CRP and TLR4 compared with rats that received LPS only. Western blot analysis showed that AIH inhibited the activation of extracellular signal-regulated kinases (ERK) 1/2, p38, c-Jun N-terminal kinase (JNK) and NF-κB in inflammatory rats. Our study concluded that AIH attenuated LPS-induced inflammation mainly by inhibiting activation on the ERK1/2, p38, JNK and NF-κB signaling pathways.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2014.09.002DOI Listing
November 2014

Narrowing down the common deleted region of 5q to 6.0 Mb in blastic plasmacytoid dendritic cell neoplasms.

Cancer Genet 2013 Jul-Aug;206(7-8):293-8. Epub 2013 Sep 14.

Department of Pathology, University of Missouri, Columbia, MO, USA.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy. Simple and complex recurrent cytogenetic abnormalities have been reported, which demonstrate predominantly genomic losses, of which deletions of 5q are the most frequent aberrations in BPDCN with or without cutaneous manifestation; however, the gene responsible for the disease remains unknown. Using microarray-based molecular characterization, a recent study on several cases of BPDCN with the 5q deletion identified a large, common deleted region (CDR) of 29 Mb that contains several possible candidate genes. We report on a 67-year-old female patient who presented with leukemic BPDCN without skin involvement and had a deletion of 5q and a t(6;8)(p21;q24). By oligo-array-comparative genome hybridization (a-CGH) method, the genomic coordinations of the 5q deletion demonstrated unique breakpoints reported for the first time. Through mapping with those published cases using the same a-CGH method, the CDR was reduced from 29 Mb to 6 Mb, which excluded the previous candidate genes and highlighted an excellent biological gene: the HINT1 gene. Moreover, a molecular cytogenetic characterization of the translocation t(6;8) was performed in search for a novel gene fusion that could be associated with tumor progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cancergen.2013.07.002DOI Listing
December 2013

Genome-wide association and fine mapping of genetic loci predisposing to colon carcinogenesis in mice.

Mol Cancer Res 2012 Jan 29;10(1):66-74. Epub 2011 Nov 29.

Department of Physiology and the Cancer Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.

To identify the genetic determinants of colon tumorigenesis, 268 male mice from 33 inbred strains derived from different genealogies were treated with azoxymethane (AOM; 10 mg/kg) once a week for six weeks to induce colon tumors. Tumors were localized exclusively within the distal colon in each of the strains examined. Inbred mouse strains exhibit a large variability in genetic susceptibility to AOM-induced colon tumorigenesis. The mean colon tumor multiplicity ranged from 0 to 38.6 (mean = 6.5 ± 8.6) and tumor volume ranged from 0 to 706.5 mm(3) (mean = 87.4 ± 181.9) at 24 weeks after the first dose of AOM. AOM-induced colon tumor phenotypes are highly heritable in inbred mice, and 68.8% and 71.3% of total phenotypic variation in colon tumor multiplicity and tumor volume, respectively, are attributable to strain-dependent genetic background. Using 97,854 single-nucleotide polymorphisms, we carried out a genome-wide association study (GWAS) of AOM-induced colon tumorigenesis and identified a novel susceptibility locus on chromosome 15 (rs32359607, P = 6.31 × 10(-6)). Subsequent fine mapping confirmed five (Scc3, Scc2, Scc12, Scc8, and Ccs1) of 16 linkage regions previously found to be associated with colon tumor susceptibility. These five loci were refined to less than 1 Mb genomic regions of interest. Major candidates in these loci are Sema5a, Fmn2, Grem2, Fap, Gsg1l, Xpo6, Rabep2, Eif3c, Unc5d, and Gpr65. In particular, the refined Scc3 locus shows high concordance with the human GWAS locus that underlies hereditary mixed polyposis syndrome. These findings increase our understanding of the complex genetics of colon tumorigenesis, and provide important insights into the pathways of colorectal cancer development and might ultimately lead to more effective individually targeted cancer prevention strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1541-7786.MCR-10-0540DOI Listing
January 2012

Adsorption of glyphosate on resin supported by hydrated iron oxide: equilibrium and kinetic studies.

Water Environ Res 2011 Sep;83(9):784-90

Department of Chemistry and Chemical Engineering, Binzhou University, Binzhou, China.

Hydrated iron oxide supported on resin (D301) was prepared as a new sorbent for the removal of glyphosate from wastewater. Batch adsorption studies were performed on glyphosate aqueous solutions with different initial glyphosate concentrations and temperatures. Experimental data were analyzed using the Langmuir and Freundlich isotherms, and the adsorption data were best fit to the Langmuir isotherm model. The thermodynamic parameters AG, AH, and AS also were calculated for the adsorption processes. Adsorption rate constants were determined using the pseudo-first-order and pseudo-second-order rate equations and Kannan-Sundaram intraparticle diffusion models. Adsorption of glyphosate clearly followed the pseudo-second-order model and was controlled by both film diffusion and intraparticle diffusion.
View Article and Find Full Text PDF

Download full-text PDF

Source
September 2011

Fine mapping of chromosome 6q23-25 region in familial lung cancer families reveals RGS17 as a likely candidate gene.

Clin Cancer Res 2009 Apr 7;15(8):2666-74. Epub 2009 Apr 7.

Washington University, St. Louis, Missouri 63110, USA.

Purpose: We have previously mapped a major susceptibility locus influencing familial lung cancer risk to chromosome 6q23-25. However, the causal gene at this locus remains undetermined. In this study, we further refined this locus to identify a single candidate gene, by fine mapping using microsatellite markers and association studies using high-density single nucleotide polymorphisms (SNP).

Experimental Design: Six multigenerational families with five or more affected members were chosen for fine-mapping the 6q linkage region using microsatellite markers. For association mapping, we genotyped 24 6q-linked cases and 72 unrelated noncancer controls from the Genetic Epidemiology of Lung Cancer Consortium resources using the Affymetrix 500K chipset. Significant associations were validated in two independent familial lung cancer populations: 226 familial lung cases and 313 controls from the Genetic Epidemiology of Lung Cancer Consortium, and 154 familial cases and 325 controls from Mayo Clinic. Each familial case was chosen from one high-risk lung cancer family that has three or more affected members.

Results: A region-wide scan across 6q23-25 found significant association between lung cancer susceptibility and three single nucleotide polymorphisms in the first intron of the RGS17 gene. This association was further confirmed in two independent familial lung cancer populations. By quantitative real-time PCR analysis of matched tumor and normal human tissues, we found that RGS17 transcript accumulation is highly and consistently increased in sporadic lung cancers. Human lung tumor cell proliferation and tumorigenesis in nude mice are inhibited upon knockdown of RGS17 levels.

Conclusion: RGS17 is a major candidate for the familial lung cancer susceptibility locus on chromosome 6q23-25.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1078-0432.CCR-08-2335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746091PMC
April 2009

Enhanced susceptibility to chemical induction of ovarian tumors in mice with a germ line p53 mutation.

Mol Cancer Res 2008 Jan;6(1):99-109

Department of Surgery, The Washington University School of Medicine, St Louis, MO 63110, USA.

Mice with a germ line p53 mutation (p53(Ala135Val/wt)) display increased susceptibility to lung, skin, and colon carcinogenesis. Here, we show that p53(Ala135Val/wt) mice developed ovarian tumors significantly more rapidly than their wild-type littermates after 7,12-dimethylbenz(a)anthracene (DMBA) treatment. Approximately 50% of the ovarian tumors in p53(wt/wt) mice and 23% in p53(Ala135Val/wt) mice are adenocarcinomas and the remaining tumors were adenocarcinoma mixed with sarcoma or ovarian sarcomas. All of the p53(Ala135Val/wt) mice had died of ovarian tumors 25 weeks after the initial DMBA treatment, whereas >50% of p53(wt/wt) mice were still alive. These mice not only have a shortened tumor latency but also closely resemble a subset of human ovarian tumors containing the p53 mutation. Microarray and GenMAPP analyses revealed that the mutant p53 (Ala135Val) affected several cellular processes, including the cell cycle, apoptosis, and Wnt pathways. These findings indicate that a germ line p53 mutation significantly enhanced DMBA-induced ovarian tumor development and progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/1541-7786.MCR-07-0216DOI Listing
January 2008

EGFR-T790M is a rare lung cancer susceptibility allele with enhanced kinase activity.

Cancer Res 2007 May;67(10):4665-70

Washington University, St. Louis, Missouri, USA.

The use of tyrosine kinase inhibitors (TKI) has yielded great success in treatment of lung adenocarcinomas. However, patients who develop resistance to TKI treatment often acquire a somatic resistance mutation (T790M) located in the catalytic cleft of the epidermal growth factor receptor (EGFR) enzyme. Recently, a report describing EGFR-T790M as a germ-line mutation suggested that this mutation may be associated with inherited susceptibility to lung cancer. Contrary to previous reports, our analysis indicates that the T790M mutation confers increased Y992 and Y1068 phosphorylation levels. In a human bronchial epithelial cell line, overexpression of EGFR-T790M displayed a growth advantage over wild-type (WT) EGFR. We also screened 237 lung cancer family probands, in addition to 45 bronchoalveolar tumors, and found that none of them contained the EGFR-T790M mutation. Our observations show that EGFR-T790M provides a proliferative advantage with respect to WT EGFR and suggest that the enhanced kinase activity of this mutant is the basis for rare cases of inherited susceptibility to lung cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/0008-5472.CAN-07-0217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460269PMC
May 2007

Identification of a novel tumor suppressor gene p34 on human chromosome 6q25.1.

Cancer Res 2007 Jan;67(1):93-9

School of Medicine, Washington University, 660 Euclid Avenue, St. Louis, MO, USA.

In this study, we observed loss of heterozygosity (LOH) in human chromosomal fragment 6q25.1 in sporadic lung cancer patients. LOH was observed in 65% of the 26 lung tumors examined and was narrowed down to a 2.2-Mb region. Single-nucleotide polymorphism (SNP) analysis of genes located within this region identified a candidate gene, termed p34. This gene, also designated as ZC3H12D, C6orf95, FLJ46041, or dJ281H8.1, carries an A/G nonsynonymous SNP at codon 106, which alters the amino acid from lysine to arginine. Nearly 73% of heterozygous lung cancer tissues with LOH and the A/G SNP also exhibited loss of the A allele. In vitro clonogenic and in vivo nude mouse studies showed that overexpression of the A allele exerts tumor suppressor function compared with the G allele. p34 is located within a recently mapped human lung cancer susceptibility locus, and association of the p34 A/G SNP was tested among these families. No significant association between the less frequent G allele and lung cancer susceptibility was found. Our results suggest that p34 may be a novel tumor suppressor gene involved in sporadic lung cancer but it seems not to be the candidate familial lung cancer susceptibility gene linked to chromosomal region 6q23-25.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1158/0008-5472.CAN-06-2723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461257PMC
January 2007

Heat stroke deaths caused by electric blankets: case report and review of the literature.

Am J Forensic Med Pathol 2006 Dec;27(4):324-7

Department of Forensic Pathology, Santou University, Santou, PR China.

Heat stroke is the most serious and potentially life-threatening condition of the heat-related illnesses. Heat stroke deaths caused by electric blanket are rarely reported. In this paper, we report 2 cases of fatal heat stroke caused by overheating from electric blankets in winter. One was a 41-year-old man who was found unresponsive in bed on an electric blanket. His wife shared the same bed with him and was found unconscious. The wife's axillary temperature was 40 degrees C (104 degrees C) when she was admitted to the hospital. She fully recovered after medical treatment. The husband was pronounced dead at scene, with rectal temperature at 41.2 degrees C (106.2 degrees C). The other was a 13-year-old girl who was found dead in bed on an electric blanket, with rectal temperature at 41 degrees C (105.8 degrees F). The literature is reviewed, and the pertinent findings, including scene investigations, postmortem examination, the risk and mechanism of fatal heat stroke caused by using electric blanket, are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/01.paf.0000233567.51784.31DOI Listing
December 2006

Synthetic protease inhibitor camostat prevents and reverses dyslipidemia, insulin secretory defects, and histological abnormalities of the pancreas in genetically obese and diabetic rats.

Metabolism 2005 May;54(5):619-27

Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.

Background: Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of type 2 diabetes, lacks the expression of cholecystokinin-1 receptor mRNA and exhibits inflammation and degeneration of the pancreas and eventually develops insulinopenic diabetes. Protease inhibitors are known to modulate inflammatory response and fibrosis as well as inhibit proteases activity.

Aim: To examine the effects of long-term treatment with camostat, a synthetic protease inhibitor, on metabolic and histopathological changes in the islets of OLETF rats.

Method: OLETF rats were fed either camostat-containing food (200 mg/100 g) from 12 or 28 weeks of age to 72 weeks of age, or fed standard rat diet.

Results: Camostat-fed rats gained less weight or lost weight, although they consumed more food than the control rat when food intake was adjusted for body weight. Camostat reduced visceral adipose depots and fasting serum concentrations of triglyceride, free fatty acids, cholesterol, glucose, and insulin. Pancreatic insulin content in camostat-treated rats was significantly higher than in control rats. Immunohistochemistry revealed marked suppression of expressions of tumor necrosis factor alpha , interleukin 1 beta , interleukin 6, and alpha-smooth muscle actin in the islets of camostat-treated rats, compared with control rats. Histologically, disruption of the islets and pancreatic fibrosis were noted in control rats but not in camostat-fed rats.

Conclusion: Our findings suggest that camostat prevents and reverses obesity, hyperinsulinemia, hyperglycemia, and hyperlipidemia and markedly inhibits inflammation, fibrosis, and disruption of the islets in the genetically obese diabetic OLETF rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.metabol.2004.12.005DOI Listing
May 2005

Preventive and therapeutic effects of the protease inhibitor camostat on pancreatic fibrosis and atrophy in CCK-1 receptor-deficient rats.

Pancreas 2005 Jan;30(1):54-61

Third Department of Internal Medicine, University of Occupational and Environmental Health Japan, School of Medicine, Kitakyushu, Japan.

Objectives: Recent studies have demonstrated that synthetic protease inhibitors could ameliorate the progression of pancreatic fibrosis in some animal models. Since oral administration of protease inhibitors increases the plasma cholecystokinin (CCK) levels and causes hypertrophy of the pancreas in rats, there is a possibility that the protease inhibitor inhibits fibrosis in the pancreas via endogenous CCK release. We examined the effects of camostat, a synthetic protease inhibitor, on histopathologic changes in Otsuka Long-Evans Tokushima Fatty (OLETF) rat that has genetically no expression of CCK-1 receptor and displays inflammation and degeneration of the pancreas.

Methods: Three groups of OLETF rats received a camostat-rich diet (200 mg/100 g normal diet) from 12 to 28 weeks of age or from 12 or 28 weeks of age to the age of 72 weeks, while the fourth group received standard rat diet.

Results: Pancreatic wet weight and pancreatic contents of protein, DNA, amylase, lipase, and trypsin in camostat-treated rats were significantly higher than those in the untreated control rats. Immunohistochemical studies of the pancreas showed that expressions of interleukin-1beta, interleukin-6, tumor necrosis factor-alpha, and alpha-smooth muscle actin in camostat-treated rats were greatly suppressed compared with those in the untreated control rats. Atrophy and fibrosis in the pancreas observed in the untreated control rats were not found in camostat-fed rats.

Conclusion: The results of the present study suggest that camostat greatly inhibits pancreatic inflammation and prevents and reverses fibrosis and atrophy of the pancreas in the genetically obese and CCK-1 receptor-deficient OLETF rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
January 2005

Bezafibrate on lipids and glucose metabolism in obese diabetic Otsuka Long-Evans Tokushima fatty rats.

Metabolism 2004 Apr;53(4):405-13

Third Department of Internal Medicine, University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu, Japan.

Type 2 diabetes is caused by insulin resistance and beta-cell dysfunction. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an established animal model of human type 2 diabetes that exhibits chronic and slowly progressive hyperglycemia and hyperlipidemia and is accompanied by progressive fibrosis in the islets. The aim of the present study was to examine whether worsening of hyperglycemia, insulin resistance, and histologic alterations of the islets in OLETF rats is related to hyperlipidemia by treating these animals with a lipid-lowering drug, bezafibrate. The bezafibrate-treated groups of OLETF and their control counterpart Long-Evans Tokushima Otsuka (LETO) rats received a bezafibrate-rich diet (150 mg/100 g normal chow) for 16 weeks, from 12 to 28 weeks of age, while the other groups of rats received standard rat chow. Bezafibrate treatment significantly reduced serum triglyceride (TG) and free fatty acid (FFA) levels, suppressed the increase in islet size, and inhibited the expression of alpha-smooth muscle actin, a marker for activated pancreatic stellate cells that are involved in the fibrosis of the pancreas, in the islets in OLETF rats, but had no influences on food intake, body weight gain, abdominal adipose depots, and pancreatic insulin content in both strains of rats. Although bezafibrate significantly reduced circulating lipid levels and suppressed the increase in insulin secretion evaluated by area under the curve (AUC) analysis in response to an intravenous glucose tolerance test (IVGTT) until the end of the experiment, improvement of insulin resistance was observed only for the first 8 weeks after the onset of bezafibrate treatment. These results suggest that dyslipidemia is not responsible for the reduced insulin sensitivity, but the impairment of glucose tolerance is the primary defect in the OLETF rats, although improvement of dyslipidemia suppressed histologic alterations in the islets and temporally improved insulin resistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.metabol.2003.10.006DOI Listing
April 2004

Bezafibrate, a peroxisome proliferator-activated receptor (PPAR)-alpha activator, prevents pancreatic degeneration in obese and diabetic rats.

Pancreas 2003 Apr;26(3):286-91

Third Department of Internal Medicine, University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu, Japan.

Introduction: Damage to the exocrine pancreas has been observed in patients and animals with hyperlipidemia and hyperglycemia. Bezafibrate, a peroxisome proliferator-activated receptor (PPAR)-alpha activator, has been shown to improve lipid and glucose metabolism, and to interfere with the inflammatory response.

Aim: To examine the effects of bezafibrate on exocrine pancreas in hyperlipidemic obese and diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats that have no cholecystokinin-1 receptor gene expression.

Methodology: One group of rats (n = 8) received a bezafibrate-rich diet (150 mg/100 g normal chow) from 12 weeks of age until 30 weeks of age, whereas a control group (n = 8) received standard rat chow.

Results: Bezafibrate treatment significantly reduced serum triglyceride, total cholesterol, and free fatty acids levels and significantly increased the pancreatic wet weight (1,145 +/- 54 vs 874 +/- 33 mg/rat, p < 0.01), and protein (169 +/- 7 vs 128 +/- 11 mg/pancreas p < 0.01) and enzyme contents in the pancreas compared with those in untreated control rats. Immunohistochemical studies of the pancreas showed that expression of proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin-1beta and interleukin-6, and alpha-smooth muscle actin in bezafibrate-treated rats was greatly suppressed compared with that in the untreated control rats. The histopathologic changes such as vacuolar degeneration and tubular complexes observed in the control rat pancreas were markedly improved in bezafibrate-treated rats.

Conclusions: Our results suggest that bezafibrate reduces hyperlipidemia, inhibits pancreatic inflammation, and prevents pancreatic degeneration in obese and diabetic OLETF rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/00006676-200304000-00013DOI Listing
April 2003