[Effect of guarana on lipid metabolism in obese rats: a study based on lipidomics].

This study investigated the effect of guarana on plasma lipid metabolites in obese rats and analyzed its mechanism in the treatment of dyslipidemia in obesity. High-fat diet was used to establish obese rat models, and the therapeutic effect of guarana on obese rats was evaluated by measuring body weight, white fat, liver weight, and lipid content, as well as observing liver histomorphology. Lipid metabolites in plasma of rats in each group were detected by UHPLC-Q-TOF-MS lipidomics. The protein expressions of fatty acid synthase, acetyl-CoA carboxylase 1, triglyceride synthesis enzyme, carnitine palmitoyltransferase Ⅰ, and acetyl-coenzyme A acyltransferase 2 in rat liver were detected using Western blot. The results revealed that guarana significantly reduced body weight, white fat, and liver weight of obese rats due to high-fat diet, and alleviated dyslipidemia and liver steatosis. Lipidomics showed that some triglycerides and phospholipids were significantly elevated in the high-fat model group, and part of them was reduced after guarana treatment. Western blot found that guarana inhibited the expression of hepatic fatty acid and triglyceride synthesis-related proteins and increased the expression of fatty acid ß-oxidation-related proteins. Abnormalities in triglyceride and phospholipid metabolism are the main characteristics of plasma lipid metabolism in obese rats induced by high-fat diet. Guarana may regulate partial triglyceride and phospholipid metabolism by inhibiting hepatic fatty acid and triglyceride synthesis and increasing fatty acid ß-oxidation, thereby improving rat obesity and dyslipidemia.

Ethanol Extract of Citrus grandis 'Tomentosa' Exerts Anticancer Effects by Targeting Skp2/p27 Pathway in Non-Small Cell Lung Cancer.

SCOPE: This study aims to investigate the anticancer properties of Citrus grandis 'Tomentosa' (CGT) in non-small cell lung cancer (NSCLC). METHODS AND RESULTS: The ethanol extract of CGT (CGTE) is prepared by using anhydrous ethanol and analyzed by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), revealing that the main chemical components in CGTE are flavonoids and coumarins, such as naringin, rhoifolin, apigenin, bergaptol, and osthole. CGTE at concentrations without inducing cell death significantly inhibits cell proliferation via inducing cell cycle G1 phase arrest by MTT, colony formation, and flow cytometry assays, implying that CGT has anticancer potential. CGTE markedly inhibits the activity of Skp2-SCF E3 ubiquitin ligase, decreases the protein level of Skp2, and promotes the accumulation of p27 by co-immunoprecipitation (co-IP) and in vivo ubiquitination assay; whereas Skp2 overexpression rescues the effects of CGTE in NSCLC cells. In subcutaneous LLC allograft and A549 xenograft mouse models, CGTE, without causing obvious side effects in mice, significantly inhibits lung tumor growth by targeting the Skp2/p27 signaling pathway. CONCLUSION: These findings demonstrate that CGTE efficiently inhibits NSCLC proliferation both in vitro and in vivo by targeting the Skp2/p27 signaling pathway, suggesting that CGTE may serve as a therapeutic candidate for NSCLC treatment.

Different subtypes of ultrasound-diagnosed adenomyosis and in vitro fertilization outcomes: A systematic review and meta-analysis.

INTRODUCTION: Adenomyosis prevalence among women with infertility is increasing; their management during in vitro fertilization is usually based on ultrasound diagnosis alone. Herein, we summarize the latest evidence on the impact of ultrasound-diagnosed adenomyosis on in vitro fertilization outcomes. MATERIAL AND METHODS: The study was registered with The International Prospective Register of Systematic Reviews (CRD42022355584). We searched PubMed, Embase, and Cochrane Library databases from inception to January 31, 2023, for cohort studies on the impact of adenomyosis on in vitro fertilization outcomes. Fertility outcomes were compared according to the presence of adenomyosis as diagnosed by ultrasound, concurrent endometriosis and adenomyosis, and MRI-based or MRI- and ultrasound-based adenomyosis diagnosis. Live birth rate was the primary outcome while clinical pregnancy and miscarriage rates were secondary outcomes. RESULTS: Women diagnosed with adenomyosis by ultrasound had lower live birth (odds ratio [OR] = 0.66; 95% confidence interval [CI]: 0.53-0.82, grade: very low), lower clinical pregnancy (OR = 0.64; 95% CI: 0.53-0.77, grade: very low), and higher miscarriage (OR = 1.81; 95% CI: 1.35-2.44, grade: very low) rates than those without adenomyosis. Notably, symptomatic and diffuse, but not asymptomatic adenomyosis as diagnosed by ultrasound, adversely affected in vitro fertilization outcomes, with lower live birth (OR = 0.57; 95% CI: 0.34-0.96, grade: very low), clinical pregnancy (OR = 0.69; 95% CI: 0.57-0.85, grade: low), and miscarriage (OR = 2.48, 95% CI: 1.28-4.82, grade: low) rates; and lower live birth (OR = 0.37; 95% CI: 0.23-0.59, grade: low) and clinical pregnancy (OR = 0.50; 95% CI: 0.34-0.75, grade: low), but not miscarriage rate (OR = 2.18; 95% CI: 0.72-6.62, grade: very low), respectively. Concurrent adenomyosis in endometriosis is associated with a significantly lower live birth rate (OR = 0.44; 95% CI: 0.26-0.75, grade: low) than endometriosis alone. Finally, the use of MRI-based or MRI- and ultrasound-based adenomyosis diagnosis showed no significant association with in vitro fertilization outcomes (grade: very low for all outcomes). CONCLUSIONS: Considering ultrasound findings, symptoms, and different subtypes of adenomyosis may aid in offering personalized counseling, improving treatment decisions, and achieving better outcomes of in vitro fertilization.

[Effect of Erjing Pills on alleviating neuroinflammation of AD rats based on TLR4/NF-κB/NLRP3 pathway and its mechanism].

This paper aimed to study the effect of Erjing Pills on the improvement of neuroinflammation of rats with Alzheimer's di-sease(AD) induced by the combination of D-galactose and Aß_(25-35) and its mechanism. SD rats were randomly divided into a sham group, a model control group, a positive drug group(donepezil, 1 mg·kg~(-1)), an Erjing Pills high-dose group(9.0 g·kg~(-1)), and an Erjing Pills low-dose group(4.5 g·kg~(-1)), with 14 rats each group. To establish the rat model of AD, Erjing Pills were intragastrically administrated to rats for 5 weeks after 2 weeks of D-galactose injection. D-galactose was intraperitoneally injected into rats for 3 weeks, and then Aß_(25-35) was injected into the bilateral hippocampus. The new object recognition test was used to evaluate the learning and memory ability of rats after 4 weeks of intragastric administration. Tissues were acquired 24 h after the last administration. The immunofluorescence method was used to detect the activation of microglia in the brain tissue of rats. The positive expressions of Aß_(1-42) and phosphory protein Tau~(404)(p-Tau~(404)) in the CA1 area of the hippocampus were detected by immunohistochemistry. The levels of inflammatory factors interleukin-1ß(IL-1ß), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) in the brain tissue were determined by enzyme-linked immunosorbent assay(ELISA). Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)/nucleotide-binding oligomerization domain-like receptors 3(NLRP3) pathway-associated proteins in the brain tissue were determined by Western blot. The results showed that as compared with the sham group, the new object recognition index of rats in the model control group decreased significantly, the deposition of Aß_(1-42) and p-Tau~(404) positive protein in the hippocampus increased significantly, and the levels of microglia activation increased significantly in the dentate gyrus. The levels of IL-1ß, TNF-α, and IL-6 in the hippocampus of the model control group increased significantly, and the expression levels of TLR4, p-NF-κB p65/NF-κB p65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus increased significantly. Compared with the model control group, the Erjing Pill groups enhanced the new object recognition index of rats, decreased the deposition of Aß_(1-42) and the expression of p-Tau~(404) positive protein in the hippocampus, inhibited the activation of microglia in the dentate gyrus, reduced the levels of inflammatory factors IL-1ß, TNF-α, and IL-6 in the hippocampus, and down-regulated the expression levels of TLR4, p-NF-κB P65/NF-κB P65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus. In conclusion, Erjing Pills can improve the learning and memory ability of the rat model of AD presumably by improving the activation of microglia, reducing the expression levels of neuroinflammatory factors IL-1ß, TNF-α, and IL-6, inhibiting the TLR4/NF-κB/NLRP3 neuroinflammation pathway, and decreasing hippocampal deposition of Aß and expression of p-Tau, thereby restoring the hippocampal morphological structure.

Kinetics-Controlled Growth of Metallic Single-Wall Carbon Nanotubes from CoRex Nanoparticles.

The controlled growth of metallic single-wall carbon nanotubes (m-SWCNTs) is very important for the fabrication of high-performance interconnecting wires, transparent conductive electrodes, light and conductive fibers, etc. However, it has been extremely difficult to synthesize m-SWCNTs due to their lower abundance and higher chemical reactivity than semiconducting SWCNTs (s-SWCNTs). Here, we report the kinetically controlled growth of m-SWCNTs by manipulating their binding energy with the catalyst and promoting their growth rate. We prepared CoRe4 nanoparticles with a hexagonal close-packed structure and an average size of ∼2.3 nm, which have a lower binding energy with m-SWCNTs than with s-SWCNTs. The selective growth of m-SWCNTs from the CoRe4 catalyst was achieved by using a low concentration of carbon source feed at a relative low temperature of 760 °C. The m-SWCNTs had a narrow diameter distribution of 1.1 ± 0.3 nm, and their content was over 80%.

ML365 inhibits TWIK2 channel to block ATP-induced NLRP3 inflammasome.

Dysregulation of NLRP3 inflammasome results in uncontrolled inflammation, which participates in various chronic diseases. TWIK2 potassium channel mediates potassium efflux that has been reported to be an essential upstream mechanism for ATP-induced NLRP3 inflammasome activation. Thus, TWIK2 potassium channel could be a potential drug target for NLRP3-related inflammatory diseases. In the present study we investigated the effects of known K2P channel modulators on TWIK2 channel expressed in a heterologous system. In order to increase plasma membrane expression and thus TWIK2 currents, a mutant channel with three mutations (TWIK2I289A/L290A/Y308A) in the C-terminus was expressed in COS-7 cells. TWIK2 currents were assessed using whole-cell voltage-clamp recording. Among 6 known K2P channel modulators tested (DCPIB, quinine, fluoxetine, ML365, ML335, and TKDC), ML365 was the most potent TWIK2 channel blocker with an IC50 value of 4.07 ± 1.5 µM. Furthermore, ML365 selectively inhibited TWIK2 without affecting TWIK1 or THIK1 channels. We showed that ML365 (1, 5 µM) concentration-dependently inhibited ATP-induced NLRP3 inflammasome activation in LPS-primed murine BMDMs, whereas it did not affect nigericin-induced NLRP3, or non-canonical, AIM2 and NLRC4 inflammasomes activation. Knockdown of TWIK2 significantly impaired the inhibitory effect of ML365 on ATP-induced NLRP3 inflammasome activation. Moreover, we demonstrated that pre-administration of ML365 (1, 10, 25 mg/kg, ip) dose-dependently ameliorated LPS-induced endotoxic shock in mice. In a preliminary pharmacokinetic study conducted in rats, ML365 showed good absolute oral bioavailability with F value of 22.49%. In conclusion, ML365 provides a structural reference for future design of selective TWIK2 channel inhibitors in treating related inflammatory diseases.

[Applicability of multiple remotely sensed vegetation indices for extracting key phenological metrics of Tamarix chinensis shrubs based on CO2 flux observation and Sentinel-2 data]. / æŸ½æŸ³çŒä¸›å ³é”®ç‰©å€™å‚æ•°å¤šç§æ¤è¢«æŒ‡æ•°é¥æ„Ÿæå–çš„é€‚ç”¨æ€§­­åŸºäºŽCO2通量观测和Sentinel-2数据.

We analyzed the relationship between gross primary productivity (GPP) and environmental factors at Sidaoqiao Superstation of the Ejina Oasis in China's Gobi Desert, by combining eddy flux and meteorological data from 2018 to 2019 and Sentinel-2 remote sensing images from 2017 to 2020. We evaluated the applicability of 12 remote sensing vegetation indices to simulate the growth of Tamarix chinensis and extract key phenological metrics. A seven-parameter double-logistic function (DL-7) + global model function (GMF) was used to fit the growth curves of GPP and vegetation indices. Three key phenological metrics, i.e., the start of the growing season (SOS), the peak of the growing season (POS), and the end of the growing season (EOS), were extracted for each year. Growing season degree days (GDD) and soil water content were the main environmental factors affecting the phenological dynamics of T. chinensis. Compared with 2018, the lower temperatures in 2019 resulted in slower accumulation rate of accumulated temperature before the SOS. T. chinensis required longer heat accumulation to enter growing season, which might cause later SOS in 2019. The hydrothermal conditions between SOS and POS were similar for 2018 and 2019. Howe-ver, the POS in 2019 was 8 days later than that in 2018, because of the late SOS in 2019. Following the POS in 2019, high GDD and low soil water content caused the T. chinensis to suffer from water stress, resulting in a shortened late growing season. The linear regression between the standardized Sentinel-2 vegetation index and the average value of GPP between 10:00 and 14:00 indicated that the enhanced vegetation index of the broadband vegetation index and the chlorophyll red edge index, inverted red edge chlorophyll index, and red-edge normalized difference vegetation index (NDVI705) of the narrowband vegetation index were highly consistent with the GPP of T. chinensis. Remote sensing extraction of SOS and POS of T. chinensis suggested that the Sentinel-2 narrowband vegetation index was more accurate than the broadband vegetation index. The modified chlorophyll absorption in reflectance index provided the most accurate extraction of SOS, while the MERIS terrestrial chlorophyll index provided the most accurate extraction of EOS. Conversely, the Sentinel-2 broadband vegetation index was the most accurate for extracting POS, especially the 2-band enhanced vegetation index and the near-infrared reflectance of vegetation. Overall, NDVI705 was the best index to estimate phenological metrics.

FNDC5 expression closely correlates with muscle fiber types in porcine longissimus dorsi muscle and regulates myosin heavy chains (MyHCs) mRNA expression in C2C12 cells.

BACKGROUND: Irisin (a glycosylated protein) is cleaved from fibronectin type III domain-containing protein 5 (FNDC5), which is expressed mainly in animal muscle tissues and has multiple metabolic regulatory activities. However, their roles in controlling myofiber types in skeletal muscle remain unclear. METHODOLOGY: Two different commercial hybridized pigs, LJH (a crossed pig containing Chinese native pig genotypes) and DLY (Duroc × Landrace × Yorkshire) were selected to analyze FNDC5 mRNA expression and the mRNA composition of four adult myosin heavy chain (MyHC) isoforms (IIIaIIxIIb) in the longissimus dorsi (LD) muscle. C2C12 myoblasts were cultured to investigate the effects of FNDC5 on the four MyHCs mRNA expressive levels, using small interfering RNA for depletion and a eukaryotic expression vector carrying FNDC5 for overexpression. ZLN005 (a small molecule activator of FNDC5's upstream control gene PGC1α) or recombinant human irisin protein were also used. RESULTS: In LD muscle, LJH pigs had the higher FNDC5 mRNA level, and MyHC I or IIa proportion than DLY pigs (P <  0.05). For C2C12 cells in vitro, small interfering RNA (si-592) silencing of FNDC5 expression markedly reduced MyHC IIa mRNA levels (P <  0.05), while FNDC5 overexpression significantly increased MyHC IIa mRNA levels (P <  0.05). Exogenous irisin increased the mRNA levels of PGC1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), FNDC5, MyHCI, MyHCIIa, NRF1 (nuclear respiratory factor 1), VEGF (vascular endothelial growth factor), and TFAM (mitochondrial transcription factor A,) (P <  0.05), and the enzyme activities of SDH (succinate dehydrogenase), CK (creatine kinase), and MDH (malate dehydrogenase) in C2C12 myotubes (P <  0.05). These results showed that FNDC5 mRNA expression had a significant association with the characteristics of myofiber types in porcine muscle, and participated in regulating MyHCs mRNA expression of C2C12 myogenic differentiation cells in vitro. FNDC5 could be an important factor to control muscle fiber types, which provides a new direction to investigate pork quality via muscle fiber characteristics.

Catch-up growth in intrauterine growth-restricted piglets associated with the restore of pancreatic and intestinal functions via porcine glucagon-like peptide-2 microspheres.

Intrauterine growth restriction (IUGR) results in abnormal morphology and gastrointestinal function, such as reduced villi height and crypt depth, thinner mucosa and muscle layers, and reduced brush border enzyme activities, delayed gastric emptying, increased stress response. As a gastrointestinal growth factor, the manner by which the porcine glucagon-like peptide-2 (pGLP-2) microsphere administration restored the gastrointestinal function and growth performance of IUGR piglets was investigated. Fourteen newborn Duroc × (Yorkshire × Landrace) IUGR piglets (0.92 ± 0.113 kg) were assigned into the IUGR (negative control group) and pGLP-2 microsphere groups. The piglets in group pGLP-2 were intraperitoneally administered with 100 mg pGLP-2 microspheres on day 1 after birth. From days 15 to 26 of trial, the body weight of the pGLP-2 group was significantly higher than that of the control. IUGR piglets of group pGLP-2 showed a significantly increased pancreas weight, serum insulin content and activity of lipase and amylase. Injection of pGLP-2 microspheres restored the intestinal absorptive capacity by significantly increasing the mRNA expression of the sodium-glucose cotransporter 1 in the jejunum and the peptide transporter 1 in the jejunum. It also restored the redox balance by increasing the catalase mRNA expression and decreasing the heat shock protein 70 mRNA expression. In addition, this improvement was associated with the significant increase in gut diameter, length and weight. Therefore, it was concluded that the injection of pGLP-2 microspheres was a suitable therapeutic strategy for compensatory growth in low birth weight IUGR piglets.

[Microbial Communities and Sludge Specific Resistance in Two SBRs Treating Leachate].

The relationship between microbial populations and sludge filtration performance was studied when active sludge was used to treat the leachate from municipal solid waste incineration plants. Two SBRs (SBR1 and SBR2) were operated at the same conditions, except that SBR1 was exposed to the sunlight and SBR2 was in the dark. To identify the difference in microbial populations in two reactors, high-throughput sequencing method was used. On the 50th day, the fungi abundance in SBR2 was higher than in SBR1. Phylum Rozellomycota became the dominant fungi in SBR1, whose relative abundance was 83.71%. Phylum Basidiomycota and Genus Trichosporon became only dominant fungi in SBR2, whose relative abundances were 99.84% and 99.78%, respectively. Bacterial abundance in SBR1 was higher than in SBR2. In SBR1, Thauera was the major bacterial genus, whose relative abundance was 39.35%. In SBR2, Planktosalinus, Thauera, and Ottowia were the major bacterial genera, whose relative abundances were 16.84%, 16.23%, and 12.55%. Rotifers and other predatory metazoan were detected on the 30th-50th days in SBR1 and sludge specific resistance began to decline on the 35th day. Filamentous fungi bulking caused by Trichosporon resulted in a continuous increase in sludge specific resistance of SBR2. The dominant microbial communities (especially fungi) and sludge specific resistances in SBR1 and SBR2 were very different because of the effect of sunlight. Therefore, sunlight plays an important role on microbial communities and sludge characteristics.

Therapeutic effects of different doses of polyethylene glycosylated porcine glucagon-like peptide-2 on ulcerative colitis in male rats.

BACKGROUND: Polyethylene glycosylated (PEGylated) porcine glucagon-like peptide-2 (pGLP-2) considerably increases half-life and stability compared with the native pGLP-2, but the effective dose for intestinal damage is still unclear. This study aims to evaluate the available dose of polyethylene glycosylated porcine glucagon-like peptide-2 (PEG-pGLP-2), a modified, long-acting form of pGLP-2 in an experimental rat model of ulcerative colitis. METHODS: Thirty-five male rats were randomly assigned into five groups: control, dextran sodium sulphate (DSS), DSS + PEG-pGLP-2(L), DSS + PEG-pGLP-2(M) and DSS + PEG-pGLP-2(H). Rats in control group received only water; other rats were fed with 5% (w/v) DSS and intraperitoneally administered with 12.5, 25 and 100 nmol/kg PEG-pGLP-2 daily for 6 days. RESULTS: Compared with the control treatment, DSS treatment significantly (p < 0.05) decreased body weight change, colonic length, duodenal villus height and expression of zonula occludens-1, whereas significantly (p < 0.05) increased colonic damage score and expression of claudin-1, interleukin (IL)-1, IL-7, IL-10, interferon-γ and tumour necrosis factor (TNF)-α in colon. However, the three doses of PEG-pGLP-2 all reduced these effects; these treatments significantly (p < 0.05) increased body weight change and duodenal villus height, whereas significantly (p < 0.05) decreased colonic damage score and expression of IL-1, IL-7 and TNF-α in colon. Specifically, low-dose (12.5 nmol/kg/d) PEG-pGLP-2 was effective. CONCLUSIONS: These results indicated that PEG-pGLP-2 is a novel and potentially effective therapy for intestinal healing in a relatively low dose.

High Royal Jelly-Producing Honeybees (Apis mellifera ligustica) (Hymenoptera: Apidae) in China.

China is the largest producer and exporter of royal jelly (RJ) in the world, supplying >90% of the global market. The high production of RJ in China is principally owing to the high RJ-producing lineage of honeybees (Apis mellifera ligustica Spinola, 1806) established by beekeepers in the 1980s. We describe the development of high royal jelly-producing honeybees and the management of this lineage today. Previous research and recent advances in the genetic characterization of this lineage, and the molecular markers and mechanisms associated with high RJ production are summarized. The gaps in our knowledge and prospects for future research are also highlighted.

Pu-erh tea powder preventive effects on cisplatin-induced liver oxidative damage in Wistar rats.

BACKGROUND: Chemotherapy is one of the major means for control of malignancies, with cisplatin (CDDP) as one of the main agents, widely used for the treatment of various malignant solid tumors. However, prevention of hepatotoxicity from cisplatin is one of the urgent issues in cancer chemotherapy. In this study, we aimed to investigate the effects of pu-erh tea on hepatotoxicity through body weight and tissue antioxidant parameters like, liver coefficient, serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), malondialdehyde(MDA) and glutathione (GSH) levels, and light microscopic evaluation by histological findings. MATERIALS AND METHODS: The rats were randomly divided into five groups: Control (n=10), cisplatin (3 mg/kg p.i., n=10), cisplatin+pu-erh (0.32 g/kg/day i.g., n=10), cisplatin+pu-erh (0.8 g/kg/day i.g., n=10) and cisplatin+pu-erh (1.6 g/kg/day i.g., n=10). Pu-erh tea powder was administrated for 31 consecutive days. The rats were sacrificed at the end on the second day after a single dose of cisplatin treatment for measuring indices. RESULTS: Pu-erh tea powder exhibited a protective effect by decreasing MDA and GSH and increasing the SOD and GSH-PX levels and GSH-PX/MDA ratio in comparison with the control group. Besides, pu-erh tea was also able to alleviate the pathological damage to some extent. CONCLUSION: Pu-erh tea powder is protective against cisplatin-induced liver oxidative damages, especially at the medium dosage (0.8 g/kg/d).

Effects of PEGylated porcine glucagon-like peptide-2 therapy in weaning piglets challenged with lipopolysaccharide.

This study aims to evaluate the therapeutic effect of polyethylene glycosylated porcine glucagon-like peptide-2 (pGLP-2), a long-acting form of pGLP-2, in lipopolysaccharide (LPS)-challenged piglets. Eighteen 21-day-old weaning piglets were randomly assigned into three groups: control (saline solution), LPS (100 µg/kg LPS), and PEG-pGLP-2 (10 nmol/kg PEG-pGLP-2+100 µg/kg LPS). All treatments were administered intraperitoneally. Compared with the control treatment, LPS treatment significantly decreased (P<0.05) the villus heights of the duodenum and jejunum, as well as the villus height/crypt depth ratio of the jejunum. However, PEG-pGLP-2 therapy reduced these effects (P>0.05). Specifically, PEG-pGLP-2 infusion significantly increased the villus height/crypt depth ratio of the duodenum (P<0.05) compared with LPS treatment. Compared with the control treatment, LPS treatment significantly increased (P<0.05) the mRNA expression levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in the jejunum. However, PEG-pGLP-2 therapy reduced these effects (P<0.05). Specifically, PEG-pGLP-2 infusion significantly decreased (P<0.05) the mRNA expression levels of interleukin (IL)-8 and TNF-α in the duodenum and jejunum, IL-10 in the duodenum, and IFN-γ in the jejunum compared with the LPS treatment. LPS treatment increased the caspase-3 activity of the ileum mucosal (P<0.05), and this effect was significantly reduced by PEG-pGLP-2 treatment. These results indicate that PEG-pGLP-2 infusion alleviates the severity of intestinal injury in weaning piglets by reducing the secretion of inflammatory cytokines and the caspase-3 activity, and increasing the villus height/crypt depth ratio.

Purified PEGylated porcine glucagon-like peptide-2 reduces the severity of colonic injury in a murine model of experimental colitis.

The rapid degradation of porcine glucagon-like peptide-2 (pGLP-2) by the enzyme dipeptidyl peptidase-IV (DPP-IV) is the main impediment in the development of pGLP-2 as a potential therapeutic agent for intestinal dysfunction and damage. In this study, one mono-modified Lys(30)-polyethylene glycol (PEG)-pGLP-2 was prepared using mPEG-succinimidyl propionate. To determine the optimized condition for PEGylation, the reactions were monitored by RP-HPLC and MALDI-TOF-MS. Stability was tested in purified DPP-IV in vitro. In vivo, the protective effects for colonic injury were measured in dextran sulfate sodium (DSS)-induced colitis in mice. The monoPEGylated products reached the maximum yield at 4:1 ratio of mPEG5k-SPA to pGLP-2. An effective method of successfully separating PEGylated pGLP-2 from mPEG-SPA5kD using CM Sepharose Fast Flow resin was established. The half-life of Lys(30)-PEG-pGLP-2 was 16-fold longer than that of pGLP-2 in DPP-IV. The DSS mice exhibited marked weight loss), which was significantly reduced by Lys(30)-PEG-pGLP-2 therapy. DSS treatment significantly increased colonic damage score, which was significantly reduced by administration of Lys(30)-PEG-pGLP-2 in DSS-mice. DSS-induced colitis clearly induced Myeloperoxidase activity in the colon, which was significantly reduced by treatments with 3% DSS-pGLP-2 or 3% DSS-PEG-pGLP-2. These results showed that site-specific Lys(30)-PEG-GLP-2 was resistant to degradation and reduced the severity of colonic injury in murine colitis. The enhanced biological potency of this product highlighted its potential as a therapeutic agent for intestinal diseases.

Pathogenesis and treatment of parenteral nutrition-associated liver disease.

BACKGROUND: Parenteral nutrition-associated liver disease (PNALD) has been common in patients who require long-term parenteral nutrition. PNALD develops in 40%-60% of infants on long-term parenteral nutrition compared with 15%-40% of adults on home parenteral nutrition for intestinal failure. The pathogenesis of PNALD is multifactorial and remains unclear. There is no specific treatment. Management strategies for its prevention and treatment depend on an understanding of many risk factors. This review aims to provide an update on the pathogenesis and treatment of this disease. DATA SOURCES: A literature search was performed on the MEDLINE and Web of Science databases for articles published up to October 2011, using the keywords: parenteral nutrition associated liver disease, intestinal failure associated liver disease, lipid emulsions and fish oil. The available data reported in the relevant literatures were analyzed. RESULTS: The literature search provided a huge amount of evidence about the pathogenesis and management strategies on PNALD. Currently, lack of enteral feeding, extended duration of parenteral nutrition, recurrent sepsis, and nutrient deficiency or excess may play important roles in the pathogenesis of PNALD. Recent studies found that phytosterols, present as contaminants in soy-based lipid emulsions, are also an important factor in the pathogenesis. Moreover, the treatment of PNALD is discussed. CONCLUSIONS: The use of lipid emulsions, phytosterols in particular, is associated with PNALD. Management strategies for the prevention and treatment of PNALD include consideration of early enteral feeding, the use of specialized lipid emulsions such as fish oil emulsions, and isolated small bowel or combined liver and small bowel transplantation. A greater understanding of the pathogenesis of PNALD has led to promising interventions to prevent and treat this condition. Future work should aim to better understand the mechanisms of PNALD and the long-term outcomes of its treatment.

[Damage control surgery for pancreatic injuries after blunt abdominal trauma].

OBJECTIVE: To summarize the management of pancreatic injuries after blunt abdominal trauma. METHODS: The clinical data of 42 patients with blunt pancreatic injury admitted from January 2001 to December 2010 was analyzed retrospectively. There were 38 male and 4 female patients, aging from 13 to 65 years with a mean of 31 years. The organ injury scaling of Committee of the American Association for the Surgery of Trauma (AAST grade): grade I in 3 patients, grade II in 12 patients, grade III in 9 patients, grade IV in 13 patients and grade V in 5 patients. The mean injury severity score was 27 ± 21. Patients above AAST grade II underwent peritoneal drainage and "three neostomy" (gastrostomy, jejunostomy and gallbladder) according to damage control theory. RESULTS: Thirty-eight patients got abdominal CT scanning with a positive rate of 79.9% (30/38). Forty patients underwent surgical procedures, and 2 patients with non-operative management. The surgical procedures include peritoneal drainage and "three neostomy" in 32 patients, pancreas suture or pancreatic tail resection in 6 patients, pancreatoduodenectomy or caudal pancreaticojejunostomy in 2 patients. Forty patients (95.2%) survived, 2 patients (4.8%) died and 16 patients (38.1%) had complications such as pancreatic fistula,pulmonary infection. CONCLUSIONS: Abdominal CT scanning will benefit the preoperative diagnosis of blunt pancreatic trauma. Although the survival rate of patients with blunt pancreatic trauma might be improved by using the damage control surgery, the management of damage control surgery also needs to be modified because of the high rate of complications.