Composition of the Midgut Microbiota Structure of Haemaphysalis longicornis Tick Parasitizing Tiger and Deer.

Haemaphysalis longicornis is a common tick species that carries several pathogens. There are few reports on the influence of different hosts on the structure of midgut microflora in H. longicornis. In this study, midgut contents of fully engorged female H. longicornis were collected from the surface of tiger (Panthera tigris) and deer (Dama dama). The bacterial genomic DNA of each sample was extracted, and the V3-V4 regions of the bacterial 16S rRNA were sequenced using the Illumina NovaSeq sequencing. The diversity of the bacterial community of the fully engorged female H. longicornis on the surface of tiger was higher than that of deer. In total, 8 phyla and 73 genera of bacteria annotations were detected in the two groups. At the phylum level, the bacterial phyla common to the two groups were Proteobacteria, Firmicutes, and Actinobacteriota. At the genus level, there were 20 common bacterial genera, among which the relative abundances of Coxiella, Morganella, Diplorickettsia, and Acinetobacter were high. The Morganella species was further identified to be Morganella morganii. The alpha diversity index indicated that the bacterial diversity of the tiger group was higher than that of the deer group. Bacteroidota, Patescibacteria, Desulfobacterota, Verrucomicrobiota, and Cyanobacteria were solely detected in the tiger group. A total of 52 bacterial genera were unique in the tiger group, while one bacterial genus was unique in the deer group. This study indicates that there are differences in the structure of the gut bacteria of the same tick species among different hosts. Further culture-based methods are needed to provide a more comprehensive understanding of the tick microbiota parasitizing different hosts.

Immunological effects of recombinant Lactobacillus casei expressing pilin MshB fused with cholera toxin B subunit adjuvant as an oral vaccine against Aeromonas veronii infection in crucian carp.

Aeromonas veronii is a zoonotic agent capable of infecting fish and mammals, including humans, posing a serious threat to the development of aquaculture and public health safety. Currently, few effective vaccines are available through convenient routes against A. veronii infection. Herein, we developed vaccine candidates by inserting MSH type VI pili B (MshB) from A. veronii as an antigen and cholera toxin B subunit (CTB) as a molecular adjuvant into Lactobacillus casei and evaluated their immunological effect as vaccines in a crucian carp (Carassius auratus) model. The results suggested that recombinant L. casei Lc-pPG-MshB and Lc-pPG-MshB-CTB can be stably inherited for more than 50 generations. Oral administration of recombinant L. casei vaccine candidates stimulated the production of high levels of serum-specific immunoglobulin M (IgM) and increased the activity of acid phosphatase (ACP), alkaline phosphatase (AKP) superoxide dismutase (SOD), lysozyme (LZM), complement 3 (C3) and C4 in crucian carp compared to the control group (Lc-pPG612 group and PBS group) without significant changes. Moreover, the expression levels of interleukin-10 (IL-10), interleukin-1ß (IL-1ß), tumour necrosis factor-α (TNF-α) and transforming growth factor-ß (TGF-ß) genes in the gills, liver, spleen, kidney and gut of crucian carp orally immunized with recombinant L. casei were significantly upregulated compared to the control groups, indicating that recombinant L. casei induced a significant cellular immune response. In addition, viable recombinant L. casei can be detected and stably colonized in the intestine tract of crucian carp. Particularly, crucian carp immunized orally with Lc-pPG-MshB and Lc-pPG-MshB-CTB exhibited higher survival rates (48% for Lc-pPG-MshB and 60% for Lc-pPG-MshB-CTB) and significantly reduced loads of A. veronii in the major immune organs after A. veronii challenge. Our findings indicated that both recombinant L. casei strains provide favorable immune protection, with Lc-pPG-MshB-CTB in particular being more effective and promising as an ideal candidate for oral vaccination.

Molecular Identification and Phylogenetic Analysis of Ascarids in Wild Animals.

Ascarid nematodes are the most common and harmful nematodes parasites in animals. By analyzing genetic variation, this study explores the genetic and phylogenetic relationship among ascarids from 11 different hosts. This study collected ascarid samples from the feces of nine animal species in Changsha Ecological Zoo of Hunan Province and two animal kinds in the College of Veterinary Medicine of Hunan Agricultural University. The mitochondrial gene (pcox1) and ribosomal ITS sequences were amplified, sequenced, and analyzed by PCR to identify the species of the samples. The phylogenetic tree was constructed based on two genes (cox1 and ITS) by the Neighbor-joining method, and the phylogenetic relationship was analyzed. The sequencing results showed that the sequence lengths of pcox1 and ITS genes in the samples were 441 bp and 838-1,177 bp, respectively. The difference rates were 0.00-1.70% in pcox1 gene and 0.00-7.30% in ITS gene. Phylogenetic analysis showed that ascarid worms from the white lion, Northeast tiger, South China tiger and cheetah were identified as Toxascaris leonina. Ascarids from the zebra were identified as Parascaris equorum, while those from chicken and peacocks were identified as Ascaridia galli. Ascarids of wolf and dog origin were Toxocara canis, the snake ascarids belonged to Ophidascaris filaria, and the bear ascarids belonged to Baylisascaris transfuga. There was a significant gap between different kinds of ascarid worms. We found that these two mitochondrial genes pcox1 and ITS showed a common characteristic that the intraspecific differences were significantly smaller than the interspecific differences, confirming that these two genes could be used as interspecific genetic markers for molecular identification of different ascarids origins. The intraspecific variation rate of the ITS gene was higher than that of pcox1, indicating that ITS can also be used in the genetic research of Ascaris species development. This study revealed the genetic evolution and phylogeny of ascarids in wild animals, and our results will help prevent and control ascarids in wild animals.

Oyster peptide prevents the occurrence of exercise-hypogonadal male condition by improving the function of pituitary gonadal axis in male rats.

This study evaluates the protective role of oyster peptide (OP) on the occurrence of Exercise-Hypogonadal Male Condition. Male rats were given heavy-load swimming training and / or OP was supplemented for 6 consecutive weeks. After heavy-load training, sperm count, sperm viability and sperm motility in epididymis, testosterone in serum and testis, glutathione peroxidase (GSH-px) and androgen receptor (AR) in testis and mating times were remarkably decreased, malondialdehyde (MDA), capture latency and mating latency were significantly increased, mRNA expression of steroidogenic acute regulatory (StAR) and P450 cholesterol side-chain cleavage enzyme (P450scc) were obviously down-regulated, but serum follicle-stimulating hormone (FSH) and luteinising hormone (LH) were not statistically changed. Conversely, when OP was supplemented at heavy-load training, sperm count, sperm viability and sperm motility in epididymis, serum FSH, LH, testosterone, GSH-px, superoxide dismutase (SOD), testosterone, AR in testis and mating times were dramatically increased, while testicular MDA, capture latency and mating latency were significantly decreased, and mRNA expression of StAR, StARD7, P450scc and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) were significantly up-regulated. In conclusion, heavy-load training causes testicular spermatogenic and steroidogenic disorders by enhancing the generation of reactive oxygen species (ROS), which can be protected by the co-administration of OP by enhancing the function of pituitary gonad axis and lowering ROS generation.

miR-155 facilitates calcium oxalate crystal-induced HK-2 cell injury via targeting PI3K associated autophagy.

Nephrolithiasis is one of the most common and highly recurrent diseases worldwide. Accumulating evidence revealed the elevated miR-155 levels both in serum and urine of nephrolithiasis patients. The aim of our research was to explore the role of miR-155 in CaOx-induced apoptosis in HK-2 cells. The expression levels of miR-155 in serum and renal tissues were quantified in 20 patients with nephrolithiasis using qRT-PCR assay. ELISA was performed to determine urinary levels of interleukin (IL)-1ß, IL-6 and tumor necrosis factor-alpha (TNF-α). Renal tubular cell model of CaOx nephrolithiasis was established to investigate the role and molelular mechanism of miR-155. Cell viability and apoptosis were assessed by MTT and flow cytometry, respectively. Immunofluoresent staining of LC3 autophagosome and western blotting were performed to evaluate the autophagic activity. Luciferase reporter assay was employed to verify the interaction between miR-155 and PI3KCA/Rheb. PI3K/Akt/mTOR signaling was further examined by western blotting. Serum and renal levels of miR-155 and inflammatory factors were significantly elevated in nephrolithiasis patients than in controls. CaOx treatment caused up-regulation of miR-155 and induced autophagy in renal tubular epithelial cells, while silencing miR-155 or inhibition of autophagy by 3-metheladenine (3-MA) ameliorated CaOx crystal-induced cell injury. PI3KCA and Rheb was identified as downstream targets of miR-155. Moreover, miR-155 activates autophagy and promotes cell injury through repressing PI3K/Akt/mTOR signaling pathway. Taken together, these findings demonstrated that miR-155 facilitates CaOx crystal-induced renal tubular epithelial cell injury via PI3K/Akt/mTOR-mediated autophagy, providing therapeutic targets for ameliorating cellular damage by CaOx crystals.

Genomic characterization of a novel astrovirus identified in Amur tigers from a zoo in China.

Astroviruses (AstVs) have a very wide range of hosts and are associated with enteric and extra-enteric disease in mammals and birds. Cross-species transmission of AstVs has been observed frequently. In the present study, the genome of a novel astrovirus from Amur tigers (Panthera tigris) from a zoo in China was characterized and was found to have the typical genomic features of other mammal AstVs. It showed the highest nucleotide sequence similarity (46.1-87.3% identity) to AstVs from cats, indicating a close phylogenetic relationship and possible cross-species transmission between them. To our knowledge, this is the first identification and characterization of AstV from tigers, and this virus is the third astrovirus identified in hosts of the family Felidae. The results of this study will be helpful for understanding the origin, genetic diversity, and cross-species transmission of AstV.

Inhibition of miR-155 Ameliorates Acute Kidney Injury by Apoptosis Involving the Regulation on TCF4/Wnt/ß-Catenin Pathway.

BACKGROUND: Acute kidney injury (AKI) is a complex clinical disorder with sudden decay in renal function. Ischemia-reperfusion injury (IRI) has been regarded as the main etiology for the occurrence of AKI. MicroRNAs have been consistently shown to be involved AKI. OBJECTIVES: We aimed to investigate the role of miR-155 in AKI and its underlying mechanism. METHODS: Ischemia-reperfusion (I/R)-induced AKI rat model and hypoxia-reoxygeneration (H/R)-induced NRK-52E cell model were established. The concentrations of serum creatinine and blood urea nitrogen were measured to evaluate renal function. Hematoxylin and eosin staining and TUNEL assay were performed to assess the severity of kidney injury. Additionally, quantitative real-time-PCR and western blot analysis were subjected to determine the expression of miR-155, TCF4, and apoptosis-related proteins, respectively. Moreover, cell proliferation and apoptosis were evaluated by Cell Counting Kit-8, bromodeoxyuridine, and flow cytometry analyses, respectively. Luciferase reporter assay was used to validate the direct targeting of TCF4 with miR-155. The protein levels of TCF4 and its downstream proteins in cells were measured by western blot. RESULTS: The expression level of miR-155 was upregulated in both I/R-induced AKI rat model and H/R-treated NRK-52E cells. Moreover, overexpression of miR-155 promoted H/R-induced NRK-52E cells apoptosis and suppressed cell proliferation, while inhibition of miR-155 expression exerted opposite effects. Additionally, TCF4 was identified as a target of miR-155, of which expression was downregulated both in vivo and in vitro. Furthermore, the activity of Wnt/ß-catenin signaling pathway was promoted following overexpression of TCF4 in NRK-52E cells, and this effect was attenuated by the increasing miR-155 expression. CONCLUSION: We demonstrated that miR-155 exacerbated AKI involving the targeting and regulation of TCF4/Wnt/ß-catenin signaling pathway, indicating a novel regulatory network and elucidating a potential target for IRI-induced AKI treatment.

Qian lie an suppository (prostant) for chronic prostatitis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Chronic prostatitis (CP) is an inflammation of the prostate gland that seriously affects the quality of life of patients. The existing evidence of antibiotics and α-blockers for the treatment of CP is limited. OBJECTIVES: This review evaluated the effectiveness and safety of Qian Lie An Suppository (Prostant) in treating CP. METHODS: Randomized controlled trials comparing Prostant (alone or plus the control) with placebo, conventional drugs, or nonpharmaceutical therapies for CP were included in this article through searching from 6 databases. Data were analyzed using RevMan 5.3 software. Meta-analysis was performed when the clinical or statistical heterogeneity was found acceptable among trials. Estimate effects were present with risk ratio (RR) or mean difference and their 95% confidence interval (CI) for dichotomies or continuous variables. Quality of the evidence for each primary outcome was assessed using GRADE criteria. RESULTS: Totally 21 trials involving 3359 participants were included. There were 2 included trials had unclear risk of bias, and the remaining trials had high risk of bias. Meta-analyses showed the number of cured patients in the Prostant group was 2 times more than that of the placebo (RR 2.05, 95%CI 1.10 to 3.81) or antibiotics (RR 1.95, 95%CI 1.18 to 3.23) groups. Similar results were found when Prostant in combination with antibiotics or hyperthermia compared with the antibiotics (RR 1.78, 95% CI 1.10-2.89) or hyperthermia (RR 1.72, 95% CI 1.23-2.40) alone. However, there was no difference in the number of cured patients between Prostant and α-blockers or hyperthermia therapy. No severe adverse event was reported in all included trials. The main adverse events in Prostant group were reported (in 8 included trials) as diarrhea and anal discomfort. CONCLUSIONS: Low-quality evidence showed that the Prostant may have add-on effect for patients with CP on increasing the number of cured patients, relieving pain, and improving the quality of life. There is not sufficient evidence to determine the effectiveness and safety of Prostant for the treatment of CP compared with placebo, antibiotics, α-blockers or the hyperthermia therapy.

Continuous Glucose Monitoring in Newly Diagnosed Type 2 Diabetes Patients Reveals a Potential Risk of Hypoglycemia in Older Men.

Objectives. We performed continuous glucose monitoring (CGM) to define the features of patients with newly diagnosed type 2 diabetes (T2D) before and after Continuous Subcutaneous Insulin Infusion (CSII) therapy. Methods. This was a retrospective analysis. Newly diagnosed T2D patients (106) were admitted from eight centers in China. They were divided into a younger patient group (<60 years) and an older patient group (≥60 years). Each group was further divided into male and female patients. CSII therapy was maintained for 3 weeks after the glycemic target was reached. CGM was performed 2 times before and after completion of insulin treatment. Results. CGM data showed the expected significant improvement of mean amplitude glycemic excursion (MAGE) with CSII therapy. The older patients had lower hourly glucose concentrations from 0200 to 0700 o'clock compared to the younger patients at baseline. Surprisingly, in the older patient group, the male patients had a potential risk of hypoglycemia after CSII therapy, especially during periods from 2300 to 2400 and 0400 to 0600. Conclusions. Our data suggested that older male patients with newly diagnosed T2D may have lower nocturnal glucose concentrations. This may potentially increase the risk of nocturnal hypoglycemia during CSII therapy. This study was registered with Chinese Clinical Trial Registry, number CliCTR-TRC-11001218.

Polysaccharides from Polygonatum Inhibit the Proliferation of Prostate Cancer-Associated Fibroblasts.

Inhibition of cancer-associated broblasts (CAFs) may improve the efficacy of cancer therapy. Polysaccharide extracted from polygonatum can selectively inhibit the growth of prostate-CAFs (<.001) without inhibiting the growth of normal broblasts (NAFs). Polysaccharides from polygonatum stimulate autophagy of prostate-CAFs. 3-methyl-adenine(3-MA) is an autophagy inhibitor. 3-MA was added to prostate-CAFs with polysaccharide from polygonatum to determine whether autophagy plays an important role in the restrained effect. Finally, polysaccharide from polygonatum treatment significantly increased the activation of Beclin-1 and LC3, key autophagy proteins. Polysaccharides from polygonatum stimulate autophagy of prostate-CAFs and inhibits prostate-CAF growth, indicating that a novel anti-cancer strategy involves inhibiting the growth of prostate- CAFs.

Promoter methylations of RASSF1A and p16 is associated with clinicopathological features in lung cancers.

UNLABELLED: Objection: The aim of this study is to investigate the association between promoter methylation of RASSF1A and p16 and the clinicopathological features in lung cancers. MATERIALS AND METHODS: PubMed, EBSCO, Ovid, Wiley, Web of Science, Wanfang, and VIP databases were searched using combinations of keywords related to RASSF1A, p16, methylation, and lung cancers. After screening for relevant studies, following a strict inclusion and exclusion criteria; the selected studies were incorporated into the present meta.analysis conducted using Comprehensive Meta Analysis 2.0. (CMA 2.0). RESULTS: We initially retrieved 402 studies, out which 13 studies met the inclusion and exclusion criteria for this meta.analysis, and contained a total of 1,259. patients with lung cancers. The results of this meta.analysis showed that the differences in promoter methylation ratio between the lung cancer patients in tumor, node, metastasis. (TNM) I.II and III.IV were not statistically significant. Based on histological types, patients with adenocarcinoma. (AC) and squamous cell carcinoma. (SCC) showed no significant differences in the promoter methylation ratios of RASSF1A, while the promoter methylation ratio of p16 was significantly higher in SCC patients compared to AC patients. Based on smoking status, the promoter methylation ratios of both RASSF1A and p16 was significantly higher in lung cancer patients with smoking history compared to nonsmokers. CONCLUSION: The present meta.analysis provides convincing evidence that the promoter methylation ratio of RASSF1A and p16 is associated with clinicopathological features in lung cancers, and could be used as effective biomarkers in early diagnosis in lung cancers.

IKKß/NFκBp65 activated by interleukin-13 targets the autophagy-related genes LC3B and beclin 1 in fibroblasts co-cultured with breast cancer cells.

Interleukin-13 (IL-13), a Th2 cytokine, plays an important role in fibrosis, inflammation, tissue hyperresponsiveness and tumor development. Although studies have demonstrated that IL-13 exerts its roles through signal transducer and activator of transcription 6 (STAT6) signaling pathway, recent studies have revealed that I kappa B kinase (IKK)/nuclear factor kappa B (NFκB) pathway may also be involved in. The aim of this study was to investigate whether IL-13 delivers signals to IKKß/NFκBp65 and whether autophagy genes are IL-13-induced the activation of NFκBp65 transcriptional targets in fibroblasts of breast tumor stroma. We examined the phosphorylation of IKKß, the activation of NFκBp65 and NFκBp65-targeted autophagy genes in fibroblasts co-cultured with breast cancer cells under the condition of IL-13 stimulation. Results of this study showed that IL-13 induced IKKß phosphorylation in the fibroblast line ESF co-cultured with breast cancer cell line BT474, and subsequently NFκBp65 was activated and aimed at beclin 1 and microtubule-associated protein 1 light chain 3 B (MAP1LC3B or LC3B) in these ESF cells. BMS345541, an inhibitor of IKK/NFκB pathway, significantly inhibited the IL-13-induced the activation of NFκB and also inhibited NFκB-targeted beclin 1 and LC3B expression. Our results suggest that IL-13 regulates beclin 1 and LC3B expression through IKKß/NFκBp65 in fibroblasts co-cultured with breast cancer cells, and IL-13 plays role in activating IKKß/NFκBp65.

Vitamin D receptor polymorphisms may contribute to asthma risk.

BACKGROUND: Asthma is a common chronic airway disorder associated with significant morbidity and mortality. OBJECTIVE: Current study aims at investigating the correlation between four vitamin D receptor (VDR) gene polymorphisms and asthma susceptibility by conducting a meta-analysis. METHODS: PubMed, EBSCO, Ovid, Wiley, Web of Science, Wanfang, CNKI and VIP databases were searched using combinations of keywords relating to VDR and asthma. The published studies were filtered using our stringent inclusion and exclusion criteria, and the resultant high-quality data from final selected studies were analyzed using Stata 12.0 software. RESULTS: A total of 77 studies were initially retrieved, and after further selection, 9 studies were eligible in current analysis. The selected studies contained 2,116 patients with asthma and 1,884 healthy controls. Our results demonstrated that rs2228570, rs7975232 and rs731236 in both allele models and dominant models, and rs3782905 in allele model in the VDR gene were linked with a high risk of asthma. No significant association between VDR gene rs3782905 in dominant model and risk of asthma was detected. CONCLUSIONS: This meta-analysis provides convincing evidence that rs2228570, rs7975232, rs731236 and rs3782905 gene polymorphisms in VDR are associated with increased susceptibility to asthma, indicating VDR polymorphisms could be developed as biomarkers for asthma susceptibility.

Single-Nucleotide Polymorphisms of IL-17 Gene Are Associated with Asthma Susceptibility in an Asian Population.

BACKGROUND: The aim of this study was to examine the associations between the single-nucleotide polymorphisms (SNPs) of interleukin-17 (IL-17), including rs763780 (7488A/G), rs2275913 (-197G/A), and rs8193036 (-737C/T), and asthma susceptibility in an Asian population. MATERIAL/METHODS: From Oct 2013 to Dec 2014, 125 asthma patients enrolled in our hospital were selected as the case group. Another 132 healthy controls undergoing physical examinations in our hospital were enrolled as the control group. The genotype frequencies of IL-17 rs763780, rs2275913 and rs8193036 SNPs were detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Comprehensive Meta-analysis 2.0 (CMA 2.0) software was applied for meta-analysis. RESULTS: Our results demonstrated that asthma patients presented with higher frequencies of GA genotype in rs2275913 and TT genotype in rs8193036 of IL-17 than healthy controls (both P<0.001). The genotype frequencies of IL-17 rs763780 between the asthma patients and healthy controls exhibited no significant differences (P>0.05). The comparisons on the rs2275913 and rs8193036 frequencies between the asthma patients and healthy controls were statistically significant in both allele and addictive models (all P<0.05). The frequency of IL-17 rs763780 between the asthma patients and healthy controls were statistically different in allele models (P<0.05), but not in addictive models (P>0.05). The overall results of our case-control study were further confirmed by meta-analysis. CONCLUSIONS: Our results revealed that, in an Asian population, IL-17 rs763780, rs2275913, and rs8193036 SNPs may be associated with asthma susceptibility, and GA genotype in rs2275913 and TT genotype in rs8193036 of IL-17 may contribute to increased risk of asthma in Asians.

Stromal Derived Factor-1/CXCR4 Axis Involved in Bone Marrow Mesenchymal Stem Cells Recruitment to Injured Liver.

The molecular mechanism of bone marrow mesenchymal stromal stem cells (BMSCs) mobilization and migration to the liver was poorly understood. Stromal cell-derived factor-1 (SDF-1) participates in BMSCs homing and migration into injury organs. We try to investigate the role of SDF-1 signaling in BMSCs migration towards injured liver. The expression of CXCR4 in BMSCs at mRNA level and protein level was confirmed by RT-PCR, flow cytometry, and immunocytochemistry. The SDF-1 or liver lysates induced BMSCs migration was detected by transwell inserts. CXCR4 antagonist, AMD3100, and anti-CXCR4 antibody were used to inhibit the migration. The Sprague-Dawley rat liver injury model was established by intraperitoneal injection of thioacetamide. The concentration of SDF-1 increased as modeling time extended, which was determined by ELISA method. The Dir-labeled BMSCs were injected into the liver of the rats through portal vein. The cell migration in the liver was tracked by in vivo imaging system and the fluorescent intensity was measured. In vivo, BMSCs migrated into injured liver which was partially blocked by AMD3100 or anti-CXCR4 antibody. Taken together, the results demonstrated that the migration of BMSCs was regulated by SDF-1/CXCR4 signaling which involved in BMSCs recruitment to injured liver.

[Metabolomics analysis on serum biomarkers timing characteristics of type 2 diabetic rats intervened by exercise].

OBJECTIVE: To analyze the combined features of serum biomarker of exercise-intervened type 2 diabetes mellitus (T2DM) rats at different time point. METHODS: Ninety SD rats randomly selected from 100 were fed with high glucose and fat diet for 4 weeks, and then received intraperitoneal injection of streptozotocin(STZ) according to 40 mg/kg by weight; after modeling for one week, Seventy-one rats were successfully modeled among which intervened with swimming at three different time points (2w, 4w and 8w). Eighty-one rats were finally divided into 8 groups as below:Normal control group (C0,n=10);DM model comparison group (DC0,n=10); DM model comparison 2w group (DC2, n=11); DM model comparison 4w group (DC4, n=10); DM model comparison 8w group (DC8, n=9); DM exercise intervention 2w group (DE2, n=11); DM exercise intervention 4w group (DE4, n=10); DM exercise intervention 8w group (DE8, n=11).The UPLC/Q-TOF MS technique was used to conduct metabonomics test of serum of rats to analyze the combined features of serum biomarkers under exercise intervention at different time points. RESULTS: According to fold change, we got the biomarker combinations (with 15 specific substances in each combination) of exercise intervention at three time points. In these serum biomarker combinations that were specific at different time points, a majority of metabolites appeared simultaneously at different time points but with obvious difference of fold change. Fold change of monoglyceride(24:6) and gluconic acid were most evident respectively at 2w and 4w intervention time points,Eicosapentaenoic Acid (EPA) andlinolenic acid(LA) contents might approach the normal level at 4~8 time point. CONCLUSIONS: Combined features of serum biomarker of exercise-intervened T2DM rats are specific at different time point. Both EPA and LA are common substances significantly up-regulated while MonoglycerideMG(24:6), Gluconic acid, Propionyl-L-carnitine(PLC), Arginine(Arg) and Sphingosine-1-phosphate (SPP) are common substances significantly down-regulated at three time points.

Downregulation of caveolin­1 upregulates the expression of growth factors and regulators in co­culture of fibroblasts with cancer cells.

Reduced expression levels of caveolin­1 (Cav­1) in tumor stromal fibroblasts influences the occurrence and progression of tumors, particularly in breast cancer, but the relevant molecular mechanism is unclear. The present study aimed to clarify the potential mechanism underlying the promotion of tumor growth by reduced Cav­1 expression levels, by investigating Cav­1­targeted molecules in fibroblasts and breast cancer cells. The expression of growth factors in the ESF fibroblast cell line transfected with Cav­1 small interfering RNA (siRNA) was examined. The expression of apoptotic regulators in the BT474 breast cancer cell line that was co­cultured with the fibroblasts, was also investigated. The transfection of Cav­1­targeting siRNA in ESF cells resulted in efficient and specific inhibition of Cav­1 expression. The downregulation of Cav­1 increased the expression and secretion of stromal cell­derived factor­1 (SDF­1), epidermal growth factor (EGF) and fibroblast­specific protein­1 (FSP­1) in ESF cells. This resulted in the accelerated proliferation of the breast cancer cells. Tumor protein 53­induced glycolysis and apoptosis regulator (TIGAR) was upregulated in the BT474 cells under the condition of co­culture with Cav­1 siRNA fibroblasts, while levels of reactive oxygen species (ROS) were decreased, resulting in apoptosis inhibition in the breast cancer cells. These results demonstrated that the downregulation of Cav­1 promoted the growth of breast cancer cells through increasing SDF­1, EGF and FSP­1 in tumor stromal fibroblasts, and TIGAR levels in breast cancer cells. To the best of our knowledge, the present study supports the hypothesis that Cav­1 possesses tumor­suppressor properties, with the mechanism of Cav­1­dependent signaling involving the regulation of SDF­1, EGF, FSP­1 and TIGAR.

Association of Left Ventricular Hypertrophy With a Faster Rate of Renal Function Decline in Elderly Patients With Non-End-Stage Renal Disease.

BACKGROUND: Several studies have indicated that chronic kidney disease is independently associated with the presence of left ventricular hypertrophy (LVH). However, little clinical data are currently available regarding the detailed correlation between LVH and renal function in elderly patients with non-end-stage renal disease. METHODS AND RESULTS: A total of 300 in- and outpatients (more than 60 years of age, non-end-stage renal disease), 251 with LVH and 49 without LVH, seen at Beijing Friendship Hospital from January 2000 to December 2010 were included in this retrospective study. One observation period of 12 months was used to detect rapid kidney function decline. The evaluations of cardiac structure and function were performed via echocardiography. The multivariable logistic analysis showed patients with LVH had a much higher risk of rapid kidney function decline than those without LVH. Additionally, the baseline left ventricular mass index was 140 (125-160) g/m(2) in the non-chronic kidney disease group, 152 (130-175) g/m(2) in the mild chronic kidney disease group (estimated glomerular filtration rate (eGFR)≥60 ml/min/1.73 m(2)), and 153 (133-183) g/m(2) in the severe chronic kidney disease group (eGFR<60 ml/min/1.73 m(2)), with a significant difference (P=0.009). CONCLUSIONS: Our data demonstrate that a high rate of renal function decline contributes to pathological LVH in non-end-stage renal disease elderly patients and that LVH is positively associated with renal function decline followed by an increased risk of rapid kidney function decline.

Associations of LIG4 and HSPB1 genetic polymorphisms with risk of radiation-induced lung injury in lung cancer patients treated with radiotherapy.

OBJECTIVE: This study aims to explore the correlations of genetic polymorphisms in LIG4 and HSPB1 genes with the radiation-induced lung injury (RILI), especially radiation pneumonitis (RP), in lung cancer patients. METHODS: A total of 160 lung cancer patients, who were diagnosed with inoperable lung cancer and received radiotherapy, were included in the present study from September 2009 to December 2011. TaqMan Real-Time PCR (RT-PCR) was used to verify the SNPs of LIG4 and HSPB1 genes. Chi-square criterion was used to compare the differences in demographic characteristics, exposure to risk factors, and SNPs genotypes. Crude odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated by logistic regression analysis. All statistical analyses were conducted in SPSS 18.0. RESULTS: A total of 32 (20.0%) lung cancer patients had RP after receiving radiotherapy. Of the 32 cases, 4 cases were of grade 2, 24 cases were of grade 3, and 4 cases were of grade 4. However, our results indicated that the general condition and treatment of all patients had no significant difference with RP risk (P > 0.05). Meanwhile, our results revealed that there was no significant association between the frequencies of LIG4 rs1805388 and HSPB1 rs2868371 genotype distribution and the risk of RP (P > 0.05). CONCLUSION: In conclusion, we demonstrated that the genetic polymorphisms in LIG4 rs1805388 and HSPB1 rs2868371 were not obviously correlated with the risk of RP and RILI of lung cancer.