Orally administered resveratrol enhances the therapeutic effect of autologous transplanted adipose-derived stem cells on rats with diabetic hepatopathy.

Stem cell therapy is a promising treatment for hepatopathy due to diabetes mellitus (DM); oral resveratrol treatment exhibits protective effects. We investigated whether protective effects could be produced in liver of diabetic rats receiving autologous adipose-derived stem cell transplantation (ADSC) plus oral resveratrol administration. Male rats were divided into four groups: sham group; streptozotocin induced DM group; DM + ADSC group, in which DM rats were treated with 106 stem cells/rat; and DM + R + ADSC group, in which DM rats were treated with ADSC and oral resveratrol. The DM group exhibited apoptosis, inflammation and fibrosis, whereas Sirt-1 and survival signaling were suppressed. Pathological conditions other than survival signaling were improved in the DM + ADSC group. All pathological conditions were improved in the DM + R + ADSC group. Also, the oxidative stress level in the blood was reduced in the DM + R + ADSC group compared to the sham group. Oral resveratrol administration appears to reduce oxidative damage and enhances survival signaling in diabetic liver. The therapeutic response in the DM + R + ADSC group was better than in the DM + ADSC group.

Efficacy and safety of high-dose vs low-dose leucovorin in patients with colorectal cancer: systematic review and meta-analysis.

AIM: The clinical benefits of a combination of leucovorin and fluorouracil have been established in the treatment of colorectal cancer. Due to a leucovorin shortage in 2008, many institutions revised their protocols to reduce the dose of leucovorin. After the shortage was resolved, some hospitals still maintained their modified protocols. Thus, we conducted a systematic review to evaluate the efficacy and safety of low- vs high-dose leucovorin in the treatment of colorectal cancer. METHOD: The PubMed, Embase and Cochrane databases were searched for studies published before May 2019. The meta-analysis was performed to estimate the pooled effect sizes by using a random effect model. The primary outcomes were median survival time and tumour response rate. Secondary outcomes were haematological and nonhaematological toxicities. RESULTS: Eight randomized controlled trials and four retrospective studies were reviewed. The pooled median survival time was similar between the two dose levels (standard mean difference -0.06, 95% CI -0.19 to 0.08). The pooled tumour response rate was comparatively higher in the high-dose leucovorin regimen (OR 0.81; 95% CI 0.55-1.18). No statistically significant difference was found between the haematological and nonhaematological toxicities of the two groups. However, there were fewer diarrhoea events in the low-dose leucovorin regimen. CONCLUSION: Low-dose leucovorin regimens seemed feasible approaches for colorectal cancer treatment when the shortage happened, because both regimens manifested comparable outcomes in survival time and tumour response rate.

[The effect of miR-155 on HBV replication and PTEN expression in vivo].

Objective: To construct the mmu-miR-155 eukaryotic overexpression vector pmR-155 and to investigate its effect on HBV replication and expression of PTEN in vivo. Methods: The mmu-mir-146a precursor gene fragment pre-mmu-mir-146a was amplified by PCR, then connected to the pmR-mCherry plasmid vector after double enzyme digestion, the accuracy of recombinant vector was verified by colony PCR、double enzyme digestion and sequencing; then the recombinant vector was transfected HBV transgene mice(Experimental Group)with hydrodynamics-based injection via vena caudalis, and pmR-mCherry plasmid、PBS were respectively transfected into the mice as Empty plasmid Group、Blank Group. The concentration of IFN-γ in the serum was detected by ELISA. The expression of SOCS1、PTEN mRNA in the liver was detected by qPCR at 30d post-transfectioned. The Western blot was performed to detect the changes in SOCS1、PTEN、HBX in the liver tissue at 30 d post-transfectioned. The results were analyzed with Student's t-test, or one-way analysis of variance and the least significant difference test. Results: the colony PCR、double enzyme digestion and sequencing verified that the gene was inserted into the pmR-mCherry vector. Compared with Blank Group, the expression of miR-155 in the Experimental Group was significantly increased(t = 8.90, P < 0.01); the concentration of IFN-γ in the Experimental Group was significantly increased(F = 26.58, P < 0.01); the mRNA(F(SOCS1 mRNA) = 19.72, P < 0.01; F(PTEN mRNA) = 7.38, P < 0.05) and protein(F(SOCS1) = 50.30, P < 0.01; F(PTEN) = 129.00, P < 0.01) expression of COCS1、PTEN was significantly decreased in the Experimental group and the protein of HBX was also significantly(F(HBX) = 77.97, P < 0.01). Conclusion: The pmR-155 eukaryotic overexpression vector is successfully constructed, this recombinant vector can express miR-155 stably; miR-155 can down-regulate cocs1、PTEN gene expression and up-regulate the expression of IFN-γ, it can inhibit the replication of HBV and a potential targets to treating hepatocellular carcinoma.

Role of brain-derived neurotrophic factor in the pathogenesis of distention-associated abdominal pain in bowel obstruction.

BACKGROUND: Previous studies found that visceral sensitivity is increased in bowel obstruction (BO). We hypothesized that mechanical stress-induced expression of BDNF in smooth muscle cells (SMC) of the distended bowel plays a critical role in visceral hypersensitivity in BO by altering voltage-gated K+ channel (Kv ) activity in sensory neurons. METHODS: Partial colon obstruction was maintained in rats for 7 days. Colon-projecting neurons in the dorsal root ganglia (DRG, T13 to L2) were isolated for electrophysiological and gene expression studies. KEY RESULTS: Compared to controls, membrane excitability of colon-projecting DRG neurons was markedly enhanced in BO. The densities of total Kv and transient A-type (IA ) K+ currents, but not sustained delayed IK current, were significantly reduced in the neurons in BO. The mRNA expression of IA subtype Kv 1.4 in colon neurons was down-regulated in BO. Expression of BDNF mRNA and protein was dramatically increased in colonic smooth muscle of the distended segment, but not in the non-distended aboral segment. Mechanical stretch of colon SMC in vitro increased BDNF expression. Treatment with anti-BDNF antibody restored total Kv and IA currents of neurons from BO rats. Administration of Trk B inhibitor ANA-12 blocked BO-associated changes of neuronal excitability, Kv activity and gene expression in obstruction. CONCLUSIONS AND INFERENCES: Mechanical stress-induced expression of BDNF in colon SMC plays a critical role in visceral hypersensitivity in BO by suppressing A-type K+ currents and gene expression in sensory nerve. These findings help to identify therapeutic targets for distention-associated abdominal pain in the gut.

The acid soluble extracellular polymeric substance of aerobic granular sludge dominated by Defluviicoccus sp.

A new acid soluble extracellular polymeric substance (acid soluble EPS) was extracted from an acetate fed aerobic granular sludge reactor operated at 35 °C. Acid soluble EPS dominated granules exhibited a remarkable and distinctive tangled tubular morphology. These granules are dominated by Defluviicoccus Cluster II organisms. Acetic acid instead of the usually required alkaline extraction medium was needed to dissolve the granules and solubilise the polymeric matrix. The extracted acid soluble EPS was analysed and identified using various instrumental analysis including 1H and 13C Nuclear Magnetic Resonance, Fourier Transform Infrared Spectroscopy and Raman spectroscopy. In addition, the glycoconjugates were characterized by fluorescence lectin-binding analysis. The acid soluble EPS is α-(1 â†’ 4) linked polysaccharide, containing both glucose and galactose as monomers. There are OCH3 groups connected to the glucose monomer. Transmission and scanning electron microscopy (TEM, SEM) as well as confocal laser scanning microscopy (CLSM) showed that the acid soluble EPS was present as a tightly bound capsular EPS around bacterial cells ordered into a sarcinae-like growth pattern. The special granule morphology is decided by the acid soluble EPS produced by Defluviicoccus Cluster II organisms. This work shows that no single one method can be used to extract all possible extracellular polymeric substances. Results obtained here can support the elucidation of biofilm formation and structure in future research.

Thermal treatments prior to and during the beginning of incubation affects development of the broiler embryo and yolk sac membranes, and live performance and carcass characteristics.

This study evaluated temperature during preincubation and embryonic day 0 (E0) E0 to E5 of incubation on broiler embryo development and subsequent live performance. Freshly laid eggs from a single 41-wk-old Ross 708 broiler breeder flock produced on a single day were weighed individually for weight matching purposes, stored overnight, and assigned to 4 treatment combinations of 2 preincubation temperatures (23.9 or 29.4°C) × 2 E0 to E5 temperatures (38.1 or 37.5°C). The 29.4°C preincubation temperature decreased (P ≤ 0.05) yolk sac membrane (YSM) vasculature at E6 and E7, and increased (P ≤ 0.05) embryo weight and length but decreased (P ≤ 0.05) yolk sac weight (YSW) at E15. No subsequent main effects were observed. The 38.1°C incubation temperature increased YSM vasculature at E7, chorioallantoic membrane (CAM) vasculature at E8 and E10, and egg weight loss, embryo weight, and embryo length at E15 and chick length at E21 in the presence of reduced BW and YSW (P ≤ 0.05). This was followed by greater male BW at 35 d, as well as improved FCR in females 0 to 14 d and in males 15 to 35 d (P ≤ 0.05). Pectoralis major and minor yields were increased (P ≤ 0.05) at 50 d of age in males and females, respectively. There were no interactions observed with regards to broiler live performance and carcass yield, which probably negated the importance of the interactions observed for preincubation temperature by E0 to E5 incubation temperature that affected YSM vasculature, CAM vasculature area, egg weight loss, embryo weight, yolk sac weight, and chick length.

Effects of dietary coarsely ground corn and 3 bedding floor types on broiler live performance, litter characteristics, gizzard and proventriculus weight, and nutrient digestibility.

The effects of zero or 50% dietary coarsely ground corn (CC) in pelleted and screened grower and finisher diets on broilers reared on 3 bedding floor types (plastic net [NET], new pine wood shavings litter [NEW], or old pine wood shavings litter [OLD]) on broiler live performance, litter characteristics, gizzard and proventriculus weight, and apparent ileal digestibility (AID) were studied in a 2 × 3 factorial arrangement of treatments. Fine corn was produced with a hammermill (271 µm) and CC with a roller mill (1145 µm). Utilization of CC reduced milling cost by 9.47 cents per MT with similar nutrient content of screened pellets. The 50% CC treatment exhibited improved (P ≤ 0.05) feed intake at 42 d (2.5%) and 49 d (3.0%), and BW (5.4%) and FCR from 28 d (1.4%). Birds on NEW litter exhibited improved (P < 0.05) BW at 28 and 35 d and 42 d FCR as compared to NET and 49 d FCR compared to NET and OLD. The 50% CC treatment exhibited increased (P < 0.05) gizzard weight but decreased proventriculus weight at 49 d. NEW litter birds exhibited increased (P ≤ 0.05) gizzard weight at 28 d and 49 d and decreased proventriculus weight as compared to NET at 49 days. The 50% CC treatment exhibited decreased (P ≤ 0.05) litter moisture at 35 and 42 d, litter N at 35 and 49 d, and litter pH at 49 days. OLD litter birds exhibited greater (P < 0.05) litter N at 14, 35, and 49 d, as well as litter moisture, pH, and ammonia concentration at 49 days. The 50% CC group also exhibited improved AID of nitrogen (P < 0.05). Broilers fed pelleted and screened diets containing 50% CC exhibited improved live performance and reduced litter moisture while use of NEW litter resulted in a somewhat similar effect, which indicated that consumption of NEW litter also facilitated gastric development and function.

Phosphorylation of cofilin-1 by ERK confers HDAC inhibitor resistance in hepatocellular carcinoma cells via decreased ROS-mediated mitochondria injury.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Despite the availability of several treatment strategies, resistance to chemotherapeutic agents, which limits the effectiveness of anticancer drugs, is a major problem in cancer therapy. In this study, we used a histone deacetylases inhibitor (HDACi) to establish drug-resistant HCC cells and further analyzed the molecular mechanisms underlying the development of resistance in HCC cells. Compared with the parental cells, HDACi-resistant cells showed high metastatic and pro-survival abilities. Two-dimensional electrophoresis data showed that the cofilin-1 (CFL-1) protein was altered in HDACi-resistant cells and was highly expressed in resistant cells compared with parental cells. The molecular function of CFL-1 is actin depolymerization, and it is involved in tumor metastasis. In this study, we showed that CFL-1 inhibition decreased cell migration and increased cell apoptosis in HDACi-resistant cells. We observed that HDACi induced ROS accumulation in cells and apoptosis via promotion of the CFL-1 interaction with Bax and CFL-1 translocation to the mitochondria, resulting in cytochrome C release. Importantly, phosphorylation of CFL-1 by activated extracellular signal-regulated kinases 1 and 2 (ERK1/2) confers strong protection against HDAC inhibitor-induced cell injury. p-CFL-1 shows a loss of affinity with Bax and will not translocate to mitochondria, stably remaining in the cytoplasm. These results indicate that phosphorylation to inactivate CFL-1 decreased the chemosensitivity to HDAC inhibitors and resulting in drug resistance of HCC cells.

Irritable bowel syndrome and the incidence of colorectal neoplasia: a prospective cohort study with community-based screened population in Taiwan.

BACKGROUND: We aim to report the prevalence of irritable bowel syndrome (IBS) and elucidate the influence of IBS on the incidence of colorectal neoplasm through a community-screening-based, longitudinal follow-up study. METHODS: We enroled 39,384 community residents aged 40 years or older who had participated in a community-based colorectal cancer-screening programme with an immunochemical faecal occult test since 1999. We followed a cohort that was free of colorectal neoplasm (excluding colorectal neoplasm at baseline) to ascertain the incident colorectal neoplasm through each round of screening and used a nationwide cancer registry. Information on IBS was obtained by linking this screened cohort with population-based health insurance claim data. Other confounding factors were also collected via questionnaire or biochemical tests. RESULTS: The overall period prevalence of IBS was 23%, increasing from 14.7% for subjects aged 40-49 years to 43.7% for those aged 70 years and more. After controlling for age, gender and family history of colorectal cancer, screenees who had been diagnosed as having IBS exhibited a significantly elevated level (21%; adjusted hazard ratio (HR)=1.21 (95% CI: 1.02-1.42)) of incident colorectal adenoma compared with those who had not been diagnosed with IBS. A similar finding was noted for invasive carcinoma; however, the size of the effect was of borderline statistical significance (adjusted HR=1.20 (95% CI: 0.94-1.53)). CONCLUSIONS: IBS led to an increased risk for incident colorectal neoplasm.

Apatite accumulation enhances the mechanical property of anammox granules.

The strength of granular sludge is essential for the mechanical stability of the granules. Inorganic precipitants form a major factor influencing the strength of the granules. To check the possibility of apatite accumulation in anammox granules, and study its contribution to the mechanical strength of granules, anammox granular sludge was collected from Dokhaven municipal wastewater treatment plant, the Netherlands. Mineral precipitation inside the granules was visualized by micro-computed tomography, and apatite was identified by electron probe microanalysis and X-ray powder diffraction. The mechanical strength of anammox granules was measured by a low load compression tester. The contribution of apatite to the mechanical strength was evaluated by the generalized Maxwell model. Ca-PO4 minerals are reported to accumulate in anammox granules. A transformation of Ca-PO4 happens, and apatite is the final stable form. The accumulation of apatite increases the mechanical strength of anammox granules. A fast method to monitor and evaluate the accumulation of minerals in anammox granules was proposed.

Effects of exercise training on cardiac apoptosis in obese rats.

BACKGROUND AND AIM: The purpose of this study was to evaluate the effects of exercise training on cardiac apoptotic pathways in obesity. METHODS AND RESULTS: Sixteen lean Zucker rats (LZR) and sixteen obese Zucker rats (OZR) of 5-6 months of age as well as the other sixteen obese rats were subjected to treadmill running exercise for 1 h everyday for 3 months (OZR-EX). After exercise training or sedentary status of the rats, the excised hearts from the three groups were measured by heart weight index, H&E staining, TUNEL assays and Western blotting. Cardiac TUNEL-positive apoptotic cells, the protein levels of TNF alpha, Fas ligand, Fas receptors, Fas-associated death domain (FADD), Bad, Bax, activated caspase 8, activated caspase 9, and activated caspase 3 were higher in OZR than those in LZR. The protein levels of TNF alpha, Fas ligand, Fas receptors, FADD, activated caspase 8, and activated caspase 3 (Fas pathway) and the protein levels of Bad, Bax, Bax-to-Bcl2 ratio, activated caspase 9, and activated caspase 3 (mitochondria pathway) were lower in OZR-EX than those in OZR. CONCLUSION: Cardiac Fas-dependent and mitochondria-dependent apoptotic pathways become more activated in obesity. Exercise training can prevent obesity-activated cardiac Fas-dependent and mitochondria-dependent apoptotic pathways. Our findings demonstrate a new therapeutic effect of exercise training to prevent delirious cardiac Fas-mediated and mitochondria-mediated apoptosis in obesity.

The chemical and mechanical differences between alginate-like exopolysaccharides isolated from aerobic flocculent sludge and aerobic granular sludge.

This study aimed to investigate differences in the gel matrix of aerobic granular sludge and normal aerobic flocculent sludge. From both types of sludge that fed with the same municipal sewage, the functional gel-forming exopolysaccharides, alginate-like exopolysaccharides, were isolated. These two exopolysaccharides were chemically fractionated, and investigated by FT-IR spectroscopy. The isolated polymers were made into a gel by calcium addition and the mechanical properties of these reconstituted gels were measured by a low load compression tester. The viscoelastic behavior of the gels was described by a generalized Maxwell model. The alginate-like exopolysaccharides derived from aerobic granules had significantly higher amount of poly(guluronic acid) blocks but lower amount of poly(guluronic acid-manuronic acid) blocks in the chemical structure, while the alginate-like exopolysaccharides derived from aerobic flocculent sludge had equal amount of poly(guluronic acid) blocks and poly(guluronic acid-manuronic acid) blocks. These differences result in a perfect gel-forming capability of alginate-like exopolysaccharides derived from aerobic granules and bestowed this exopolysaccharides gel a stronger mechanical property as compared to alginate-like exopolysaccharides derived from aerobic flocculent sludge. The different chemical and mechanical properties of these two exopolysaccharides contributed to the distinguished characteristics between aerobic granular sludge and aerobic flocculent sludge.

Mechano-transcription of COX-2 is a common response to lumen dilation of the rat gastrointestinal tract.

BACKGROUND: In obstructive bowel disorders (OBDs) such as achalasia, pyloric stenosis, and bowel obstruction, the lumen of the affected segments is markedly dilated and the motility function is significantly impaired. We tested the hypothesis that mechanical stress in lumen dilation leads to induction of cyclooxygenase-2 (COX-2) in smooth muscle throughout the gastrointestinal (GI) tract, contributing to motility dysfunction. METHODS: Lumen dilation was induced in vivo with obstruction bands (12 × 3 mm) applied over the lower esophageal sphincter (LES), the pyloric sphincter, and the ileum in rats for 48 h. Mechanical stretch in vivo was also emulated by balloon distension of the distal colon. Direct stretch of muscle strips from the esophagus, gastric fundus, and ileum was mimicked in an in vitro tissue culture system. KEY RESULTS: Partial obstruction in the LES, pylorus, and ileum significantly increased the expression of COX-2 mRNA and protein in the muscularis externae of the dilated segment oral to the occlusions, but not in the aboral segment. Direct stretch of the lumen in vivo or of muscle strips in vitro markedly induced COX-2 expression. The smooth muscle contractility was significantly suppressed in the balloon-distended segments. However, treatment with COX-2 inhibitor NS-398 restored the contractility. Furthermore, in vivo administration of NS-398 in gastric outlet obstruction significantly improved gastric emptying. CONCLUSIONS & INFERENCES: Mechanical dilation of the gut lumen by occlusion or direct distension induces gene expression of COX-2 throughout the GI tract. Mechanical stress-induced COX-2 contributes to motility dysfunction in conditions with lumen dilation.

The contribution of exopolysaccharides induced struvites accumulation to ammonium adsorption in aerobic granular sludge.

Aerobic granular sludge from a lab-scale reactor with simultaneous nitrification/denitrification and enhanced biological phosphorus removal processes exhibited significant amount of ammonium adsorption (1.5 mg NH4+-N/g TSS at an ammonium concentration of 30 mg N/L). Potassium release accompanied ammonium adsorption, indicating an ion exchange process. The existence of potassium magnesium phosphate (K-struvite) as one of potassium sources in the granular sludge was studied by X-ray diffraction analysis (XRD). Artificially prepared K-struvite was indeed shown to adsorb ammonium. Alginate-like exopolysaccharides were isolated and their inducement for struvite formation was investigated as well. Potassium magnesium phosphate proved to be a major factor for ammonium adsorption on the granular sludge. Struvites (potassium/ammonium magnesium phosphate) accumulate in aerobic granular sludge due to inducing of precipitation by alginate-like exopolysaccharides.

Assessment of urinary N-acetyl-ß-glucosaminidase as an early marker of contrast-induced nephropathy.

Early detection and timely intervention are important for improving contrast-induced nephropathy (CIN) prognosis. Whether urinary N-acetyl-ß-glucosaminidase (NAG) is a useful marker for early detection of CIN was investigated in 590 patients undergoing diagnostic coronary angiography (CA) and/or therapeutic percutaneous coronary intervention (PCI) for acute coronary syndromes or stable angina, and who received low-osmolality nonionic contrast agent. Urinary NAG, osmolality and serum creatinine were measured before and 1, 2 and 6 days after contrast agent exposure. CIN occurred in 33 patients; its incidence in high-risk patients (pre-existing renal dysfunction with/without diabetes mellitus) was significantly higher than in others. In patients with CIN, urinary NAG and serum creatinine levels on days 1 and 2 were significantly higher than at baseline and compared with patients without CIN; mean levels were gradually returning to baseline by day 6. Compared with serum creatinine, urinary NAG levels peaked earlier in CIN patients and increased much more. The results suggest that, following CA and/or PCI, CIN occurs to a certain degree and that NAG may be a useful early CIN marker as it is noninvasive, simple, inexpensive and sensitive.

Identification and characterization of a novel Rab GTPase-activating protein in spermatids.

We have previously identified novel testis-specific genes by microarray analysis of human testicular tissues. One of the novel genes is Male Germ Cells Rab GTPase- Activating Proteins (MgcRabGAP), which is characterized by the conserved RabGAP catalytic domain, TBC (Tre2/Bub2/Cdc16). RabGAPs are involved in various physiological processes (e.g. vesicular trafficking, cytoskeletal remodelling, cell migration, etc.) by inactivating Rab proteins. In this study, we found that MgcRabGAP transcripts are mainly expressed in the mouse and human testes. The MgcRabGAP protein is expressed in the elongating and elongated spermatids. Immunofluorescence assay of mouse germ cells showed that the protein expression is enriched at the edge of the acrosomal region, neck and annulus during spermiogenesis. This MgcRabGAP is co-localized with its candidate substrate Rab3A at the acrosome/acroplaxome and neck regions of spermatids. Meanwhile, MgcRabGAP is co-localized and interacts with ß-actin. In humans, the expression of MgcRabGAP is enriched at the stage of elongating spermatids. The amount of MGCRABGAP transcript is reduced in the testicular tissues of men with various types of spermatogenic defects. Considering that MGCRABGAP is exclusively expressed in post-meiotic male germ cells, the decreased transcript amount may be a phenomenon secondary to loss of germ cells in the testicular samples. Our finding strongly suggests that MgcRabGAP is involved in acrosome/acroplaxome formation and cytoskeletal reorganization via Rab activity during mammalian spermiogenesis.

100-GHz transistors from wafer-scale epitaxial graphene.

The high carrier mobility of graphene has been exploited in field-effect transistors that operate at high frequencies. Transistors were fabricated on epitaxial graphene synthesized on the silicon face of a silicon carbide wafer, achieving a cutoff frequency of 100 gigahertz for a gate length of 240 nanometers. The high-frequency performance of these epitaxial graphene transistors exceeds that of state-of-the-art silicon transistors of the same gate length.