Pentadecanoic acid (C15:0, PA) induces mild maternal glucose intolerance and promotes the growth of the offspring partly through up-regulating liver PPARα and MAPK signaling pathways.

Gestational diabetes mellitus (GDM) is one of the most common metabolic disturbances during pregnancy, which poses a serious threat to both maternal and offspring health. Pentadecanoic acid (C15:0, PA) is one of the most common odd-chain saturated fatty acids (OCS-FAs). However, its safety and nutritional value are yet to be verified. Herein, we provide a systematic assessment of the effects of PA on maternal and progeny health and insulin sensitivity for the first time. Our results showed that consumption of 1% PA during pregnancy could increase the contents of PA and heptadecanoic acid (C17:0) in maternal plasma, fetal tissue and offspring plasma, but it had no effect on embryonic development. During pregnancy, PA treatment caused mild insulin resistance, while it had little effect on the maternal body composition. During lactation, PA treatment caused mild insulin resistance and oxidative stress. Maternal body fat deposition was also reduced, but the growth rate of the offspring was faster. It is worth noting that PA treatment decreased plasma and liver TG content and increased the antioxidant capacity of the offspring. The effect of PA on the transcription and expression genes in the liver of pregnant mice was investigated using RNA-seq. PPARα and MAPK signaling pathways, both closely related to lipolysis, inflammation, oxidative stress, and insulin resistance were significantly increased. The expression of c-JUN, ERK, JNK and P65 proteins was also significantly up-regulated. In conclusion, our results suggest that 1% PA can induce a mild decrease in the maternal glucose tolerance and lipolysis mainly by activated MAPK and PPARα signaling. Moreover, low concentrations of PA may be an effective nutrient to alleviate the oxidative stress and reduce blood lipid levels of offspring.

Supernatural Beliefs-Based Intervention to Improve Type-2 Diabetes Self-Management: A Pilot Randomized Controlled Trial from China.

China has over 100 million people living with type 2 diabetes mellitus (T2DM). Interventions framed around pre-existing personal beliefs in the supernatural may improve T2DM self-management, but such interventions are lacking in China. This pilot randomized controlled trial (RCT) assessed the feasibility of a full-scale RCT to evaluate the efficacy of a supernatural beliefs-based intervention on T2DM management self-efficacy in China. In 2019, 62 T2DM patients were enrolled at two hospitals in Suzhou, China. Participants were randomly assigned to view a 30-s control or intervention video at baseline. The control video showed general diabetes self-management information. The intervention video showed identical information, but also indicated that some diabetics with supernatural beliefs (chao ziran xinnian) have lower glycemic levels, because their beliefs enhance their confidence in diabetes self-management. Development of the intervention was guided by the theory of planned behavior and literature on spiritual framing health interventions. Baseline and follow-up measures after two weeks were assessed by interviewer administered surveys in-person and by telephone, respectively. Diabetes management self-efficacy was assessed with the diabetes management self-efficacy scale. Randomization of intervention allocation appeared to be successful. However, follow-up retention was low, especially for the intervention group (3% vs. 31%). A full-size efficacy RCT using the current study design is unlikely to succeed. T2DM patients shown the supernatural beliefs-based intervention had significantly higher loss to follow-up that was insurmountable. T2DM patients in Suzhou, China may not be receptive to brief, non-tailored supernatural beliefs-based interventions delivered to a general population in clinical settings.

Wearable electrochemical glucose sensor of high flexibility and sensitivity using novel mushroom-like gold nanowires decorated bendable stainless steel wire sieve.

Long-term high blood glucose levels brings extremely detrimental effect on diabetic patients, such as blindness, renal failure, and cardiovascular diseases. Therefore, there is an urgent need to develop highly flexible and sensitive sensors for precisely non-invasive and continuous monitoring glucose levels. Herein, we present a highly flexible and sensitive wearable sensor for non-enzymatic electrochemical glucose analysis with vertically aligned mushroom-like gold nanowires (v-AuNWs) chemically grown on stainless steel wire sieve (SSWS) as integrated electrode. Owing to the unique nanostructures and excellent catalysis of the v-AuNWs, the as-fabricated glucose sensors exhibit superior flexibility and excellent electro-catalytic capability. In detail, these sensors display rapid response towards glucose within 5 s, and the sensor constructed with v-AuNWs for growth time of 15 min shows the highest sensitivity of 180.1 µA mM-1 cm-2 within a wide linear range of 6.5 × 10-4 mM-12.0 mM and the lowest detection limit of 0.65 µM (S/N = 3). It is noteworthy that due to the good ductility of the v-AuNWs and their strong contact with the SSWS substrate, these glucose sensors exhibit no obvious response variation after repeated bending for 100 times at bending angle of 180°. Additionally, the glucose sensors display superior anti-interfering capability as well as desirable repeatability. More importantly, these glucose sensors can be attached on human skin to determine sweat glucose reliably and analyze glucose concentration in human serum in vitro.

Chemical Synthesis, Safety and Efficacy of Antihypertensive Candidate Drug 221s (2,9).

Hypertension is the main risk factor of cardiovascular and cerebrovascular diseases. In this paper, a novel compound known as 221s (2,9), which includes tanshinol, borneol and a mother nucleus of ACEI, was synthesized by condensation esterification, deprotection, amidation, deprotection, and amidation, with borneol as the initial raw material, using the strategy of combinatorial molecular chemistry. The structure of the compound was confirmed by 1H NMR, 13C NMR, and high-resolution mass spectrometry, with a purity of more than 99.5%. The compound 221s (2,9) can significantly reduce the systolic and diastolic blood pressure of SHR rats by about 50 mmHg and 35 mmHg after 4 weeks of administration. The antihypertensive effect of 221s (2,9) is equivalent to that of captopril. The use of 221s (2,9) can reduce the content of Ren, Ang II and ACE in the serum of SHR rats, inhibit the RAAS and enhance the vascular endothelial function by upregulating the level of NO. Pathological studies in this area have shown that high dosage of 221s (2,9) can notably protect myocardial fibrosis in rats and reduce the degeneration and necrosis of myocardial fibers, inflammatory cell infiltration, and proliferation of fibrous tissue in the heart of rat. Therefore, the existing work provided a foundation for preclinical research and follow-up clinical research of 221s (2,9) as a new drug.

Multi-omics analysis reveals gut microbiota-ovary axis contributed to the follicular development difference between Meishan and Landrace × Yorkshire sows.

BACKGROUND: The mechanism by which Meishan (MS) sows are superior to white crossbred sows in ovarian follicle development remains unclear. Given gut microbiota could regulate female ovarian function and reproductive capacity, this study aimed to determine the role of gut microbiota-ovary axis on follicular development in sows. METHODS: We compared the ovarian follicular development, gut microbiota, plasma metabolome, and follicular fluid metabolome between MS and Landrace × Yorkshire (L × Y) sows. A H2O2-induced cell apoptosis model was used to evaluate the effects of multi-omics identified metabolites on the apoptosis of porcine ovarian granulosa cells in vitro. RESULTS: Compared with L × Y sows, MS sows have greater ovary weight and improved follicular development, including the greater counts of large follicles of diameter ≥ 5 mm, secondary follicles, and antral follicles, but lesser atretic follicles. The ovarian granulosa cells in MS sows had alleviated apoptosis, which was indicated by the increased BCL-2, decreased caspases-3, and decreased cleaved caspases-3 than in L × Y sows. The ovarian follicular fluid of MS sows had higher concentrations of estradiol, progesterone, follicle-stimulating hormone, luteinizing hormone, and insulin like growth factor 1 than L × Y sows. Gut microbiota of MS sows formed a distinct cluster and had improved alpha diversity, including increased Shannon and decreased Simpson than those of L × Y sows. Corresponding to the enhanced function of carbohydrate metabolism and elevated short-chain fatty acids (SCFAs) in feces, the differential metabolites in plasma between MS and L × Y sows are also mainly enriched in pathways of fatty acid metabolism. There were significant correlations among SCFAs with follicular development, ovarian granulosa cells apoptosis, and follicular fluid hormones, respectively. Noteworthily, compared with L × Y sows, MS sows had higher follicular fluid SCFAs concentrations which could ameliorate H2O2-induced porcine granulosa cells apoptosis in vitro. CONCLUSION: MS sows have more secondary and antral follicles, but fewer atretic follicles and apoptotic ovarian granulosa cells, as well as harbored a distinctive gut microbiota than L × Y sows. Gut microbiota may participate in regulating ovarian follicular development via SCFAs affecting granulosa cells apoptosis in sows.

Evaluation of Solubility, Physicochemical Properties, and Cytotoxicity of Naproxen-Based Ionic Liquids.

To solve the problems associated with poorly water-soluble nonsteroidal anti-inflammatory drugs (NSAIDs), naproxen-based ionic liquids (ILs) containing naproxen as an active pharmaceutical ingredient (API) anion were prepared with benzalkonium (tetradecyldimethylbenzyl ammonium), choline, and 1-octyl-3-methylimidazole as the cation. The structures and thermal properties were analyzed. Through the conductivity method, the solubility at 25 and 37 °C and the critical micelle concentration (CMC) at 25 °C were determined in water and ethanol. The octanol-water partition coefficients (K ow) at 25 °C were measured with the shake-flask method. The cytotoxicity was evaluated with the MTT method. The results showed that the conversion of naproxen into the API-ILs increased the API's solubility in water by more than 850 times compared with the original API, and the thermostability was satisfactory with a lower glass transition temperature (t g). Moreover, the variation trends of solubility, hydrophilicity, and K ow were consistent with the different structures of naproxen-based ILs, except for benzalkonium naproxen. The CMC (10-5-10-6 M) in water and ethanol demonstrated that the naproxen-based ILs were surface activite ILs. The IC50 values exhibited the low cytotoxicity of the naproxen-based ILs, which was better than 100 µM. The results provide essential information and a research basis for future topical and transdermal administration and oral administration of naproxen-based ILs.

Investigation on the surface morphologies of reduced graphene oxide coating on the interfacial characteristics and electro-catalytic capacity of enzymatic glucose sensors.

In this study, reduced graphene oxide (rGO) were subject to ultrasonic treatment to acquire varied morphologies, and the enzymatic glucose sensors were constructed by coating the rGO onto indium tin oxide electrodes and physically linking glucose oxidase to the rGO coatings. The effects of the surface morphologies of the rGO coatings on the interfacial characteristics and the electro-catalytic capacity of the enzymatic glucose sensors were systematically investigated. It turns out that, the rGO coating with a rough surface is more hydrophilic, and exhibits uniform glucose oxidase adsorption and higher electron migration rate at the solid/liquid interface between the analytical liquid and the working electrode. As a result, the corresponding glucose sensor shows excellent electro-catalytic capacity towards glucose with a broader linear range of 0-10.0 mM, a higher sensitivity of 38.9µA·mM-1·cm-2, and a lower detection limit of 0.1µM (signal-to-noise ratio of 3). Additionally, the as-prepared glucose sensor exhibits excellent accuracy for detecting actual blood samples as well as superior resistance to interference from other substances (such as L-phenylalanine, urea, ascorbic acid, uric acid, NaCl, and KCl). These results establish the theoretical and experimental foundation for the application of rGO coating in the field of biosensors.

Effects of palmitic acid and eicosapentaenoic acid on angiogenesis of porcine vascular endothelial cells.

Restricted placental angiogenesis is an important cause of intrauterine growth retardation in piglets. During pregnancy, sow obesity can result in an increase in placental lipid deposition, subsequently inhibiting placental angiogenesis and fetal development. However, the effect of different types of fatty acids on placental angiogenesis is still unclear. Trophoblast cells and vascular endothelial cells constitute two important types of placental tissue. In this study, we used palmitic acid (C16:0) and eicosapentaenoic acid (C20:5, n-3), respectively, to treat porcine trophectoderm cells (pTr2) and porcine iliac artery endothelial cells (PIEC) to study the effects of saturated fatty acids and n-3 polyunsaturated fatty acids (PUFAs) on placental angiogenesis in vitro. We found that C16:0 caused significant cytotoxicity in pTr2 and PIEC (p < 0.01) and inhibited the proliferation and migration of PIEC (p < 0.01), whereas C20:5 treatment exhibited very low cytotoxicity and minimal inhibition of cellular proliferation. Meanwhile, a low concentration of C16:0 had no effect on the tube formation in PIEC, whereas C20:5 significantly promoted tube formation of PIEC (p < 0.01). These results suggested that saturated fatty acids and n-3 PUFAs had different effects on placental angiogenesis. As essential functional fatty acid, n-3 PUFA might be effective measure in alleviating the placental lipotoxicity caused by sow obesity during pregnancy.

Gut health: The results of microbial and mucosal immune interactions in pigs.

There are a large number of microorganisms in the porcine intestinal tract. These microorganisms and their metabolites contribute to intestinal mucosal immunity, which is of great importance to the health of the host. The host immune system can regulate the distribution and composition of intestinal microorganisms and regulate the homeostasis of intestinal flora by secreting a variety of immune effector factors, such as mucin, secretory immunoglobulin A (sIgA), regenerating islet-derived III (RegIII)γ, and defensin. Conversely, intestinal microorganisms can also promote the differentiation of immune cells including regulatory T cells (Treg) and Th17 cells through their specific components or metabolites. Studies have shown that imbalances in the intestinal flora can lead to bacterial translocation and compromised intestinal barrier function, affecting the health of the body. This review focuses on the composition of the pig intestinal flora and the characteristics of intestinal mucosal immunity, discusses the interaction mechanism between the flora and intestinal mucosal immunity, as well as the regulation through fecal microbiota transplantation (FMT), dietary nutritional composition, probiotics and prebiotics of pig intestinal microecology. Finally, this review provides insights into the relationship between intestinal microorganisms and the mucosal immune system.

Gut microbiota contributes to the development of endometrial glands in gilts during the ovary-dependent period.

BACKGROUND: The hyper-prolificacy Meishan gilts achieved a superior endometrial gland development (EGD) than white crossbred gilts during the ovary-independent period (before 60 d of age). Then, the EGD continues under the management of ovary-derived steroid hormones that regulated by gut microbiota (after 60 d of age). However, whether Meishan gilts' superiority in EGD lasting to the ovary-dependent period (after 60 d of age) and the role of gut microbiota in this period both remain unclear. METHODS: Meishan gilts and Landrace x Yorkshire (LxY) gilts were raised under the same housing and feeding conditions until sexual maturity and then we compared their EGD and gut microbiota. Meanwhile, we transplanted fecal microbiota from Meishan gilts to L×Y gilts to explore the role of gut microbiota in EGD. We sampled plasma every 3 weeks and collected the uterus, ovary, liver, and rectal feces after the sacrifice. We then determined the hormone concentrations and expressions of the EGD-related genes. We also profiled the gut microbiota using 16S rDNA sequencing and metabolites of plasma and liver tissue using untargeted metabolomics. Finally, the correlation analysis and significant test was conducted between FMT-shifted gut microbes and EGD-related indices. RESULTS: Meishan gilts have larger endometrial gland area (P < 0.001), longer uterine horn length (P < 0.01) but lighter uterine horn weight (P < 0.05), a distinctive gut microbiota compared with L×Y gilts. Fecal microbiota transplantation (FMT) increased endometrial gland area (P < 0.01). FMT markedly shifted the metabolite profiles of both liver and plasma, and these differential metabolites enriched in steroid hormone biosynthesis pathway. FMT increased estradiol and insulin-like growth factor 1 but decreased progesterone dynamically. FMT also increased the expression of the EGD-related genes estrogen receptor 1 gene, epithelial cadherin, and forkhead box protein A2. There is a significant correlation between FMT-shifted gut microbes and EGD-related indices. CONCLUSION: Sexually matured Meishan gilts achieved a superior EGD than LxY gilts. Meanwhile, gut microbiota contribute to the EGD potentially via regulating of steroid hormones during the ovary-dependent period.

Dietary glycyl-glutamine supplementation ameliorates intestinal integrity, inflammatory response, and oxidative status in association with the gut microbiota in LPS-challenged piglets.

During weaning transition, mammalian newborns suffer severe enteric infections and thus induced gut microbiota dysbiosis, which in turn aggravates enteric disorder. The synthetic dipeptide glycyl-glutamine (GlyGln) has been used as a diet supplement to improve the weaning transition of newborns. However, the effect of dietary GlyGln supplementation on the gut microbiota of piglets with enteric infection remains unclear. Here, weaned piglets received a basal diet or a basal diet supplemented with 0.25% GlyGln for 3 weeks. Five piglets in each group received an intraperitoneal injection of lipopolysaccharide (LPS) (100 µg per kg BW) (LPS and GlyGln + LPS groups) and meanwhile five piglets in a control group received an intraperitoneal injection of saline (Ctrl group). The results showed that dietary GlyGln supplementation improved the LPS induced inflammation response and damage to the ileum morphology by increasing interleukin 10, tight junction proteins, villus height, and the ratio villus height/crypt depth, but decreasing the crypt depth. For the oxidative status, dietary GlyGln supplementation increased the ileal superoxide dismutase and meanwhile reduced the malondialdehyde and nitric oxide synthase activity (NOS) (total NOS and inducible NOS), compared with that in the LPS group. LPS challenge reduced the diversity of gut microbiota and enriched the facultative anaerobic Escherichia coli. The GlyGln restored alpha diversity and the structure of the gut microbiota by enriching obligate anaerobes and short-chain fatty acid (SCFA)-producing bacteria, including Clostridium, Lachnospira, Phascolarctobacterium, Roseburia, Lachnospiraceae, and Synergistetes. GlyGln enriched the gut microbiota function of carbohydrate metabolism and elevated the ileal SCFA concentrations of propionic acid and butyric acid that had been decreased by the LPS challenge. The beneficial effects of dietary GlyGln supplementation are closely associated with its enriched bacteria and SCFAs. Taken together, dietary GlyGln supplementation improved the gut microbiota dysbiosis induced by LPS challenge and enriched obligate anaerobes and SCFA-producing bacteria, which contributed to the amelioration of intestinal integrity, inflammatory responses, and oxidative status.

G Protein-Coupled Receptor 109A Maintains the Intestinal Integrity and Protects Against ETEC Mucosal Infection by Promoting IgA Secretion.

Several studies have reported an intricate link between the G protein-coupled receptor 109A (GPR109A) and intestinal health. Upon activation, induced by butyric acid and ß-hydroxybutyric acid, GPR109A regulates the expression of tight junction proteins, exerts anti-inflammatory effects, and maintains the integrity of the intestinal barrier. However, its function and the mechanism of action in combating the infection caused by exogenous pathogenic microorganisms remain unclear. This study established an animal model of infection by oral enterotoxigenic Escherichia coli (ETEC) gavage to examine the underlying mechanism(s) and protective effects of GPR109A on the intestinal tract. Experimental GPR109A-/-and GPR109A+/+ mice were orally administered with 1 × 109 colony-forming units (CFUs) of ETEC, and changes in body weight were then observed. The colonization and translocation of ETEC in the intestine were detected by the plate counting method. The expression of tight junction proteins and the levels of inflammatory factors and secretory IgA (SIgA) in the intestine were detected by quantitative real-time polymerase chain reaction (q-PCR), western blotting, enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry. The results demonstrated that GPR109A-/-mice were more susceptible to ETEC infection, showing more severe inflammatory reactions and intestinal damage. Moreover, the secretion of IgA in the intestinal tract of GPR109A+/+ mice was significantly increased after ETEC infection, whereas the IgA levels in GPR109A-/-mice did not change significantly. We added 5 g/L sodium butyrate to the drinking water of all mice. The GPR109A+/+ mice were protected against ETEC infection and no effect was observed in GPR109A-/-mice. Similarly, sodium butyrate increased the SIgA content in the gut of the GPR109A+/+ mice and no effect was observed in GPR109A-/-mice. In conclusion, activated GPR109A is effective against the colonization and translocation of ETEC in the gut and maintains the integrity of the intestinal barrier, possibly by promoting the secretion of intestinal IgA.

Modulation of Gut Microbial Community and Metabolism by Dietary Glycyl-Glutamine Supplementation May Favor Weaning Transition in Piglets.

Gut microbiota plays a crucial role in diet nutrient metabolism and maintaining host health. The synthetic dipeptides glycyl-glutamine (Gly-Gln) used as diet supplementation to improve the weaning transition of newborns could be metabolized by certain bacteria in vitro. However, the effect of diet Gly-Gln supplementation on gut microbiota in vivo remains largely unknown. 240 piglets at the age of 28 days (day 28) were randomly assigned to two groups that received a basal diet (Ctrl group) or a basal diet supplemented with 0.25% Gly-Gln (Gly-Gln group) for 3 weeks. Five piglets from each group were euthanized for sampling after overnight fasting on day 38 and day 49, respectively. We determined their structure shifts of the gut microbiota using 16S rDNA-based high-throughput sequencing analysis. Microbial metabolites short-chain fatty acids (SCFAs) in the ileum and the colon were determined with high-performance gas chromatography. The concentrations of endocrine peptides including epidermal growth factor, glucagon-like peptide-1, and glucagon-like peptide-2 in ileal mucosa, as well as the serum concentration of interleukin 1 beta, interleukin 6, interleukin 10, and tumor necrosis factor alpha were determined using Enzyme-Linked Immunosorbent Assay. In addition, we also checked the diarrhea ratio, growth performance, and intestinal morphology to assess the favorable effect of dietary Gly-Gln supplementation during the weaning transition. Dietary Gly-Gln supplementation beneficially altered the gut microbiota by increasing bacterial loading, elevating alpha diversity, and increasing the relative abundance of anaerobes and fiber-degrading bacteria (Phylum Fibrobacteres). Accordingly, the microbial metabolites SCFAs in both colon and ileum, as well as the downstream endocrine peptides in the ileum increased. Meanwhile, dietary Gly-Gln's favorable weaning transition was reflected in the increase of growth performance indices and the reduced inflammatory response in a time dependent manner. There were significant correlations among the bacteria which responded to dietary Gly-Gln supplementation and these checked indices. Taken together, dietary Gly-Gln supplementation selectively modulated the gut microbiota, which may favor piglets' weaning-transition. These findings suggest that gut microbiota targeted approaches can be potentially used to improve weaning transition of piglets by dietary functional amino acid.

Standardized Preparation for Fecal Microbiota Transplantation in Pigs.

The intestine of pigs harbors a mass of microorganisms which are essential for intestinal homeostasis and host health. Intestinal microbial disorders induce enteric inflammation and metabolic dysfunction, thereby causing adverse effects on the growth and health of pigs. In the human medicine, fecal microbiota transplantation (FMT), which engrafts the fecal microbiota from a healthy donor into a patient recipient, has shown efficacy in intestinal microbiota restoration. In addition, it has been used widely in therapy for human gastrointestinal diseases, including Clostridium difficile infection, inflammatory bowel diseases, and irritable bowel syndrome. Given that pigs share many similarities with humans, in terms of anatomy, nutritional physiology, and intestinal microbial compositions, FMT may also be used to restore the normal intestinal microbiota of pigs. However, feasible procedures for performing FMT in pigs remains unclear. Here, we summarize a standardized preparation for FMT in pigs by combining the standard methodology for human FMT with pig production. The key issues include the donor selection, fecal material preparation, fecal material transfer, stool bank establishment, and the safety for porcine FMT. Optimal donors should be selected to ensure the efficacy of porcine FMT and reduce the risks of transmitting infectious diseases to recipients during FMT. Preparing for fresh fecal material is highly recommended. Alternatively, frozen fecal suspension can also be prepared as an optimal choice because it is convenient and has similar efficacy. Oral administration of fecal suspension could be an optimal method for porcine fecal material transfer. Furthermore, the dilution ratio of fecal materials and the frequency of fecal material transfer could be adjusted according to practical situations in the pig industry. To meet the potential large-scale requirement in the pig industry, it is important to establish a stool bank to make porcine FMT readily available. Future studies should also focus on providing more robust safety data on FMT to improve the safety and tolerability of the recipient pigs. This standardized preparation for porcine FMT can facilitate the development of microbial targeted therapies and improve the intestinal health of pigs.

Lactobacillus frumenti Facilitates Intestinal Epithelial Barrier Function Maintenance in Early-Weaned Piglets.

Increased intestinal epithelial barrier function damages caused by early weaning stress have adverse effects on swine health and feed utilization efficiency. Probiotics have emerged as the promising antibiotic alternatives used for intestinal barrier function damage prevention. Our previous data showed that Lactobacillus frumenti was identified as a predominant Lactobacillus in the intestinal microbiota of weaned piglets. However, whether the intestinal epithelial barrier function in piglets was regulated by L. frumenti is still unclear. Here, piglets received a PBS vehicle or PBS suspension (2 ml, 108 CFU/ml) containing the L. frumenti by oral gavage once a day during the period of 6-20 days of age prior to early weaning. Our data demonstrated that oral administration of L. frumenti significantly improved the intestinal mucosal integrity and decreased the serum endotoxin and D-lactic acid levels in early-weaned piglets (26 days of age). The intestinal tight junction proteins (including ZO-1, Occludin, and Claudin-1) were significantly up-regulated by L. frumenti administration. The serum immunoglobulin G (IgG) levels, intestinal secretory immunoglobulin A (sIgA) levels, and interferon-γ (IFN-γ) levels were significantly increased by L. frumenti administration. Furthermore, our data revealed that oral administration of L. frumenti significantly increased the relative abundances of health-promoting microbes (including L. frumenti, Lactobacillus gasseri LA39, Parabacteroides distasonis, and Kazachstania telluris) and decreased the relative abundances of opportunistic pathogens (including Desulfovibrio desulfuricans and Candida humilis). Functional alteration of the intestinal bacterial community by L. frumenti administration was characterized by the significantly increased fatty acids and protein metabolism and decreased diseases-associated metabolic pathways. These findings suggest that L. frumenti facilitates intestinal epithelial barrier function maintenance in early-weaned piglets and may be a promising antibiotic alternative used for intestinal epithelial barrier function damage prevention in mammals.

Role of gene polymorphisms/haplotypes and serum levels of interleukin-17A in susceptibility to viral myocarditis.

Interleukin-17A (IL-17A) has been implicated in the pathogenesis of viral myocarditis (VMC). However, the role of IL-17A polymorphisms in susceptibility to VMC has not been reported to date. The aim of this study was to explore the association between IL-17A variants as well as serum IL-17 levels with VMC. Three single-nucleotide polymorphisms (SNPs) (rs2275913, rs3819025, and rs3748067) were analyzed by the polymerase chain reaction-restriction fragment length polymorphism method in 236 VMC patients and 259 controls from China. Serum IL-17A levels were measured by enzyme-linked immunosorbent assay kits. Multivariable logistic regression analysis that the rs2275913 AA genotype and the haplotype -197A/+45G/+1249G (AGG) were associated with an increased risk of VMC (all P < 0.05). Consistent with these findings, the rs2275913 AA genotype was linked to higher serum IL-17A compared to GG/AG genotype (all P < 0.001). We observed no associations between the other two SNPs and risk of VMC. Serum IL-17A levels were significantly higher in the VMC group than controls (P < 0.001) and gradually increased with the increase of New York Heart Association grade in VMC patients (P < 0.05). Spearman correlation test revealed that the serum IL-17A level was correlated with the cardiac damage and left ventricular systolic functions among VMC patients (all P < 0.05). Our study reveals that IL-17A expression may contribute to the development and severity of VMC. The SNP rs2275913 in the IL-17A gene might exert influence on susceptibility to VMC via linking with the serum IL-17A level.

Preparation of bovine serum albumin imprinting sensitive hydrogels using ionic liquid as co-monomer and stabilizer.

Through consulting the Hofmeister series, a novel biocompatible and polymerizable ionic liquid (IL) was designed and used as stabilizer and co-monomer to prepare bovine serum albumin (BSA) imprinted hydrogels. N-isopropylacrylamide (NIPA) was chosen as the assistant monomer for imparting environmental sensitivity to the hydrogels. The stabilizing effect of the IL was verified by circular dichroism. Several parameters, such as the mass ratio of the template protein, IL and crosslinker, the drying method of hydrogels and the elution method of MIHs that could affect the performance of molecular imprinted hydrogels (MIHs) were investigated. The optimum mass ratio of BSA, IL and crosslinker was found to be 200:30:6. The best drying and preferred elution method for the MIHs was achieved by slowly evaporating and washing with 0.5M NaCl solution at 15 °C, respectively. The MIHs prepared under optimized conditions were subsequently used in the adsorption isotherm, adsorption dynamics, adsorption selectivity, and competition test. The adsorption isotherm revealed that the MIHs showed the best imprinted effect at a BSA concentration of 0.2 mg mL(-1) and their imprinting factor at 2.66. The adsorption dynamic studies revealed that the adsorptive rate of the MIHs was much faster than the non-imprinted hydrogels (NIHs), and both of them could be equilibrated in 1h. The adsorption selectivity and competition tests were conducted to estimate the specific recognition property of the MIHs for BSA. The MIHs showed excellent selectivity and recognition ability to BSA. The strategy of applying biocompatible and polymerizable ILs to imprinting technology may provide a new approach for effective biomacromolecular imprinting.

[Effect of Santalum album on tissue distribution of danshensu in rabbits by HPLC].

OBJECTIVE: To investigate the influence of Shi herb (Santalum album, SA) to the tissue distribution of danshensu (DSS) which is the main hydrosoluble component of Jun herb (Salvia miltiorrhiza, SM) in rabbits by HPLC. METHOD: Rabbits were oral administrated decoction of SM and SM-SA, respectively. Perchloric acid (10%) was used to precipitate the tissue samples of rabbits heart, brain, liver, kidney, acetic ether was used to extracte supernatant, and the internal standard was p-hydroxybenzoic acid. The content of DSS of SM in tissues was detected. RESULT: The content of DSS reached the highest point close to 50 min in the mentioned tissues. Before and after co-administration, the sequences of average concentration of DSS in tissues were C(kidney) > C(heart) > C(brain) > C(liver) and C(kidney) > C(liver) > C(brain) > C(heart) respectively. Compared with SM administrated singly, the content of DSS in every tissues of co-administration was higher. CONCLUSION: In Danshenyin Formulae, SA can increase concentration of DSS in target tissues significantly, and therefore therapeutic effect of SM for cardiovascular disease is raised.