Establishment of an immune-related gene prognostic model for head and neck tumors.

This study aimed to screen the key immune-related genes (IRGs) in head and neck squamous cell carcinoma (HNSC) and construct the IRGs-related prognostic model to predict the overall survival (OS) of patients with HNSC. The RNA-seq data and clinical data were downloaded from The Cancer Genome Atlas database, and IRGs were obtained from the Immunology Database and Analysis Portal. Differentially expressed genes (DEGs) between HNSC and normal samples were identified, followed by integration with IRGs to screen differentially expressed IRGs. After univariate and multivariate proportional hazard regression analyses, an IRG-based risk model was constructed. Meanwhile, data chip of GSE65858 as the validation set to assess the predicted performance of established model. Next, univariate and multivariate Cox regression analyses were performed to identify the independent prognostic factor of HNSC, and the Nomogram model was developed to predict patient outcome. Furthermore, the correlation between immune cell infiltration and risk score was analyzed. A total of 65 differently expressed IRGs associated with prognosis of HNSC were screened, and finally a 26-gene IRG signature was identified to construct a prognostic prediction model. The AUC of ROC curve was 0.750. Survival analysis showed that patients in the high-risk group had a worse prognosis. Independent prognostic analysis showed that risk score could be considered as an independent predictor for HNSC prognosis. Nomogram assessment showed that the model had high reliability for predicting the survival of patients with HNSC in 1, 2, 3 years. Ultimately, the abundance of B cells and CD4+ T cell infiltration in HNSC showed negative correlations with risk score. Our IRG-based prognostic risk model may be used to estimate the prognosis of HNSC patients.

Antimicrobial effects of three herbs (Brassica juncea, Forsythia suspensa, and Inula britannica) on membrane permeability and apoptosis in Salmonella.

AIMS: This study aimed synergistic effects of three herbs in Salmonella via increased membrane permeability and apoptosis. METHODS AND RESULTS: Using high-performance liquid chromatography, four types of phenylethyl glycosides and a lignan were detected in the herb mixture (Brassica juncea, Forsythia suspensa, and Inula britannica). During treatment with the herb mixture (1×, 2×, or 4× the MIC), viable cells decreased to 1·87 log CFU per ml (Salmonella Gallinarum) and 2·33 log CFU per ml (Salmonella Enteritidis) after 12 h of incubation according to inhibition of tricarboxylic acid cycle (P < 0·01). In addition, N-phenyl-1-naphthylamine uptake increased from 229·00 to 249·67 AU in S. Gallinarum and from 232·00 to 250·67 AU in S. Enteritidis (P < 0·05), whereas membrane potential decreased from 8855·00 to 3763·25 AU and from 8703·67 to 4300·38 AU, respectively. Apoptotic Salmonella cells were observed by confocal laser scanning microscopy and flow cytometry. Transmission electron microscopy observations with negative staining showed protein leakage from damaged Salmonella. CONCLUSIONS: These results showed the synergistic effect of the three herbs against avian pathogenic Salmonella induced by membrane damage and apoptosis. SIGNIFICANCE AND IMPACT OF THE STUDY: Salmonella causes enormous economic losses in the poultry industry. These results indicated that potency of natural antimicrobial agents due to apoptosis in Salmonella.

Tuning the hysteresis of a metal-insulator transition via lattice compatibility.

Structural phase transitions serve as the basis for many functional applications including shape memory alloys (SMAs), switches based on metal-insulator transitions (MITs), etc. In such materials, lattice incompatibility between transformed and parent phases often results in a thermal hysteresis, which is intimately tied to degradation of reversibility of the transformation. The non-linear theory of martensite suggests that the hysteresis of a martensitic phase transformation is solely determined by the lattice constants, and the conditions proposed for geometrical compatibility have been successfully applied to minimizing the hysteresis in SMAs. Here, we apply the non-linear theory to a correlated oxide system (V1-xWxO2), and show that the hysteresis of the MIT in the system can be directly tuned by adjusting the lattice constants of the phases. The results underscore the profound influence structural compatibility has on intrinsic electronic properties, and indicate that the theory provides a universal guidance for optimizing phase transforming materials.

Clinical significance of serum EGFR gene mutation and serum tumor markers in predicting tyrosine kinase inhibitor efficacy in lung adenocarcinoma.

OBJECTIVE: To study the clinical significance of serum epidermal growth factor receptor (EGFR) gene mutation and serum tumor markers in the prediction of tyrosine kinase inhibitor (TKI) efficacy in patients with lung adenocarcinoma. METHODS: Ninety patients with pathologically diagnosed lung adenocarcinoma were enrolled. Further, 51 out of 90 patients received the EGFR-TKI therapy, oral gefitinib. The correlations among serum EGFR gene mutations in exons 18-21, serum tumor markers such as carcinoembryonic antigen (CEA), carbohydrate antigen 24-2 (CA24-2), carbohydrate antigen 125, carbohydrate antigen 15-3 as well as carbohydrate antigen 19-9 (CA19-9) levels, and EGFR-TKI efficacy were determined. RESULTS: There was a high consistency of EGFR gene mutation rate between serum and tissue samples. The serum EGFR gene mutation rate in female patients or non-smokers was significantly higher than that in male patients or smokers, respectively. Serum CA19-9, CA24-2, and CEA levels were significantly correlated with serum EGFR mutation. After receiving gefitinib, the progression-free survivals (PFSs) of patients with high serum CEA level, high serum CA19-9 level, or serum EGFR gene mutation were significantly higher than those of normal patients, respectively. The PFSs were significantly prolonged in patients with EGFR gene mutation and high serum CEA level or patients with EGFR gene mutation and high serum CA19-9 level compared with those in patients with one abnormal biomarker and normal patients. CONCLUSION: Combined detection of EGFR gene mutations as well as CA19-9 and CEA levels in peripheral blood can predict the efficacy of EGFR-TKI in the treatment of patients with lung adenocarcinoma.

Immunoexpression of aquaporins 1, 2, 3 and 4 in kidney of yak (Bos grunniens) on the Qinghai-Tibetan Plateau.

Aquaporins (AQP) 1, 2, 3 and 4 belong to the aquaporin water channel family and play an important role in urine concentration by reabsorption of water from renal tubule fluid. Renal AQPs have not been reported in the yak (Bos grunniens), which resides in the Qinghai Tibetan Plateau. We investigated AQPs 1-4 expressions in the kidneys of Yak using immunohistochemical staining. AQP1 was expressed mainly in the basolateral and apical membranes of the proximal tubules and descending thin limb of the loop of Henle. AQP2 was detected in the apical plasma membranes of collecting ducts and distal convoluted tubules. AQP3 was located in the proximal tubule, distal tubule and collecting ducts. AQP4 was located in the collecting ducts, distal straight tubule, glomerular capillaries and peritubular capillaries. The expression pattern of AQPs 1-4 in kidney of yak was different from other species, which possibly is related to kidney function in a high altitude environment.

[Prenatal diagnosis of women with an adverse reproductive history using both traditional karyotyping and SNP-array].

Objective: To explore the occurrence of fetal chromosomal abnormalities among pregnant women with an adverse reproductive history using traditional karyotyping and single nucleotide polymorphism microarray (SNP-array) technology. Methods: Totally 94 in 2 163 (4.35%) cases of singleton pregnant women with an adverse reproductive history were performed amniocentesis in Jinhua Maternal and Child Health Care Hospital from June 2015 to June 2017. Traditional karyotyping and SNP-array were employed simultaneously for prenatal diagnosis, and the detection rates of the two methods were compared. Results: All of the 94 specimens were successfully analyzed, 11 cases were found with chromosomal anomaly, the overall detection rate was 11.7%(11/94). Seven (7.4%,7/94) abnormalities cases were detected by karyotyping, and 7(7.4%) by SNP-array. The karyotyping results of trisomy 21, and 45,X and the deletion of chromosome 13 were consistent with SNP-array. Only 3 (3.2%, 3/94) microdeletion/duplications (the sizes of duplications and deletions were between 422.4-1 708.4 kb) and 1 (1/4) loss of heterozygosity were detected by SNP-array, but were missed by karyotyping. Furthermore, 2 cases' copy number variation were found pathogenic gene related, while the other 2 were considered benign or variant of uncertain significance. Four cases (4/7) of abnormalities were detected by karyotyping, while confirmed balanced translocation and inversion by SNP-array. All patients were informed and chosen to continue the pregnancy. Conclusions: The rate of abnormal fetal chromosomes in pregnant women with an adverse reproductive history is still high. SNP-array is a new molecular genetic technique, and combined with use of traditional karyotyping, it could improve the detection rate of fetal chromosomal abnormalities and reduce abortion rate, thus providing a basis for genetic counseling and prenatal diagnosis.

Changes in psychological health, subjective food intake ability and oral health-related quality of life during orthodontic treatment.

Assessing changes in patient's psychological health and oral health-related quality of life (OHRQoL) over time during orthodontic treatment may help clinicians to treat patients more carefully. To evaluate changes in mental health, self-reported masticatory ability and OHRQoL during orthodontic treatment in adults, this prospective study included 66 adults (30 men, 36 women; mean age, 24·2 ± 5·2 years). Each patient completed the Korean versions of the State-Trait Anxiety Inventory, Zung Self-Rating Depression Scale, Rosenberg self-esteem scale, key subjective food intake ability (KFIA) test for five key foods and Oral Health Impact Profile-14 (OHIP-14K) at baseline (T0), 12 months after treatment initiation (T1) and debonding (T2). All variables changed with time. Self-esteem and the total OHIP-14K score significantly decreased and increased, respectively, at T1, with a particular increase in the psychological and social disabilities scores. There were no significant differences in any questionnaire scores before and after treatment. The total OHIP-14K score was positively correlated with trait anxiety and depression, and negatively correlated with self-esteem and KFIA at T0, regardless of the treatment duration. Older patients showed a significant increase in the total OHIP-14K score at T1 and T2. OHRQoL worsened with an increase in the treatment duration. Our results suggest that OHRQoL temporarily deteriorates, with the development of psychological and social disabilities, during orthodontic treatment. This is related to the baseline age, psychological health and self-reported masticatory function. However, patients recover once the treatment is complete.

[Feasibility of the 2014 European guidelines risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy in Chinese patients].

Objective: Exploring the feasibility of the 2014 European Society of Cardiology(ESC)guideline's risk prediction model for sudden cardiac death in hypertrophic cardiomyopathy (HCM Risk-SCD) in Chinese patients. Methods: The study population consisted of a consecutive cohort of 172 Chinese patients with HCM without prior sudden cardiac death (SCD) event who were in patients in Nanjing Drum Tower Hospital from December 2010 to October 2015.The endpoint event was a composite of SCD and appropriate implantable cardioverter-defibrillator (ICD) therapy.Clinical data were collected to calculate the 5-year SCD risk using the HCM Risk-SCD formula and to observe the actual risk during the follow-up.Receiver operating characteristic curves (ROC) and the area under curve (AUC) were calculated for the HCM Risk-SCD and risk stratification methods of the 2011 American Heart Association (AHA) guideline. Results: During follow-up of (2.69±1.36) years, five patients achieved the endpoint event.The predicated rate of SCD event using HCM Risk-SCD was (2.36±1.73)%, (1.93±0.78)%, (5.18±0.65)%, (8.77±2.38)% for all patients, low-risk group, medium-risk group and high-risk group respectively.However, the actual rate of SCD event was 2.91%, 1.27%, 25.00% and 14.29%, respectively.The AUC of 2014 ESC guideline and 2011 AHA guidelinewas 0.93(95%CI 0.85-1.00) vs. 0.87(95%CI 0.75-0.98). Conclusion: The predicated rate of SCD event calculated by HCM Risk-SCD is lower than actual rate of SCD, but the prediction efficiency and indication for ICD implantation of HCM Risk-SCD are better than that of 2011 AHA guideline.

Subjective food intake ability related to oral health-related quality of life and psychological health.

Reduced food intake ability can restrict an individual's choice of foods and might have a significant impact on the individual's quality of life and mental health. The aim of this study was to evaluate the correlations between self-reported masticatory ability and oral health-related quality of life (OHRQOL) and psychological health. The study included 72 (26 men, 46 women) adults with a mean age of 26·4 ± 8·6 years. Each participant completed the key subjective food intake ability (KFIA) test for five key foods, the Korean version of the Oral Health Impact Profile-14 (OHIP-14K) and three questionnaires for measuring anxiety, depression and self-esteem. The participants were distributed into two groups by sex (a mean age of 23·9 ± 5·2 for men and 27·9 ± 9·8 for women) and by the median KFIA score. There were no significant differences in any of the variables according to sex. Thirty-two participants (12 men, 20 women) in the lower KFIA group had a higher total OHIP-14K (P < 0·001) and depression level (P < 0·05) than the 40 participants (14 men, 26 women) in the higher KFIA group. As the KFIA decreased, OHRQOL worsened (P < 0·001) and depression increased (P < 0·05). Participants with lower KFIA scores were more than 4·3 times as likely as to have a poor OHRQOL than the reference group (odds ratio, 4·348; 95% confidence interval, 1·554-12·170, P < 0·01). Lower subjective food intake ability is associated with a poor oral health-related quality of life and higher depression level.

Anomalous magnetoresistance in the spinel superconductor LiTi2O4.

LiTi2O4 is a unique compound in that it is the only known spinel oxide superconductor. The lack of high quality single crystals has thus far prevented systematic investigations of its transport properties. Here we report a careful study of transport and tunnelling spectroscopy in epitaxial LiTi2O4 thin films. An unusual magnetoresistance is observed which changes from nearly isotropic negative to prominently anisotropic positive as the temperature is decreased. We present evidence that shows that the negative magnetoresistance likely stems from the suppression of local spin fluctuations or spin-orbit scattering centres. The positive magnetoresistance suggests the presence of an orbital-related state, also supported by the fact that the superconducting energy gap decreases as a quadratic function of magnetic field. These observations indicate that the spin-orbital fluctuations play an important role in LiTi2O4 in a manner similar to high-temperature superconductors.

TLR2-dependent amelioration of allergic airway inflammation by parasitic nematode type II MIF in mice.

In our previous studies, the recombinant type II macrophage migration inhibitory factor homologue (rAs-MIF) secreted from Anisakis simplex suppressed experimental inflammation mouse model through IL-10 production and CD4(+)CD25(+)Foxp3(+) T-cell recruitment. Also, TLR2 gene expression was significantly increased following rAs-MIF treatment. To know the relation between TLR2 and amelioration mechanisms of rAs-MIF, we induced allergic airway inflammation by ovalbumin and alum with or without rAs-MIF under TLR2 blocking systems [anti-TLR2-specific antibody (α-mTLR2 Ab) treatment and using TLR2 knockout mice]. As a result, the amelioration effects of rAs-MIF in allergic airway inflammation model (diminished inflammation and Th2 response in the lung, increased IL-10 secretion, CD4(+)CD25(+)Foxp3(+) T-cell recruitment) were diminished under two of the TLR2 blocking model. The expression of TLR2 on the surface of lung epithelial cell was significantly elevated by rAs-MIF treatment or Pam3CSK (TLR2-specific agonist) treatment, but they might have some competition effect on the elevation of TLR2 expression. In addition, the elevation of IL-10 gene expression by rAs-MIF treatment was significantly inhibited by α-mTLR2 Ab or Pam3CSK pretreatment. In conclusion, anti-inflammatory effects of the rAs-MIF on OVA-induced allergic airway inflammation might be closely related to TLR2.

Galectin isolated from parasite inhibits remission of experimental autoimmune encephalomyelitis by up-regulating autoantibody.

Recently, parasite infections or parasite-derived products have been suggested as a therapeutic strategy with suppression of immunopathology, which involves the induction of regulatory T cells or/and T helper type 2 (Th2) responses. In a recent study, researchers reported that constructed recombinant galectin (rTl-gal) isolated from an adult worm of the gastrointestinal nematode parasite Toxascaris leonina attenuated clinical symptoms of inflammatory bowel disease in mice treated with dextran sulphate sodium. Noting the role of rTl-gal in inflammatory disease, we attempted to investigate the effect of the parasite via its rTl-gal on neuronal autoimmune disease using experimental autoimmune encephalomyelitis (EAE), a mouse inflammatory and demyelinating autoimmune disease model of human multiple sclerosis. In this model, rTl-gal-treated experimental autoimmune encephalomyelitis (EAE) mice failed to recover after the peak of the disease, leading to persistent central nervous system (CNS) damage, such as demyelination, gliosis and axonal damage. Further, rTl-gal-treated EAE mice markedly increased the number of CD45R/B220(+) B cells in both infiltrated inflammation and the periphery, along with the increased production of autoantibody [anti-myelin oligodendrocyte glycoprotein (MOG)35-55 ] in serum at chronic stage. Upon antigen restimulation, rTl-gal treatment affected the release of overall cytokines, especially interferon (IFN)-γ and tumour necrosis factor (TNF)-α. Our results suggest that galectin isolated from a gastrointestinal parasite can deliver a harmful effect to EAE contrary to its beneficial effect on inflammatory bowel disease.

Short communication: Physicochemical and antioxidant properties of milk supplemented with red ginseng extract.

This study investigated the effect of red ginseng extract (RGE) on the physicochemical properties, sensory test, and antioxidant activity of milk. The milk samples with RGE added at 0.5, 1, 1.5, and 2% were analyzed during storage at 4°C. The physicochemical properties included composition of milk, pH, titratable acidity, and color. The antioxidant activity of milk samples was determined using the 2,2-diphenyl-1-picrylhydrazyl method, ß-carotene bleaching assay, and ferric thiocyanate assay. An increase in the amount of RGE in milk resulted in an increase of lactose and total solids content, titratable acidity, and a* and b* values, whereas fat and protein contents remained unchanged. Also, pH and L* value decreased. The antioxidant activity of milk samples supplemented with RGE was higher than that of the control sample. Sensory evaluation was performed using a quantitative descriptive analysis. Two types of samples were used: (1) sterilized milk fortified with RGE (0.5, 1, 1.5, and 2%) and (2) 2% RGE, 2% RGE with oligosaccharide, and 2% RGE with oligosaccharide and cyclodextrin. The addition of oligosaccharide and cyclodextrin could effect an increase of sweetness, a decrease of bitterness and flavor of RGE, and aftertaste. Therefore, milk supplemented with RGE could be useful as a functional food.

Effects of low dose pre-irradiation on hepatic damage and genetic material damage caused by cyclophosphamide.

OBJECTIVE: Cyclophosphamide (CTX) can attack tumour cells, but can also damage the other cells and microstructures of an organism at different levels, such as haematopoietic cells, liver cells, peripheral lymphocyte DNA, and genetic materials. Low dose radiation (LDR) can induce general adaptation reaction. In this study, we explore the effects of low dose radiation on hepatic damage and genetic material damage caused by CTX. MATERIALS AND METHODS: Mice were implanted subcutaneously with S180 cells in the left groin (control group excluded). On days 8 and 11, mice of the LDR and LDR+CTX groups were given 75 mGy of whole-body γ-irradiation; whereas mice of the CTX and LDR+CTX groups were injected intraperitoneally with 3.0 mg of CTX. All mice were sacrificed on day 13. DNA damage of the peripheral lymphocytes, alanine aminotransferase (ALT) activity, total protein (TP), albumin (ALB) of the plasma, malonyl-dialdheyde (MDA) content, superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activity of the hepatic homogenate, and micronucleus frequency (MNF) of polychromatoerythrocytes in the bone marrow were analysed. RESULTS: The control group had the lowest MDA content and the highest SOD and GSH-PX activity, whereas the CTX group had the highest MDA content and the lowest SOD and GSH-PX activity. Compared with the CTX group, the MDA content decreased significantly (p < 0.01) and the SOD and GSH-PX activity increased significantly (p < 0.05) in the LDR+CTX group. TP and ALB in control group were higher than that of the other groups. Compared with the sham-irradiated group, TP and ALB in the LDR group elevated significantly (p < 0.05). The control group had the lightest DNA damage, whereas the CTX group had the severest. DNA damage in LDR+CTX group was much lighter compared with that of the CTX group (p < 0.05). MNF in the CTX group increased significantly compared with the control and the sham-irradiated groups (p < 0.01). Compared with the CTX group, MNF in LDR+CTX group had a tendency of decline, but without statistical significance (p > 0.05). CONCLUSIONS: Pre-chemotherapeutic LDR can induce the activities of anti-oxidative enzymes and promote the elimination of free radicles to alleviate the damaging effects of oxidative stress to hepatic tissue caused by high-dose CTX. At the same time, LDR has no obvious effect on the ALT activity of plasma, but may have protective effect on the protein synthesis function of the liver. High-dose CTX chemotherapy can cause DNA damage of peripheral lymphocytes; however, LDR before chemotherapy may have certain protective effect on DNA damage. Moreover, CTX has potent mutagenic effect; however, LDR may have no protective effect against the genetic toxicity of CTX chemotherapy.

Androgen receptor-mediated apoptosis in bovine testicular induced pluripotent stem cells in response to phthalate esters.

The androgen receptor (AR) has a critical role in promoting androgen-dependent and -independent apoptosis in testicular cells. However, the molecular mechanisms that underlie the ligand-independent apoptosis, including the activity of AR in testicular stem cells, are not completely understood. In the present study, we generated induced pluripotent stem cells (iPSCs) from bovine testicular cells by electroporation of octamer-binding transcription factor 4 (OCT4). The cells were supplemented with leukemia inhibitory factor and bone morphogenetic protein 4, which maintained and stabilized the expression of stemness genes and pluripotency. The iPSCs were used to assess the apoptosis activity following exposure to phthalate esters, including di (2-ethyhexyl) phthalates, di (n-butyl) phthalate, and butyl benzyl phthalate. Phthalate esters significantly reduced the expression of AR in iPSCs and induced a higher ratio of BAX/BCL-2, thereby favoring apoptosis. Phthalate esters also increased the expression of cyclin-dependent kinase inhibitor 1 (p21(Cip1)) in a p53-dependent manner and enhanced the transcriptional activity of p53. The forced expression of AR and knockdown of p21(Cip1) led to the rescue of the phthalate-mediated apoptosis. Overall, this study suggests that testicular iPSCs are a useful system for screening the toxicity of environmental disruptors and examining their effect on the maintenance of stemness and pluripotency, as well as for identifying the iPSC signaling pathway(s) that are deregulated by these chemicals.

Factors affecting accurate drill sleeve insertion in locking compression plates.

BACKGROUND: Accurate positioning of locking screws depends on accurate insertion of the drill sleeve into the locking compression plate (LCP). The purpose of the present study was to determine factors affecting accurate drill sleeve insertion. HYPOTHESIS: Tilting and shallow locking screw holes and combination-type holes make it difficult to insert the drill sleeve in the LCP. MATERIALS AND METHODS: Twenty-seven 3.5mm LCP metaphyseal insertion holes were selected (Philos(®), LPHP(®), DMTP(®), low-band DMTP(®) [Synthes, Solothurn, Switzerland]). Two orthopedic surgeons checked the time taken for accurate insertion of the drill sleeve into the plate. Variables relating to LCP drill sleeve insertion time were analyzed. RESULTS: It took an average 6.6seconds to insert the drill sleeve accurately in the holes. Insertion time increased with the tilt of the screw hole but not with shallowness. Insertion time in combination-type holes was longer (8.8seconds) than in single locking holes (5.6seconds). DISCUSSION: Tilted screw holes and combination-type holes affect the insertion of the drill sleeve into 3.5mm LCPs. LEVEL OF EVIDENCE: Level IV, experimental study.

Effects of Lactobacillus rhamnosus on asthma with an adoptive transfer of dendritic cells in mice.

AIM: This study was designed to investigate whether the protective effects of Lactobacillus rhamnosus (Lcr35) on allergic asthma are associated with the adoptive transfer of dendritic cells (DCs) and regulatory T cells (Tregs), using a mouse experimental model of asthma. METHODS AND RESULTS: BALB/c mice were orally administered Lcr35 or intravenously treated with in vivo Lcr35-treated DCs daily and were then sensitized and challenged with ovalbumin (OVA) in accordance with a model of asthma protocol. Both the oral application of Lcr35 and intravenous administration of Lcr35-treated DCs suppressed all aspects of the asthmatic response, including bronchial hyperresponsiveness (BHR), total cell counts in the bronchoalveolar lavage (BAL) fluid, the production of OVA-specificimmunoglobulin E (IgE), and pulmonary eosinophilic inflammation. The mechanism of action of Lcr35 is related to Tregs, which suppress the Th2 response in the respiratory organs, and this is mediated by DCs in the mouse model of asthma. CONCLUSIONS: These results confirm that the mechanism underlying the effects of Lcr35 on asthma involves the adoptive transfer of DCs. SIGNIFICANCE AND IMPACT OF THE STUDY: This finding broadens the possibility that Lcr35 has potential as an alternative therapeutic approach to the treatment of human asthma.

Polychlorinated biphenyls (PCBs) decrease the placental syncytiotrophoblast volume and increase Placental Growth Factor (PlGF) in the placenta of normal pregnancy.

INTRODUCTION: Polychlorinated biphenyls (PCBs) are a class of biologically active, highly stable compounds. Exposure risks include consumption of fatty fish, meat, dairy products and human breast milk, as well as environmental and occupational settings. Numerous reports have described PCB-dependent adverse effects on human fetal growth, including increased risk for IUGR, changes in endocrine function and hormone metabolism, and immunosuppressive and neurological deficits. Here we test the prediction that in utero PCB exposure adversely effects placental morphology, potentially leading to placental insufficiency en route to fetal growth restriction. METHODS: PCB homologs (10) were measured in the maternal and fetal blood of a small cohort of normotensive pregnancies (22) by gas chromatography-mass spectrometry. PCB levels were compared with angiogenesis associated proteins Placental Growth Factor (PlGF) and sFlt-1, determined by ELISA, and the total estimated syncytiotrophoblast (ST) volume. RESULTS: Significant associations between PCB exposure and both PlGF and ST volume were identified. DISCUSSION: PCB effects on placenta morphology and predicted function are discussed. CONCLUSION: These results demonstrate that the human placenta, including ST, is a target of PCB toxicity, and that current environmental PCB exposure levels are a risk to reproductive health.