Publications by authors named "Xiling Wu"

39 Publications

Comparative analysis of the main outer membrane proteins of Brucella in the diagnosis of brucellosis.

Biochem Biophys Res Commun 2021 Jun 11;560:126-131. Epub 2021 May 11.

Key Lab of Environment and Health, School of Public Health, Xuzhou Medical University, Xuzhou, 221004, China. Electronic address:

Brucellosis has placed a heavy economic burden on numerous countries and has consumed considerable medical resources worldwide. To improve the specificity and sensitivity of serological methods for diagnosing brucellosis, it is important to develop new diagnostic antigens. Brucella outer membrane proteins(omps) possess good immunogenicity, but there is a scarcity of comparative studies of these proteins in the clinical diagnosis of brucellosis. In this study, six recombinant Brucella outer membrane proteins, omp10, omp16, omp19, omp25, omp31 and BP26, were expressed in prokaryotic cells and utilized as diagnostic antigens. The clinical sera of humans, bovines and goats with brucellosis were analyzed by indirect ELISA using these proteins, lipopolysaccharide(LPS) and Rose Bengale Ag, served as positive-control antigens. In diagnosing human and goat serum, BP26 exhibited the highest diagnostic accuracy of 96.45% and 95.00%, respectively, while omp31 exhibited the strongest ability to detect Brucella in bovine serum with an accuracy of 84.03%. Cross-reaction experiments also confirmed that the diagnostic specificities of omp31 and BP26 were higher than those of the LPS and Rose Bengale Ag antigens. The results of this study indicate that omp31 and BP26 are candidate antigens with high potential application value in the clinical diagnosis of brucellosis.
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http://dx.doi.org/10.1016/j.bbrc.2021.04.127DOI Listing
June 2021

Association between serum uric acid and bone mineral density in patients with type 2 diabetes: A 6-year longitudinal study in China.

Medicine (Baltimore) 2021 Apr;100(17):e25733

Beijing Xiao-Tang-Shan Hospital, Xiao-Tang-Shan Town, Changping District, Beijing, China.

Abstract: The relationship between serum uric acid (UA) and bone mineral density (BMD) has been proposed by several researchers. However, there has been no consensus regarding the relationships among serum UA, diabetes, and BMD. The aim of this study is to investigate the association between UA, BMD, and at least osteopenia in type 2 diabetes patients.This research was a longitudinal study performed at Xiao-Tang-Shan Hospital in Beijing. Type 2 diabetes diagnosis was consistent with the WHO standard classification. Participants with osteopenia or osteoporosis documented by dual-energy X-ray absorptiometry were defined as having "at least osteopenia." A generalized additive model and multivariable logistic regressions were performed to explore the relationship between serum UA and at least osteopenia. Receiver operating characteristic analysis was conducted. Propensity score matching was used to verify the correctness of the cutoff point.In total, 3476 type 2 diabetes patients free of any osteopenia-related diseases were recruited in 2012 and followed up to 2018. The general proportions of patients with at least osteopenia in 2018 was 16.46% (572/3476). Serum UA was negatively associated with BMD stratified by sex, age group, and BMI level. Setting the first quartile as the reference, the risk of at least osteopenia in the fourth quartile was significant among all patients (odds ratio [OR]: 0.75; 95% confidence interval [CI]: 0.57, 0.98) and specifically in females (OR: 0.79; 95% CI: 0.43, 0.97), patients aged over 50 years (OR: 0.79; 95% CI: 0.60, 0.97) and patients with a BMI greater than 25 (OR: 0.74; 95% CI: 0.47, 0.97). The optimal cutoff point for the serum UA level to distinguish at least osteopenia in diabetic patients was 395 μmol/L.Serum UA concentration is negatively associated with the occurrence of at least osteopenia in Chinese patients with type 2 diabetes.
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http://dx.doi.org/10.1097/MD.0000000000025733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084059PMC
April 2021

Outcomes in Endovascular Therapy for Basilar Artery Occlusion: Intracranial Atherosclerotic Disease . Embolism.

Aging Dis 2021 Apr 1;12(2):404-414. Epub 2021 Apr 1.

8Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.

Acute ischemic stroke due to basilar artery occlusion (BAO) carries a very poor prognosis. Functional outcomes in BAO patients undergoing endovascular therapy (EVT) may differ according to the specific pathological mechanisms. We aimed to explore the impact of the underlying pathological mechanisms on prognosis at 90-days and long-term follow-up in BAO patients treated with EVT. We analyzed consecutive BAO patients undergoing EVT from December 2012 to December 2018 at a single center (Xuanwu Hospital). Patients were classified into either an intracranial atherosclerotic disease (ICAD) group or an embolic group according to the corresponding angiographic findings. The baseline characteristics and functional outcomes were compared between the two groups. Multivariable logistic regression analysis was performed. Among the 167 patients enrolled, 78 patients (46.7%) were in the ICAD group and 89 patients (53.3%) were assigned to the embolic group. Overall, 149 patients (89.2%) achieved successful reperfusion post-EVT. There were no significant differences in functional outcomes at 90-days and long-term follow-up between the two groups. Similarly, a Kaplan-Meier survival analysis showed similar long-term survival probabilities (P = 0.438). The pathological mechanism was not associated with functional independence (OR, 1.818; 95% CI, 0.694-4.761; P = 0.224), favorable outcome (OR, 1.476; 95% CI, 0.592-3.681; P = 0.403), or mortality (OR, 1.249; 95% CI, 0.483-3.226; P = 0.646). However, based on subgroup analysis, embolic BAO versus ICAD was significantly associated with better functional independence in those aged 60 years and younger (OR, 4.513; 95% CI, 1.138-17.902). In this study, no differences in either 90-days or long-term functional outcomes between ICAD-related BAO and embolic BAO patients undergoing EVT were observed. However, in BAO patients aged ≤ 60 years, the pathological mechanism of embolism was associated with better functional independence.
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http://dx.doi.org/10.14336/AD.2020.0704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990363PMC
April 2021

Effects of peer relationship and peer presence on giving and repaying in preschoolers' triad interactions.

Psych J 2021 Apr 15;10(2):254-262. Epub 2021 Feb 15.

CAS Key Laboratory of Mental Health, Institute of Psychology, Beijing, China.

This study aimed to assess social preferences in dynamic interpersonal interactions among preschool children and to examine the effects of peer relationship (friend vs. stranger) and peer presence (peer presence vs. peer absence) on giving and repaying. Ninety-nine children participated in a triad game, which consisted of two mixed-dictator games. The allocations from a proposer in the first dictator game were evaluated as giving, and the allocations from two respondents in the second dictator game were evaluated as repaying friends and strangers. The results indicated that children did not have any specific social preferences for friends in giving and repaying but had altruistic and fair preferences for giving to strangers, and strangers had egoistic preferences in repaying. Furthermore, children allocated more to strangers than to friends and allocated more in peer presence. Besides, friends positively reciprocated to proposers in peer absence and repaid less in peer presence. However, strangers consistently repaid less regardless of whether peers were present or not. These results provide more evidence for the assumption of weak ties in giving and demonstrate the strength of strong ties in repaying. These findings enhance our understanding of the interplay of childhood interactions in the development of early relationships.
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http://dx.doi.org/10.1002/pchj.418DOI Listing
April 2021

Validation of the protective effects of Lonicera japonica polysaccharide on lipopolysaccharide-induced learning and memory impairments via regulation of autophagy based on network pharmacology.

Ann Palliat Med 2021 Feb 15;10(2):1089-1100. Epub 2020 Sep 15.

Department of Traditional Chinese Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.

Background: Learning and memory impairments are important indexes in assessing Alzheimer's disease (AD). Lonicera japonica (L. japonica), a traditional Chinese herbal medicine, inhibits inflammation, but its role in neuroprotection is unclear. Polysaccharide is the main active ingredient in L. japonica. Here, we aimed to validate the effects of L. japonica polysaccharide (LJP) on lipopolysaccharide (LPS)-induced cognitive impairment and the underlying mechanism.

Methods: The Chinese medicine system pharmacology database and analysis platform was used to predict the target of L. japonica; the GeneCards system was used to predict the AD target. We also performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Experiments were performed after bioinformatic analysis for verification. A chronic learning and memory impairment model was established by a single administration of LPS. Learning and memory abilities of Kunming mice were examined after 7 days of induction. The protective effects of LJP on LPS-induced impairment were investigated. Neuronal damage was observed by Nissl staining. Key proteins involved in the autophagy pathway were examined.

Results: Bioinformatic analysis showed that there were 151 genes in the intersection of the target and ADrelated genes, and KEGG analysis suggested that these genes may act via multiple pathways. LPS-induced changes in learning and memory in mice were significantly attenuated by LJP. Nissl staining revealed that the neurons in the control group were lost and cellular arrangement was disrupted. LJP alleviated the pathological changes in the neurons of mice. The autophagy pathway was selected to verify the mechanism. ATG5, Beclin 1, Vps34, and LC3 II expression in the LPS group was significantly increased, and it was further increased in the LJP group.

Conclusions: LJP improved behavioral changes and neuronal loss associated with LPS-induced learning and memory impairments. The underlying mechanism may be related to the regulation of the autophagy pathways.
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http://dx.doi.org/10.21037/apm-20-357DOI Listing
February 2021

The Important Role of Endoscopy in Management of Pediatric Pseudomembranous Necrotizing Tracheitis.

Front Pediatr 2020 9;8:360. Epub 2020 Jul 9.

Department of Pulmonology, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.

Pseudomembranous necrotizing tracheitis is a rare, but life-threatening cause of central airway obstruction. Here, we reported three cases of pediatric pseudomembranous necrotizing tracheitis. The infectious etiologies were secondary to influenza A virus . Endoscopy was used in diagnosis and management of all patients and two patients survived. The improvement in mortality rate of these diseases need early recognition and prompt treatment with mechanical debridement by endoscope and early initiation of broad spectrum antibiotics. Endoscopy is a promising tool to diagnose and remove the pseudomembrane, therefore relieving central airway obstruction.
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http://dx.doi.org/10.3389/fped.2020.00360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7363969PMC
July 2020

The Effects of Yuan-Zhi Decoction and Its Active Ingredients in Both and Models of Chronic Cerebral Hypoperfusion by Regulating the Levels of A and Autophagy.

Evid Based Complement Alternat Med 2020 22;2020:6807879. Epub 2020 Feb 22.

Department of Traditional Chinese Medicine, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.

Chronic cerebral hypoperfusion (CCH) is closely related to the occurrence of Alzheimer's disease (AD) in the elderly. CCH can induce overactivation of autophagy, which increases the deposition of amyloid- (A) plaques in the brain, eventually impairing the cognitive function. Yuan-Zhi decoction (YZD) is a traditional Chinese medicine (TCM) formulation that is used to treat cognitive dysfunction in the elderly, but the specific mechanism is still unclear. In this study, we simulated CCH in a rat model through bilateral common carotid artery occlusion (BCCAO) and treated the animals with YZD. Standard neurological tests indicated that YZD significantly restored the impaired cognitive function after BCCAO in a dose-dependent manner. Furthermore, YZD also decreased the levels of A aggregates and the autophagy-related proteins ATG5 and ATG12 in their hippocampus. An model of CCH was also established by exposing primary rat hippocampal neurons to hypoxia and hypoglycemia (H-H). YZD and its active ingredients increased the survival of these neurons and decreased the levels of A1-40 and A1-42, autophagy-related proteins Beclin-1 and LC3-II, and the APP secretases BACE1 and PS-1. Finally, both A aggregates showed a positive statistical correlation with the expression levels of the above proteins. Taken together, YZD targets A, autophagy, and APP-related secretases to protect the neurons from hypoxic-ischemic injury and restore cognitive function.
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http://dx.doi.org/10.1155/2020/6807879DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060441PMC
February 2020

IL-4/IL-13 upregulates Sonic hedgehog expression to induce allergic airway epithelial remodeling.

Am J Physiol Lung Cell Mol Physiol 2020 05 4;318(5):L888-L899. Epub 2020 Mar 4.

Department of Respiratory Medicine, The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

We have previously demonstrated that upregulation of Sonic hedgehog (SHH) expression in allergic airway epithelia essentially contributes to the goblet cell metaplasia and mucous hypersecretion. However, the mechanism underlying the upregulation of SHH expression remains completely unknown. In cultured human airway epithelial cells, IL-4/IL-13 but not IL-5 robustly induces the mRNA and protein expression of SHH and in turn activates SHH signaling by promoting the JAK/STAT6-controlling transcription of gene. Moreover, intratracheal instillation of IL-4 and/or IL-13 robustly activates STAT6 and concomitantly upregulates SHH expression in mouse airway epithelia, whereas, in Club cell 10-kDa protein (CC10)-positive airway epithelial cells of children with asthma, activated STAT6 closely correlates with the increased expression of SHH and high activity of SHH signaling. Finally, intratracheal inhibition of STAT6 by AS-1517499 significantly diminished the allergen-induced upregulation of SHH expression, goblet cell phenotypes, and airway hyperresponsiveness, in an ovalbumin- or house dust mite-induced mouse model with allergic airway inflammation,. Together, upregulation of SHH expression by IL-4/IL-13-induced JAK/STAT6 signaling contributes to allergic airway epithelial remodeling, and this study thus provides insight into how morphogen signaling is coordinated with Th2 cytokine pathways to regulate tissue remodeling in chronic airway diseases.
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http://dx.doi.org/10.1152/ajplung.00186.2019DOI Listing
May 2020

Protein tyrosine phosphatase 11 acts through RhoA/ROCK to regulate eosinophil accumulation in the allergic airway.

FASEB J 2019 11 30;33(11):11706-11720. Epub 2019 Jul 30.

Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou, China.

Src homology domain 2-containing protein tyrosine phosphatase 2 (SHP2) participates in multiple cell functions including cell shape, movement, and differentiation. Therefore, we investigated the potential role of SHP2 in eosinophil recruitment into lungs in allergic airway inflammation and explored the underlying mechanism. Both SHP2 and Ras homolog family member A (RhoA) kinase were robustly activated in the airway eosinophils of children with allergic asthma and of a mouse model with allergic airway inflammation. Moreover, inhibition of SHP2 activity by its specific inhibitors reverses the dephosphorylation of p190-A Rho GTPase-activating protein and in turn attenuates RhoA/Rho-associated protein kinase (ROCK) signaling, resulting in the attenuation of eosinophil migration in response to platelet-activating factor stimulation. Specifically, deletion in myeloid cells did not affect the number and classification of circulating leukocytes but significantly attenuated the allergen-induced inflammatory cell, especially eosinophil, infiltration into lungs, and airway hyperreactivity. Notably, genetic interaction between and indicated that RhoA inactivation and deletion synergistically attenuated the allergen-induced eosinophil infiltration into lungs and airway hyperreactivity, whereas overexpression of active RhoA robustly restored the deletion-resultant attenuation of allergen-induced eosinophil recruitment into lungs and airway hyperreactivity as well. Thus, this study demonstrates that SHP2 RhoA/ROCK signaling regulates eosinophil recruitment in allergic airway inflammation and possibly in allergic asthma.-Xu, C., Wu, X., Lu, M., Tang, L., Yao, H., Wang, J., Ji, X., Hussain, M., Wu, J., Wu, X. Protein tyrosine phosphatase 11 acts through RhoA/ROCK to regulate eosinophil accumulation in the allergic airway.
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http://dx.doi.org/10.1096/fj.201900698RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902720PMC
November 2019

Chinese Herbal Complex 'Bu Shen Jie Du Fang' (BSJDF) Modulated Autophagy in an MPP-Induced Cell Model of Parkinson's Disease.

Evid Based Complement Alternat Med 2019 13;2019:8920813. Epub 2019 Mar 13.

Department of Chinese Medicine, Xuanwu Hospital, Capital Medical University, Beijing, China.

Autophagy plays an important role in the development of Parkinson disease (PD). Previous studies showed that autophagy could protect cells from -synuclein toxicity and promote functional coupling of mitochondria. But it is still a question whether modulating autophagy can be used to treat PD. In traditional Chinese medicine, a specific Chinese herbal complex called Bu Shen Jie Du Fang (BSJDF) has a long history of treating motor impairments similar to Parkinson disease, while its mechanism is still unclear. As a pilot study, we aimed to evaluate the efficacy and its mechanism of Bu Shen Jie Du Fang in an MPP-induced cell model of Parkinson's disease. And the phase contrast microscope (PCM) revealed that the BSJDF group had the greatest surviving cell counts compared with all other treated cell groups except the normal group. And Cell Counting Kit 8 (CCK8) assays showed a similar result. In BSJDF group, 3.7 ×10 cells/dish was identified by hemocytometer counts, which was significantly higher than other groups except the normal cells (p<0.05). In the BSJDF group, autophagy can be observed by transmission electron microscopy (TEM). Protein expression of Atg12 and LC3 in the BSJDF group was upregulated compared to the PD model group (p<0.05). Atg12 mRNA expression was also upregulated in the BSJDF group (p<0.05). In conclusion, our study indicated that the therapeutic mechanisms of BSJDF may be mediated by stimulating autophagy, and modulating autophagy can be used to treat PD.
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http://dx.doi.org/10.1155/2019/8920813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436328PMC
March 2019

A CRTH2 antagonist, CT-133, suppresses NF-κB signalling to relieve lipopolysaccharide-induced acute lung injury.

Eur J Pharmacol 2019 Jul 3;854:79-91. Epub 2019 Apr 3.

Department of Critical Care Medicine and Orthopedics, The First Affiliated Hospital, Zhejiang University, School of Medicine, Hangzhou City, 310009, China. Electronic address:

Acute lung injury (ALI) and acute respiratory distress syndrome are life-threatening conditions that still have no definite pharmacotherapy. Hence, we investigate the potential effectiveness and underlying mechanism of CT-133, a newly developed selective antagonist of prostaglandin D2 receptor 2 (DP2) or of chemoattractant receptor homologous molecule expressed on Th2 cells (CRTH2), against lipopolysaccharide (LPS)-induced ALI. CT-133 (10 or 30 mg/kg) or dexamethasone (1 mg/kg, positive control) were intragastrically administered 1 h before and 12 h after intratracheal LPS instillation, and primary neutrophils and macrophages and RAW264.7 macrophages were used to investigate the role of CT-133 in regulation of their functions. LPS induced a significant secretion of PGD from primary macrophages, however, CT-133 dose-dependently and markedly decreased the infiltration of neutrophils and macrophages into lungs, reduced the IL-1β, TNF-α, IL-6, and KC levels in broncho-alveolar lavage (BAL) fluids, decreased the wet weight and myeloperoxidase activity of lungs, reduced Evans blue and albumin exudation into lungs, and improved the lung histopathological changes and hypoxemia. Moreover, CT-133 significantly suppressed the primary neutrophil migration toward the PGD and robustly inhibited the mRNA and protein expression of IL-1β, TNF-α, IL-6, and KC in primary and RAW264.7 macrophages in response to either LPS- or PGD stimulation. Finally, CT-133 significantly blocked the LPS-induced P65 activation in both RAW264.7 macrophages and mouse lungs. Thus, This is the first report that a CRTH2 antagonist, CT-133, is capable of significantly alleviating LPS-induced lung injury by probably down-regulating the NF-κB signalling.
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http://dx.doi.org/10.1016/j.ejphar.2019.03.053DOI Listing
July 2019

CRTH2 antagonist, CT‑133, effectively alleviates cigarette smoke-induced acute lung injury.

Life Sci 2019 Jan 22;216:156-167. Epub 2018 Nov 22.

Department of Pharmacology, Zhejiang University, School of Medicine, Hangzhou City 310058, China. Electronic address:

Aims: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), characterized by overwhelming lung inflammation, are associated with high mortality. Cigarette smoke (CS) is one of the major causes of ALI/ARDS. Since high expression of prostaglandin (PG) D has been observed in CS-induced lung injury. Currently, no effective pharmacological therapies are available to treat ALI, and supportive therapies remain the mainstay of treatment. Therefore, we investigated the protective effect of CT‑133, a newly discovered selective CRTH2 antagonist, on CS-induced ALI in vivo and in vitro.

Main Methods: CT‑133 (10 and 30 mg/kg), dexamethasone (1 mg/kg) and normal saline were intratracheally administrated 1 hr prior to whole-body CS-exposure for seven consecutive days to study the key characteristics of ALI. Subsequently, CSE (4%)- and PGD-stimulated RAW 264.7 macrophages were used to evaluate the protective effect of CT‑133.

Key Findings: CT‑133 remarkably attenuated infiltration of inflammatory cells, neutrophils, and macrophages in the BALF, albumin contents, expression of IL‑1β, IL‑6, TNF‑α and KC, lung myeloperoxidase (MPO) activity and lung histopathological alterations caused by CS exposure in mice. Moreover, CT‑133 not only reversed the uncontrolled secretion of IL‑1β, IL-6, TNF‑α and KC from CSE- and PGD-stimulated RAW 264.7 macrophages but also augmented IL-10 production in both in vivo and in vitro studies. Additionally, CT‑133 alleviated in vitro neutrophil migration chemoattracted by PGD.

Significance: Our results provide the first evidence that targeting CRTH2 could be a new potential therapeutic option to treat CS-induced ALI.
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http://dx.doi.org/10.1016/j.lfs.2018.11.039DOI Listing
January 2019

Inhibition of p21-activated kinase 1 attenuates the cardinal features of asthma through suppressing the lymph node homing of dendritic cells.

Biochem Pharmacol 2018 08 12;154:464-473. Epub 2018 Jun 12.

Department of Pharmacology and Key Laboratory of CFDA for Respiratory Drug Research, Zhejiang University School of Medicine, Hangzhou 310058, China. Electronic address:

Dendritic cell (DC) trafficking from lung to the draining mediastinal lymph nodes (MLNs) is a key step for initiation of T cell responses in allergic asthma. In the present study, we investigate the role of DC-mediated airway inflammation after inhibition of p21-activated kinase-1 (PAK1), an effector of Rac and Cdc42 small GTPases, in the allergen-induced mouse models of asthma. Systemic administration of PAK1 specific inhibitor IPA-3 significantly attenuates not only the airway inflammation but also the airway hyperresponsiveness in a mouse model of ovalbumin-induced asthma. Specifically, intratracheal administration of low dosage of IPA-3 consistently decreases not only the airway inflammation but also the DC trafficking from lung to the MLNs. Importantly, intratracheal instillation of IPA-3-treated and ovalbumin-pulsed DCs behaves largely the same as that of either Rac inhibitor-treated and ovalbumin-pulsed DCs or Cdc42 inhibitor-treated and ovalbumin-pulsed DCs in attenuation of the airway inflammation in ovalbumin-challenged mice. Mechanistically, PAK1 is not involved in the maturation, apoptosis, antigen uptake, and T cell activation of cultured DCs, but PAK1 dose lie on the downstream of Rac and Cdc42 to regulate the DC migration toward the chemokine C-C motif chemokine ligand 19. Taken together, this study demonstrates that inhibition of PAK1 attenuates the cardinal features of asthma through suppressing the DC trafficking from lung to the MLN, and that interfere with DC trafficking by a PAK1 inhibitor thus holds great promise for the therapeutic intervention of allergic diseases.
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http://dx.doi.org/10.1016/j.bcp.2018.06.012DOI Listing
August 2018

High expression of Sonic hedgehog in allergic airway epithelia contributes to goblet cell metaplasia.

Mucosal Immunol 2018 09 4;11(5):1306-1315. Epub 2018 Jun 4.

Department of Pharmacology, Zhejiang University School of Medicine, 310058, Hangzhou, China.

Sonic hedgehog (SHH) is abundantly expressed and critical for morphogenesis in embryonic lungs; however, SHH expression drops to a much lower level in mice from E17.5 and in humans from the 21st gestational week. We find that SHH expression is robustly upregulated in the airway epithelia of children with asthma or mouse models with allergic airway disease. Specifically, airway-specific SMO loss of function significantly suppresses allergen-induced goblet cell phenotypes, whereas an airway-specific SMO gain of function markedly enhances the goblet cell phenotypes in mouse models with allergic airway disease. Notably, intratracheal administration with SHH-neutralizing antibody or cyclopamine robustly attenuates goblet cell phenotypes in mouse models with allergic airway disease. Finally, we identify that Muc5AC gene encoding MUC5AC mucin serves as a direct target of GLI transcriptional factors in response to SHH, whereas the SAM-pointed domain-containing ETS transcription factor and Forkhead box A2, critical transcriptional factors for goblet cell phenotypes, both function as the effectors of GLIs in response to SHH stimulation. Together, the upregulation of SHH expression in allergic bronchial epithelia contributes to goblet cell metaplasia; thus, blockage of SHH signaling is a rational approach in a therapeutic intervention of epithelial remodeling in chronic airway diseases.
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http://dx.doi.org/10.1038/s41385-018-0033-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160330PMC
September 2018

Fatal choking in infants and children treated in a pediatric intensive care unit: A 7- year experience.

Int J Pediatr Otorhinolaryngol 2018 Jul 1;110:67-69. Epub 2018 May 1.

Department of Pulmonology, Child's Hospital, Zhejiang University School of Medicine, Hangzhou, PR China. Electronic address:

Introduction: Foreign bodies aspiration can lead to significant morbidity, few have examined in detail the deaths resulting from foreign bodies aspiration.

Methods: We conducted a review of children who presented to the pediatric intensive care unit of a university hospital due to fatal foreign bodies aspiration during the period of 2010-2017.

Result: Of the 28 patients, 17 (61%) patients were male and 11 (39%) were female. The range of age was 1-63 months, with mean of 15.2 months. The common foreign bodies included milk, nuts and fruits. Majority of them had round shapes. All the patients died due to asphyxia or serious complications after foreign bodies aspiration.

Conclusions: Prevention and early recognition remains a critical factor to reduce the mortality of foreign bodies aspiration.
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http://dx.doi.org/10.1016/j.ijporl.2018.04.026DOI Listing
July 2018

Acute Respiratory Distress Syndrome: Bench-to-Bedside Approaches to Improve Drug Development.

Clin Pharmacol Ther 2018 09 27;104(3):484-494. Epub 2018 Feb 27.

Department of Pharmacology, Hangzhou City, 310058, China.

Despite 50 years of extensive research, no definite drug is currently available to treat acute respiratory distress syndrome (ARDS), and the supportive therapies remain the mainstay of treatment. To improve drug development for ARDS, researchers need to deeply analyze the "omics" approaches, reevaluate the suitable therapeutic targets, resolve the problems of inadequate animal modeling, develop the strategies to reduce the heterogeneity, and reconsider new therapeutic and analytical approaches for better designs of clinical trials.
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http://dx.doi.org/10.1002/cpt.1034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162218PMC
September 2018

Notch Signaling: Linking Embryonic Lung Development and Asthmatic Airway Remodeling.

Mol Pharmacol 2017 12 12;92(6):676-693. Epub 2017 Oct 12.

Department of Pharmacology and The Key Respiratory Drug Research Laboratory of China Food and Drug Administration, School of Medicine, Zhejiang University, Hangzhou City, China (M.H., C.X., M.A., Xim.W.); The Second People's Hospital of Wenling, Wenling City, Zhejiang Province, China (Y.Y.); and Department of Respiratory Medicine, the Affiliated Children Hospital, School of Medicine, Zhejiang University, Hangzhou City, China (M.L., Xil.W., L.T.)

Lung development is mediated by assorted signaling proteins and orchestrated by complex mesenchymal-epithelial interactions. Notch signaling is an evolutionarily conserved cell-cell communication mechanism that exhibits a pivotal role in lung development. Notably, both aberrant expression and loss of regulation of Notch signaling are critically linked to the pathogenesis of various lung diseases, in particular, pulmonary fibrosis, lung cancer, pulmonary arterial hypertension, and asthmatic airway remodeling; implying that precise regulation of intensity and duration of Notch signaling is imperative for appropriate lung development. Moreover, evidence suggests that Notch signaling links embryonic lung development and asthmatic airway remodeling. Herein, we summarized all-recent advances associated with the mechanistic role of Notch signaling in lung development, consequences of aberrant expression or deletion of Notch signaling in linking early-impaired lung development and asthmatic airway remodeling, and all recently investigated potential therapeutic strategies to treat asthmatic airway remodeling.
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http://dx.doi.org/10.1124/mol.117.110254DOI Listing
December 2017

Wnt/β-catenin signaling links embryonic lung development and asthmatic airway remodeling.

Biochim Biophys Acta Mol Basis Dis 2017 12 1;1863(12):3226-3242. Epub 2017 Sep 1.

Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou City 310058, China; The Key Respiratory Drug Research Laboratory of China Food and Drug Administration, School of Medicine, Zhejiang University, Hangzhou City 310058, China. Electronic address:

Embryonic lung development requires reciprocal endodermal-mesodermal interactions; mediated by various signaling proteins. Wnt/β-catenin is a signaling protein that exhibits the pivotal role in lung development, injury and repair while aberrant expression of Wnt/β-catenin signaling leads to asthmatic airway remodeling: characterized by hyperplasia and hypertrophy of airway smooth muscle cells, alveolar and vascular damage goblet cells metaplasia, and deposition of extracellular matrix; resulting in decreased lung compliance and increased airway resistance. The substantial evidence suggests that Wnt/β-catenin signaling links embryonic lung development and asthmatic airway remodeling. Here, we summarized the recent advances related to the mechanistic role of Wnt/β-catenin signaling in lung development, consequences of aberrant expression or deletion of Wnt/β-catenin signaling in expansion and progression of asthmatic airway remodeling, and linking early-impaired pulmonary development and airway remodeling later in life. Finally, we emphasized all possible recent potential therapeutic significance and future prospectives, that are adaptable for therapeutic intervention to treat asthmatic airway remodeling.
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http://dx.doi.org/10.1016/j.bbadis.2017.08.031DOI Listing
December 2017

Inhibition of Myosin Light-Chain Kinase Enhances the Clearance of Lipopolysaccharide-Induced Lung Inflammation Possibly by Accelerating Neutrophil Apoptosis.

Shock 2017 09;48(3):377-386

*Department of Critical Care Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou City, China †Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou City, China ‡Department of Paediatrics, The First People's Hospital of Wenling City, Wenling City, China §Department of Respiratory Medicine, The Affiliated Children's Hospital, Zhejiang University School of Medicine, Hangzhou City, China.

Neutrophils are a population of inflammatory cells involved in acute lung injury (ALI), and lipopolysaccharide (LPS)-induced prolonged neutrophil survival and delayed neutrophil apoptosis hinder the alleviation of lung inflammation. Myosin light-chain kinase (MLCK) involved the RhoA/Rho kinase signaling pathway responsible for the cytoskeletal arrangement, and previous studies have revealed that inhibition of MLCK induces apoptosis in vitro and in vivo. In this study, glycogen-induced neutrophils isolated from rats or mice were incubated with ML-7, a MLCK-specific inhibitor, and LPS-induced ALI mice administrated with ML-7 were investigated, to demonstrate the roles of MLCK in neutrophil apoptosis as well as its possibility of contributing to the clearance of inflammation. We found that ML-7 dramatically promoted neutrophil apoptosis that possibly signal through the p38 to upregulate the expression of the apoptotic proteins caspase-9 and B-cell lymphoma 2 and to downregulate the expression of the antiapoptotic protein Bcl-2-associated X protein and myeloid cell leukemia-1. In mice, ML-7 accelerated the clearance of inflammation in LPS-induced ALI through attenuating neutrophil accumulation, histopathological changes, and pulmonary edema. ML-7 promoted elimination of inflammation possibly by accelerating neutrophil apoptosis and macrophage-mediated clearance. Moreover, ML-7 also reduced the LPS-induced production of proinflammatory cytokines interleukin-1β and tumor necrosis factor-α, and the activity of myeloperoxidase. Taken together, the present study uncovers a hitherto uncharacterized role of MLCK in neutrophil apoptosis that contributes to the alleviation of inflammation in response to LPS.
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http://dx.doi.org/10.1097/SHK.0000000000000863DOI Listing
September 2017

The Clinical Characteristics and Predictors of Refractory Mycoplasma pneumoniae Pneumonia in Children.

PLoS One 2016 26;11(5):e0156465. Epub 2016 May 26.

Department of Pulmonology, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, P.R. China.

Objective: To analyze the clinical characteristics of refracory Mycoplasma pneumoniae pneumonia (RMPP), and explore the related factors predicting RMPP.

Methods: Retrospective analysis was performed on 634 children with Mycoplasma pneumoniae pneumonia (MPP) hospitalized in our hospital between January 1, 2011 and December 31, 2014. The clinical features, laboratory data, radiological findings between the RMPP group and the general Mycoplasma pneumoniae pneumonia (GMPP) group were compared and the predictive values of related factors were analyzed.

Results: The median age of the RMPP patients (n = 145) was much older than that of the GMPP patients (n = 489) (P<0.01). We also found more severe presentations, higher incidence of extra-pulmonary complications and more serious radiological findings in RMPP group, which needed oxygen more often, longer antibiotics administration and intensive care (P<0.05). Meanwhile, the levels of C-reactive protein (CRP), lactic dehydrogenase (LDH), immunoglobulin A (IgM), interleukin (IL)-6, IL-10, interferon gamma (IFN-γ) and the percentage of neutrophils, CD8+ in RMPP group were significantly higher than those in GMPP group (P<0.05); while the levels of prealbumin (PAB) were lower than that in GMPP group (P<0.01). In ROC curve analysis, the percentage of neutrophil, CRP, LDH, PAB, IL-6, IL-10 and IFN-γ were useful for differentiating patients with RMPP from those with GMPP. Multiple logistic regression analysis showed that the CRP≥16.5mg/L, LDH ≥417IU/L and IL-6 ≥14.75pg/ml were significant predictors regarding to RMPP.

Conclusions: CRP≥16.5mg/L, LDH ≥417IU/L and IL-6 ≥14.75pg/ml might be the significant predictors of RMPP in children, which can aid in early recognition of RMPP.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0156465PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882022PMC
July 2017

Propranolol treatment of subglottic hemangiomas: a review of the literature.

Int J Clin Exp Med 2015 15;8(11):19886-90. Epub 2015 Nov 15.

Department of Pulmonology, Children's Hospital, Zhejiang University School of Medicine Hangzhou, P. R. China.

Subglottic hemangiomas (SGH), which are rare benign tumors of the airway, are potentially life-threatening conditions that may require intervention. Propranolol appears to be an effective treatment for these tumors and should therefore be a first-line treatment for SGH that require intervention. This review presents the clinical presentation and diagnosis of SGH and discusses current knowledge regarding the use of propranolol for the treatment of SGH.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4723745PMC
February 2016

hMSH5 Facilitates the Repair of Camptothecin-induced Double-strand Breaks through an Interaction with FANCJ.

J Biol Chem 2015 Jul 8;290(30):18545-58. Epub 2015 Jun 8.

From the School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, Washington 99164-7520

Replication stress from stalled or collapsed replication forks is a major challenge to genomic integrity. The anticancer agent camptothecin (CPT) is a DNA topoisomerase I inhibitor that causes fork collapse and double-strand breaks amid DNA replication. Here we report that hMSH5 promotes cell survival in response to CPT-induced DNA damage. Cells deficient in hMSH5 show elevated CPT-induced γ-H2AX and RPA2 foci with concomitant reduction of Rad51 foci, indicative of impaired homologous recombination. In addition, CPT-treated hMSH5-deficient cells exhibit aberrant activation of Chk1 and Chk2 kinases and therefore abnormal cell cycle progression. Furthermore, the hMSH5-FANCJ chromatin recruitment underlies the effects of hMSH5 on homologous recombination and Chk1 activation. Intriguingly, FANCJ depletion desensitizes hMSH5-deficient cells to CPT-elicited cell killing. Collectively, our data point to the existence of a functional interplay between hMSH5 and FANCJ in double-strand break repair induced by replication stress.
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http://dx.doi.org/10.1074/jbc.M115.642884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4513114PMC
July 2015

DNA damage induced MutS homologue hMSH4 acetylation.

Int J Mol Sci 2013 Oct 18;14(10):20966-82. Epub 2013 Oct 18.

School of Molecular Biosciences, Mail Drop 64-7520, Washington State University, Pullman, WA 99164-7520, USA.

Acetylation of non-histone proteins is increasingly recognized as an important post-translational modification for controlling the actions of various cellular processes including DNA repair and damage response. Here, we report that the human MutS homologue hMSH4 undergoes acetylation following DNA damage induced by ionizing radiation (IR). To determine which acetyltransferases are responsible for hMSH4 acetylation in response to DNA damage, potential interactions of hMSH4 with hTip60, hGCN5, and hMof were analyzed. The results of these experiments indicate that only hMof interacts with hMSH4 in a DNA damage-dependent manner. Intriguingly, the interplay between hMSH4 and hMof manipulates the outcomes of nonhomologous end joining (NHEJ)-mediated DNA double strand break (DSB) repair and thereby controls cell survival in response to IR. This study also shows that hMSH4 interacts with HDAC3, by which HDAC3 negatively regulates the levels of hMSH4 acetylation. Interestingly, elevated levels of HDAC3 correlate with increased NHEJ-mediated DSB repair, suggesting that hMSH4 acetylation per se may not directly affect the role of hMSH4 in DSB repair.
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http://dx.doi.org/10.3390/ijms141020966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3821653PMC
October 2013

MutS Homologues hMSH4 and hMSH5: Genetic Variations, Functions, and Implications in Human Diseases.

Curr Genomics 2013 Apr;14(2):81-90

STARS Program, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-7520, USA ; School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164-7520, USA.

The prominence of the human mismatch repair (MMR) pathway is clearly reflected by the causal link between MMR gene mutations and the occurrence of Lynch syndrome (or HNPCC). The MMR family of proteins also carries out a plethora of diverse cellular functions beyond its primary role in MMR and homologous recombination. In fact, members of the MMR family of proteins are being increasingly recognized as critical mediators between DNA damage repair and cell survival. Thus, a better functional understanding of MMR proteins will undoubtedly aid the development of strategies to effectively enhance apoptotic signaling in response to DNA damage induced by anti-cancer therapeutics. Among the five known human MutS homologs, hMSH4 and hMSH5 form a unique heterocomplex. However, the expression profiles of the two genes are not correlated in a number of cell types, suggesting that they may function independently as well. Consistent with this, these two proteins are promiscuous and thought to play distinct roles through interacting with different binding partners. Here, we describe the gene and protein structures of eukaryotic MSH4 and MSH5 with a particular emphasis on their human homologues, and we discuss recent findings of the roles of these two genes in DNA damage response and repair. Finally, we delineate the potential links of single nucleotide polymorphism (SNP) loci of these two genes with several human diseases.
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http://dx.doi.org/10.2174/1389202911314020002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637681PMC
April 2013

MutS homologue hMSH5: recombinational DSB repair and non-synonymous polymorphic variants.

PLoS One 2013 4;8(9):e73284. Epub 2013 Sep 4.

School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Pullman, Washington, United States of America.

Double-strand breaks (DSBs) constitute the most deleterious form of DNA lesions that can lead to genome alterations and cell death, and the vast majority of DSBs arise pathologically in response to DNA damaging agents such as ionizing radiation (IR) and chemotherapeutic agents. Recent studies have implicated a role for the human MutS homologue hMSH5 in homologous recombination (HR)-mediated DSB repair and the DNA damage response. In the present study, we show that hMSH5 promotes HR-based DSB repair, and this property resides in the carboxyl-terminal portion of the protein. Our results demonstrate that DSB-triggered hMSH5 chromatin association peaks at the proximal regions of the DSB and decreases gradually with increased distance from the break. Furthermore, the DSB-triggered hMSH5 chromatin association is preceded by and relies on the assembly of hMRE11 and hRad51 at the proximal regions of the DSB. Lastly, the potential effects of hMSH5 non-synonymous variants (L85F, Y202C, V206F, R351G, L377F, and P786S) on HR and cell survival in response to DSB-inducing anticancer agents have been analyzed. These experiments show that the expression of hMSH5 variants elicits different survival responses to anticancer drugs cisplatin, bleomycin, doxorubicin and camptothecin. However, the effects of hMSH5 variants on survival responses to DSB-inducing agents are not directly correlated to their effects exerted on HR-mediated DSB repair, suggesting that the roles of hMSH5 variants in the processes of DNA damage response and repair are multifaceted.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0073284PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3762724PMC
April 2014

MutS homologue hMSH4: interaction with eIF3f and a role in NHEJ-mediated DSB repair.

Mol Cancer 2013 Jun 2;12:51. Epub 2013 Jun 2.

School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Mail Drop 64-7520, Pullman, WA 99164, USA.

Background: DNA mismatch repair proteins participate in diverse cellular functions including DNA damage response and repair. As a member of this protein family, the molecular mechanisms of hMSH4 in mitotic cells are poorly defined. It is known that hMSH4 is promiscuous, and among various interactions the hMSH4-hMSH5 interaction is involved in recognizing DNA intermediate structures arising from homologous recombination (HR).

Results: We identified a new hMSH4 interacting protein eIF3f--a protein that functions not only in translation but also in the regulation of apoptosis and tumorigenesis in humans. Our studies have demonstrated that hMSH4-eIF3f interaction is mediated through the N-terminal regions of both proteins. The interaction with eIF3f fosters hMSH4 protein stabilization, which in turn sustains γ-H2AX foci and compromises cell survival in response to ionizing radiation (IR)-induced DNA damage. These effects can be, at least partially, attributed to the down-regulation of NHEJ activity by hMSH4. Furthermore, the interplay between hMSH4 and eIF3f inhibits IR-induced AKT activation, and hMSH4 promotes eIF3f-mediated bypass of S phase arrest, and ultimately enhancing an early G2/M arrest in response to IR treatment.

Conclusion: Our current study has revealed a role for hMSH4 in the maintenance of genomic stability by suppressing NHEJ-mediated DSB repair.
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http://dx.doi.org/10.1186/1476-4598-12-51DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3689047PMC
June 2013

Assessment of anti-recombination and double-strand break-induced gene conversion in human cells by a chromosomal reporter.

J Biol Chem 2012 Aug 7;287(35):29543-53. Epub 2012 Jul 7.

From the School of Molecular Biosciences, Washington State University, Pullman, Washington 99164-7520.

Gene conversion is one of the frequent end results of homologous recombination, and it often underlies the inactivation of tumor suppressor genes in cancer cells. Here, we have developed an integrated assay system that allows simultaneous examination of double-strand break (DSB)-induced gene conversion events at the site of a DSB (proximal region) and at a surrounding region ~1 kb away from the break (distal region). Utilizing this assay system, we find that gene conversion events at the proximal and distal regions are relatively independent of one another. The results also indicate that synthesis-dependent strand annealing (SDSA) plays a major role in DSB-induced gene conversion. In addition, our current study has demonstrated that hMLH1 plays an essential role in anti-recombination and gene conversion. Specifically, the anti-recombination activity of hMLH1 is partially dependent on its interaction with hMRE11. Our data suggests that the role of hMLH1 and hMRE11 in the process of gene conversion is complex, and these proteins play different roles in DSB-induced proximal and distal gene conversions. In particular, the involvement of hMLH1 and hMRE11 in the distal gene conversion requires both hMSH2 and heteroduplex formation.
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http://dx.doi.org/10.1074/jbc.M112.352302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3436158PMC
August 2012

MutS homologue hMSH5: role in cisplatin-induced DNA damage response.

Mol Cancer 2012 Mar 8;11:10. Epub 2012 Mar 8.

School of Molecular Biosciences, College of Veterinary Medicine, Washington State University, Mail Drop 64-7520, Pullman, WA 99164, USA.

Background: Cisplatin (cis-diamminedichloroplatinum (II), CDDP) and its analogues constitute an important class of anticancer drugs in the treatment of various malignancies; however, its effectiveness is frequently affected by mutations in genes involved in the repair and signaling of cisplatin-induced DNA damage. These observations necessitate a need for a better understanding of the molecular events governing cellular sensitivity to cisplatin.

Results: Here, we show that hMSH5 mediates sensitization to cisplatin-induced DNA damage in human cells. Our study indicates that hMSH5 undergoes cisplatin-elicited protein induction and tyrosine phosphorylation. Silencing of hMSH5 by RNAi or expression of hMSH5 phosphorylation-resistant mutant hMSH5Y742F elevates cisplatin-induced G2 arrest and renders cells susceptible to cisplatin toxicity at clinically relevant doses. In addition, our data show that cisplatin promotes hMSH5 chromatin association and hMSH5 deficiency increases cisplatin-triggered γ-H2AX foci. Consistent with a possible role for hMSH5 in recombinational repair of cisplatin-triggered double-strand breaks (DSBs), the formation of cisplatin-induced hMSH5 nuclear foci is hRad51-dependent.

Conclusion: Collectively, our current study has suggested a role for hMSH5 in the processing of cisplatin-induced DSBs, and silencing of hMSH5 may provide a new means to improve the therapeutic efficacy of cisplatin.
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http://dx.doi.org/10.1186/1476-4598-11-10DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325843PMC
March 2012

Causal link between microsatellite instability and hMRE11 dysfunction in human cancers.

Mol Cancer Res 2011 Nov 17;9(11):1443-8. Epub 2011 Aug 17.

School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA.

Maintenance of genomic integrity is essential for cell survival, and genomic instability is a commonly recognized intrinsic property of all cancers. Microsatellite instability (MSI) represents a frequently occurring and easily traceable simple form of sequence variation, signified by the contraction or expansion of specific DNA sequences containing short tandem repeats. MSI is frequently detected in tumor cells with DNA mismatch repair (MMR) deficiency. It is commonly conceived that instability at individual microsatellite loci can arise spontaneously in cells independent of MMR status, and different microsatellite loci are generally not affected uniformly by MMR deficiency. It is well recognized that MMR deficiency per se is not sufficient to initiate tumorigenesis; rather, the biological effects have to be exerted by mutations in genes controlling cell survival, DNA damage response, and apoptosis. Recently, shortening of an intronic hMRE11 poly(T)11 tract has been associated with MMR deficiency, raising the possibility that hMRE11 may be inactivated by defective MMR. However, the molecular nature underlying this association is presently unknown, and review of the current literature suggests that hMRE11 is most likely involved with the MMR pathway in a more complex fashion than simply being a MMR target gene. An alternative scenario is proposed to better reconcile the differences among various studies. The potential role of hMRE11 in telomere repeats stability is also discussed.
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http://dx.doi.org/10.1158/1541-7786.MCR-11-0322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219828PMC
November 2011

Congenital monoblastic leukemia presenting as jaundice, pleural effusion, and ascites: case report and literature review.

Fetal Pediatr Pathol 2011 ;30(1):27-31

The Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Congenital leukemias are a rare group of hematologic neoplasms with a wide range of clinical signs and symptoms. Here we reported a neonate presenting with jaundice, pleural effusion and ascites. The total protein and serum albumin were markedly low at 48 and 12 g/L. Computerized tomography showed the density of liver was asymmetry with several hypoechoic regions. Initial blood routine examination revealed only thrombocytopenia while blood white cells increased to 30.0×10(9)/L with 17% blast cells several days later. Bone marrow biopsy showed the proportion of blasts and promonocytes increased and she was diagnosed as acute monoblastic leukemia.
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http://dx.doi.org/10.3109/15513815.2010.494701DOI Listing
April 2011