Publications by authors named "Yinglei Xu"

26 Publications

  • Page 1 of 1

Chitosan nanoparticles attenuate intestinal damage and inflammatory responses in LPS-challenged weaned piglets via prevention of IκB degradation.

J Anim Physiol Anim Nutr (Berl) 2021 Nov 24. Epub 2021 Nov 24.

Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology • College of Veterinary Medicine, Zhejiang A&F University, Hangzhou, China.

Chitosan nanoparticles (CNP), widely applied as oral drug/gene/vaccine carrier, were found to have anti-inflammatory properties. In this study, the effects of CNP on lipopolysaccharide (LPS)-induced intestinal damage in weaned piglets and the related mechanisms were investigated. Twenty-four weaned piglets (Duroc × Landrace × Yorkshire, 21 ± 2 day of age, initial mass: 8.58 ± 0.59 kg) were randomly assigned into four groups: control, LPS, CNP and CNP + LPS. The control and LPS groups were fed a corn-soybean meal-based control diet, whereas the CNP and CNP + LPS groups were fed a control diet supplemented with 400 mg/kg CNP. After 28 days of feeding, piglets in LPS and CNP + LPS groups were injected with LPS (100 μg/kg); meanwhile, the piglets in control and CNP groups were injected with sterile saline. After 4 h from the LPS challenge, pigs were sacrificed to collect the intestinal samples for analysis. The results showed that CNP could attenuate the intestinal damages and inflammatory response stimulated by LPS treatment. LPS induced dramatically higher levels of CD177 neutrophils invasion in jejunum mucosa (p < 0.01), which accompanied by increased secretion of marks of inflammation (p < 0.01) compared with the control, whereas CNP administration obviously inhibited LPS-induced CD177 neutrophils invasion (p < 0.01) and secretion of marks of inflammation, such as interleukin-8 (p < 0.05), intercellular adhesion molecule-1 (p < 0.05) secretion in jejunum mucosa compared with LPS group. Moreover, CNP was shown to inhibit IκB-α degradation in cytoplasm, which resulted in reduced nuclear translocation of NF-κB p65 in LPS-challenged piglets. These findings suggest that CNP attenuates intestinal damage and inflammatory responses in LPS-challenged weaned piglets by impairing the NF-κB signalling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jpn.13664DOI Listing
November 2021

The Value of Circulating microRNAs for Diagnosis and Prediction of Preeclampsia: a Meta-analysis and Systematic Review.

Reprod Sci 2021 Nov 24. Epub 2021 Nov 24.

Department of Medical Genetic, The Affiliated Hospital of Qingdao University, 16 Jiangsu Road, Qingdao, 266003, China.

Preeclampsia (PE) is one of the main causes of maternal death worldwide, but our understanding of the molecular characteristics of disease progression is limited. In this meta-analysis, we aimed to assess the value of peripheral blood microRNAs (miRNAs) as diagnostic and predictive markers of PE. We screened PubMed, Web of Science, and Embase databases; searched articles about "miRNAs and PE" up to November 30, 2020; and conducted biological information and subgroup analysis. We used QUADAS-2 (quality assessment of diagnostic accuracy studies-2) to evaluate the included articles by two independent reviewers, calculated the combined diagnostic and predictive indicators using the random effects model, explored the sources of potential heterogeneity through subgroup analysis, and evaluated publication bias using Deeks' funnel plot asymmetry test using Stata 14.0 and Review Manager 5.3 software. Forty-three miRNAs from 15 studies, including 2042 healthy controls and 2685 PE patients, had a pooled sensitivity of 0.86 (95% CI: 0.81-0.90), specificity of 0.89 (95% CI: 0.85-0.92), and an AUC of 0.94 (95% CI: 0.91-0.96). Moreover, before 20 weeks of gestation, the combined sensitivity was 0.86 (95% CI: 0.75-0.92), and the specificity was 0.90 (95% CI: 0.83-0.95), which indicated that some of the circulating miRNAs had changed significantly before the clinical symptoms appeared in PE patients. Circulating miRNAs have high diagnostic and predictive accuracy and may be used as non-invasive biomarkers for the diagnosis and prediction of PE. However, a large sample prospective study is still needed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s43032-021-00799-6DOI Listing
November 2021

Integrating Serum Metabolome and Gut Microbiome to Evaluate the Benefits of Lauric Acid on Lipopolysaccharide- Challenged Broilers.

Front Immunol 2021 15;12:759323. Epub 2021 Oct 15.

College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang Agricultural and Forestry University, Hangzhou, China.

Lauric acid (LA) is a crucial medium-chain fatty acid (MCFA) that has many beneficial effects on humans and animals. This study aimed to investigate the effects of LA on the intestinal barrier, immune functions, serum metabolism, and gut microbiota of broilers under lipopolysaccharide (LPS) challenge. A total of 384 one-day-old broilers were randomly divided into four groups, and fed with a basal diet, or a basal diet supplemented with 75 mg/kg antibiotic (ANT), or a basal diet supplemented with 1000 mg/kg LA. After 42 days of feeding, three groups were intraperitoneally injected with 0.5 mg/kg - derived LPS (LPS, ANT+LPS and LA+LPS groups) for three consecutive days, and the control (CON) group was injected with the same volume of saline. Then, the birds were sacrificed. Results showed that LA pretreatment significantly alleviated the weight loss and intestinal mucosal injuries caused by LPS challenge. LA enhanced immune functions and inhibited inflammatory responses by upregulating the concentrations of immunoglobulins (IgA, IgM, and IgY), decreasing IL-6 and increasing IL-4 and IL-10. Metabolomics analysis revealed a significant difference of serum metabolites by LA pretreatment. Twenty-seven serum metabolic biomarkers were identified and mostly belong to lipids. LA also markedly modulated the pathway for sphingolipid metabolism, suggesting its ability to regulate lipid metabolism. Moreover,16S rRNA analysis showed that LA inhibited LPS-induced gut dysbiosis by altering cecal microbial composition (reducing , and , and increasing and ), and modulating the production of volatile fatty acids (VFAs). Pearson's correlation assays showed that alterations in serum metabolism and gut microbiota were strongly correlated to the immune factors; there were also strong correlations between serum metabolites and microbiota composition. The results highlight the potential of LA as a dietary supplement to combat bacterial LPS challenge in animal production and to promote food safety.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2021.759323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8554146PMC
October 2021

A review of key cytokines based on gene polymorphism in the pathogenesis of pre-eclampsia.

Am J Reprod Immunol 2021 Oct 2:e13503. Epub 2021 Oct 2.

Medical genetic department, The Affiliated Hospital of Qingdao University, Qingdao, China.

Although a number of theories have been suggested, including roles for oxidative stress, an abnormal maternal-fetal interface, and genetic and environmental factors, the etiopathology of pre-eclampsia (PE) remains unclear. Maternal immune tolerance is important for maintaining pregnancy, and researchers have increasingly focused on the critical roles of cytokines in the pathogenesis of PE in recent years. The assessment of candidate genetic polymorphisms in PE could partially elucidate the mechanisms of susceptibility to disease, and contribute to seeking for new diagnosis and treatment methods of PE. PE can lead to severe complications, and even the death of both mother and fetus. Although the complex pathology is not yet clear, some evidence suggested that the occurrence of PE is related to inflammatory factors. We reviewed the current understandings of roles of cytokines in PE, and provided an extensive overview of the role of single nucleotide chain polymorphisms (SNPs) in the genes potentially underlying the pathophysiology of PE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/aji.13503DOI Listing
October 2021

Inulin and isomalto-oligosaccharide alleviate constipation and improve reproductive performance by modulating motility-related hormones, short-chain fatty acids, and feces microflora in pregnant sows.

J Anim Sci 2021 Oct;99(10)

Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang Provincial Engineering Laboratory for Animal Health and Internet Technology, College of Animal Science and Technology·College of Veterinary Medcine, Zhejiang A & F University, Hangzhou 311300, China.

Constipation in gestating and lactating sows is common and the inclusion of dietary fiber may help to alleviate this problem. We investigated the effects of inulin (INU) and isomalto-oligosaccharide (IMO), two sources of soluble dietary fiber, on gastrointestinal motility-related hormones, short-chain fatty acids (SCFA), fecal microflora, and reproductive performance in pregnant sows. On day 64 of gestation, 30 sows were randomly divided into three groups and fed as follows: a basal diet, a basal diet with 0.5% INU, and a basal diet with 0.5% IMO. We found that INU and IMO significantly modulated the levels of gastrointestinal motility-related hormones, as evidenced by an increase in substance P (P < 0.05), and a decrease in the vasoactive intestinal peptide concentrations (P < 0.05), indicating the capacity of INU and IMO to alleviate constipation. Furthermore, IMO enhanced the concentrations of acetic, propionic, isobutyric, butyric, isovaleric, and valeric acids in the feces (P < 0.05). High-throughput sequencing showed that IMO and INU increased the fecal microflora α- and β-diversity (P < 0.05). Methanobrevibacter was more abundant (P < 0.05), whereas the richness of Turicibacter was lower in the INU and IMO groups than in the control group (P < 0.05). In addition, IMO significantly increased litter size (P < 0.05). Overall, our findings indicate that INU and IMO can relieve constipation, optimize intestinal flora, and promote reproductive performance in pregnant sows.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jas/skab257DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493891PMC
October 2021

Effects of Bacillus subtilis and Bacillus licheniformis on growth performance, immunity, short chain fatty acid production, antioxidant capacity, and cecal microflora in broilers.

Poult Sci 2021 Sep 26;100(9):101358. Epub 2021 Jun 26.

Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang Provincial Engineering Laboratory for Animal Health and Internet Technology, College of Animal Science and Technology College of Veterinary Medicine, Zhejiang Agriculture & Forestry University, Hangzhou 311300, China. Electronic address:

This study investigated the effects of dietary supplementation with Bacillus subtilis (B. subtilis) or Bacillus licheniformis (B. licheniformis) on growth performance, immunity, antioxidant capacity, short chain fatty acid (SCFA) production, and the cecal microflora in broiler chickens. In total, 360 male, 1-day-old Cobb 500 birds were randomly divided into 3 groups: the control group was fed a basal diet; the B. subtilis group was fed a basal diet supplemented with 1.5 × 10 CFU/kg B. subtilis; the B. licheniformis group was fed a basal diet supplemented with 1.5 × 10 CFU/kg B. licheniformis. Results showed that chickens supplemented with either B. subtilis or B. licheniformis had comparatively higher (P < 0.05) body weight and average daily gain, whereas no difference (P > 0.05) was observed in feed efficiency. Concentrations of serum IgA, IgY, and IgM, as well as anti-inflammatory IL-10 were significantly increased (P < 0.05), and proinflammatory IL-1β and IL-6 were significantly decreased (P < 0.05) by B. subtilis or B. licheniformis supplementation. Moreover, chickens fed with diets supplemented by either B. subtilis or B. licheniformis had greater antioxidant capacity, indicated by the notable increases (P < 0.05) in glutathione peroxidase, superoxide dismutase, and catalase, along with decrease (P < 0.05) in malondialdehyde. Compared to the control group, levels of SCFA, excluding acetic and propionic acid, in cecal content had improved (P < 0.05) by adding B. licheniformis, and significant increase (P < 0.05) in acetic and butyric acid was observed with B. subtilis supplementation. Microbial analysis showed that both B. subtilis or B. licheniformis supplementation could increase butyrate-producing bacteria such as Alistipes and Butyricicoccus, and decrease pathogenic bacteria such as the Synergistetes and Gammaproteobacteria. In summary, dietary supplemented with B. subtilis or B. licheniformis improved growth performance, immune status, and antioxidant capacity, increased SCFA production, and modulated cecal microbiota in chickens. Moreover, B. licheniformis was more effective than B. subtilis with the same supplemental amount.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psj.2021.101358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350532PMC
September 2021

Effects of - and spp.-Based Potential Probiotics on the Growth Performance, Intestinal Morphology, Immune Responses, and Caecal Microbiota in Broilers.

Antibiotics (Basel) 2021 May 24;10(6). Epub 2021 May 24.

Key Laboratory of Applied Technology on Green-Eco-Health Animal Husbandry of Zhejiang Province, College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang A & F University, Hangzhou 311300, China.

We aimed to investigate the effects of -, -, and -based potential probiotics on the growth performance, intestinal morphology, immune responses, and caecal short chain fatty acids (SCFAs) and microbial structure in broiler chickens. Three treatment groups containing a total of 1200 one-day-old AA broilers were included: birds fed with a basal diet only (Con), birds fed with added 10 probiotics cfu/kg (ProL), and birds fed with added 10 probiotics cfu/kg (ProH). The dietary probiotics significantly improved the final and average body weights and serum immunoglobulins A, M, and Y. The probiotics also enhanced the ileal morphology and improved the caecal acetate, butyrate, and propionate contents. Furthermore, 16S rRNA sequencing revealed that dietary compound probiotics modulated the caecal microflora composition as follows: (1) all birds shared 2794 observed taxonomic units; (2) treatment groups were well separated in the PCA and PCoA analysis; (3) the relative abundance of , _UCG-014, , , [_coprostanoligenes_group], []_torques_group, and significantly varied between treatments. The compound probiotics improved the growth performance, serum immune responses, the ratio of ileal villus height to crypt depth, and major caecal SCFAs in broiler chickens. The dietary -, -, and -based probiotics improved overall broiler health and would benefit the poultry industry.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antibiotics10060624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225201PMC
May 2021

Polymorphisms of TGF-β1 and TGF-β3 in Chinese women with gestational diabetes mellitus.

BMC Pregnancy Childbirth 2020 Dec 7;20(1):759. Epub 2020 Dec 7.

Department of Endocrinology and Metabolism, the Affiliated Hospital of Qingdao University, Qingdao, 266000, China.

Background: Gestational diabetes mellitus (GDM) is a pregnancy-specific carbohydrate intolerance Which can cause a large number of perinatal and postpartum complications. The members of Transforming growth factor-β (TGF-β) superfamily play key roles in the homeostasis of pancreatic β-cell and may involve in the development of GDM. This study aimed to explore the association between the polymorphisms of TGF-β1, TGF-β3 and the risk to GDM in Chinese women.

Methods: This study included 919 GDM patients (464 with preeclampsia and 455 without preeclampsia) and 1177 healthy pregnant women. TaqMan allelic discrimination real-Time PCR was used to genotype the TGF-β1 (rs4803455) and TGF-β3 (rs2284792 and rs3917201), The Hardy-Weinberg equilibrium (HWE) was evaluated by chi-square test.

Results: An increased frequency of TGF-β3 rs2284792 AA and AG genotype carriers was founded in GDM patients (AA vs. AG + GG: χ = 6.314, P = 0.012, OR = 1.270, 95%CI 1.054-1.530; AG vs. GG + AA: χ = 8.545, P = 0.003, OR = 0.773, 95%CI 0.650-0.919). But there were no significant differences in the distribution of TGF-β1 rs4803455 and TGF-β3 rs3917201 between GDM and healthy women. In addition, no significant differences were found in allele and genotype frequencies among GDM patients with preeclampsia (PE).

Conclusions: The AA and AG genotype of TGF-β3 rs2284792 polymorphism may be significantly associated with increased risk of GDM in Chinese population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12884-020-03459-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720537PMC
December 2020

Compound heterozygous DYSF variants causing limb-girdle muscular dystrophy type 2B in a Chinese family.

J Gene Med 2020 11 28;22(11):e3272. Epub 2020 Sep 28.

Medical Genetic Department, The Affiliated Hospital of Qingdao University, Qingdao, China.

Background: The dysferlin gene or the DYSF gene encodes the Ca -dependent phospholipid-binding protein dysferlin, which belongs to the ferlin family and is associated with muscle membrane regeneration and repair. Variants in the DYSF gene are responsible for limb-girdle muscular dystrophy type 2B (LGMD2B), also called limb-girdle muscular dystrophy recessive 2 (LGMDR2), a rare subtype of muscular dystrophy involving progressive muscle weakness and atrophy. The present study aimed to identify the variants responsible for the clinical symptoms of a Chinese patient with limb girdle muscular dystrophies (LGMDs) and to explore the genotype-phenotype associations of LGMD2B.

Methods: A series of clinical examinations, including blood tests, magnetic resonance imaging scans for the lower legs, electromyography and muscle biopsy, was performed on the proband diagnosed with muscular dystrophies. Whole exome sequencing was conducted to detect the causative variants, followed by Sanger sequencing to validate these variants.

Results: We identified two compound heterozygous variants in the DYSF gene, c.1058 T>C, p.(Leu353Pro) in exon 12 and c.1461C>A/p.Cys487* in exon 16 in this proband, which were inherited from the father and mother, respectively. In silico analysis for these variants revealed deleterious results by PolyPhen-2 (Polymorphism Phenotyping v2; http://genetics.bwh.harvard.edu/pph2), SIFT (Sorting Intolerant From Tolerant; https://sift.bii.a-star.edu.sg), PROVEAN (Protein Variation Effect Analyzer; http://provean.jcvi.org/seq_submit.php) and MutationTaster (http://www.mutationtaster.org). In addition, the two compound heterozygous variants in the proband were absent in 100 control individuals who had an identical ethnic origin and were from the same region, suggesting that these variants may be the pathogenic variants responsible for the LGMD2B phenotypes for this proband.

Conclusions: The present study broadens our understanding of the mutational spectrum of the DYSF gene, which provides a deep insight into the pathogenesis of LGMDs and accelerates the development of a prenatal diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jgm.3272DOI Listing
November 2020

Protective roles and mechanisms of rosmarinic acid in cyclophosphamide-induced premature ovarian failure.

J Biochem Mol Toxicol 2020 Dec 25;34(12):e22591. Epub 2020 Jul 25.

Department of Gynecology, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University, Shanghai, China.

The aim of this study was to investigate the protective effect of rosmarinic acid (RA) in a premature ovarian failure (POF) mouse model and the potential mechanisms. The POF model was induced by a single intraperitoneal injection of 120 mg/kg cyclophosphamide (CP). Additionally, 40 mg/kg RA was administered for 7 days before CP injection. The concentration of sex hormones was determined by fluorescence immunohistochemistry. Histological analysis was performed after ovarian tissue sections were stained with hematoxylin and eosin. The expression of the NLRP3 inflammasome was examined by western blot analysis and polymerase chain reaction. The expression of apoptosis markers of cytochrome c and caspase-3 was also detected by western blot analysis and immunohistochemistry. The results showed that RA not only decreased the ovarian index in POF mice but also improved the abnormal secretion of reproductive hormones associated with POF. Treatment with RA suppressed the ovarian expression of the NLRP3 inflammasome and regulated the ovarian expression of apoptosis-related proteins. The results suggested that RA exhibited a protective effect against CP-induced POF potentially by suppressing apoptosis and the NLRP3 inflammasome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbt.22591DOI Listing
December 2020

WSSV proteins and DNA genome released by ultrasonic rupture can infect crayfish as effectively as intact virions.

J Virol Methods 2020 09 21;283:113917. Epub 2020 Jun 21.

Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology, College of Veterinary Medicine, Zhejiang Agriculture and Forestry University, Hangzhou 311300, China.

Proteins and nucleic acids from ultrasonically ruptured white spot syndrome virus (WSSV) can infect crayfish and cause death as effectively as intact WSSV virions. In this study, ultrasound was used to rupture the virus and the resulting suspension was filtered through a 50 nm membrane. Analysis by PCR and SDS-PAGE showed that both viral genes (VP19, VP26, VP28 and DNA polymerase) and proteins (VP15, VP19, VP26 and VP28) were present in the filtered solution. Electron microscopy showed that there were no intact virions in the filtered solution. When crayfish were injected with the filtered solution or with intact WSSV, the mortality in each group was 100 %. The same result was seen when crayfish were challenged orally with the filtered solution and intact WSSV. The filtered solution of ultrasonically ruptured virus, which contains viral proteins and residual DNA genome, can thus infect the host as effectively as intact virions. When the solution of viral proteins and residual DNA genome was digested with DNase I and then injected into crayfish, the survival rate was 100 %. We also found that, although viral proteins (except VP15) in the solution of ruptured virus were destroyed by treatment with DNase I, DNase I did not destroy the structural proteins of intact virions. A remaining viral protein in the DNase I-treated solution protects the DNA genome from degradation and we concluded that this protein is VP15, which is a DNA-binding protein. Our study highlights the extreme danger in producing vaccines from proteins obtained by ultrasonic rupture of viruses sincethe viral DNA genome is difficult to degrade and, if present, will lead to viral infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jviromet.2020.113917DOI Listing
September 2020

Hypomethylation of DNA promoter upregulates ADAMTS7 and contributes to HTR-8/SVneo and JEG-3 cells abnormalities in pre-eclampsia.

Placenta 2020 04 24;93:26-33. Epub 2020 Feb 24.

Medical Genetic Department, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China; Prenatal Diagnosis Center, The Affiliated Hospital of Qingdao University, Qingdao, 266003, China. Electronic address:

Introduction: Accumulating evidences have suggested a crucial role of epigenetics in the initiation and progression of pre-eclampsia (PE). Here, we studied the expression of the metalloproteinase ADAMTS7 and the methylation level of its promoter in PE placentas and investigated ADAMTS7 role in the pathogenesis of PE.

Methods: We first explored ADAMTS7 expression in PE and normal placentas by reverse transcription quantitative PCR (RT-qPCR), western blot, and immunohistochemistry. Methylation specific PCR (MSP) and bisulfite sequencing PCR (BSP) were performed to evaluate the methylation status of ADAMTS7 promoter. Treatment with 5'-Aza was used to induce demethylation and thereby to explore the direct relationship between promoter methylation and ADAMTS7 expression. CCK8 assay, colony formation assay, and trans-well assay were conducted to assess the viability, migration, and invasion of HTR-8/SVneo and JEG-3 cells.

Results: Our results showed that ADAMTS7 expression was upregulated in PE placentas. Methylation analysis revealed a hypomethylated status of ADAMTS7 promoter regions in PE placenta tissues. Besides, demethylation induced by 5'-Aza directly restored ADAMTS7 expression in trophoblast cells. Finally, overexpression of ADAMTS7 inhibited viability, migration, and invasion of HTR-8/SVneo and JEG-3 cells, while silence of ADAMTS7 by RNA interference reciprocally facilitated cell viability, migration and invasion in vitro.

Discussion: Upregulation of ADAMTS7 by promoter hypomethylation in placenta might contribute to the etiology of PE via suppressing cell functions of trophoblasts.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.placenta.2020.02.013DOI Listing
April 2020

Circulating levels of IFN-γ, IL-1, IL-17 and IL-22 in pre-eclampsia: A systematic review and meta-analysis.

Eur J Obstet Gynecol Reprod Biol 2020 May 19;248:211-221. Epub 2020 Mar 19.

Department of Clinical Laboratory, Affiliated Hospital of Qingdao University, Qingdao, Shandong, China. Electronic address:

Objective: Pre-eclampsia (PE) is a common multi-systemic disease, and the effect of cytokines on PE is not clear. The purpose of this meta-analysis was to evaluate the circulating levels of interferon gamma (IFN-γ), interleukin (IL)-1, IL-17 and IL-22 in patients with PE.

Study Design: Relevant studies were identified after a preliminary investigation of studies published up to May 2019 using PubMed and Embase. In this study, all 27 included articles underwent quality rating, with a total of 495 patients with PE and 557 controls. Among them, eight papers and 932 subjects contributed to the meta-analysis of IFN-γ, and six papers and 343 subjects contributed to the meta-analysis of IL-17. Based on the inclusion and exclusion criteria, the retrieved papers were screened and evaluated independently. Relevant data for IFN-γ and IL-17 were extracted for meta-analysis and subgroup analysis, and the stability of the results was evaluated by sensitivity analysis. At the same time, a systematic evaluation was carried out for IL-1 and IL-22 with a small number of included papers.

Results: Several papers included in the systematic review showed that the circulating levels of IL-22 were higher in patients with severe PE than in controls, while IL-1 levels did not differ significantly between the two groups. The meta-analysis showed that patients with PE had higher circulating levels of IFN-γ than controls [standardized mean difference (SMD) 1.45, 95 % confidence interval (CI) 0.56-2.34]. There was no evidence of a difference in the circulating levels of IL-17 between patients with PE and controls (SMD 0.53, 95 %CI -0.43 to 1.48).

Conclusion: This meta-analysis suggested that changes in circulating levels of IFN-γ might be associated with PE.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejogrb.2020.03.039DOI Listing
May 2020

Effects of chitosan nanoparticle supplementation on growth performance, humoral immunity, gut microbiota and immune responses after lipopolysaccharide challenge in weaned pigs.

J Anim Physiol Anim Nutr (Berl) 2020 Mar 30;104(2):597-605. Epub 2019 Dec 30.

Experimental Animal Research Center, Zhejiang Chinese Medical University, Hangzhou, China.

In this study, we aimed to determine the effects of dietary supplementation with chitosan nanoparticles (CNP) on growth performance, immune status, gut microbiota and immune responses after lipopolysaccharide challenge in weaned pigs. A total of 144 piglets were assigned to four groups receiving different dietary treatments, including basal diets supplemented with 0, 100, 200 and 400 mg/kg CNP fed for 28 days. Each treatment group included six pens (six piglets per pen). The increase in supplemental CNP concentration improved the average daily gain (ADG) and decreased the feed and gain (F/G) and diarrhoea rate (p < .05). However, significant differences in the average daily feed intake (ADFI) among different CNP concentrations were not observed. CNP also increased plasma immunoglobulin (Ig)A and IgG, and C3 and C4 concentrations in piglets in a dose-dependent manner on day 28, whereas IgM concentration was not affected by CNP. A total of 24 piglets in the control diet and control diet with 400 mg/kg CNP supplementation groups were randomly selected for the experiment of immunological stress. Half of the pigs in each group (n = 6) were injected i.p. with Escherichia coli lipopolysaccharide (LPS) at a concentration of 100 μg/kg. The other pigs in each group were injected with sterile saline solution at the same volume. Plasma concentrations of cortisol, prostaglandin E2 (PEG2), interleukin (IL)-6, tumour necrosis factor (TNF)-α and IL-1β dramatically increased after LPS challenge. However, CNP inhibited the increase in cortisol, PEG2, IL-6 and IL-1β levels in plasma, whereas TNF-α level slightly increased. Moreover, the effects of CNP on the gut microbiota were also evaluated. Our results showed that dietary supplementation with CNP modified the composition of colonic microbiota, where it increased the amounts of some presumably beneficial intestinal bacteria and suppressed the growth of potential bacterial pathogens. These findings suggested CNP supplementation improved the growth performance and immune status, alleviated immunological stress and regulated intestinal ecology in weaned piglets. Based on these beneficial effects, CNP could be applied as a functional feed additives supplemented in piglets diet.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jpn.13283DOI Listing
March 2020

Targeted regions sequencing identified four novel PNPLA1 mutations in two Chinese families with autosomal recessive congenital ichthyosis.

Mol Genet Genomic Med 2020 02 13;8(2):e1076. Epub 2019 Dec 13.

Medical Genetic Department, The Affiliated Hospital of Qingdao University, Qingdao, China.

Background: Autosomal recessive congenital ichthyosis (ARCI) is a rare genetically heterogeneous cutaneous disease predominantly characterized by erythroderma, generalized abnormal scaling of the whole body and a collodion membrane at birth. Numerous causative genes have been demonstrated to be responsible for ARCI including PNPLA1 which can cause ARCI type 10. The objectives of this study are to describe clinical features of three ARCI patients from two Chinese unrelated families and to identify the underlying causative mutations.

Methods: Genomic DNA was extracted from peripheral venous blood obtained from the two Chinese ARCI families in Shandong province. Subsequently, targeted regions sequencing (TRS) followed by Sanger sequencing was conducted to identify and validate the likely pathogenic mutations of the ARCI families.

Results: Genetic analyses revealed four novel PNPLA1 variants that are predicted to be probably to lead to ARCI in three patients of two families. Patient 1 in one family was in compound heterozygous status for c.604delC/p.Arg202Glyfs*27 and c.820dupC/p.Arg274Profs*15, whereas c.738_742delinsCCCACAGATCCTGC/ p.Gly247_Tyr248delinsProGlnIleLeuHis, and c.816dupC/p.Arg274Profs*15 were found in patient 2 and 3 of the other family. In addition, these variants cosegregate in the two pedigrees and are all within highly conserved regions of the PNPLA1 protein, which indicate that the four mutations are likely pathogenic.

Conclusion: Our findings not only broaden the mutational spectrum of PNPLA1, but also contribute to establishing genotype-phenotype correlations for different forms of ARCI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mgg3.1076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005637PMC
February 2020

Mutations in ASH1L confer susceptibility to Tourette syndrome.

Mol Psychiatry 2020 02 31;25(2):476-490. Epub 2019 Oct 31.

The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Institute for Brain Disorders Center of Schizophrenia, Beijing Anding Hospital, Capital Medical University, Beijing, China.

Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder characterized by repetitive motor movements and vocal tics. The clinical manifestations of TS are complex and often overlap with other neuropsychiatric disorders. TS is highly heritable; however, the underlying genetic basis and molecular and neuronal mechanisms of TS remain largely unknown. We performed whole-exome sequencing of a hundred trios (probands and their parents) with detailed records of their clinical presentations and identified a risk gene, ASH1L, that was both de novo mutated and associated with TS based on a transmission disequilibrium test. As a replication, we performed follow-up targeted sequencing of ASH1L in additional 524 unrelated TS samples and replicated the association (P value = 0.001). The point mutations in ASH1L cause defects in its enzymatic activity. Therefore, we established a transgenic mouse line and performed an array of anatomical, behavioral, and functional assays to investigate ASH1L function. The Ash1l mice manifested tic-like behaviors and compulsive behaviors that could be rescued by the tic-relieving drug haloperidol. We also found that Ash1l disruption leads to hyper-activation and elevated dopamine-releasing events in the dorsal striatum, all of which could explain the neural mechanisms for the behavioral abnormalities in mice. Taken together, our results provide compelling evidence that ASH1L is a TS risk gene.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41380-019-0560-8DOI Listing
February 2020

A Novel Mutation Associated with X-Linked Hyper IgM Syndrome in a Chinese Family.

Immunol Invest 2020 Apr 12;49(3):307-316. Epub 2019 Aug 12.

Medical Genetic Department, the Affiliated Hospital of Qingdao University, Qingdao, China.

: Mutations in CD40 ligand gene () affecting immunoglobulin class-switch recombination and somatic hypermutation can result in X-Linked Hyper IgM Syndrome (HIGM1, XHIGM), a kind of rare serious primary immunodeficiency disease (PID) characterized by the deficiency of IgG, IgA and IgE and normal or increased serum concentrations of IgM. The objective of this study is to explain genotype-phenotype correlation and highlight the mutation responsible for a Chinese male patient with XHIGM.: Whole exome sequencing (WES) and Sanger sequencing validation were performed to identify and validate the likely pathogenic mutation in the XHIGM family.: The results of the sequencing revealed that a new causative mutation in (c.714delT in exon 5, p.F238Lfs*4) which leads to the change in amino acids (translation terminates at the third position after the frameshift mutation) appeared in the proband. As his mother in the family was carrier with this heterozygous mutation, the hemizygous mutation in this patient came from his mother indicating that genetic mode of XHIGM is X-linked recessive inheritance.: This study broadens our knowledge of the mutation in and lays a solid foundation for prenatal diagnosis and genetic counseling for the XHIGM family.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08820139.2019.1638397DOI Listing
April 2020

Effects of Clostridium butyricum and Enterococcus faecalis on growth performance, intestinal structure, and inflammation in lipopolysaccharide-challenged weaned piglets.

J Anim Sci 2019 Oct;97(10):4140-4151

Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang Provincial Engineering Laboratory for Animal Health and Internet Technology, College of Animal Science and Technology, Zhejiang A & F University, Hangzhou, China.

This study was conducted to investigate the effects of Clostridium butyricum and Enterococcus faecalis on growth performance, immune function, inflammation-related pathways, and microflora community in weaned piglets challenged with lipopolysaccharide (LPS). One hundred and eighty 28-d-old weaned piglets were randomly divided into 3 treatments groups: piglets fed with a basal diet (Con), piglets fed with a basal diet containing 6 × 109 CFU C. butyricum·kg-1 (CB), and piglets fed with a basal diet containing 2 × 1010 CFU E. faecali·kg-1 (EF). At the end of trial, 1 pig was randomly selected from for each pen (6 pigs per treatment group) and these 18 piglets were orally challenged with LPS 25 μg·kg-1 body weight. The result showed that piglets fed C. butyricum and E. faecalis had greater final BW compared with the control piglets (P < 0.05). The C. butyricum and E. faecalis fed piglets had lower levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), IL-1β, tumor inflammatory factor-α (TNF-α), and had greater level of serum interferon-γ (IFN-γ) than control piglets at 1.5 and 3 h after injection with LPS (P < 0.05). Furthermore, piglets in the C. butyricum or E. faecalis treatment groups had a greater ratio of jejunal villus height to crypt depth (V/C) compared with control piglets after challenge with LPS for 3 h (P < 0.05). Compared with the control treatment, the CB and EF treatments significantly decreased the expression of inflammation-related pathway factors (TLR4, MyD88, and NF-κB) after challenge with LPS for 3 h (P < 0.05). High-throughput sequencing revealed that C. butyricum and E. faecalis modulated bacterial diversity in the colon. The species richness and alpha diversity (Shannon) of bacterial samples in CB or EF piglets challenged with LPS were higher than those in LPS-challenged control piglets. Furthermore, the relative abundance of Bacteroidales-Rikenellanceae in the CB group was higher than that in the control group (P < 0.05), whereas EF piglets had a higher relative abundance of Lactobacillus amylovorus and Lactobacillus gasseri (P < 0.05). In conclusion, dietary supplementation with C. butyricum or E. faecalis promoted growth performance, improved immunity, relieved intestinal villus damage and inflammation, and optimized the intestinal flora in LPS-challenged weaned piglets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jas/skz235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6776315PMC
October 2019

Ameliorates Dextran Sulfate Sodium-Induced Colitis by Improving Gut Microbial Dysbiosis in Mice Model.

Front Microbiol 2018 8;9:3260. Epub 2019 Jan 8.

Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, College of Animal Science and Technology, Zhejiang A and F University, Hangzhou, China.

Several strains exert beneficial effects on the maintenance of intestinal homeostasis and host health. However, whether (BA) can improve gut microbial dysbiosis and ameliorate colitis is unknown. Therefore, we conducted the present study to investigate the effects of BA administration on intestinal morphology, inflammatory response, and colonic microbial composition in a mouse model of dextran sulfate sodium (DSS)-induced colitis. Results showed that BA administration significantly ameliorated body weight loss, decreased disease activity index, and improved colonic tissue morphology in DSS-treated mice. In addition, levels of immunoglobulins, as well as pro-inflammatory cytokines, were decreased after BA administration. Importantly, colonic microbiota profiling indicated a significant ( < 0.05) difference in beta-diversity between BA-administrated and DSS-treated mice, according to weighted principal coordinate analysis (PCoA) results. The relative abundance of the genus was increased, whereas that of was decreased by BA administration. Furthermore, phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) analysis showed that the most significantly changed pathways between the four groups of mice were carbohydrate, lipid, and amino acid metabolism. In conclusion, our results showed that BA administration has beneficial effects on DSS-induced colitis, suggesting that this strategy might be useful for the treatment of dysbiosis during ulcerative colitis. Further, the changes in metabolism, especially amino acid metabolism, might contribute to the beneficial effects of BA on the amelioration of DSS-induced colitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2018.03260DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331537PMC
January 2019

Effects of dietary supplementation with essential oils and organic acids on the growth performance, immune system, fecal volatile fatty acids, and microflora community in weaned piglets.

J Anim Sci 2019 Jan;97(1):133-143

College of Animal Science and Technology, Zhejiang A & F University, Hangzhou, China.

The present study was conducted to assess the effects of a mixture of essential oils and organic acids on the growth performance, immune system, major fecal volatile fatty acids (VFAs), and microflora community in the weaned piglets. We also evaluated the antibacterial activity of the essential oil mixture on Escherichia coli and Staphylococcus aureus. Three hundred weaned piglets (Duroc × Landrace × Yorkshire) were randomly divided into the following 3 treatment groups: basal diet (C), basal diet supplemented with the mixture of essential oils and organic acids (T1), and basal diet supplemented with antibiotics (T2). The mixture of essential oils and organic acids comprised of cinnamaldehyde (15%), thymol (5%), citric acid (10%), sorbic acid (10%), malic acid (6.5%), and fumaric acid (13.5%). In vitro studies showed that the mixture of essential oils extremely damaged the cell structure of pathogenic bacteria by deforming the membranes and disorganizing the intracellular components. In vivo studies revealed that diet supplementation with a mixture of essential oils and organic acids improved the final body weight and ADG of piglets (P < 0.05), increased the concentration of serum complement 4 (P < 0.05), and enhanced the fecal level of isovaleric acid (P < 0.05) compared with controls on day 28. Result of high-throughput sequencing revealed that: 1) a total of 1,177 and 1,162 observed taxonomic units (OTUs) were shared between all treatment groups on day 14 and 28, respectively; 2) the T1 exhibited higher (P < 0.05) beta diversity (unweighted UniFrac distance) than control and antibiotics treatment on day 28; 3) the samples in principle component analysis plot and tree of relative abundance were separated from each other based on dietary treatments and age; 4) Firmicutes and Bacteroidetes were the most 2 dominate phyla; Lactobacillus and Streptococcus were the 2 top species among the recognized microbiota; 5) T1 had higher (P < 0.05) relative abundance of Lactobacillus mucosae than control and antibiotics treatment on day 28. To conclude, the mixture of cinnamaldehyde and citric acids damaged the structure of pathogens in vitro; the mixture of essential oils and organic acids improved the growth performance, increased the fecal concentration of isovaleric acid, and modulated the microflora community in weaned piglets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jas/sky426DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6312551PMC
January 2019

Next-generation sequencing of NKX2.1, FOXE1, PAX8, NKX2.5, and TSHR in 100 Chinese patients with congenital hypothyroidism and athyreosis.

Clin Chim Acta 2017 Jul 25;470:36-41. Epub 2017 Apr 25.

Genetic Medicine Center, Xuzhou Maternal and Children Health's Hospital, Xuzhou 221009, China. Electronic address:

Background: The abnormal expression of certain transcription factors (NKX2.1, FOXE1, NKX2.5, and PAX8) and thyroid stimulating hormone receptor (TSHR) genes has been associated with athyreosis, which is a form of thyroid dysgenesis (TD). We aimed to identify candidate gene mutations in CH patients with athyreosis and to establish the genotype-phenotype correlations in a Chinese population.

Methods: The exons and flanking sequences of NKX2.1, FOXE1, NKX2.5, PAX8, and TSHR were screened by next-generation sequencing and further confirmed by direct Sanger sequencing. The mutation frequencies were calculated and compared against databases. The relationship between genotype and phenotype was also determined.

Results: Seven variants were detected in TSHR-p.P52T, p.G132R, p.M164K, p.R450H, p.C700E, p.A522V, and p.R528S. The p. G132R, p. M164K and p. R528S variants were first identified in public databases. Five variants (p.G44D, p.G360V, p.R401Q, p.L418I, and p.E453Q) were found in NKX2.1 and one variant (p.P243T) was detected in FOXE1. In addition, one variant (p.N291I) was found in NKX2.5 and two variants (p.A355V and c.-26G>A) were detected in PAX8.

Conclusions: Our study indicated that TSHR mutations have phenotypic variability and has further expanded the mutation spectrum of TSHR. We also revealed that the rate of NKX2.1, FOXE1, NKX2.5, and PAX8 mutations were low in patients with CH and athyreosis, in contrast to the higher rate of TSHR mutations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cca.2017.04.020DOI Listing
July 2017

Choline acetyltransferase may contribute to the risk of Tourette syndrome: Combination of family-based analysis and case-control study.

World J Biol Psychiatry 2018 10 14;19(7):521-526. Epub 2017 Feb 14.

a Department of Pediatrics , The Affiliated Hospital of Qingdao University , Qingdao , China.

Objectives: Twin and family analyses have revealed a genetic contribution to Tourette syndrome (TS) and post-mortem studies have raised the intriguing possibility of a reduction in cholinergic interneuronsin TS patients.

Methods: We selected five tag SNPs (rs100824791, rs12264845, rs1880676, rs3793790 and rs3793798) of choline acetyltransferase (CHAT) from the Han Chinese population Hapmap database. Genotyping was conducted on 401 TS nuclear family trios and 405 control subjects. Transmission disequilibrium test (TDT) and haplotype relative risk (HRR) analyses were used to analyse the family-based study and a case-control study was also used to assess the genetic susceptibility to TS.

Results: The results revealed a significant over-transmission of rs3793790 (TDT, χ=9.121, P = 0.003; HRR, χ=6.579, P = 0.01), while case-control analysis found no differences between the two groups (genotype, χ=0.436, P = 0.804; allele, χ=0.149, P = 0.700). Also, rs3793798 also indicated a positive association associated with TS (TDT, χ=5.025, P = 0.028; HRR, χ=0.250, P = 0.617). However, the other three SNPs investigated were found not to be associated with TS in both in the family-based and case-control studies.

Conclusions: Our association analysis demonstrates that CHAT may contribute to TS susceptibility in the Han Chinese population. This gives strong support to the involvement of cholinergic interneurons in the aetiology of TS and reveals a potential therapeutic target.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15622975.2017.1282176DOI Listing
October 2018

Chitosan nanoparticles reduce LPS-induced inflammatory reaction via inhibition of NF-κB pathway in Caco-2 cells.

Int J Biol Macromol 2016 May 17;86:848-56. Epub 2016 Mar 17.

Experimental Animal Research Center, Zhejiang Chinese Medical University, PR China.

Chitosan nanoparticles (CNP), an extensively oral-administered drug carrier, was investigated for the anti-inflammatory effects on LPS-inflamed Caco-2 cells and the relate mechanisms. CNP could alleviate the decrease of transepithelial electrical resistance (TEER) induced by LPS in Caco-2 monolayer, and significantly inhibit LPS-induced production of TNF-α, MIF, IL-8 and MCP-1 in a dose-dependent manner. PCR array assay revealed that CNP down-regulated the mRNA expression levels of TLR4 in LPS-inflamed Caco-2 cells. CNP was further showed to reduce cytoplasmic IκB-α degradation and nuclear NF-κB p65 levels in LPS-inflamed Caco-2 cells. These results suggested that CNP suppressed LPS-induced inflammatory response by decreasing permeability of intestinal epithelial monolayer and secretion of pro-inflammatory cytokine in Caco-2 cells, which were partially mediated by NF-κB signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijbiomac.2016.02.015DOI Listing
May 2016

Steroidogenic factor-1 is required for TGF-beta3-mediated 17beta-estradiol synthesis in mouse ovarian granulosa cells.

Endocrinology 2011 Aug 17;152(8):3213-25. Epub 2011 May 17.

Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, People's Republic of China.

The TGF-β superfamily members are indicated to play key roles in ovarian follicular development, such as granulosa cell proliferation, estrogens, and progesterone production. However, little is known about the roles of TGF-β3 in follicular development. In this study, we found that TGF-β3 was predominantly expressed in granulosa cells of mouse ovarian follicles, and it significantly promoted 17β-estradiol (E(2)) release in a dose-dependent manner. The orphan nuclear receptor steroidogenic factor-1 (SF-1) was required in TGF-β3-induced Cyp19a1 (a key rate-limiting enzyme for estrogen biosynthesis) expression and E(2) release. Additionally, TGF-β3 enhanced the binding of SF-1 to endogenous ovary-specific Cyp19a1 type II promoter, as evidenced by chromatin immunoprecipitation assays. The enhanced effect of SF-1 by TGF-β3 may be mediated through functional interactions between SF-1 and mothers against decapentaplegic homolog (Smad)3 (a mediator of TGF-β signaling pathway), because disruption of the interaction abolished the synergistic effects of SF-1, Smad3, and TGF-β3 on Cyp19a1 mRNA expression. RNA interference and chromatin immunoprecipitation studies also demonstrated that Smad3 was required for SF-1 binding to Cyp19a1 type II promoter and activation of Cyp19a1. Smad3 thus acts as a point of convergence that involves integration of SF-1 and TGF-β signaling in affecting E(2) production. Taken together, our data provide mechanistic insights into the roles of SF-1 in TGF-β3-mediated E(2) synthesis. Understanding of potential cross-points between extracellular signals affecting estrogen production will help to discover new therapeutic targets in estrogen-related diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/en.2011-0102DOI Listing
August 2011

Chitosan nanoparticles inhibit the growth of human hepatocellular carcinoma xenografts through an antiangiogenic mechanism.

Anticancer Res 2009 Dec;29(12):5103-9

Key Laboratory of Molecular Animal Nutrition of Ministry of Education, College of Animal Sciences, Zhejiang University, Hangzhou 310029, China.

Chitosan nanoparticles (CNP) have demonstrated anticancer activity in vitro and in vivo by a few recent researches. However, the mechanisms involved in their potential anticancer activity remain to be elucidated. In this study, the effects of CNP on tumor growth were investigated using a model of nude mice xenografted with human hepatocellular carcinoma (HCC) (BEL-7402) cells. The results demonstrated that the treatment of these nude mice with CNP significantly inhibited tumor growth and induced tumor necrosis. Furthermore, microvessel density (MVD) determination by counting immunohistologically stained tumor microvessels suggested that CNP dose-dependent tumor suppression was correlated with the inhibition of tumor angiogenesis. Mechanistically, immunohistochemical and quantitative real-time reverse transcription-polymerase reaction assays provided evidence that CNP-mediated inhibition of tumor angiogenesis was linked to impaired levels of vascular endothelial growth factor receptor 2 (VEGFR2). Due to their low or non-toxicity, CNP and their derivatives may represent a novel class of anti-cancer drug.
View Article and Find Full Text PDF

Download full-text PDF

Source
December 2009
-->