A Comprehensive Survey on Deep Graph Representation Learning.

Graph representation learning aims to effectively encode high-dimensional sparse graph-structured data into low-dimensional dense vectors, which is a fundamental task that has been widely studied in a range of fields, including machine learning and data mining. Classic graph embedding methods follow the basic idea that the embedding vectors of interconnected nodes in the graph can still maintain a relatively close distance, thereby preserving the structural information between the nodes in the graph. However, this is sub-optimal due to: (i) traditional methods have limited model capacity which limits the learning performance; (ii) existing techniques typically rely on unsupervised learning strategies and fail to couple with the latest learning paradigms; (iii) representation learning and downstream tasks are dependent on each other which should be jointly enhanced. With the remarkable success of deep learning, deep graph representation learning has shown great potential and advantages over shallow (traditional) methods, there exist a large number of deep graph representation learning techniques have been proposed in the past decade, especially graph neural networks. In this survey, we conduct a comprehensive survey on current deep graph representation learning algorithms by proposing a new taxonomy of existing state-of-the-art literature. Specifically, we systematically summarize the essential components of graph representation learning and categorize existing approaches by the ways of graph neural network architectures and the most recent advanced learning paradigms. Moreover, this survey also provides the practical and promising applications of deep graph representation learning. Last but not least, we state new perspectives and suggest challenging directions which deserve further investigations in the future.

Galactooligosaccharides as a protective agent for intestinal barrier and its regulatory functions for intestinal microbiota.

Present study was conducted to comprehensively investigate the protective effects of galactooligosaccharides (GOS, 100%) against LPS-induced intestinal barrier damages, and the regulatory effect for intestinal microbes. Results showed that GOS intervention restored villi (jejunum and ileum) integrity, which were atrophic and broken in LPS-challenged mice. Electron microscopy, western blotting and immunofluorescence analysis exhibited that mice administrated with GOS showed higher expression of tight junction, which was confirmed in IPEC-J2 cells model. Meanwhile, the GOS increased the secretion of mucin and SIgA, as well as it alleviated inflammatory response caused by LPS in NF-κB dependent way. Administration of GOS could also increase the relative abundances of several specific friendly bacteria, and enhance the adaptability of intestinal microbiota. Collectively, these results indicated the potential of GOS for protecting intestine from injuries caused by stress as LPS challenge.

A Potential Probiotic for Diarrhea: Clostridium tyrobutyricum Protects Against LPS-Induced Epithelial Dysfunction via IL-22 Produced By Th17 Cells in the Ileum.

Probiotics are clinically used for diarrhea and inflammatory bowel diseases in both humans and animals. Previous studies have shown that Clostridium tyrobutyricum (Ct) protects against intestinal dysfunction, while its regulatory function in the gut needs further investigation and the related mechanisms are still not fully elucidated. This study aims to further verify the protective function of Ct and reveal its underlying mechanisms in alleviating diarrhea and intestinal inflammation. Ct inhibited LPS-induced diarrhea and intestinal inflammation in the ileum. IL-22 was identified and the protective role of Ct in the ileum presented an IL-22-dependent manner according to the transcriptomic analysis and in vivo interference mice experiments. The flow cytometric analysis of immune cells in the ileum showed that Ct enhanced the proportions of Th17 cells in response to LPS. The results of in situ hybridization further verified that Ct triggered Th17 cells to produce IL-22, which combined with IL-22RA1 expressed in the epithelial cells. Moreover, Ct was unable to enhance the levels of short-chain fatty acids (SCFAs) in the ileum, suggesting that the protective role of Ct in the ileum was independent of SCFAs. This study uncovered the role of Ct in alleviating diarrhea and inflammation with the mechanism of stimulating Th17 cells in the lamina propria to produce IL-22, highlighting its potential application as a probiotic for diarrhea and inflammation in the ileum.

Optimization and comparison of the production of galactooligosaccharides using free or immobilized Aspergillus oryzae ß-galactosidase, followed by purification using silica gel.

The aim of this study was to optimize and compare the production of galactooligosaccharides (GOSs) by free and cotton cloth-immobilized Aspergillus oryzae ß-galactosidase, and perform economical evaluation of production of GOSs (100%) between them. Using the response surface method, the optimal reaction time (3.9 h), initial lactose concentration (57.13%), and enzyme to lactose ratio (44.81 U/g) were obtained for the free enzyme, which provided a GOSs yield of 32.62%. For the immobilized enzyme, the optimal yield of GOSs (32.48%) was obtained under reaction time (3.09 h), initial lactose concentration (52.74%), and temperature (50.0 ℃). And it showed desirable reusability during five successive enzymatic reactions. The recovery rate of GOSs (100%) is 65% using silica gel filtration chromatography. The economical evaluation showed almost no difference in the manufacturing cost for the GOSs (100%) between these two systems, and that the recovery rate had a great impact on the cost.

A Potential Prophylactic Probiotic for Inflammatory Bowel Disease: The Overall Investigation of Clostridium tyrobutyricum ATCC25755 Attenuates LPS-Induced Inflammation via Regulating Intestinal Immune Cells.

SCOPE: This study aims to roundly investigate whether Clostridium tyrobutyricum (Ct) alleviates inflammation via regulating immune cells in the small intestines. METHODS AND RESULTS: Mice are pre-treated with different concentrations of Ct follow by LPS stimulation. Ct maintains the mice body weight under inflammation. In response to LPS, 107 CFU mL-1 Ct decreases the mRNA expression of inflammatory cytokines in the duodenum, while 108 CFU mL-1 Ct reduces inflammatory cytokines expression in both duodenum and ileum and protected intestinal morphology. The small intestinal immune cells are analyzed using flow cytometry. Ct decreases the numbers of macrophages and mast cells in the intestines in response to LPS. In the duodenum, Ct enhances dentritic cells (DCs), regulatory T cells (Tregs), and T helper cell 17 (Th17) proportions. Ct decreases DCs and Tregs proportions, while enhances Th17 numbers in the ileum. The underlying mechanism of Ct in preventing inflammation may rely on the physiological immune cell composition of the intestines. In response to LPS, Ct may mainly stimulate Tregs via activating DCs in the duodenum while trigger Th17 cells in the ileum, thereby maintaining the intestinal homeostasis. CONCLUSION: Ct alleviates the LPS-induce inflammation via regulating different immune cell types in the small intestines, highlighting that Ct is a potential prophylactic probiotic in intestinal diseases.

Effects of Supranutritional Selenium Nanoparticles on Immune and Antioxidant Capacity in Sprague-Dawley Rats.

The present study was conducted to investigate the effects of supranutritional selenium nanoparticles (SeNPs) on immune and antioxidant capacity in rats. Forty male Sprague-Dawley (SD) rats were randomly divided into four groups and given intragastric administration of SeNPs at doses of 0, 0.2, 0.4, and 0.8 mg Se/kg BW, respectively, for 2 weeks. Serum immune parameters, serum and organic tissues (liver, heart, kidney) antioxidant indices, and liver mRNA expression of glutathione peroxidase 1 (GPx1) and glutathione peroxidase 4 (GPx4) were examined. The results showed that supranutritional doses of 0.4 and 0.8 mg Se/kg BW SeNPs promoted the immune responses in serum. SeNPs administration improved antioxidant capacity in the liver and kidney, and the best improvement on antioxidant capacity was found in the kidney. Furthermore, intragastric administration of SeNPs upregulated mRNA expression of GPx1 and GPx4 in the liver. The results obtained indicated that SeNPs administration at supranutritional levels had beneficial effects on immune and antioxidant capacity and supplemental SeNPs at dose of 0.4 mg Se/kg BW exhibited the best response in SD rats.

Galactooligosaccharide pretreatment alleviates damage of the intestinal barrier and inflammatory responses in LPS-challenged mice.

Galactooligosaccharides (GOS) have been identified as beneficial prebiotics for animals and human beings. Most studies have focused on the effect of GOS on the hindgut populated with abundant microbes. However, few research studies have been conducted on the small intestine, and many results are inconsistent due to the purity of GOS, commonly mixed with monosaccharides or lactose. Therefore, pure GOS with definite structures were prepared and used in the present study to evaluate their effects on intestinal barrier function, inflammatory responses and short-chain fatty acids (SCFAs) produced in the colon of mice challenged with lipopolysaccharide (LPS). The results of 1H and 13C nuclear magnetic resonance spectral analyses indicated that the main structures of GOS with a degree of polymerization of 3 (trisaccharide) and 4 (tetrasaccharide) are [ß-Gal-(1 → 6)-ß-Gal(1 → 4)-ß-Glc] and [ß-Gal-(1 → 6)-ß-Gal-(1 → 6)-ß-Gal-(1 → 4)-ß-Glc], respectively. The results of an in vivo study in mice showed that intragastric administration of 0.5 g per kg BW GOS attenuated intestinal barrier damage and inflammatory responses induced by LPS in the jejunum and ileum, as indicated by increasing villus height and villus-to-crypt ratio, up-regulated intestinal tight junction (ZO-1, occludin, and claudin-1) gene expression, and down-regulated pro-inflammatory cytokines such as IL-1ß, IL-6, IFN-γ, and TNF-α gene expression. Nevertheless, the protective effects of GOS on the intestinal barrier are independent of glucagon-like peptide 2. In addition, 0.5 g per kg BW GOS administration promoted the recovery of colonic acetate, propionate, butyrate, and total SCFA production reduced by LPS challenge. The obtained results provide practical evidence that pure GOS can act as protective agents for intestinal health.

Clostridium tyrobutyricum Protects against LPS-Induced Colonic Inflammation via IL-22 Signaling in Mice.

This study aimed to investigate the effects of Clostridium tyrobutyricum (C. tyrobutyricum) on colonic immunity and the role of IL-22 in the protective function of C. tyrobutyricum. Mice were supplemented with 108 CFU/mL C. tyrobutyricum daily for 20 days, followed by injecting with LPS for 24 h. In vivo interference of IL-22 via injecting with an adeno-associated virus was conducted to elucidate the role of IL-22 in C. tyrobutyricum attenuating colonic inflammation. The results showed that C. tyrobutyricum decreased the mRNA expression of IL-6 and IL-1ß. C. tyrobutyricum enhanced the mRNA expression of IL-22 and the expression of MUC2 in the colon. The in vivo interference results showed that C. tyrobutyricum enhanced the mRNA expression of IL-6 and IL-1ß while decreased the expression of MUC2 after knocking down IL-22. The flow cytometric analysis showed that C. tyrobutyricum decreased the proportions of macrophages, DCs, and mast cells and effectively regulated the proportion of Th17 cells, indicating that C. tyrobutyricum may stimulate the expression of IL-22 via regulating Th17 cells. Our study concluded that C. tyrobutyricum protected against LPS-induced colonic barrier dysfunction and inflammation via IL-22 signaling, suggesting that C. tyrobutyricum could be a potential probiotic in regulating colonic health.

Prooxidation and Cytotoxicity of Selenium Nanoparticles at Nonlethal Level in Sprague-Dawley Rats and Buffalo Rat Liver Cells.

The effects of selenium nanoparticles (SeNPs) on the antioxidant capacity in Sprague-Dawley (SD) rats were investigated. The rats were given intragastric administration of an SeNP suspension at doses of 0, 2, 4, and 8 mg Se/kg BW for two weeks. The antioxidant capacity in serum and organic tissues (liver, heart, and kidney) and the gene expression levels of glutathione peroxidase 1 (GPX1) and glutathione peroxidase 4 (GPX4) in the liver were measured. Buffalo rat liver (BRL) cell lines were further constructed to explore the cytotoxicity mechanism induced by SeNPs through the determination of antioxidant capacity; cell activity; apoptosis; and Caspase-3, Caspase-8, and Caspase-9 family activities. The results showed that SeNP administration over 4.0 mg Se/kg BW decreased the antioxidant capacities in the serum, liver, and heart and downregulated mRNA expression of GPX1 and GPX4 in the liver. The BRL cell line experiments showed that treatment with over 24 µM SeNPs decreased the viability of the cells and damaged the antioxidant capacity. Flow cytometry analysis showed that decreased cell viability induced by SeNPs is mainly due to apoptosis, rather than cell necrosis. Caspase-3 and Caspase-8 activities were also increased when BRL cells were treated with 24 µM and 48 µM SeNPs. Taken together, a nonlethal level of SeNPs could impair the antioxidant capacity in serum and organic tissues of rats, and the liver is the most sensitive to the toxicity of SeNPs. A pharmacological dose of SeNPs could lead to cytotoxicity and induce cell death through apoptosis and extrinsic pathways contributing to SeNP-induced apoptosis in BRL cells.

Effects of inorganic trace minerals replaced by complexed glycinates on reproductive performance, blood profiles, and antioxidant status in broiler breeders.

This study was conducted to investigate the effects of replacing inorganic trace minerals (ITM) with organic trace minerals (OTM; complexed glycinates) on reproductive performance, blood profiles, and antioxidant status in broiler breeders. A total of 648, 23-week-old healthy broiler breeders (ZhenNing), with similar body weight (1.40 ± 0.002 kg), were randomly divided into 4 groups with 6 replicates in each group (27 hens/replicate) and fed the respective experimental diets for 14 wk (including 2 wk for adaptation). The experimental treatments consisted of T1: Cont., commercially recommended levels of ITM (Cu, Zn, Fe, and Mn sulfates); T2: Mix, half trace minerals (TM) were provided from ITM and half from OTM (glycinates); T3: M-OTM, TM were provided from glycinates and reduced to 70% of T1; T4: L-OTM, TM were provided from glycinates and reduced to 50% of T1. The results showed that commercial level of inorganic trace minerals replaced by low-dose complexed glycinates (T3 and T4) exhibited no significant effects on laying performance, 50% ITM replaced by complexed glycinates (T2) numerically improved laying rate by 1.23% than cont. treatment (T1). Broiler breeders fed complexed glycinates tended to produce more qualified eggs (P = 0.05) in T3, with better yolk color (P < 0.01) and eggshell thickness (P = 0.05) in T2 treatment. Replacement of low-dose complexed glycinates reduced fertilization rate (P < 0.01), while it did not affect hatchability. There were no significant differences in serum reproductive hormones such as estrogen and progesterone among the treatments. Serum total protein, albumin, and phosphorus were increased respectively with the replacement of ITM by low-dose OTM from complexed glycinates (P < 0.05). Total liver antioxidant capacity in M-OTM and L-OTM treatment was higher than that of Cont. and Mix treatments (P < 0.01). In conclusion, replacement of high levels of ITM by lower levels of OTM in the form of complexed glycinates is beneficial for egg quality and liver antioxidant status in broiler breeders during the peak laying period.

Effects of Replacing Inorganic with Respective Complexed Glycinate Minerals on Apparent Mineral Bioavailability and Deposition Rate in Tissues of Broiler Breeders.

The study was conducted to evaluate the effects of replacing inorganic trace minerals (ITMs) with respective low-dose complexed glycinate minerals (CGMs) on their bioavailability and retention during peak laying period of broiler breeders. In this experiment, 648 ZhenNing broiler breeders (23 weeks old) were randomly allocated to four treatments with six replicates (27 birds/replicate) and fed for 14 weeks including 2 weeks adaptation period. The treatments were T1-ITM, commercially recommended levels of ITMs (Cu, Zn, Fe, and Mn sulphates); T2-MIX, half of the minerals were supplemented with ITMs and half with CGMs; T3-L-CGMs, minerals were supplemented with CGMs (50% level of T1); and T4-M-CGMs, minerals were supplemented with CGMs (70% level of T1). The results showed that birds fed on ITM had lower bioavailability of Fe, Mn, and Zn (P < 0.05) than those fed on L-CGMs, but the highest (P < 0.01) bioavailability of Cu was found in those fed on MIX. Mineral retention (in serum, muscle, bone, and tissues) was not affected by reducing supplementation levels of trace minerals up to 50% of ITMs, but Zn (in serum, liver, kidney, heart, and albumen) and Fe (in serum and the yolk) retention was negatively affected (P < 0.05). In conclusion, replacing dietary ITMs with low-dose complexed glycinate minerals increases the apparent bioavailability of Fe, Mn, and Zn without compromising the mineral retention rates in most of the tissues tested.

Optimization for galactooligosaccharides synthesis: A potential alternative for gut health and immunity.

AIMS: Present study was conducted to optimize the processing parameters for galactooligosaccharides (GOS) synthesis from whey powder followed by exploring its prebiotic efficiency. MAIN METHODS: All factors (initial lactose concentration, pH, reaction time, temperature and enzyme to substrate ratio; E/S) were analyzed by single factor analysis and optimization for GOS yield was done following the orthogonal experimental design. For in vivo analysis, 60 mice were equally divided into four groups (normal control, NC; low, medium, and high dose of GOS, LG, MG and HG) and fed varying levels (0, 0.25, 0.5 and 1.0 g/kg bw per day) of GOS, for 30 days and sampling was done at the end of experiment regarding gut health, immunity, cecal microbiota and metabolites. KEY FINDINGS: Optimum yield of GOS (25.1%) was obtained at reaction time 25 min, temperature 50 °C, pH 4.5 and the enzyme to substrate ratio (E/S) of 20 U/g. In vivo experiment, shallower crypt and greater villus to crypt ratio (V/C) were found in the duodenum of LG treatment compared to NC mice (P < .05). The GOS promotes thymus development and improve immunity. Intervention with GOS increased the population of bifidobacterium and lactobacillus in MG and bifidobacterium in LG mice (P < .05), and was accompanied by decreased proliferation of desulfovibrio. Correlation analysis also supported the above findings. SIGNIFICANCE: This study optimized the processing parameters for GOS preparation and provided data encouraging to suggest that GOS can be a potential option to improve the gut health and immunity.

Chitosan Oligosaccharide Attenuates Nonalcoholic Fatty Liver Disease Induced by High Fat Diet through Reducing Lipid Accumulation, Inflammation and Oxidative Stress in C57BL/6 Mice.

Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease closely associated with metabolic syndrome, but there are no validated pharmacological therapies. The aim of this study was to investigate the effect of chitosan oligosaccharide (COS) on NAFLD. Mice were fed either a control diet or a high-fat diet (HFD) with or without COS (200 or 400 mg/kg body weight (BW)) by oral gavage for seven weeks. Administration with COS significantly lowered serum lipid levels in the HFD-fed mice. The hepatic lipid accumulation was significantly decreased by COS, which was attributed to decreased expressions of lipogenic genes and increased expressions of fatty ß-oxidation-related genes. Moreover, pro-inflammatory cytokines, neutrophils infiltration, and macrophage polarization were decreased by COS in the liver. Furthermore, COS ameliorated hepatic oxidative stress by activating the nuclear factor E2-related factor 2 (Nrf2) pathway and upregulating gene expressions of antioxidant enzymes. These beneficial effects were mediated by the activation of the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Therefore, COS might be a potent dietary supplement to ameliorate NAFLD.

Comparison of Inorganic and Organically Bound Trace Minerals on Tissue Mineral Deposition and Fecal Excretion in Broiler Breeders.

This study investigated the effects of replacement of inorganic trace minerals (ITMs) by organic trace minerals (OTMs) on tissue mineral retention and fecal excretion in "Zhen Ning" yellow feather broiler breeders. Six hundred hens (initial BW: 1.70 ± 0.07 kg) aged 40 weeks were randomly divided into five treatments, with four replicates of 30 broiler breeders each. Experimental treatments were as follows: (1) ITM (Cu, Zn, Fe, Mn, Se providing commercially recommended concentrations), (2) L-ITM (50% of the ITM, except for Se), (3) VL-OTM (37.5% of the ITM, except for Se), (4) L-OTM (equivalent to L-ITM), and (5) OTM (62.5% of the ITM, except for Se). The duration of the study was 10 weeks including 2 weeks for adaptation. Compared with the L-ITM treatment, high-level supplementation of minerals in ITM and OTM increased the concentration of serum Mn and Se, pectoral Fe and pancreas Cu, and Fe (P < 0.05). Birds fed with OTM dietary exhibited comparable mineral retention in muscle compared with ITM. Differences were observed between L-ITM and L-OTM in serum Mn and Se, pectoral Fe, Zn, and Se, and heart Se with L-OTM retaining higher mineral concentrations than L-ITM (P < 0.05). L-OTM retained identical concentration with ITM treatment, except for the pancreatic Fe. All three organic diets reduced the Zn in excreta compared with the two inorganic diets (P < 0.05). This study indicates that replacement of dietary ITMs by OTMs improved mineral deposition in tissues and reduced fecal mineral excretion in broiler breeders under the conditions of this study.

Effects of dietary zinc oxide nanoparticles supplementation on growth performance, zinc status, intestinal morphology, microflora population, and immune response in weaned pigs.

BACKGROUND: This study evaluated the effects of dietary zinc oxide nanoparticles (nano-ZnOs) on growth performance, zinc status, intestinal morphology, microflora population, and immune response in weaned piglets. A total of 150 weaned piglets (9.37 ± 0.48 kg) were randomly allotted to five dietary treatments and fed with a basal diet (control), or the basal diet supplemented with nano-ZnOs at 150, 300, or 450 mg kg-1 , and 3000 mg kg-1 ZnO for 21 days. After a feeding test, six pigs from the control, 450 mg kg-1 nano-ZnOs and 3000 mg kg-1 ZnO groups were slaughtered. RESULTS: Compared with the control, dietary supplements of nano-ZnOs and ZnO could improve (P < 0.05) average daily weight gain (ADG), average daily feed intake (ADFI), and villus height to crypt depth ratio in the duodenum and jejunum, and decrease (P < 0.05) diarrhea incidence. Zinc retention in the serum, heart, liver, spleen and kidney of pigs supplemented with nano-ZnOs and ZnO was increased (P < 0.05). Nano-ZnOs decreased (P < 0.05) the zinc excretion compared with conventional ZnO. Lower Escherichia coli counts in the cecum, colon, and rectum were observed (P < 0.05) in the nano-ZnOs group compared with the other groups. Compared with the control, ZnO and nano-ZnOs increased (P < 0.05) the serum concentration of IgA, IL-6, and TNF-α, and decreased (P < 0.05) the concentration of IgM. CONCLUSION: These results indicated that low doses of nano-ZnOs can have beneficial effects on growth performance, intestinal morphology and microflora, and immunity in weanling pigs, which are similar to the effects of pharmacological dosages of conventional ZnO. Nano-ZnOs may reduce mineral excretion, which may reduce environmental challenges. © 2018 Society of Chemical Industry.

Production of butyric acid from acid hydrolysate of corn husk in fermentation by Clostridium tyrobutyricum: kinetics and process economic analysis.

BACKGROUND: Butyric acid is an important chemical currently produced from petrochemical feedstocks. Its production from renewable, low-cost biomass in fermentation has attracted large attention in recent years. In this study, the feasibility of corn husk, an abundant agricultural residue, for butyric acid production by using Clostridium tyrobutyricum immobilized in a fibrous bed bioreactor (FBB) was evaluated. RESULTS: Hydrolysis of corn husk (10% solid loading) with 0.4 M H2SO4 at 110 °C for 6 h resulted in a hydrolysate containing ~ 50 g/L total reducing sugars (glucose:xylose = 1.3:1.0). The hydrolysate was used for butyric acid fermentation by C. tyrobutyricum in a FBB, which gave 42.6 and 53.0% higher butyric acid production from glucose and xylose, respectively, compared to free-cell fermentations. Fermentation with glucose and xylose mixture (1:1) produced 50.37 ± 0.04 g L-1 butyric acid with a yield of 0.38 ± 0.02 g g-1 and productivity of 0.34 ± 0.03 g L-1 h-1. Batch fermentation with corn husk hydrolysate produced 21.80 g L-1 butyric acid with a yield of 0.39 g g-1, comparable to those from glucose. Repeated-batch fermentations consistently produced 20.75 ± 0.65 g L-1 butyric acid with an average yield of 0.39 ± 0.02 g g-1 in three consecutive batches. An extractive fermentation process can be used to produce, separate, and concentrate butyric acid to > 30% (w/v) sodium butyrate at an economically attractive cost for application as an animal feed supplement. CONCLUSION: A high concentration of total reducing sugars at ~ 50% (w/w) yield was obtained from corn husk after acid hydrolysis. Stable butyric acid production from corn husk hydrolysate was achieved in repeated-batch fermentation with C. tyrobutyricum immobilized in a FBB, demonstrating that corn husk can be used as an economical substrate for butyric acid production.

Clostridium Tyrobutyricum Protect Intestinal Barrier Function from LPS-Induced Apoptosis via P38/JNK Signaling Pathway in IPEC-J2 Cells.

BACKGROUND/AIMS: The intestinal mucosa forms a physical and metabolic barrier against the diffusion of pathogens, toxins, and allergens from the lumen into the circulatory system. Early weaning, a critical phase in swine production, can compromise intestinal barrier function through mucosal damage and alteration of tight junction integrity Maintenance of intestinal barrier function plays a pivotal role in optimum gastrointestinal health. In this study, we investigated the effects of Clostridium tyrobutyricum (C.t) on intestinal barrier dysfunction induced by lipopolysaccharide (LPS) and the underlying mechanisms involved in intestinal barrier protection. METHODS: A Transwell model of IPEC-J2 cells was used to imitate the intestinal barrier. Fluorescence microscopy and flow cytometry were used to evaluate apoptosis. Real-time PCR was used to detect apoptosis-related genes and the downstream genes of the p38/c-Jun N-terminal kinase (JNK) signaling pathways. Western blotting was used to measure the expressions of tight junction proteins and mitogen-activated protein kinases. RESULTS: C.t efficiently maintained trans-epithelium electrical resistance values and intestinal permeability after LPS-induced intestinal barrier disruption. The expressions of tight junction proteins (ZO-1, claudin-1, and occludin) were promoted when IPEC-J2 cells were treated with C.t. Fluorescence imaging and flow cytometry revealed that C.t qualitatively and quantitatively inhibited LPS-induced cell apoptosis. C.t also increased the relative expression of the anti-apoptotic gene Bcl-2 and decreased that of the apoptotic genes Bax and caspase-3/-8. Moreover, the protective effect of C.t on damaged intestinal cell models was associated with suppression of p38 and JNK phosphorylation, negative regulation of the relative expressions of downstream genes including AP-1, ATF-2, ELK-1, and p53, and activation of Stat3 expression. CONCLUSIONS: These findings indicate that C.t may promote intestinal integrity, suggesting a novel probiotic effect on intestinal barrier function.

Coaxial technique-promoted diagnostic accuracy of CT-guided percutaneous cutting needle biopsy for small and deep lung lesions.

Coaxial technique is extensively applied to facilitate percutaneous lung lesion biopsy. However, the impact of coaxial technique on diagnostic accuracy remains undecided. We reviewed 485 patients who underwent percutaneous CT-guided needle biopsies of lung lesions in our hospital. All of these biopsies were performed using either a cutting needle alone (n = 268) or a cutting needle combined with a coaxial needle (n = 217). The diagnostic accuracy and complications resulting from the two techniques were then compared. The diagnostic accuracies of the two techniques were comparably high, at 98.2% (with coaxial technique) and 95.9% (without coaxial technique), p = 0.24. Subgroup analysis discovered that for patients with lesions measuring < 1.5 cm and needle path length ≥ 4 cm, the coaxial technique achieved a higher diagnostic accuracy (95.5% vs. 72.7%, p = 0.023). The biopsy was well tolerated in all of the patients. Pneumothorax occurred less often in patients who were biopsied with the coaxial technique (19 versus 43, p = 0.024). Thus, the application of the coaxial technique could improve diagnostic accuracy in patients with small and deep lung lesions, and could reduce the risk of pneumothorax. The combined use of cutting needles with coaxial needles is the preferred technique for performing percutaneous CT-guided lung biopsies.

Effect of Ku80 on the radiosensitization of cisplatin in the cervical carcinoma cell line HeLa.

Cisplatin chemotherapy in combination with radiotherapy is the primary therapeutic strategy for the treatment of cervical cancer; however, the underlying molecular mechanism for cisplatin radiosensitization remains unknown. The aim of the present study was to investigate the effect of Ku80, a DNA double-strand break (DSB) repair protein, on cisplatin radiosensitization in cervical cancer. The pre-established Ku80 suppression cervical cancer cell line HeLa/Ku80-siRNA and the normal HeLa cell line underwent 6 MV X-ray irradiation (6 Gy) individually or in combination with 5 µg/ml cisplatin treatment. Alterations in apoptosis, the cell cycle and γH2AX expression were detected. Following irradiation individually and combined with cisplatin, compared with normal HeLa cells, HeLa/Ku80-siRNAexhibited an increased rate of apoptosis (P<0.05). It was identified that the earlier cisplatin was administered following irradiation, the higher the rate of apoptosis. Cell cycle analysis indicated that, following irradiation combined with cisplatin, the cells were arrested in G1 and S phase rather than in G2/M phase following irradiation alone. Microscopic imaging of immunofluorescence staining and western blotting identified that HeLa/Ku80-siRNA cells exhibited more γH2AX foci remaining following treatment with irradiation and cisplatin, particularly in the group treated with 6 Gy irradiation for 1 h together with 23 h of exposure to cisplatin. Irradiation in combination with cisplatin promoted the apoptosis of HeLa cells in association with the inhibition of Ku80, and it was identified that the earlier cisplatin was administered following irradiation, the more apoptosis was induced. This maybe because irradiation combined with cisplatin is able to arrest cells in G1 and S phase to rapidly repair damaged DNA, and the lack of Ku80 induces the inability to repair DSB, resulting in increased apoptosis. The results of the present study suggest that Ku80 may be a potent molecular target in cisplatin radiosensitization.

Effects of Selenium Nanoparticles on Reproductive Performance of Male Sprague-Dawley Rats at Supranutritional and Nonlethal Levels.

This research investigated the influence of selenium nanoparticles (SeNPs) on the reproductive performance of male Sprague-Dawley (SD) rats. A suspension of SeNPs was consecutively administered by oral gavage for 2 weeks at supranutritional (0.2, 0.4, or 0.8 mg Se/kg bw) and nonlethal (2.0, 4.0, or 8.0 mg Se/kg bw) levels to male SD rats. The normal control (NC) rats were exposed to physiological saline alone. Biochemical parameters, sperm motility, gene expression of GPx1 and GPx4, and histopathological evaluation of male spermary were measured in this work. The supranutritional doses could promote the sperm motility (P < 0.001) and movement parameters (P < 0.05). The nonlethal levels of 4.0 and 8.0 mg Se/kg bw reduced the testis weight (P < 0.001), sperm concentration, and motility (P < 0.05), and also caused histopathological injury of testis and epididymis tissues to various degrees. The content of testosterone in serum was increased in the 0.8 group (P < 0.05) and decreased in the 4.0 (P < 0.01) and 8.0 mg Se/kg bw groups (P < 0.001), respectively. No significant effects were observed on antioxidant enzyme activities and mRNA concentration of GPx in the supranutritional dose group, and nonlethal levels were also not observed. In conclusion, SeNPs in the supranutritional dose has a positive effect on the reproductive function of male SD rats and has damaging effect higher than 4.0 mg Se/kg bw.