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1.  Major parasitic diseases of poverty in mainland China: perspectives for better control 
Significant progress has been made in the prevention, control, and elimination of human parasitic diseases in China in the past 60 years. However, parasitic diseases of poverty remain major causes of morbidity and mortality, and inflict enormous economic costs on societies.
In this article, we review the prevalence rates, geographical distributions, epidemic characteristics, risk factors, and clinical manifestations of parasitic diseases of poverty listed in the first issue of the journal Infectious Diseases of Poverty on 25 October 2012. We also address the challenges facing control of parasitic diseases of poverty and provide suggestions for better control.
Electronic supplementary material
The online version of this article (doi:10.1186/s40249-016-0159-0) contains supplementary material, which is available to authorized users.
PMCID: PMC4967992  PMID: 27476746
China; Poverty; Parasitic diseases of poverty; Epidemic characteristics; Prevention; Control; Elimination
2.  Gliomatosis peritonei: a series of eight cases and review of the literature 
Gliomatosis peritonei (GP) is a rare condition characterized by mature glial tissue implants widespread in the peritoneum. The GP is often associated with ovarian teratoma. However, little is known about the characteristics and prognosis of GP. The purpose of this study was to describe the features, treatment, and prognosis of GP. Additionally, we review previously reported cases of GP, summarizing the presently known data.
From January 2000 to January 2016, cases of ovarian teratoma and GP treated at Peking Union Medical College Hospital were reviewed. We assessed the pathology, treatments, and outcomes along with prognostic information. Additionally, the literature regarding this clinical condition was also reviewed.
Eight patients met the inclusion criteria. Patients had a median age of 20 (range, 15–25) years. GP was diagnosed as the primary tumor in 6 patients and at a secondary surgery in two patients. The primary ovarian tumor consisted of immature teratoma (n = 7) and mature teratoma (n = 1). Grades of immature ovarian teratoma were 2, grade 1; 3, grade 2; and 2, grade 3. Tumors mean had a size of 20.4 (range, 11–30) cm. The median follow-up time was 60.5 (range, 3–144) months. All cases had conservative surgery and seven of them had macroscopic residual disease postoperatively. During the study period, the eight patients remained alive and asymptomatic. Three patients in the study experienced spontaneous pregnancy. After reviewing the existing literature, a total of 14 patients with nodal gliomatosis were present and 10 of them were alive. According to the literature review, five articles reported more than five cases. Of a total of 67 patients, 60 of them remained alive.
The prognosis of immature ovarian teratoma with GP is favorable. Complete resection of GP is often difficult. Residual peritoneal disease in GP can be asymptomatic and quiescent over a long period. A more conservative surgical approach may be carried out in patients with massive peritoneal spread after the presence of metastatic immature elements is excluded. Owing to the risk of recurrence and malignant transformation of GP, a long-term follow-up is necessary for patients with residual peritoneal disease.
PMCID: PMC4966768  PMID: 27473411
Ovarian teratoma; Gliomatosis peritonei; Prognosis
3.  Childhood Injuries in Singapore: Can Local Physicians and the Healthcare System Do More to Confront This Public Health Concern? 
Childhood injury is one of the leading causes of death globally. Singapore is no exception to this tragic fact, with childhood injuries accounting up to 37% of Emergency Department visits. Hence, it is important to understand the epidemiology and risk factors of childhood injuries locally. A search for relevant articles published from 1996–2016 was performed on PubMed, Cochrane Library and Google Scholar using keywords relating to childhood injury in Singapore. The epidemiology, mechanisms of injury, risk factors and recommended prevention strategies of unintentional childhood injuries were reviewed and described. Epidemiological studies have shown that childhood injury is a common, preventable and significant public health concern in Singapore. Home injuries and falls are responsible for majority of the injuries. Injuries related to childcare products, playground and road traffic accidents are also important causes. Healthcare professionals and legislators play an important role in raising awareness and reducing the incidence of childhood injuries in Singapore. For example, despite legislative requirements for many years, the low usage of child restraint seats in Singapore is worrisome. Thus, greater efforts in public health education in understanding childhood injuries, coupled with more research studies to evaluate the effectiveness and deficiencies of current prevention strategies will be necessary.
PMCID: PMC4962259  PMID: 27438844
childhood injuries; emergency visits; Singapore; preventable accidents; prevention strategies
4.  First report of Cryptosporidium canis in farmed Arctic foxes (Vulpes lagopus) in China 
Parasites & Vectors  2016;9:126.
Cryptosporidium is an important genus of enteric zoonotic parasites, which can infect a wide range of animals including foxes. Little information is available concerning the prevalence and molecular characterisation of Cryptosporidium spp. in farmed Arctic foxes (Vulpes lagopus) in China. Thus, the objective of the present study was to investigate the prevalence of Cryptosporidium spp. in Arctic foxes in China using nested PCR amplification of the small subunit ribosomal RNA (SSU rRNA) gene.
The overall prevalence of Cryptosporidium spp. in Arctic foxes was 15.9 % (48/302), with 12.9 % in male (18/139) and 18.4 % in female (30/163) foxes, respectively. The prevalence in different farms varied from 0 to 31.43 %. The prevalence of infection in different age groups varied from 14.1 % to 19.0 %. Foxes from Hebei Province (7.8 %, 11/141) had a significantly lower Cryptosporidium spp. prevalence than those from Heilongjiang Province (22.9 %, 16/70) and Jilin Province (23.1 %, 21/91) (P= 0.0015). Sequence analysis of the SSU rRNA gene indicated that all the 48 isolates represented C. canis.
This is the first report of C. canis infection in farmed Arctic foxes in China, which also provides foundation data for preventing and controlling Cryptosporidium infection in foxes, other animals and humans.
PMCID: PMC4776383  PMID: 26934975
Cryptosporidium canis; Prevalence; Arctic fox; China
5.  Prevalence, risk factors and multilocus genotyping of Enterocytozoon bieneusi in farmed foxes (Vulpes lagopus), Northern China 
Parasites & Vectors  2016;9:72.
Microsporidiosis is a common disease in animals and humans around the world. Enterocytozoon bieneusi is the most common microsporidian species in humans. Many animal species may be a potential source of human microsporidiosis. However, information concerning prevalence and genotypes of E. bieneusi infection in farmed foxes (Vulpes lagopus) is scarce. Therefore, the present study examined prevalence, risk factors and genotypes of E. bieneusi in farmed foxes in northern China using a genetic approach.
Of 302 fecal samples from farmed foxes, 37 (12.25 %, 95 % CI 8.55–15.95) were PCR-positive for E. bieneusi, and the prevalence was highly associated with the farming mode in that foxes raised outdoors (26.03 % positive, 95 % CI 18.91–33.15) had a significantly higher E. bieneusi prevalence than those raised indoors. Eleven internal transcribed spacer (ITS) genotypes were identified among the positive samples: four known E. bieneusi genotypes (Peru 8, Types IV, CHN-DC1 and D) and seven novel genotypes (NCF1-NCF7). Genotype NCF2 was the commonest (n = 13) and was found in five farms across three provinces (Jilin, Heilongjiang and Hebei). All genotypes belonged to phylogenetic group 1. Multilocus sequence typing (MLST) analyses revealed additional diversity.
These findings indicate the presence of zoonotic E. bieneusi infection in farmed foxes in northern China. This is also the first report of genotypes Peru8, CHN-DC1 and Type IV, and seven novel genotypes (NCF1-NCF7) in farmed foxes by ITS combining with microsatellite and minisatellite markers for the first time. The results will provide baseline data for preventing and controlling E. bieneusi infection in farmed foxes, other animals and humans.
PMCID: PMC4743323  PMID: 26847241
Enterocytozoon bieneusi; Foxes (Vulpes lagopus); Prevalence; Genotyping; Northern China
6.  Coxiella burnetii Seroprevalence and Risk Factors in Cattle Farmers and Farm Residents in Three Northeastern Provinces and Inner Mongolia Autonomous Region, China 
BioMed Research International  2016;2016:7059196.
Little is known about Coxiella burnetii infection among cattle farmers and farm residents in China. Thus, the present study was conducted to detect the seroprevalence of C. burnetii infection and estimate associated risk factors among cattle farmers and farm residents in China. A cross-sectional study was designed, and sera of 362 people living or working on 106 cattle farms were tested for C. burnetii IgG and IgM antibodies by immunofluorescence assay. Overall C. burnetii seroprevalence was 35.6% (129/362, 95% CI: 30.70–40.57), and 112 participants had experienced a past infection and seventeen (4.7%) had experienced a relatively recent infection. In the final combined multilevel model, the following activities were significantly associated with presence of antibodies against C. burnetii: milking cattle, providing general healthcare to cattle, providing birth assistance, contact dead-born animals, urbanization, and presence of mice and/or rats in the stable. Moreover, presence of disinfection equipment was a significant protective factor. This is the first study addressing the seroprevalence and risk factors of C. burnetii infection in cattle farmers and farm residents in three northeastern provinces and Inner Mongolia Autonomous Region, China.
PMCID: PMC4757716  PMID: 26966688
7.  Seroprevalence of Encephalitozoon cuniculi and Toxoplasma gondii in domestic rabbits (Oryctolagus cuniculus) in China 
The breeding of domestic rabbits (Oryctolagus cuniculus) for human consumption has a long tradition in China. Infections that can affect the production of meat or even be transmitted from animals to humans are important to monitor, especially for public health reasons as well as for their impact on animal health. Thus, a total of 1,132 domestic rabbit sera from 4 regions in China were collected for serological screening for Encephalitozoon cuniculi and for Toxoplasma gondii by ELISA and modified agglutination test (MAT), respectively. Antibodies to E. cuniculi were detected in 248/1,132 (21.9%) sera tested while antibodies against T. gondii revealed a seroprevalence of 51/1,132 (4.5%). We believe that the present results are of epidemiological implications and public health importance due to the acknowledged susceptibility of humans to E. cuniculi and T. gondii infections. Therefore, routine screening tests of domestic rabbits are proposed considering the zoonotic potential of these parasites.
PMCID: PMC4725227  PMID: 26797446
Encephalitozoon cuniculi; Toxoplasma gondii; domestic rabbit; seroprevalence; China
8.  Toxoplasma gondii Infection in Pregnant Women: A Seroprevalence and Case-Control Study in Eastern China 
BioMed Research International  2015;2015:170278.
Very limited information is available concerning the epidemiology of T. gondii infection in pregnant women in eastern China. Therefore, a case-control study was conducted to estimate the seroprevalence of toxoplasmosis in this population group and to identify risk factors and possible routes of contamination. Serum samples were collected from 965 pregnant women and 965 age-matched nonpregnant control subjects in Qingdao and Weihai between October 2011 and July 2013. These were screened with enzyme linked immunoassays for the presence of anti-Toxoplasma IgG and anti-Toxoplasma IgM antibodies. 147 (15.2%) pregnant women and 167 (17.3%) control subjects were positive for anti-T. gondii IgG antibodies, while 28 (2.9%) pregnant women and 37 (3.8%) controls were positive for anti-T. gondii IgM antibodies (P = 0.256). There was no significant difference between pregnant women and nonpregnant controls with regard to the seroprevalence of either anti-T. gondii IgG or IgM antibodies. Multivariate analysis showed that T. gondii infection was associated with location, cats in home, contact with cats and dogs, and exposure to soil. The results indicated that the seroprevalence of T. gondii infection in pregnant women is high compared to most other regions of China and other East Asian countries with similar climatic conditions.
PMCID: PMC4619758  PMID: 26539465
9.  Mycobacterium avium Subspecies paratuberculosis and Bovine Leukemia Virus Seroprevalence and Associated Risk Factors in Commercial Dairy and Beef Cattle in Northern and Northeastern China 
BioMed Research International  2015;2015:315173.
Mycobacterium avium subspecies paratuberculosis (MAP) and bovine leukemia virus (BLV) are important pathogens, commonly responsible for economical loss to cattle farms all over the world, yet their epidemiology in commercial dairy and beef cattle in China is still unknown. Thus, from September 2013 to December 2014, a large-scale seroprevalence study was conducted to determine the seroprevalence and identify herd-level risk factors associated with MAP and BLV infection. The source sample was 3674 cattle from 113 herds in northern and northeastern China. Antibodies against MAP and BLV were detected using ELISA tests. At animal-level, the seroprevalence of antibodies against MAP and BLV was 11.79% (433/3674) and 18.29% (672/3674), respectively. At herd-level, the seroprevalence of antibodies against MAP and BLV was 20.35% and 21.24% (24/113), respectively. Herd size was identified to be associated with MAP infection while herd size and presence of cattle introduced from other farms were significantly associated with BLV infection. Further research is needed to confirm these findings and improve the knowledge of the epidemiology of these two pathogens in these regions and elsewhere in China.
PMCID: PMC4609356  PMID: 26504798
10.  Prevalence of Toxoplasma gondii in Dogs in Zhanjiang, Southern China 
Toxoplasmosis, caused by Toxoplasma gondii, is a parasitic zoonosis with worldwide distribution. The present study investigated the prevalence of T. gondii in dogs in Zhanjiang city, southern China, using both serological and molecular detection. A total of 364 serum samples and 432 liver tissue samples were collected from the slaughter house between December 2012 and January 2013 and were examined for T. gondii IgG antibody by ELISA and T. gondii DNA by semi-nested PCR based on B1 gene, respectively. The overall seroprevalence of T. gondii IgG antibody was 51.9%, and T. gondii DNA was detected in 37 of 432 (8.6%) liver tissue samples. These positive DNA samples were analyzed by PCR-RFLP at 3'- and 5'-SAG2. Only 8 samples gave the PCR-RFLP data, and they were all classified as type I, which may suggest that the T. gondii isolates from dogs in Zhanjiang city may represent type I or type I variant. This study revealed the high prevalence of T. gondii infection in dogs in Zhanjiang city, southern China. Integrated measures should be taken to prevent and control toxoplasmosis in dogs in this area for public health concern.
PMCID: PMC4566514  PMID: 26323850
Toxoplasma gondii; dog; prevalence; genotyping; Zhanjiang (China)
11.  Metabolic abnormalities and hypoleptinemia in α-synuclein A53T mutant mice 
Neurobiology of aging  2013;35(5):1153-1161.
Parkinson’s disease (PD) patients frequently display loss of body fat mass and increased energy expenditure, and several studies have outlined a relationship between these metabolic abnormalities and disease severity, yet energy metabolism is largely unstudied in mouse models of PD. Here we characterize metabolic and physiologic responses to a high calorie diet (HCD) in mice expressing in neurons a mutant form of human α-synuclein (A53T) that causes dominantly inherited familial forms of the disease. A53T (SNCA) and wild type (WT) littermate mice were placed on a HCD for 12 weeks and evaluated for weight gain, food intake, body fat, blood plasma leptin, hunger, glucose tolerance, and energy expenditure. Results were compared to both SNCA and WT mice on a control diet. Despite consuming similar amounts of food, WT mice gained up to 66% of their original body weight on a HCD whereas SNCA mice gained only 17%. Further, after 12 weeks on a HCD, MRI analysis revealed that WT mice had significantly greater total and visceral body fat compared to SNCA mice (p<0.007). At 24 weeks of age SNCA mice displayed significantly increased hunger compared to WT (p<0.03). At 36 weeks of age, SNCA mice displayed significant hypoleptinemia compared to WT, both on a normal diet and a HCD (p<0.03). The HCD induced insulin insensitivity in WT, but not SNCA mice, as indicated by an oral glucose tolerance test. Finally, SNCA mice displayed greater energy expenditure compared to WT, as measured in a Comprehensive Lab Animal Monitoring System, after 12 weeks on a HCD. Thus, SNCA mice are resistant to HCD-induced obesity and insulin resistance and display reduced body fat, increased hunger, hypoleptinemia and increased energy expenditure. Our findings reveal a profile of metabolic dysfunction in a mouse model of PD that is similar to that of human PD patients, thus providing evidence that α-synuclein pathology is sufficient to drive such metabolic abnormalities and providing an animal model for discovery of the underlying mechanisms and potential therapeutic interventions.
PMCID: PMC3946232  PMID: 24239384
Parkinson’s disease; energy metabolism; leptin; insulin; body fat
12.  Longitudinal Analysis of Calorie Restriction on Rat Taste Bud Morphology and Expression of Sweet Taste Modulators 
Calorie restriction (CR) is a lifestyle intervention employed to reduce body weight and improve metabolic functions primarily via reduction of ingested carbohydrates and fats. Taste perception is highly related to functional metabolic status and body adiposity. We have previously shown that sweet taste perception diminishes with age; however, relatively little is known about the effects of various lengths of CR upon taste cell morphology and function. We investigated the effects of CR on taste bud morphology and expression of sweet taste–related modulators in 5-, 17-, and 30-month-old rats. In ad libitum (AL) and CR rats, we consistently found the following parameters altered significantly with advancing age: reduction of taste bud size and taste cell numbers per taste bud and reduced expression of sonic hedgehog, type 1 taste receptor 3 (T1r3), α-gustducin, and glucagon-like peptide-1 (GLP-1). In the oldest rats, CR affected a significant reduction of tongue T1r3, GLP-1, and α-gustducin expression compared with age-matched AL rats. Leptin receptor immunopositive cells were elevated in 17- and 30-month-old CR rats compared with age-matched AL rats. These alterations of sweet taste–related modulators, specifically during advanced aging, suggest that sweet taste perception may be altered in response to different lengths of CR.
PMCID: PMC3991138  PMID: 24077597
Taste buds; Sweet taste; Calorie restriction; T1r3; Aging.
13.  Seroprevalence of Toxoplasma gondii Infection in Patients of Intensive Care Unit in China: A Hospital Based Study 
BioMed Research International  2015;2015:908217.
The objective of this study was to estimate the seroprevalence of Toxoplasma gondii infection in 394 patients of intensive care unit (ICU) in a hospital between April 2010 and March 2012 and analyze the association between T. gondii infection and ICU patients according to the species of disease. Toxoplasma serology was evaluated by ELISA method using a commercially available kit. Data of patients were obtained from the patients, informants, and medical examination records. Seventy-four (18.78%) of 394 patients were positive for anti-T. gondii IgG antibodies demonstrating latent infection. Of these, the highest T. gondii seroprevalence was found in the age group of 31–45 years (27.45%), and the lowest was found in the age group of <30 years (12.5%). In addition, females (21.6%) had a higher seroprevalence than males (18.36%). With respect to the species of disease, the patients with kidney diseases (57.14%), lung diseases (27.84%), and brain diseases (24%) had high T. gondii seroprevalence. The present study represents the first survey of T. gondii seroprevalence in ICU patients in China, revealing an 18.78% seropositivity. Considering the particularities of ICU patients, molecular identification, genetic characterization, and diagnosis of T. gondii should be considered in future study.
PMCID: PMC4415447  PMID: 25961046
14.  Vismodegib, an antagonist of hedgehog signaling, directly alters taste molecular signaling in taste buds 
Cancer Medicine  2014;4(2):245-252.
Vismodegib, a highly selective inhibitor of hedgehog (Hh) pathway, is an approved treatment for basal-cell carcinoma. Patients on treatment with vismodegib often report profound alterations in taste sensation. The cellular mechanisms underlying the alterations have not been studied. Sonic Hh (Shh) signaling is required for cell growth and differentiation. In taste buds, Shh is exclusively expressed in type IV taste cells, which are undifferentiated basal cells and the precursors of the three types of taste sensing cells. Thus, we investigated if vismodegib has an inhibitory effect on taste cell turnover because of its known effects on Hh signaling. We gavaged C57BL/6J male mice daily with either vehicle or 30 mg/kg vismodegib for 15 weeks. The gustatory behavior and immunohistochemical profile of taste cells were examined. Vismodegib-treated mice showed decreased growth rate and behavioral responsivity to sweet and bitter stimuli, compared to vehicle-treated mice. We found that vismodegib-treated mice had significant reductions in taste bud size and numbers of taste cells per taste bud. Additionally, vismodegib treatment resulted in decreased numbers of Ki67- and Shh-expressing cells in taste buds. The numbers of phospholipase Cβ2- and α-gustducin-expressing cells, which contain biochemical machinery for sweet and bitter sensing, were reduced in vismodegib-treated mice. Furthermore, vismodegib treatment resulted in reduction in numbers of T1R3, glucagon-like peptide-1, and glucagon-expressing cells, which are known to modulate sweet taste sensitivity. These results suggest that inhibition of Shh signaling by vismodegib treatment directly results in alteration of taste due to local effects in taste buds.
PMCID: PMC4329008  PMID: 25354792
Basal-cell carcinoma; sonic hedgehog; taste buds; taste perception; Vismodegib
15.  GIT2 Acts as a Systems-Level Coordinator of Neurometabolic Activity and Pathophysiological Aging 
Aging represents one of the most complicated and highly integrated somatic processes. Healthy aging is suggested to rely upon the coherent regulation of hormonal and neuronal communication between the central nervous system and peripheral tissues. The hypothalamus is one of the main structures in the body responsible for sustaining an efficient interaction between energy balance and neurological activity and therefore likely coordinates multiple systems in the aging process. We previously identified, in hypothalamic and peripheral tissues, the G protein-coupled receptor kinase interacting protein 2 (GIT2) as a stress response and aging regulator. As metabolic status profoundly affects aging trajectories, we investigated the role of GIT2 in regulating metabolic activity. We found that genomic deletion of GIT2 alters hypothalamic transcriptomic signatures related to diabetes and metabolic pathways. Deletion of GIT2 reduced whole animal respiratory exchange ratios away from those related to primary glucose usage for energy homeostasis. GIT2 knockout (GIT2KO) mice demonstrated lower insulin secretion levels, disruption of pancreatic islet beta cell mass, elevated plasma glucose, and insulin resistance. High-dimensionality transcriptomic signatures from islets isolated from GIT2KO mice indicated a disruption of beta cell development. Additionally, GIT2 expression was prematurely elevated in pancreatic and hypothalamic tissues from diabetic-state mice (db/db), compared to age-matched wild type (WT) controls, further supporting the role of GIT2 in metabolic regulation and aging. We also found that the physical interaction of pancreatic GIT2 with the insulin receptor and insulin receptor substrate 2 was diminished in db/db mice compared to WT mice. Therefore, GIT2 appears to exert a multidimensional “keystone” role in regulating the aging process by coordinating somatic responses to energy deficits.
PMCID: PMC4716144  PMID: 26834700
GIT2; metabolism; keystone; aging; dysglycemia; trajectory
16.  DNA polymerase β deficiency leads to neurodegeneration and exacerbates Alzheimer disease phenotypes 
Nucleic Acids Research  2014;43(2):943-959.
We explore the role of DNA damage processing in the progression of cognitive decline by creating a new mouse model. The new model is a cross of a common Alzheimer's disease (AD) mouse (3xTgAD), with a mouse that is heterozygous for the critical DNA base excision repair enzyme, DNA polymerase β. A reduction of this enzyme causes neurodegeneration and aggravates the AD features of the 3xTgAD mouse, inducing neuronal dysfunction, cell death and impairing memory and synaptic plasticity. Transcriptional profiling revealed remarkable similarities in gene expression alterations in brain tissue of human AD patients and 3xTg/Polβ+/− mice including abnormalities suggestive of impaired cellular bioenergetics. Our findings demonstrate that a modest decrement in base excision repair capacity can render the brain more vulnerable to AD-related molecular and cellular alterations.
PMCID: PMC4333403  PMID: 25552414
17.  Molecular detection and genotypic characterization of Toxoplasma gondii infection in bats in four provinces of China 
Parasites & Vectors  2014;7:558.
Toxoplasma gondii is an intracellular protozoan parasite that infects a wide variety of warm-blooded hosts, including humans. Limited information about T. gondii infection in bats is available in China. The objective of the present study was to determine prevalence and genetic characterization of T. gondii infection in bats in Jilin, Liaoning, Jiangxi and Guangdong provinces, China.
During May 2005 to August 2013, bats were sampled from Jilin, Liaoning, Jiangxi, and Guangdong provinces, China, and liver tissues were collected for the detection of T. gondii by a nested PCR targeting the B1 gene. The positive samples were genotyped at 11 genetic markers (SAG1, 5′-and 3′-SAG2, alternative SAG2, SAG3, BTUB, GRA6, L358, PK1, c22-8, c29-2, and Apico) using multilocus polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
A total of 626 bats representing 10 species were examined for T. gondii infection, 38 (6.1%) were tested positive with by PCR, 8 positive DNA samples were completely genotyped, of which 3 samples (2 from Cynopterus sphinx, and 1 from Murina leucogaster) represented ToxoDB#10, and 5 samples (2 from Murina leucogaster, 2 from Myotis chinensis, and 1 from Rhinolophus ferrumequinum) belonged to ToxoDB#9 (
The present study revealed an overall T. gondii prevalence of 6.1% in bats from Jilin, Liaoning, Jiangxi and Guangdong provinces in China, and reported two T. gondii genotypes (ToxoDB#9 and #10) having a wide geographical distribution in China. These results provide new genetic information about T. gondii infection in bats, and have implications for better understanding of the genetic diversity of T. gondii in China and elsewhere.
PMCID: PMC4258805  PMID: 25465220
Toxoplasma gondii; Bats; Prevalence; Genetic characterization; China
18.  Seroprevalence and Risk Factors Associated with Hepatitis E Virus Infection in Three Species of Pet Birds in Northwest China 
The Scientific World Journal  2014;2014:296285.
Hepatitis E virus (HEV), the causative agent of hepatitis E, has been reported in a wide variety of animals, including birds, but little is known of HEV infection in pet birds in northwest China. The objective of the present investigation was to examine HEV seroprevalence in three species of pet birds, namely, Eurasian siskin, Oriental skylark, and black-tailed grosbeak from Gansu. Serum samples collected from 685 pet birds from August 2011 to September 2012 were examined independently for the presence of antibodies against HEV. A total of 59 (8.31%) pet birds were tested positive for HEV antibodies by the commercially available enzyme immunoassay kits. Of these, the seroprevalence was diverse in different species pet birds; the most frequent level was 10.83% (39/360) in Eurasian siskin, followed by 6.57% (19/289) in Oriental skylark, and 2.29% (1/36) in black-tailed grosbeak. Age and collecting region of pet birds were the main risk factors associated with HEV infection. The present study firstly revealed the seroprevalence of HEV infection in three species of pet birds in northwest China, which provided the baseline data for taking comprehensive countermeasures and measures for effectively preventing and controlling HEV infection in birds.
PMCID: PMC4230193  PMID: 25530995
19.  Seroprevalence and Risk Factors of Chlamydia abortus Infection in Tibetan Sheep in Gansu Province, Northwest China 
The Scientific World Journal  2014;2014:193464.
Chlamydia abortus, an important pathogen in a variety of animals, is associated with abortion in sheep. In the present study, 1732 blood samples, collected from Tibetan sheep between June 2013 and April 2014, were examined by the indirect hemagglutination (IHA) test, aiming to evaluate the seroprevalence and risk factors of C. abortus infection in Tibetan sheep. 323 of 1732 (18.65%) samples were seropositive for C. abortus antibodies at the cut-off of 1 : 16. A multivariate logistic regression analysis was used to evaluate the risk factors associated with seroprevalence, which could provide foundation to prevent and control C. abortus infection in Tibetan sheep. Gender of Tibetan sheep was left out of the final model because it is not significant in the logistic regression analysis (P > 0.05). Region, season, and age were considered as major risk factors associated with C. abortus infection in Tibetan sheep. Our study revealed a widespread and high prevalence of C. abortus infection in Tibetan sheep in Gansu province, northwest China, with higher exposure risk in different seasons and ages and distinct geographical distribution.
PMCID: PMC4226191  PMID: 25401129
20.  High-Glucose Inhibits Human Fibroblast Cell Migration in Wound Healing via Repression of bFGF-Regulating JNK Phosphorylation 
PLoS ONE  2014;9(9):e108182.
One of the major symptoms of diabetes mellitus (DM) is delayed wound healing, which affects large populations of patients worldwide. However, the underlying mechanism behind this illness remains elusive. Skin wound healing requires a series of coordinated processes, including fibroblast cell proliferation and migration. Here, we simulate DM by application of high glucose (HG) in human foreskin primary fibroblast cells to analyze the molecular mechanism of DM effects on wound healing. The results indicate that HG, at a concentration of 30 mM, delay cell migration, but not cell proliferation. bFGF is known to promote cell migration that partially rescues HG effects on cell migration. Molecular and cell biology studies demonstrated that HG enhanced ROS production and repressed JNK phosphorylation, but did not affect Rac1 activity. JNK and Rac1 activation were known to be important for bFGF regulated cell migration. To further confirm DM effects on skin repair, a type 1 diabetic rat model was established, and we observed the efficacy of bFGF on both normal and diabetic rat skin repair. Furthermore, proteomic studies identified an increase of Annexin A2 protein nitration in HG-stressed fibroblasts and the nitration was protected by activation of bFGF signaling. Treatment with FGFR1 and JNK inhibitors delayed cell migration and increased Annexin A2 nitration levels, indicating that Annexin A2 nitration is modulated by bFGF signaling via activation of JNK. Together with these results, our data suggests that the HG-mediated delay of cell migration is linked to the inhibition of bFGF signaling, specifically through JNK suppression.
PMCID: PMC4171528  PMID: 25244316
21.  Implications of the Wnt5a/CaMKII Pathway in Retinoic Acid-Induced Myogenic Tongue Abnormalities of Developing Mice 
Scientific Reports  2014;4:6082.
Although proper tongue development is relevant to other structures in the craniofacial region, the molecular details of muscle development in tongue remain poorly understood. Here, we report that pregnant mice treated with retinoic acid (+RA) produce embryos with tongue malformation and a cleft palate. Histological analyses revealed that at E14.5, the tongues of +RA fetuses failed to descend and flatten. Ultrastructural analysis showed that at perinatal stage E18.5, the myofilaments failed to form normal structures of sarcomeres, and arranged disorderly in the genioglossus. The proliferation and levels of myogenic determination markers (Myf5 and MyoD) and myosin in the genioglossus were profoundly reduced. Wnt5a and Camk2d expressions were down-regulated, while levels of Tbx1, Ror2, and PKCδ were up-regulated in the tongues of +RA fetuses. In mock- and Wnt5a-transfected C2C12 (Wnt5a-C2C12) cells, Wnt5a overexpression impaired proliferation, and maintained Myf5 at a relative high level after RA treatment. Furthermore, Wnt5a overexpression positively correlated with levels of Camk2d and Ror2 in C2C12 cells after RA exposure. These data support the hypothesis that the Wnt5a/CaMKII pathway is directly involved in RA-induced hypoplasia and disorder of tongue muscles.
PMCID: PMC4133706  PMID: 25124193
22.  Toxocara Seroprevalence among Clinically Healthy Individuals, Pregnant Women and Psychiatric Patients and Associated Risk Factors in Shandong Province, Eastern China 
Toxocarosis is a widespread zoonosis caused by the ascarid nematodes Toxocara canis and Toxocara cati, which primarily infect dogs and cats, respectively. Most human infections with Toxocara are asymptomatic; however, some infected individuals may develop a serious illness and even death. Nevertheless, epidemiological knowledge regarding the prevalence and risks associated with Toxocara infection is limited in China. Therefore, we performed a cross-sectional pilot study and estimated the seroprevalence of Toxocara infection in humans in Shandong Province, eastern China for the first time, from June 2011 to July 2013, involving clinically healthy individuals, pregnant women and psychiatric patients, aiming to attract public attention to Toxocara infection.
Methodology/Principle Findings
Seroprevalence of Toxocara was determined using an enzyme-linked immunosorbent assay based on a cross-sectional study conducted in Qingdao and Weihai, Shandong Province, eastern China. Factors potentially associated with Toxocara infection were identified by logistic regression analysis. The overall Toxocara seroprevalence among the study population (n = 2866) was 12.25%, and a significantly higher seroprevalence in psychiatric patients (16.40%, 73/445) than that in clinically healthy individuals (13.07%, 187/1431) and pregnant women (9.19%, 91/990) was revealed. Univariate analyses suggested that keeping dogs at home (OR = 0.06, 95% CI 0.05–0.08, P<0.001), contact with cats and dogs (OR = 0.42, 95% CI 0.33–0.53, P<0.001) and exposure with soil (OR = 0.37, 95% CI 0.28–0.49, P<0.001) were risk factors associated with Toxocara infection.
The present study revealed, for the first time, that human infection with Toxocara is common in eastern China, posing a significant public health concern. Increasing human and dog populations, population movements and climate change all will serve to increase the importance of this zoonosis. Further studies under controlled conditions are necessary to define potential morbidity associated with Toxocara infection.
Author Summary
Toxocarosis, a typical neglected and underestimated human health problem, is caused by the ascarid nematodes Toxocara canis and Toxocara cati, which primarily infect dogs and cats, respectively. Previous studies have reported an increased risk for Toxocara infection in humans worldwide, especially in children and psychiatric patients. This pilot study was aimed to investigate the Toxocara serology in clinically healthy individuals, pregnant women and psychiatric patients in Shandong Province, eastern China using an enzyme-linked immunosorbent assay. The overall Toxocara seroprevalence among the study population (n = 2866) was 12.25%, and a significantly higher seroprevalence in psychiatric patients (16.40%, 73/445) than that in clinically healthy individuals (13.07%, 187/1431) and pregnant women (9.19%, 91/990) was revealed. Keeping dogs at home, contact with cats and dogs, and exposure with soil were found to be associated with Toxocara infection. Our findings indicate that human infection with Toxocara is common in eastern China, posing a significant public health concern.
PMCID: PMC4125144  PMID: 25101756
23.  Metabolic Dysfunction in Alzheimer’s Disease and Related Neurodegenerative Disorders 
Current Alzheimer research  2012;9(1):5-17.
Alzheimer’s disease and other related neurodegenerative diseases are highly debilitating disorders that affect millions of people worldwide. Efforts towards developing effective treatments for these disorders have shown limited efficacy at best, with no true cure to this day being present. Recent work, both clinical and experimental, indicates that many neurodegenerative disorders often display a coexisting metabolic dysfunction which may exacerbate neurological symptoms. It stands to reason therefore that metabolic pathways may themselves contain promising therapeutic targets for major neurodegenerative diseases. In this review, we provide an overview of some of the most recent evidence for metabolic dysregulation in Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease, and discuss several potential mechanisms that may underlie the potential relationships between metabolic dysfunction and etiology of nervous system degeneration. We also highlight some prominent signaling pathways involved in the link between peripheral metabolism and the central nervous system that are potential targets for future therapies, and we will review some of the clinical progress in this field. It is likely that in the near future, therapeutics with combinatorial neuroprotective and ‘eumetabolic’ activities may possess superior efficacies compared to less pluripotent remedies.
PMCID: PMC4097094  PMID: 22329649
Neurodegenerative diseases; metabolic dysfunction; bodyweight; diabetes; glucose homeostasis; insulin; leptin; ghrelin; adiponectin; glucagon-like peptide 1; Alzheimer’s disease; Huntington’s disease; Parkinson’s disease
24.  3xTgAD mice exhibit altered behavior and elevated Aβ after chronic mild social stress 
Neurobiology of aging  2011;33(4):830.e1-830.12.
Chronic stress may be a risk factor for developing Alzheimer’s disease (AD), but most studies of the effects of stress in models of AD utilize acute adverse stressors of questionable clinical relevance. The goal of this work was to determine how chronic psychosocial stress affects behavioral and pathological outcomes in an animal model of AD, and to elucidate underlying mechanisms. A triple-transgenic mouse model of AD (3xTgAD mice) and nontransgenic control mice were used to test for an affect of chronic mild social stress on blood glucose, plasma glucocorticoids, plasma insulin, anxiety and hippocampal Aβ, ptau and BDNF levels. Despite the fact that both control and 3xTgAD mice experienced rises in corticosterone during episodes of mild social stress, at the end of the 6 week stress period 3xTgAD mice displayed increased anxiety, elevated levels of Aβ oligomers and intraneuronal Aβ, and decreased BDNF levels, whereas control mice did not. Findings suggest 3xTgAD mice are more vulnerable than control mice to chronic psychosocial stress, and that such chronic stress exacerbates Aβ accumulation and impairs neurotrophic signaling.
PMCID: PMC4074356  PMID: 21855175
Alzheimer’s disease; amyloid oligomers; psychosocial stress; corticosterone; hippocampus; BDNF
25.  Metabolic and hormonal signatures in pre-manifest and manifest Huntington's disease patients 
Huntington's disease (HD) is an inherited neurodegenerative disorder typified by involuntary body movements, and psychiatric and cognitive abnormalities. Many HD patients also exhibit metabolic changes including progressive weight loss and appetite dysfunction. Here we have investigated metabolic function in pre-manifest and manifest HD subjects to establish an HD subject metabolic hormonal plasma signature. Individuals at risk for HD who have had predictive genetic testing showing the cytosine-adenine-guanine (CAG) expansion causative of HD, but who do not yet present signs and symptoms sufficient for the diagnosis of manifest HD are said to be “pre-manifest.” Pre-manifest and manifest HD patients, as well as both familial and non-familial controls, were evaluated for multiple peripheral metabolism signals including circulating levels of hormones, growth factors, lipids, and cytokines. Both pre-manifest and manifest HD subjects exhibited significantly reduced levels of circulating growth factors, including growth hormone and prolactin. HD-related changes in the levels of metabolic hormones such as ghrelin, glucagon, and amylin were also observed. Total cholesterol, HDL-C, and LDL-C were significantly decreased in HD subjects. C-reactive protein was significantly elevated in pre-manifest HD subjects. The observation of metabolic alterations, even in subjects considered to be in the pre-manifest stage of HD, suggests that in addition, and prior, to overt neuronal damage, HD affects metabolic hormone secretion and energy regulation, which may shed light on pathogenesis, and provide opportunities for biomarker development.
PMCID: PMC4066441  PMID: 25002850
Huntington's disease; pre-manifest; metabolic hormones; lipids; peripheral energy metabolism

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