Stage III deficient mismatch repair colon patients get greater benefit from earlier starting oxaliplatin-based chemotherapy regimen.

We evaluate the prognostic value of chemotherapy and other prognostic factors on overall survival among colon patients with deficient mismatch repair (dMMR), and determine the optimum time to start chemotherapy after surgery. Data of 306 colon cancer patients with dMMR who received radical surgery were collected from three Chinese centers between August 2012 and January 2018. Overall survival (OS) was assessed with the Kaplan-Meier method and log-rank. Cox regression analysis were used to assess influencing prognosis factors. The median follow-up time for all patients was 45.0 months (range, 1.0-100). There was a nonsignificant OS benefit from chemotherapy for patients with stage I and stage II disease, including high-risk stage II disease (log-rank p: 0.386, 0.779, 0.921), and a significant OS benefit for patients with stage III and stage IV disease for receiving post-operation chemotherapy (log-rank p = 0.002, 0.019). Stage III patients benefitted from chemotherapy regimens that contained oxaliplatin (log-rank p = 0.004), and Starting chemotherapy with oxaliplatin treatment earlier resulted in better outcomes (95% CI 0.013-0.857; p = 0.035). Chemotherapy regimens containing oxaliplatin can prolong the survival time of stage III and IV dMMR colon cancer patients. This beneficial manifestation was more pronounced after starting chemotherapy treatment early post operation. High risk stage II dMMR colon patients including T4N0M0 cannot benefit from chemotherapy.

Phenolipid JE improves metabolic profile and inhibits gluconeogenesis via modulating AKT-mediated insulin signaling in STZ-induced diabetic mice.

Phenolipids are characteristic phytochemicals of Syzygium genus. However, the antidiabetic potential and underlying molecular mechanism of these components are not fully elucidated. Herein, we studied the anti-diabetic effects of jambone E (JE), a phenolipid from S. cumini, with in vitro and in vivo models. Data from current study showed that JE enhanced glucose consumption and uptake, promoted glycogen synthesis, and suppressed gluconeogenesis in insulin resistant (IR)-HepG2 cells and primary mouse hepatocytes. JE also attenuated streptozotocin-induced hyperglycemia and hyperlipidemia in type 1 diabetic (T1D) mice. Eleven metabolites (e.g. trimethylamine n-oxide, 4-pyridoxic acid, phosphatidylinositol 39:4, phenaceturic acid, and hippuric acid) were identified as potential serum biomarkers for JE's antidiabetic effects by an untargeted metabolomics approach. The further molecular mechanistic study revealed that JE up-regulated phosphorylation levels of protein kinase B (AKT), glycogen synthase kinase 3 beta, and forkhead box O1 (FoxO1), promoted nuclear exclusion of FoxO1 whilst decreased gene expression levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha, phosphoenolpyruvate carboxykinase and glucose 6-phosphatase in IR-HepG2 cells and T1D mice. Our data suggested that JE might be a potent activator for AKT-mediated insulin signaling pathway, which was confirmed by the usage of AKT inhibitor and AKT-target siRNA interference, as well as the cellular thermal shift assay. Findings from the current study shed light on the anti-diabetic effects of phenolipids in the Syzygium species, which supports the use of medicinal plants in the Syzygium genus for potential pharmaceutical applications.

Effects of deficient mismatch repair on the prognosis of patients with stage II and stage III colon cancer during different postoperative periods.

BACKGROUND: We evaluated the prognostic role of deficient mismatch repair (dMMR) systems in stage II and stage III colon cancer patients during different postoperative periods. We also assessed whether patients aged ≥75 could benefit from chemotherapy. METHODS: This retrospective study was conducted across three medical centers in China. Kaplan-Meier survival methods and Cox proportional hazards models were used to evaluate the differences in overall survival (OS) and disease-free survival (DFS) rates. Propensity score matching was performed to reduce imbalances in the baseline characteristics of the patients. Landmark analysis was performed to evaluate the role of dMMR during different postoperative periods. RESULTS: The median follow-up time for all patients was 45.0 months (25-75 IQR: 38.0-82.5). There was no significant OS (p = 0.350) or DFS (p = 0.752) benefit associated with dMMR for stage II and III patients during the first postoperative year. However, significant OS (p < 0.001) and DFS (p < 0.001) benefits were observed from the second postoperative year until the end of follow-up. These differences remained after propensity score matching. Moreover, chemotherapy produced no OS (HR = 0.761, 95% CI: 0.43-1.34, p = 0.341) or DFS (HR = 0.98, 95% CI: 0.51-1.88, p = 0.961) benefit for patients aged ≥75 years. CONCLUSION: The benefits of dMMR in stage III patients were observed from the second postoperative year until the end of follow-up. However, the prognosis of patients with dMMR is not different from that of patients with proficient mismatch repair (pMMR) during the first postoperative year. In addition, elderly patients aged ≥75 years obtained no significant survival benefits from postoperative chemotherapy.

Efficacy of Hyperbaric Oxygen on Idiopathic Sudden Sensorineural Hearing Loss and Its Correlation with Treatment Course: Prospective Clinical Research.

OBJECTIVES: This study was conducted to explore the effectiveness of hyperbaric oxygen (HBO) in the treatment of idiopathic sudden sensorineural hearing loss (ISSNHL) and recommend the appropriate course of treatment. METHODS: 102 patients (105 diseased ears) with ISSNHL were recruited from the Department of Neurology and Otorhinolaryngology, West China Fourth Hospital, Sichuan University, between January 2018 and September 2020. Of them, 45 patients (group A) received intravenous steroid (IVS), and the remaining patients (group B) received IVS and HBO therapy (HBOT). Pure-tone audiometry (PTA) was performed twice at baseline and 10 days after treatment. Patients in group B were subdivided into group 1 (≤10 sessions) and group 2 (>11 sessions) to verify the correlation between the efficacy and course of HBOT, at the follow-up endpoint, the PTA was performed again. The multivariate logistical regression model was used to analyze the related factors of prognosis. RESULTS: Compared with the control group, significantly larger hearing gains and better hearing recovery rate were observed in the IVS + HBOT group (p < 0.05). The time of treatment and course of HBOT were significantly correlated with the hearing threshold after treatment (p < 0.05) and had no significant relationship with tinnitus and age (p > 0.05). CONCLUSION: HBOT + IVS is an effective method for ISSNHL, especially for the recovery of low-frequency hearing and initial hearing levels of severe and profound. Tinnitus is the most common concomitant symptom of ISSNHL, and prolonging the course of HBOT did not significantly improve it. Initiating HBOT within 7 days for 10-25 sessions of treatment was more beneficial.

FK506 ameliorates osteoporosis caused by osteoblast apoptosis via suppressing the activated CaN/NFAT pathway during oxidative stress.

OBJECTIVE: Osteoporosis is affecting the health of postmenopausal women in the world. In case of that, we explored whether FK-506 could ameliorate osteoporosis by inhibiting the activated CaN/NFAT pathway during oxidative stress. METHODS: First, the castrated rat model is constructed through the bilateral ovariectomy. Hologic Discovery (S/N 80347) dual-energy X-ray absorptiometry assessed bone mineral density (BMD) implemented at left femur of rats. Next, hematoxylin-eosin (H&E) staining observed and calculated the changes of bone trabecular, mean trabecular plate separation (Tb.Sp), mean trabecular plate thickness (Tb.Th), and bone volume fraction (BV/TV). Then, CCK-8 assay, TUNEL assay, ALP kit and alizarin red staining detected the viability, apoptosis, alkaline phosphatase (ALP) activity, and capacity of mineralization respectively. At last, commercially available kits detected the levels of ROS and SOD in transfected MC3T3-E1 cells and bone tissues, and Western blot analysis detected proteins related to apoptosis and CaN/NFAT pathway. RESULTS: FK-506 increased the BMD and changes of bone trabecular in female castrated rats. FK-506 inhibited the oxidative stress and apoptosis by suppressing the activated CaN/NFAT pathway. Low dose of FK-506 improved the viability, ALP activity, and mineralization capacity. What's more, it suppressed the apoptosis of H2O2-induced MC3T3-E1 cells, which was deteriorated by the high dose of FK-506. Briefly, low dose of FK-506 inhibited the oxidative stress by suppressing the activated CaN/NFAT pathway, while high dose of that further inhibited the oxidative stress by suppressing the CaN/NFAT pathway. CONCLUSION: FK-506 ameliorates osteoporosis resulted from osteoblastic apoptosis which caused by suppressing the activated CaN/NFAT pathway during oxidative stress.

New anti-inflammatory withanolides from Physalis pubescens fruit.

Physalis pubescens L. is a medicinal plant widely cultivated in northeast of China. Investigation on the extract of P. pubescens fruit led to the isolation and identification of four new withanolides, namely, physapubescins J-M (1, 2, 4 and 5), together with four known analogues (3, 6-8) and fifteen other compounds. Their structures were elucidated on the basis of comprehensive NMR, MS, and ECD spectroscopic data analysis. Among isolates, physapubescin J (1) contained an unusual sulphide linkage, and four withanolides (3, 5, 7 and 8) showed anti-inflammatory potential in LPS-induced RAW264.7 cells. This study supports P. pubescens fruit could be a valuable source of withanolides. Further studies to investigate anti-inflammatory activities of isolated withanolides using in vivo models are warranted.

Comparative Proteomic Analysis of the Hevea brasiliensis Latex under Ethylene and Calcium Stimulation.

BACKGROUND: Calcium ions usually act as a second messenger in the signal transmission process and a major element required by plants. In Hevea, calcium ion could alleviate the negative effects of long-term ethylene application to a certain extent. However, the molecular mechanisms remain unclear. METHODS: Two-dimensional electrophoresis was used to determine the pattern of protein changes in latex after treatments with calcium and/or ethylene. Quantitative real-time polymerase chain reaction and Western blotting were used to determine the expression levels of some proteins and genes. STRING software was used to determine the protein-protein interaction network of the identified proteins. RESULTS: Comparative proteomics identified 145 differentially expressed proteins, which represented 103 unique proteins. The abundance change patterns of some proteins involved in signal transduction, rubber particle aggregation, and natural rubber biosynthesis were altered upon calcium stimulation. Quantitative real-time polymerase chain reaction analysis of 29 proteins showed that gene expression did not always maintain the same trend as protein expression. The increased enzyme activities of superoxide dismutase, ascorbate peroxidase, and glutathione reductase suggested that calcium can enhance the antistress ability of plants by increasing the activity of their antioxidant enzyme systems. CONCLUSION: These results supplement the rubber latex proteome, and provide evidence for investigating the molecular mechanisms by which calcium alleviates the negative effects of ethylene stimulation.

Phenolics from Eugenia jambolana seeds with advanced glycation endproduct formation and alpha-glucosidase inhibitory activities.

Published data suggest that dietary-derived phenolics exert beneficial effects against hyperglycemia-mediated diseases, such as diabetes, through inhibiting the formation of advanced glycation endproducts (AGEs) and carbohydrate hydrolyzing enzyme activities. In the course of our investigation on the edible berry, Eugenia jambolana (known as Jamun), 21 phenolics (1-21) were isolated and identified from its seeds. Among these, one compound (1) is new and eleven compounds (3, 6, 9-13, 17, and 19-21) are being reported from E. jambolana for the first time. The anti-AGE activities of thirteen pure isolates (2-7, 9-12, 14, 15, and 20) were either comparable or superior to the synthetic anti-glycation agent, aminoguanidine, at three test concentrations (20, 50, and 100 µM) in the BSA-fructose assay. Most of these phenolics with anti-AGE activity exhibited potent free radical scavenging activity in the DPPH assay, and attenuated intracellular levels of LPS-induced reactive oxygen species in RAW264.7 macrophage. In addition, compounds 2-6, and 14 showed superior α-glucosidase inhibitory activity (IC50 = 5.0-21.2 µM) compared to the clinical α-glucosidase inhibitor, acarbose (IC50 = 289.9 µM). This is the first report of the anti-AGE effects of compounds 2-6 and 9-12, and α-glucosidase inhibitory activities of compounds 3-6, 9, 11 and 14. The current study supports the role of phenolics in the antidiabetic properties attributed to this edible berry, and warrants further animal studies to evaluate their potential as dietary agents for the prevention and/or therapy of hyperglycemia-mediated diseases.

Ecdysterones from Rhaponticum carthamoides (Willd.) Iljin reduce hippocampal excitotoxic cell loss and upregulate mTOR signaling in rats.

Glutamate-induced excitotoxicity is a key pathological mechanism in many neurological disease states. Ecdysterones derived from Rhaponticum carthamoides (Willd.) Iljin (RCI) have been shown to alleviate glutamate-induced neuronal damage; although their mechanism of action is unclear, some data suggest that they enhance signaling in the mechanistic target of rapamycin (mTOR) signaling pathway. This study sought to elucidate the mechanisms underlying ecdysterone-mediated neuroprotection. We used in silico target prediction and simulation methods to identify putative ecdysterone binding targets, and to specifically identify those that represent nodes where several neurodegenerative diseases converge. We then used histological analyses in a rat hippocampal excitotoxicity model to test the effectiveness of ecdysterones in vivo. We found that RCI-derived ecdysterones should bind to glutamatergic NMDA-type receptors (NMDARs); specifically, in vivo modeling showed binding to the GRIN2B subunit of NMDARs, which was found also to be a node of convergence in several neurodegenerative disease pathways. Computerized network construction by using pathway information from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database showed putative links between GRIN2B and mTOR pathway elements including phosphoinositide-3kinase (PI3K), mTOR, and protein kinase C (PKC); these elements are associated with neuronal survival. Brain tissue western blots of ecdysterone-treated rats showed upregulated PI3K, Akt, mTOR, and phosphorylated Akt and mTOR, and down regulated GRIN2B and the apoptotic enzyme cleaved caspase-3. Ecdysterone treatment also prevented glutamate-induced rat hippocampal cell loss. In summary, RCI-derived ecdysterones appear to prevent glutamatergic excitotoxicity by increasing mTOR/Akt/PI3K signaling activity.

Polyporus umbellatus inhibited tumor cell proliferation and promoted tumor cell apoptosis by down-regulating AKT in breast cancer.

Breast cancer (BC) is the foremost cause of cancer-related mortality in women worldwide. Polyporus umbellatus is a polysaccharide preparation of the Chinese traditional herb medicine, which has been explored as an inhibitory compounds in suppressing many cancers. And AKT has been known as an essential signaling pathway to regulate cell proliferation and apoptosis via Mdm2/p53 and Caspase-3 signaling pathways respectively. In our study, western blot, RT-PCR, immunochemical assay, immunofluorescence as well as flow cytometry were performed in vitro or in vivo to determine the effects of Polyporus umbellatus on the progression of human laryngeal cancer. First, the breast cancer cell growth, invasion and migration were inhibited, as well as the tumor volume in nude mice was down-regulated for Polyporus umbellatus use. Additionally, our data also showed that Polyporus umbellatus suppressed breast cancer cells proliferation, which was linked with the down-regulation of AKT activation by Polyporus umbellatus treatment. Mdm was inactivated while p53 was stimulated for Polyporus umbellatus administration, displaying inhibitory role in tumor growth. Furthermore, Polyporus umbellatus could up-regulate breast cancer cells in G0/G1 phase during cell cycle, and at the same time reducing cells in S phase. Also, flow cytometry and western blot assays suggested that apoptosis was induced by the administration of Polyporus umbellatus, which enhanced Caspase-3 expressions by AKT-regulated anti-apoptotic and pro-apoptotic signals. In conclusion, our data indicated that Polyporus umbellatus had a potential role in controlling human breast cancer through inhibiting tumor cell proliferation, inducing apoptosis regulated by AKT, which might provide a therapeutic strategy for breast cancer suppression in the future.

New triterpenoids from the latex of Euphorbia resinifera Berg.

Nine novel compounds, six euphane triterpenes, Euphorol A-D (1-4), H (8) and I (9), and three tirucallane triterpenes, Euphorol E-G (5-7) including four nortriterpenes, together with seven known compounds (10-16) have been isolated from the methanol extraction of Euphorbium. Their structures were established on the basis of extensive analyses of their HR-ESI-MS, UV, IR, 1D and 2D NMR methods. A putative biogenetic relationship to these compounds was proposed. The cytotoxicity of all these isolates against MCF-7, U937 and C6 cancer cell lines was evaluated. Compounds 1-3, 10, 11 and 13-16 exhibited moderate cytotoxic activities.

In Vitro and in Vivo Inhibitory Effects of Glycyrrhetinic Acid in Mice and Human Cytochrome P450 3A4.

Glycyrrhetinic acid (GA) has been used clinically in the treatment of patients with chronic hepatitis. This study evaluated the effect of GA on the activity of five P450(CYP450) cytochrome enzymes: CYP2A6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, in human liver microsomes (HLMs) and recombinant cDNA-expressed enzyme systems using a HPLC-MS/MS CYP-specific probe substrate assay. With midazolam as the probe substrate, GA greatly decreased CYP3A4 activity with IC50 values of 8.195 µM in HLMs and 7.498 µM in the recombinant cDNA-expressed CYP3A4 enzyme system, respectively. It significantly decreased CYP3A4 activity in a dose- but not time-dependent manner. Results from Lineweaver-Burk plots showed that GA could inhibit CYP3A4 activity competitively, with a Ki value of 1.57 µM in HLMs. Moreover, CYP2C9 and CYP2C19 could also be inhibited significantly by GA with IC50 of 42.89 and 40.26 µM in HLMs, respectively. Other CYP450 isoforms were not markedly affected by GA. The inhibition was also confirmed by an in vivo study of mice. In addition, it was observed that mRNA expressions of the Cyps2c and 3a family decreased significantly in the livers of mice treated with GA. In conclusion, this study indicates that GA may exert herb-drug interactions by competitively inhibiting CYP3A4.

The role of mycorrhizal symbiosis in aluminum and phosphorus interactions in relation to aluminum tolerance in soybean.

Arbuscular mycorrhizal (AM) fungi protect plants against aluminum (Al) toxicity, but the mechanisms of Al and phosphorus (P) interactions in relation to Al tolerance in mycorrhizal plants are only poorly understood. In this study, varying Al and P treatments were applied to soybean plants cultivated in the presence or absence of three different AM fungi. The results showed that plants in symbiotic association with Gigaspora margarita displayed higher Al tolerance than Rhizophagus irregularis or Glomus claroideum. The effectiveness of G. margarita appeared to be associated with more abundant arbuscules and less affected intraradical hyphae compared to no Al controls. The highest levels of Al toxicity mitigation were observed with the combination of high P availability and AM fungal inoculation, which was associated with a concomitant increase in the expression of the AM-inducible phosphate (Pi) transporter gene GmPT9 in soybean. Taken together, these results suggest that AM symbiosis can alleviate Al toxicity in soybean through enhanced P nutrition, as well as, the alteration of the abundance of mycorrhizal infection structures. These findings highlight the importance of P nutrition status in ameliorating Al toxicity in mycorrhizal plants.

[Good agricultural practice (GAP) of Chinese materia medica (CMM) for ten years: achievements, problems and proposals].

This paper aims to summarize the achievements during the implementation process of good agricultural practice (GAP) in Chinese Materia Medica (CMM), and on basis of analyzing the existing problems of GAP, to propose further implementation of GAP in TCM growing. Since the launch of GAP in CMM growing ten years ago, it has acquired great achievements, including: (1) The promulgation of a series of measures for the administration of the GAP approval in the CMM growing; (2) The expanded planting area of CMM; (3) The increased awareness of standardized CMM growing among farmers and enterprises; (4) The establishment of GAP implementation bases for CMM growing; (5) The improvement of theory and methodology for CMM growing; (6) The development of a large group of experts and scholars in GAP approval for CMM production. The problems existing in the production include: (1) A deep understanding of GAP and its certification is still needed; (2) The distribution of the certification base is not reasonable; (3) The geo-economics effect and the backward farming practices are thought to be the bottlenecks in the standardization of CMM growing and the scale production of CMM; (4) Low comparative effectiveness limits the development of the GAP; (5) The base of breeding improved variety is blank; (6) The immature of the cultivation technique lead to the risk of production process; (7) The degradation of soil microbial and the continuous cropping obstacle restrict the sustainable development of the GAP base. To further promote the health and orderly GAP in the CMM growing, the authors propose: (1) To change the mode of production; (2) To establish a sound standard system so as to ensure quality products for fair prices; (3) To fully consider the geo-economic culture and vigorously promote the definite cultivating of traditional Chinese medicinal materials; (4) To strengthen the transformation and generalization of basic researches and achievements, in order to provide technical support for the CMM production; (5) To deepen the understanding of GAP, to vigorously promote ecological planting and precision agriculture, in order to overcome the continuous cropping obstacle. The authors think that despite the fact that we are still facing with a huge array of management and technological problems, the GAP in the CMM growing has already enjoyed widespread support and showed great potential. In the future, with people's deeper understanding of GAP and the great progress of the science and technology, the GAP will constantly be fused with the theory, methodology and technology in the modern agriculture like precision agriculture, eco-agriculture and etc.

Amelioration of colorectal cancer using negative lipidoid nanoparticles to encapsulate siRNA against APRIL by enema delivery mode.

A proliferation-inducing ligand (APRIL) is a key cell proliferation-regulatory molecule and have been investigated well enough in immunity regulation and a few of immune diseases. APRIL can stimulate tumor cell growth and is up-expressed in cancer tissues, especially in CRC (colorectal cancer). However, whether inhibition of APRIL can regulate tumor-relative genes expression in vivo and subsequently ameliorate the pathological progress of CRC remains obscure. To address this question, we developed a novel negative lipidoid nanoparticles (NLNs) encapsulating small interference RNA (siRNA) for selectively silencing APRIL in the parenchyma of CRC focus in vivo, which uptake proceeded through a lipid raft endocytotic pathway. Local enema delivery of APRIL-NLNs silenced APRIL in CRC cells and animal models, and then ameliorated experimentally the progress of CRC by suppressing CRC cell proliferation, metastasis, and apoptosis-related cytokine expression and did not affect the function of liver and kidneys and not trigger the immune response of CRC models. This study reveals APRIL to be a potential anti-CRC target by in vivo experiments, and suggests that the application of similar modes of siRNA delivery may be feasible in other therapeutic settings.

Magnetic fluid hyperthermia inhibits the growth of breast carcinoma and downregulates vascular endothelial growth factor expression.

The application of magnetic fluid hyperthermia (MFH) with nanoparticles has been shown to inhibit tumor growth in several animal models. However, the feasibility of using MFH in vivo to treat breast cancer is uncertain, and the mechanism is unclear. In the present study, it was observed that the intratumoral administration of MFH induced hyperthermia significantly in rats with Walker-265 breast carcinomas. The hyperthermia treatment with magnetic nanoparticles inhibited tumor growth in vivo and promoted the survival of the tumor-bearing rats. Furthermore, it was found that MFH treatment downregulated the protein expression of vascular endothelial growth factor (VEGF) in the tumor tissue, as observed by immunohistochemistry. MFH treatment also decreased the gene expression of VEGF and its receptors, VEGF receptor 1 and 2, and inhibited angiogenesis in the tumor tissues. Taken together, these results indicate that the application of MFH with nanoparticles is feasible for the treatment of breast carcinoma. The MFH-induced downregulation of angiogenesis may also contribute to the induction of an anti-tumor effect.

Efficacy of topical versus oral 5-aminosalicylate for treatment of 2,4,6-trinitrobenzene sulfonic acid-induced ulcerative colitis in rats.

5-aminosalicylic acid (5-ASA) is drug of choice for the treatment of ulcerative colitis (UC). In this study, the efficacy of topical versus oral 5-ASA for the treatment of UC was examined as well as the action mechanism of this medication. A flexible tube was inserted into the rat cecum to establish a topical administration model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced UC. A total of 60 rats were divided into sham operation group (receiving an enema of 0.9% saline solution instead of the TNBS solution via the tube), model group, topical 5-ASA group, oral Etiasa group (a release agent of mesalazine used as positive control) and oral 5-ASA group (n=12 each). Different treatments were administered 1 day after UC induction. The normal saline (2 mL) was instilled twice a day through the tube in the sham operation group and model group. 5-ASA was given via the tube in the topical 5-ASA group (7.5 g/L, twice per day, 100 mg/kg), and rats in the oral Etiasa group and oral 5-ASA group intragastrically received Etiasa (7.5 g/L, twice per day, 100 mg/kg) and 5-ASA (7.5 g/L, twice per day, 100 mg/kg), respectively. The body weight was recorded every day. After 7 days of treatment, blood samples were drawn from the heart to harvest the sera. Colonic tissues were separated and prepared for pathological and related molecular biological examinations. The concentrations of 5-ASA were detected at different time points in the colonic tissues, feces and sera in different groups by using the high pressure liquid chromatography (HPLC). The results showed that the symptoms of acute UC, including bloody diarrhea and weight loss, were significantly improved in topical 5-ASA-treated rats. The colonic mucosal damage, both macroscopical and histological, was significantly relieved and the myeloperoxidase activity was markedly decreased in rats topically treated with 5-ASA compared with those treated with oral 5-ASA or Etiasa. The mRNA and protein expression of IL-1ß, IL-6, and TNF-α was down-regulated in the colonic tissue of rats topically treated with 5-ASA, significantly lower than those from rats treated with oral 5-ASA or Etiasa. The concentrations of 5-ASA in the colonic tissue were significantly higher in the topical 5-ASA group than in the oral 5-ASA and oral Etiasa groups. It was concluded that the topical administration of 5-ASA can effectively increase the concentration of 5-ASA in the colonic tissue, decrease the expression of proinflammatory cytokines, alleviate the colonic pathological damage and improve the symptoms of TNBS-induced acute UC in rats.

Photoelectrochemical biosensing platform for microRNA detection based on in situ producing electron donor from apoferritin-encapsulated ascorbic acid.

A novel signal "on" type of photoelectrochemical biosensor for microRNA-21 hybridization detection was fabricated, where Bi2S3 nanorods were used as photoactive material with a maximum adsorption at 450 nm visible light, hairpin-structure DNA as detecting probe, streptavidin as signal capturing unit and biotin functionalized ascorbic acid loaded apoferritin as signal amplification unit. Hybridization between the probe and the target microRNA-21 was confirmed by the increased photocurrent of the biosensor after electron donor of ascorbic acid was introduced into the detection buffer by digesting the apoferritin by trypsase, indicating that this method could be used fProd. Type: FTPor quantitative measurements, and the discrimination of the complementary from mismatched microRNA-21. Under the optimal detection conditions, the photoelectrochemical biosensor displayed a linear range of 1-5000 fM and a low detection limit of 0.35 fM for microRNA-21 determination. Moreover, the down-regulated expression of microRNA-21 in poultry cells and tissues infecting with avian leukosis viruses was confirmed by directly detecting microRNA-21 in extracted total RNA. This proposed strategy may open a new avenue for the applications of photoelectrochemical biosensor for oligonucleotides detection using visible light irradiation, which could largely reduce the destructive effect of UV light on biomolecules.

[Study on five heavy metal elements dissolution characteristics of Fructus Aurantii by ICP-MS].

The method for the determination of 5 kinds of trace heavy metal elements (Cu, As, Hg, Cd and Pb) in Fructus Aurantii by inductively coupled plasma-mass (ICP-MS) with HNO3-H2O2 microwave digestion was established. The recoveries of the elements detected were in the range of 85%-109% and the relative standard deviations (RSD) was in the range of 3.6%-5.4%. It indicates that the method is rapid, sensitive and accurate. It was suitable for the determination of the contents of 5 trace heavy metal elements in Fructus Aurantii. The dissolution characteristics of the 5 heavy metal elements in different extraction methods (microwave-assisted extraction, ultrasonic extraction and decocting extraction, respectively) were studied. The results showed that the concentrations of trace elements As and Pb obtained by microwave-assisted extraction were relatively lower than that by ultrasonic extraction and decocting extraction. The dissolving concentrations of the 5 trace heavy metal elements (Cu, As, Hg, Cd and Pb) in Fructus Aurantii in different extracting methods were all lower than the limits of Chinese Pharmacopoeia and Green Trade Standard for Importing and Exporting Medicinal Plant and Preparation. Microwave-assisted extraction for effective constituent was rapid, effective and safe.

[Effects of all-trans retinoic acid on the expression of TGF-beta 1 and COL-I in rat model of peritoneal dialysis].

OBJECTIVE: To investigate the effects of all-trans retinoic acid (ATRA) on the expression of transforming growth factor-beta 1 (TGF-beta 1) and collagen I (COL-I )in rat model of peritoneal dialysis, which may relate to the prevention peritoneal fibrosis. METHODS: Peritoneal dialysis model was established in rats, and then the rats were given ATRA 2 mg/kg (small dose group) or 5 mg/kg (large dose group) by the way of intraperitoneal injection once a day. All the rats were sacrificed on day 28. TGF-beta 1 and COL-I protein expression of peritoneum were measured by immunohistochemistry. TGF-beta 1 mRNA expression were examined with real time polymerase chain reaction (RT-PCR). RESULTS: Masson stain showed that the peritoneum thickness was significantly increased in the rats model, and collagen deposition was evident in the thickened submesothelial compact zone. With the treatment of ATRA, either in small or large dose, pathological changes were significantly lessened. The expression of TGF-beta 1 and COL-I of peritoneum was increased significantly in the rats model, but the levels in the two ATRA treated groups were lower than those of the untreated group. CONCLUSION: ATRA could decrease the experession of TGF-beta 1 and COL-I in peritoneum and delay the progression of peritoneal fibrosis.