Miracle-dz/UniFAR-FTUs huggingface dataset:
Reversal of Morphine Tolerance and Dependence by Passiflora incarnata – A Traditional Medicine to Combat Morphine Addiction

This paper describes the use of Passiflora incarnata Linneaus in reversing the development of dependence and tolerance of morphine in mice. A fraction (BZF) derived from the methanol extract of P. incarnata that had exhibited good anxiolytic activity, delayed the development of tolerance to the analgesic effect of morphine when administered at 10, 50 and 100 mg/kg doses along with 10 mg/kg dose of morphine for 9 days. A single dose of P. incarnata bioactive fraction (BZF) also decreased the naloxoneprecipitated withdrawal jumps in mice that had already been rendered tolerant due to chronic treatment with 10mg/kg of morphine.
The widespread crucifer species Cardamine flexuosa is an allotetraploid with a conserved subgenomic structure.

The origin of Cardamine flexuosa (Wavy Bittercress) has been a conundrum for more than six decades. Here we identify its parental species, analyse its genome structure in comparison to parental genomes and describe intergenomic structural variations in C. flexuosa. Genomic in situ hybridization (GISH) and comparative chromosome painting (CCP) uncovered the parental genomes and the chromosome composition of C. flexuosa and its presumed diploid progenitors. Cardamine flexuosa is an allotetraploid (2n = 4x = 32), originating from two diploid species, Cardamine amara and Cardamine hirsuta (2n = 2x = 16). The two parental species display almost perfectly conserved chromosomal collinearity for seven out of the eight chromosomes. A 13 Mb pericentric inversion distinguishes chromosome CA1 from CH1. A comparative cytomolecular map was established for C. flexuosa by CCP/GISH. Whereas conserved chromosome collinearity between the C. amara and C. hirsuta subgenomes might have promoted intergenomic rearrangements through homeologous recombination, only one reciprocal translocation between two homeologues has occurred since the origin of C. flexuosa. The genome of C. flexuosa demonstrates that allopolyploids can maintain remarkably stable subgenomes over 10(4) -10(5) yr throughout a wide distribution range. By contrast, the rRNA genes underwent genome-specific elimination towards a diploid-like number of loci.
A MYB coiled-coil transcription factor interacts with NSP2 and is involved in nodulation in Lotus japonicus.

Transcription factor complex formation is a central step in regulating gene expression. In this report, a novel MYB coiled-coil transcription factor referred to as IPN2, for Interacting Protein of NSP2, is described. The interaction between IPN2 and NSP2 was examined by protein pull-down assays and bimolecular fluorescence complementation (BiFC). Subcellular localization of proteins, gene expression and gene function were assessed in transgenic hairy roots expressing tagged recombinant proteins, promoter-reporter and RNA interference (RNAi) constructs, respectively. The GRAS domain of NSP2 and the coiled-coil domain of IPN2 were found to be responsible for the interaction between the two proteins. IPN2 had strong transcription activation activity, bound directly to the NIN gene promoter, and was localized to the nuclei of Lotus japonicus root cells. The expression of IPN2 was elevated during nodule development, coinciding with increased NSP2 gene expression during nodule organogenesis. RNAi-mediated knockdown expression of IPN2 did not affect arbuscular mycorrhizal development, but had deleterious effects on rhizobial infection and nodule formation in L. japonicus. These results demonstrate an important role of IPN2 in nodule organogenesis and place a new MYB transcription factor in the Nod signaling pathway.
Carbon monoxide ameliorates hepatic ischemia/reperfusion injury via sirtuin 1‐mediated deacetylation of high‐mobility group box 1 in rats

Carbon monoxide (CO) exerts protective effects on hepatic ischemia/reperfusion injury (IRI), but the underlying molecular mechanisms are not fully understood. High‐mobility group box 1 (HMGB1) is an important mediator of injury and inflammation in hepatic IRI. Here, we investigated whether CO could attenuate hepatic IRI via inhibition of HMGB1 release, particularly through sirtuin 1 (SIRT1). CO was released by treatment with carbon monoxide–releasing molecule (CORM)–2. CORM‐2–delivered CO ameliorated hepatic IRI, as indicated by lower serum aminotransferase levels, lower hepatic inflammatory responses, and less severe ischemia/reperfusion‐associated histopathologic changes. Treatment with CORM‐2 significantly inhibited IRI‐induced HMGB1 translocation and release. SIRT1 expression was increased by CORM‐2 pretreatment. When CORM‐2–induced SIRT1 expression was inhibited using EX527, HMGB1 translocation and release were increased and hepatic IRI was worsened, whereas SIRT1 activation by resveratrol reversed this trend. In vitro, CORM‐2 reduced hypoxia/reoxygenation–induced HMGB1 translocation and release, these inhibitions were blocked by SIRT1 inhibition using EX527 or SIRT1 small interfering RNA both in alpha mouse liver 12 cells and RAW264.7 macrophages. Moreover, SIRT1 directly interacted with and deacetylated HMGB1. IRI increased HMGB1 acetylation, which was abolished by CORM‐2 treatment via SIRT1. In conclusion, these results suggest that CO may increase SIRT1 expression, which may decrease HMGB1 acetylation and subsequently reduce its translocation and release, thereby protecting against hepatic IRI. Liver Transplantation 23 510–526 2017 AASLD.
Double‐blind randomized controlled trial of the routine perioperative use of terlipressin in adult living donor liver transplantation

Perioperative terlipressin (Tp) during living donor liver transplantation (LDLT) has been shown to reduce intraoperative portal pressures and improve renal function. Its role and safety profile have never been evaluated in a double‐blind randomized controlled trial (RCT). The aim was to evaluate the hemodynamic effects, clinical benefits, and safety of perioperative Tp infusion in adult LDLT. This was a single‐center double‐blind RCT. Consenting adults with chronic liver disease and low risk of posttransplant renal dysfunction undergoing their first LDLT were randomized. The study group (terlipressin group [TpG]) received an initial bolus of Tp during surgery followed by a Tp infusion for 72 hours in the postoperative period. The placebo group (PbG) received a saline infusion. The primary endpoint was portal pressure after arterial reperfusion. Multiple intraoperative and postoperative variables served as secondary endpoints. A total of 41 patients were enrolled in the trial (TpG, 21; PbG, 20). There were no significant differences in intraoperative portal pressures, blood loss, fluid requirement, vasopressor requirement, or urine output. Peak intraoperative and end of surgery lactate levels were significantly higher in the Tp group. There was no difference in postoperative liver function tests. Incidence of acute kidney injury as assessed by Risk, Injury, Failure, Loss, and End‐Stage Kidney Disease criteria was lower in the Tp group (27% versus 60%; P = 0.04). The TpG had less postoperative ascites, a lower need for percutaneous interventions, and a shorter hospital stay. Incidence of bradycardia requiring pharmacological intervention and withdrawal from study was significantly higher in the TpG. In conclusion, this study has not demonstrated a reduction in postreperfusion portal pressure with Tp. However, Tp infusion reduced postoperative ascitic drain output resulting in less frequent percutaneous interventions and reduced hospital stay. Intraoperative hyperlactatemia and symptomatic bradycardia are major concerns. Its use should be restricted to patients with high‐volume ascites, and it needs close monitoring during drug infusion. Liver Transplantation 23 1007–1014 2017 AASLD.
National assessment of early hospitalization after liver transplantation: Risk factors and association with patient survival

Hospitalization is known to occur frequently in the first 6 months following liver transplantation (LT). Using a novel data linkage between the Scientific Registry of Transplant Recipients and Centers for Medicare and Medicaid Services, our study has 2 objectives: (1) to determine risk factors for “early” hospitalization (ie, within 6 months of LT); and (2) to quantify the importance of hospitalization history in the first 6 months with respect to subsequent patient survival (ie, survival, conditional on surviving 6 months post‐LT). The study population consisted of patients aged ≥18 years who underwent deceased donor LT between January 1, 2003 and December 31, 2010, with Medicare as primary or secondary insurance and were discharged alive from the index LT hospitalization (n = 7220). The early hospitalization rate was 2.76 per patient‐year and was significantly associated with many recipient factors (eg, recipient age, hepatitis C, diabetes, poor renal function including dialysis, and recipient of transjugular intrahepatic portosystemic shunt procedure before LT), as well as donor race and donation after cardiac death. Conditional on surviving 6 months after LT, the covariate‐adjusted death rate increased by 22% for each additional hospitalization occurring in the first 6 months (hazard ratio, 1.22; P < 0.001). In conclusion, several LT recipient factors are significantly associated with early hospitalization. Moreover, a patient's hospitalization profile during follow‐up months 0‐6 is a very strong predictor of survival thereafter. Efforts and resources should be devoted toward identifying LT recipients at risk for early hospitalization and modifying the actionable risk factors such as hepatitis C, diabetes, and body mass index to improve resource utilization and overall outcomes. Liver Transplantation 23 1143–1152 2017 AASLD.
Glial cell-derived neurotrophic factor enhances synaptic communication and 5-hydroxytryptamine 3a receptor expression in enteric neurons.

BACKGROUND & AIMS Glial cell-derived neurotrophic factor (GDNF) is essential for the development of the enteric nervous system during embryogenesis. We have observed the presence of Gdnf transcripts in the gastrointestinal tract of adult mice, and its early up-regulation after inflammation. We therefore investigated the effects of GDNF on enteric neuronal function in vitro. METHODS Primary neuronal cultures were established from isolated myenteric plexi, and characterized by immunostaining and Ca(2+) imaging. Gene expression of several ion channels was analyzed by quantitative polymerase chain reaction (PCR) and the electrophysiologic properties of the neurons were studied by patch clamp. RESULTS GDNF enhanced synaptogenesis and intercellular communication in primary myenteric neuronal cultures. Expression profiling revealed that GDNF exposure results in an up-regulation of Htr3a expression in the cultures and a similar increase was observed in inflamed colonic tissue where Gdnf expression was also increased. The increased Htr3a expression was accompanied by a functional increase in the response of neurons to acute challenge with 5-hydroxytryptamine (5-HT). GDNF treatment also caused inhibition of delayed rectifying voltage-gated potassium (Kv) currents, which correlated with the up-regulation of Htr3a and 5-HT-induced responses. Furthermore, pharmacologic blockade of Kv channels mimicked the effect of GDNF by increasing Htr3a expression as well as enhancing 5-HT-induced responses in the cultured myenteric neurons. CONCLUSIONS GDNF promotes synaptic communication in cultured myenteric neurons. It also up-regulates 5-HT(3a)-receptor expression via modulation of Kv channel activity. Up-regulation of Gdnf after gastrointestinal inflammation might play an important role in the pathophysiology of gastrointestinal diseases.
Aplicación de cuatro técnicas de ELISA (dos para IgM y dos para IgG) en el diagnóstico serológico de un brote de fiebre Q

Objetivo Evaluar cuatro tecnicas de analisis de inmunoabsorcion ligada a enzimas (ELISA) (comercializadas por Panbio y Serion) para la deteccion de inmunoglobulinas (IgM e IgG) en un brote de fiebre Q. Metodos Se procesaron 53 muestras de suero correspondientes a 29 personas. El metodo de referencia fue inmunofluorescencia indirecta (IFI). Resultados La sensibilidad y especificidad en la deteccion de IgM fueron del 100 y del 74% (Panbio) y del 91 y el 88% (Serion). La sensibilidad para IgG fue del 72% (Panbio) y del 89% (Serion). Las dos tecnicas obtuvieron para IgG una especificidad del 97%. Conclusiones Ambos ELISA parecen ser buenos metodos de cribado para la deteccion de IgM en brotes.
Intracorporeal knotting versus metal endoclip application for the closure of the appendiceal stump during laparoscopic appendectomy in uncomplicated appendicitis.

PURPOSE The goal of the study was to compare the efficacy of two methods--intracorporeal knotting and metal endoclip application--for closure of the appendiceal stump during laparoscopic appendectomy in a specific group of patients with uncomplicated appendicitis. METHODS The patients were randomized into two groups who had their appendiceal stump secured by intracorporeal knotting (Group 1) and metal endoclipping (Group 2). Primary outcome measure was postoperative complications, whereas secondary outcome measures were intraoperative complications, operative time, length of hospital stay, and re-admissions (including rehospitalizations and reoperations). RESULTS One hundred seven patients were prospectively recruited in a randomized study between December 2010 and May 2011. Group 1 and Group 2 included 46 and 61 patients, respectively. The rate of postoperative complications in Group 1 and Group 2 was 8.7% (4/46) and 4.9% (3/61) (P>.05). There were no significant differences between the groups in secondary outcome measures except the mean operative time (61.9 minutes versus 46.3 minutes, P=.0008). CONCLUSIONS The closure of the appendiceal stump by either intracorporeal knotting or metal endoclipping during laparoscopic appendectomy in uncomplicated appendicitis is safe with comparable morbidity and mortality rates.
Changes in food intake, metabolic parameters and insulin resistance are induced by an isoenergetic, medium-chain fatty acid diet and are associated with modifications in insulin signalling in isolated rat pancreatic islets

Long-chain fatty acids are capable of inducing alterations in the homoeostasis of glucose-stimulated insulin secretion (GSIS), but the effect of medium-chain fatty acids (MCFA) is poorly elucidated. In the present study, we fed a normoenergetic MCFA diet to male rats from the age of 1 month to the age of 4 months in order to analyse the effect of MCFA on body growth, insulin sensitivity and GSIS. The 45 % MCFA substitution of whole fatty acids in the normoenergetic diet impaired whole body growth and resulted in increased body adiposity and hyperinsulinaemia, and reduced insulin-mediated glucose uptake in skeletal muscle. In addition, the isolated pancreatic islets from the MCFA-fed rats showed impaired GSIS and reduced protein kinase Bα (AKT1) protein expression and extracellular signal-related kinase isoforms 1 and 2 (ERK1/2) phosphorylation, which were accompanied by increased cellular death. Furthermore, there was a mildly increased cholinergic sensitivity to GSIS. We discuss these findings in further detail, and advocate that they might have a role in the mechanistic pathway leading to the compensatory hyperinsulinaemic status found in this animal model.
One to 2-year surveillance intervals reduce risk of colorectal cancer in families with Lynch syndrome.

BACKGROUND & AIMS Two percent to 4% of all cases of colorectal cancer (CRC) are associated with Lynch syndrome. Dominant clustering of CRC (non-Lynch syndrome) accounts for 1%-3% of the cases. Because carcinogenesis is accelerated in Lynch syndrome, an intensive colonoscopic surveillance program has been recommended since 1995. The aim of the study was to evaluate the effectiveness of this program. METHODS The study included 205 Lynch syndrome families with identified mutations in one of the mismatch repair genes (745 mutation carriers). We also analyzed data from non-Lynch syndrome families (46 families, 344 relatives). Patients were observed from January 1, 1995, until January 1, 2009. End points of the study were CRC or date of the last colonoscopy. RESULTS After a mean follow-up of 7.2 years, 33 patients developed CRC under surveillance. The cumulative risk of CRC was 6% after the 10-year follow-up period. The risk of CRC was higher in carriers older than 40 years and in carriers of MLH1 and MSH2 mutations. After a mean follow-up of 7.0 years, 6 cases of CRC were detected among non-Lynch syndrome families. The risk of CRC was significantly higher among families with Lynch syndrome, compared with those without. CONCLUSIONS With surveillance intervals of 1-2 years, members of families with Lynch syndrome have a lower risk of developing CRC than with surveillance intervals of 2-3 years. Because of the low risk of CRC in non-Lynch syndrome families, a less intensive surveillance protocol can be recommended.
Guard cell-specific upregulation of sucrose synthase 3 reveals that the role of sucrose in stomatal function is primarily energetic.

Isoform 3 of sucrose synthase (SUS3) is highly expressed in guard cells; however, the precise function of SUS3 in this cell type remains to be elucidated. Here, we characterized transgenic Nicotiana tabacum plants overexpressing SUS3 under the control of the stomatal-specific KST1 promoter, and investigated the changes in guard cell metabolism during the dark to light transition. Guard cell-specific SUS3 overexpression led to increased SUS activity, stomatal aperture, stomatal conductance, transpiration rate, net photosynthetic rate and growth. Although only minor changes were observed in the metabolite profile in whole leaves, an increased fructose level and decreased organic acid levels and sucrose to fructose ratio were observed in guard cells of transgenic lines. Furthermore, guard cell sucrose content was lower during light-induced stomatal opening. In a complementary approach, we incubated guard cell-enriched epidermal fragments in (13) C-NaHCO3 and followed the redistribution of label during dark to light transitions; this revealed increased labeling in metabolites of, or associated with, the tricarboxylic acid cycle. The results suggest that sucrose breakdown is a mechanism to provide substrate for the provision of organic acids for respiration, and imply that manipulation of guard cell metabolism may represent an effective strategy for plant growth improvement.
Novel Hsp90 inhibitor NVP-AUY922 radiosensitizes prostate cancer cells

Outcomes for poor-risk localized prostate cancers treated with radiation are still insufficient. Targeting the “non-oncogene” addiction or stress response machinery is an appealing strategy for cancer therapeutics. Heat-shock-protein-90 (Hsp90), an integral member of this machinery, is a molecular chaperone required for energy-driven stabilization and selective degradation of misfolded “client” proteins, that is commonly overexpressed in tumor cells. Hsp90 client proteins include critical components of pathways implicated in prostate cancer cell survival and radioresistance, such as androgen receptor signaling and the PI3K-Akt-mTOR pathway. We examined the effects of a novel non-geldanamycin Hsp90 inhibitor, AUY922, combined with radiation (RT) on two prostate cancer cell lines, Myc-CaP and PC3, using in vitro assays for clonogenic survival, apoptosis, cell cycle distribution, γ-H2AX foci kinetics and client protein expression in pathways important for prostate cancer survival and radioresistance. We then evaluated tumor growth delay and effects of the combined treatment (RT-AUY922) on the PI3K-Akt-mTOR and AR pathways in a hind-flank tumor graft model. We observed that AUY922 caused supra-additive radiosensitization in both cell lines at low nanomolar doses with enhancement ratios between 1.4–1.7 (p < 0.01). RT-AUY922 increased apoptotic cell death compared with either therapy alone, induced G2-M arrest and produced marked changes in client protein expression. These results were confirmed in vivo, where RT-AUY922 combination therapy produced supra-additive tumor growth delay compared with either therapy by itself in Myc-CaP and PC3 tumor grafts (both p < 0.0001). Our data suggest that combined RT-AUY922 therapy exhibits promising activity against prostate cancer cells, which should be investigated in clinical studies.
Dietary fibre affects intestinal mucosal barrier function and regulates intestinal bacteria in weaning piglets

The objective of the present study was to evaluate the effects of fibre source on intestinal mucosal barrier function in weaning piglets. A total of 125 piglets were randomly allotted on the basis of their body weight and litters to one of five experimental diets, i.e. a control diet without fibre source (CT), and diets in which expanded maize was replaced by 10 % maize fibre (MF), 10 % soyabean fibre (SF), 10 % wheat bran fibre (WBF) or 10 % pea fibre (PF). The diets and water were fed ad libitum for 30 d. Piglets on the WBF and PF diets had lower diarrhoea incidence compared with the MF- and SF-fed animals. A higher ratio of villous height:crypt depth in the ileum of WBF-fed piglets and higher colonic goblet cells in WBF- and PF-fed piglets were observed compared with CT-, MF- and SF-fed piglets. In the intestinal digesta, feeding WBF and PF resulted in increased Lactobacillus counts in the ileum and Bifidobacterium counts in the colon. Lower Escherichia coli counts occurred in the ileum and colon of WBF-fed piglets than in SF-fed piglets. Tight junction protein (zonula occludens 1; ZO-1) and Toll-like receptor 2 (TLR2) gene mRNA levels were up-regulated in the ileum and colon of pigs fed WBF; however, feeding MF and SF raised IL-1α and TNF-α mRNA levels. Furthermore, higher diamine oxidase activities, transforming growth factor-α, trefoil factor family and MHC-II concentration occurred when feeding WBF and PF. In conclusion, the various fibre sources had different effects on the ileal and colonic barrier function. Clearly, WBF and PF improved the intestinal barrier function, probably mediated by changes in microbiota composition and concomitant changes in TLR2 gene expression.
Treatment of the irritable bowel syndrome with Bentyl (dicyclomine hydrochloride).

AbstractThe effectiveness of Bentyl (dicyclomine hydrochloride) 40 mg 4 times daily was evaluated in an ambulatory population with recent irritable bowel syndrome (IBS). During the 2-week double-blind study, the effects of dicyclomine hydrochloride compared to placebo were assessed by: 1) physicians