Protective Effect of Bojungikki-Tang against Radiation-Induced Intestinal Injury in Mice: Experimental Verification and Compound-Target Prediction.

Bojungikki-tang (BJIT) is a traditional herbal medicine used in Korea, Japan, and China to treat gastrointestinal disorders. In this study, we aimed to investigate whether BJIT has protective effects against radiation-induced intestinal injury and to predict the underlying therapeutic mechanisms and related pathways via network pharmacological analyses. BJIT was injected intraperitoneally (50 mg/kg body weight) to C3H/HeN mice at 36 and 12 h before exposure to partial abdominal irradiation (5 Gy and 13 Gy) to evaluate the apoptotic changes and the histological changes and variations in inflammatory cytokine mRNA levels in the jejunum, respectively. Through in silico network analysis, we predicted the mechanisms underlying BJIT-mediated regulation of radiation-induced intestinal injury. BJIT reduced the level of apoptosis in the jejunal crypts 12 h post 5-Gy irradiation. Histological assessment revealed intestinal morphological changes in irradiated mice 3.5 days post 13-Gy irradiation. Furthermore, BJIT decreased inflammatory cytokine levels following radiation exposure. Apoptosis, TNF, p53, VEGF, toll-like receptor, PPAR, PI3K-Akt, and MAPK signaling pathways, as well as inflammatory bowel disease (IBD), were found to be linked to the radioprotective effects of BJIT against intestinal injury. According to our results, BJIT exerted its potential protective effects by attenuating histopathological changes in jejunal crypts and suppressing inflammatory mediator levels. Therefore, BJIT is a potential therapeutic agent that can treat radiation-induced intestinal injury and its associated symptoms.

Effect of urea cream on sorafenib-associated hand-foot skin reaction in patients with hepatocellular carcinoma: A multicenter, randomised, double-blind controlled study.

BACKGROUND: Hand-foot skin reaction (HFSR) is the most common adverse event during sorafenib treatment in patients with hepatocellular carcinoma (HCC). In the present study, we aimed to investigate the role of urea cream in the prevention of HFSR or amelioration of HFSR severity. PATIENTS AND METHODS: Patients with HCC were treated with either placebo cream or urea cream for 12 weeks concomitantly with sorafenib treatment. HFSR development, the Hand-Foot Skin Reaction and Quality of Life (HF-QoL) questionnaire score, and adverse events were assessed at 2, 4, 8 and 12 weeks. RESULTS: Of the 288 patients, 247 patients, with 117 patients in the placebo control group and 130 patients in the urea cream group, were analysed. The urea cream group showed a trend towards a lower cumulative incidence of any-grade HFSR (log-rank, P = 0.247) and severe HFSR of grade II or higher (log-rank, P = 0.394) without statistical significance. In the incidence by time point, the incidence of severe HFSR of grade II or higher was significantly lower in the urea cream group than in the placebo control group at 2 weeks (13.8% versus 23.9%, P = 0.042). The urea cream group showed a significantly better HF-QoL questionnaire score than the placebo control group (11.8 versus 19.7, P = 0.014) at 12 weeks. CONCLUSIONS: Treatment with urea cream showed a lower incidence of severe sorafenib-induced HFSR at 2 weeks and reduced the tendency of HFSR development in HCC patients. Therefore, treatment with urea cream may be considered for prophylaxis or improvement of HFSR grade in HCC patients treated with sorafenib. TRIAL REGISTRATION: ClinicalTrials.gov (NCT03212625).

Ginseng for Treating Hypertension: A Systematic Review and Meta-Analysis of Double Blind, Randomized, Placebo-Controlled Trials.

BACKGROUND: Evidence of ginseng for reducing blood pressure (BP) in hypertensive patients is controversial. This systematic review updated the previous reviews and evidence for it. METHODS: Ten databases were searched from their inception through October 2016, without language restriction. Randomized clinical trials (RCTs) were included if any types of ginseng were tested as the sole treatment or as an adjunct to other treatments for pre-hypertension or hypertension. The risk of bias (ROB) was assessed with Cochrane ROB tools by two independent reviewers. RESULTS: We found 528 potentially relevant articles, of which 9 RCTs met our inclusion criteria. Two studies reported positive effects of Korean red ginseng (KRG) on acute reduction of systolic BP (SBP: n=54, mean differences (MD), -6.52; P=0.0002; I2=0%) and diastolic BP DBP: MD, -5.21; P=0.0001; I2=0%), while two other trials failed to do so with north American ginseng (NAG) in both SBP and DBP. Five RCTs assessed the long-term effects of ginseng (KRG or NAG) on SBP and DBP. Two studies showed positive effects of KRG on reducing SBP and DBP compared with placebo (SBP: n = 183, MD, -2.92, P=0.04; I2 = 0%; DBP: MD, -3.19, P=0.008; I2 = 0%). CONCLUSION: This systematic review provides positive evidence for the efficacy of KRG on reducing blood pressure in patients with pre-hypertension and hypertension in acute and long-term. Future RCTs appear to be warranted.

Ruminal tryptophan-utilizing bacteria degrade ergovaline from tall fescue seed extract.

The objectives of this study were to evaluate degradation of ergovaline in a tall fescue [ (Schreb.) Darbysh.] seed extract by rumen microbiota ex vivo and to identify specific bacteria capable of ergovaline degradation in vitro. Rumen cell suspensions were prepared by harvesting rumen fluid from fistulated wether goats ( = 3), straining, and differential centrifugation. Suspensions were dispensed into anaerobic tubes with added Trypticase with or without extract (∼10 µg kg ergovaline). Suspensions were incubated for 48 h at 39°C. Samples were collected at 0, 24, and 48 h for ergovaline analysis and enumeration of hyper-ammonia producing (HAB) and tryptophan-utilizing bacteria. Ergovaline values were analyzed by repeated measures using the mixed procedure of SAS. Enumeration data were log transformed for statistical analysis. When suspensions were incubated with extract, 11 to 15% of ergovaline disappearance was observed over 48 h ( = 0.02). After 24 h, suspensions with added extract had 10-fold less HAB than controls ( = 0.04), but treatments were similar by 48 h ( = 1.00). However, after 24 h and 48 h, suspensions with extract had 10-fold more tryptophan-utilizing bacteria ( < 0.01) that were later isolated and identified by their 16S RNA gene sequence as . The isolates and other known rumen pure cultures ( JB1, B159, HD4, B, F, MD1, SR) were evaluated for the ability to degrade ergovaline in vitro. Pure culture cell suspensions were incubated as described above and samples were taken at 0 and 48 h for ergovaline analysis. Data were analyzed using the ANOVA procedure of SAS. All HAB, including the isolates, tested degraded ergovaline (54 to 75%; < 0.05). B14 was also able to degrade ergovaline but to a lesser capacity (12%; < 0.05), but all other bacteria tested did not degrade ergovaline. The results of this study indicate which rumen bacteria may play an important role in ergovaline degradation and that microbiological strategies for controlling their activity could have ramifications for fescue toxicosis and other forms of ergotism in ruminants.

Adverse event due to a likely interaction between sodium aescinate and ginkgo biloba extract: a case report.

WHAT IS KNOWN AND OBJECTIVE: Drug-induced nephrotoxicity is potentially lethal. When sodium aescinate is given to surgical inpatients to treat postoperative inflammation and oedema, adverse drug reactions and drug-drug interactions must be closely monitored. CASE DESCRIPTION: We report a case of a 58-year-old man with phalangeal fractures who suffered from acute kidney injury that was most likely induced by the drug interaction between sodium aescinate and ginkgo biloba extract due to the protein-binding and metabolic characteristics of these drugs. WHAT IS NEW AND CONCLUSION: Close monitoring and the prompt discontinuation of drugs that have high protein-binding capacity and hepatic metabolism are necessary to avoid drug-drug interactions in patients who are treated with sodium aescinate.

[The relationship of vitamin D receptor gene and blood lead: a meta-analysis].

OBJECTIVE: The correlation of vitamin D receptor (VDR) gene polymorphism and blood lead level had been in doult, which allowed us to write this article. METHODS: Relevant studies about the blood lead and VDR B/b gene polymorphism which published from 1979-2015, were searched in multiple bibliographic databases, such as: CNKI, Wanfang Database, PUBMED. Of the ten references selceted, three were divided into two groups which were classified as different researches, so there were thirteen studies in the meta-analysis. According to the level of blood lead, the studies were analyzed by three groups: normal group, low dose grou and high dose group. The analysis was performed by stata 12.0 software. RESULTS: The blood lead level of VDR B/b genotype was significantly difference in all the three groups (P<0.05) , but there were apparent heterogeneity between normal group and low dose group (P<0.05, I(2)=84.2%; P<0.05, I(2)=88.9%) , except the high dose group (P>0.05, I(2)=12.7%) ; after adjusted, all showed no heterogeneity, and the results were still the same. CONCLUSION: The genotype of VDR may be correlated with blood lead, and the levels of blood lead varied with different genetypes.

Stimulation of dendritic cell maturation and induction of apoptosis in lymphoma cells by a stable lectin from buckwheat seeds.

The present study aims to purify and characterize lectin from tartary buckwheat seeds and study its properties as well as biological activities to determine its possible biomedical applications in promoting maturation and proliferation of peripheral blood DCs derived from healthy donors and to study the effect of inducing apoptosis in human leukemia U937 cells. A novel tartary buckwheat lectin (TBL) protein, purified from tartary buckwheat seeds, showed a single band with a molecular mass of 65 kDa in SDS-PAGE. The purified TBL hemagglutinated both human and animal erythrocytes and showed preference for blood type O and the rabbit blood type. TBL is active at up to 60°C, and it is acid- and alkali-stable. TBL (25 µg/mL) combined with 5 x 10(-5) M rhIL-4 promotes maturation and proliferation of peripheral blood dendritic cells (DCs), which is stronger than that promoted by rhTNF-α (20 ng/mL). Exposure of DCs to 50 µg/mL TBL for 48 h resulted in extensive upregulation of maturation markers CD83 and CD40. These TBL-DCs were capable of producing several pro-inflammatory cytokines such as interleukin-10 (IL-10) and interleukin-12 (IL-12). The results of the treatment of human leukemia U937 cells with TBL in doses of 12.5, 25, 50, and 100 µg/mL showed that tartary buckwheat-derived lectin induces apoptosis in a dose-dependent manner. Our results encourage the use of tartary buckwheat and tartary buckwheat-derived lectins as immunopotentiating foods, targeted to strengthen immune responses and display a potential dietary supplement for cancer prevention.

Comparison between the robo-horse and real horse movements for hippotherapy.

While the novel robotic hippotherapy system has gradually gained clinical application for therapeutic intervention on postural and locomotor control in individuals with neurological or musculoskeletal impairments, the system's validity and reliability for the robotic hippotherapy system has not been well established. The objective of the current study was to investigate the validity and test-retest reliability of the robotic hippotherapy system by comparing with real horse movements. The 3-axis accelerometer sensors attached on the robotic and real horse saddles were used to collect 3-dimensional acceleration data at a preferred walking velocity. Linear regression analysis showed an excellent correlation in the time-to-peak acceleration (TPA) (R(2)=0.997), but little correlation in X-axis acceleration between the real and robotic horses (R(2)=0.177), thus confirming consistent time control and a certain degree of variability between the robotic and real horse movements. The mean resultant accelerations for a real horse and robotic horse were 3.22 m/s(2) and 0.67 m/s(2), respectively, accounting for almost five times greater acceleration in the real horse than the robotic horse.

Bergamot essential oil differentially modulates intracellular Ca2+ levels in vascular endothelial and smooth muscle cells: a new finding seen with fura-2.

In this study, we compared the effect of the essential oil of Citrus bergamia Risso [bergamot, bergamot essential oil (BEO)] on the intracellular Ca levels in vascular endothelial (EA) and mouse vascular smooth muscle (MOVAS) cells, using the fura-2 fluorescence technique. BEO caused an initial transient increase in intracellular Ca concentration ([Ca]i) in EA cells, followed by a decrease, whereas it induced a sustained increase in [Ca]i in MOVAS cells. Linalyl acetate (LA) as a major component of BEO-induced [Ca]i mobilization was similar to BEO in EA cells. The increase of [Ca]i by LA was higher in EA cells than in MOVAS cells. [Ca]i rise induced by extracellular Ca application was significantly blocked by BEO or LA in EA cells but not in MOVAS cells, suggesting that BEO and LA block Ca influx in EA cells. The present results suggest that BEO and LA differentially modulate intracellular Ca levels in vascular endothelial and smooth muscle cells. In addition, blockade of Ca influx by BEO and LA in EA cells may explain the protective effects of BEO on endothelial dysfunction associated with cardiovascular disease.

Effects of resveratrol and essential oils on growth performance, immunity, digestibility and fecal microbial shedding in challenged piglets.

A study was conducted to evaluate the effects of resveratrol and essential oils from medicinal plants on the growth performance, immunity, digestibility, and fecal microbial shedding of weaned piglets. A total of 48 weaned piglets (8 kg initial weight, 28-d-old) were randomly allotted to four dietary treatments with 3 replications of 4 piglets each. The dietary treatments were NC (negative control; basal diet), PC (positive control; basal diet+0.002% apramycin), T1 (basal diet+0.2% resveratrol), and T2 (basal diet+0.0125% essential oil blend). All piglets were orally challenged with 5 ml culture fluid containing 2.3×10(8) cfu/ml of Escherichia coli KCTC 2571 and 5.9×10(8) cfu/ml Salmonella enterica serover Typhimurium. The PC group (p<0.05) showed the highest average daily gain (ADG) and average daily feed intake (ADFI) throughout the experimental period, although feed conversion ratio (FCR) was improved in the T1 group (p>0.05). Serum IgG level was increased in the T1 group, whereas TNF-α levels was reduced in the supplemented groups compared to control (p<0.05). The PC diet improved the dry matter (DM) digestibility, whereas PC and T2 diets improved nitrogen (N) digestibility compared to NC and T1 diets (p<0.05). Fecal Salmonella and E. coli counts were reduced in all treatment groups compared to control (p<0.05). Fecal Lactobacillus spp. count was increased in the T2 group compared to others (p<0.05). Dietary treatments had no significant effect on fecal Bacillus spp. count throughout the entire experimental period. Based on these results, resveratrol showed strong potential as antibiotic alternatives for reversing the adverse effects of weaning stress on growth performance, immunity and microbial environment in E. coli and Salmonella-challenged piglets.

Measurement of calcitonin and calcitonin gene-related peptide mRNA refines the management of patients with medullary thyroid cancer and may replace calcitonin-stimulation tests.

BACKGROUND: Serum calcitonin (sCT) is the main tumor marker for medullary thyroid cancer (MTC), but it has certain limitations. Various sCT assays may have important intra-assay or interassay variation and may yield different and sometimes conflicting results. A pentagastrin- or calcium-stimulation calcitonin (CT) test may be desirable in some situations. Alternatively, or in the absence of the stimulation test, mRNA detection offers the advantages of being more comfortable and less invasive; it only requires blood collection and has no side effects. The objective of this study was to investigate the applicability of measuring calcitonin-related polypeptide alpha (CALCA) gene transcripts (CT-CALCA and calcitonin gene-related peptide [CGRP]-CALCA) in patients with MTC and in relatives diagnosed with a RET mutation and to test mRNA as an alternative diagnostic tool for the calcitonin-stimulation test. METHODS: Twenty-three healthy controls and 26 individuals evaluated for MTC were selected, including patients with sporadic or hereditary MTC and RET mutation-carrying relatives. For molecular analysis, RNA was extracted from peripheral blood, followed by cDNA synthesis using 3.5 µg of total RNA. Quantitative real-time polymerase chain reaction (RT-qPCR) was performed with SYBR Green and 200 nM of each primer for the two specific mRNA targets (CT-CALCA or CGRP-CALCA) and normalized with the ribosomal protein S8 as the reference gene. RESULTS: We detected CALCA transcripts in the blood samples and observed a positive correlation between them (r=0.946, p<0.0001). Both mRNAs also correlated with sCT (CT-CALCA, r=0.713, p<0.0001; CGRP-CALCA, r=0.714, p<0.0001). The relative expression of CT-CALCA and CGRP-CALCA presented higher clinical sensitivity (86.67 and 100, respectively), specificity (97.06 and 97.06), positive predictive value (92.86 and 93.75), and negative predictive value (94.29 and 100), than did sCT (73.33, 82.35, 64.71, and 87.50, respectively). In addition, the CALCA transcript measurement mirrored the response to the pentagastrin test. CONCLUSION: We demonstrate that the measurement of CALCA gene transcripts in the bloodstream is feasible and may refine the management of patients with MTC and RET mutation-carrying relatives. We propose considering the application of this diagnostic tool as an alternative to the calcitonin-stimulation test.

Turmeric (Curcuma longa) inhibits inflammatory nuclear factor (NF)-κB and NF-κB-regulated gene products and induces death receptors leading to suppressed proliferation, induced chemosensitization, and suppressed osteoclastogenesis.

SCOPE: The incidence of cancer is significantly lower in regions where turmeric is heavily consumed. Whether lower cancer incidence is due to turmeric was investigated by examining its effects on tumor cell proliferation, on pro-inflammatory transcription factors NF-κB and STAT3, and on associated gene products. METHODS AND RESULTS: Cell proliferation and cell cytotoxicity were measured by the MTT method, NF-κB activity by EMSA, protein expression by Western blot analysis, ROS generation by FACS analysis, and osteoclastogenesis by TRAP assay. Turmeric inhibited NF-κB activation and down-regulated NF-κB-regulated gene products linked to survival (Bcl-2, cFLIP, XIAP, and cIAP1), proliferation (cyclin D1 and c-Myc), and metastasis (CXCR4) of cancer cells. The spice suppressed the activation of STAT3, and induced the death receptors (DR)4 and DR5. Turmeric enhanced the production of ROS, and suppressed the growth of tumor cell lines. Furthermore, turmeric sensitized the tumor cells to chemotherapeutic agents capecitabine and taxol. Turmeric was found to be more potent than pure curcumin for cell growth inhibition. Turmeric also inhibited NF-κB activation induced by RANKL that correlated with the suppression of osteoclastogenesis. CONCLUSION: Our results indicate that turmeric can effectively block the proliferation of tumor cells through the suppression of NF-κB and STAT3 pathways.

Nateglinide and acarbose for postprandial glucose control after optimizing fasting glucose with insulin glargine in patients with type 2 diabetes.

AIMS: Basal insulin treatment is frequently used in type 2 diabetes, but the successful control of postprandial glucose is challenging. We compared the effect of preferential postprandial glucose targeting drugs for postprandial glucose control after optimizing fasting glucose with basal insulin. METHODS: This study was performed in 58, insulin naïve type 2 diabetes. After fasting glucose was optimized by insulin glargine, nateglinide or acarbose was initiated and then crossed over after second wash out period. 75 g oral glucose tolerance test and 7 point self monitoring blood glucose for 3 days at the end of each period was performed. RESULTS: Both drugs effectively reduced postprandial glucose levels compared with the insulin glargine monotherapy. No significant differences were found between nateglinide and acarbose in terms of mean glucose level, standard deviation of glucose levels, mean average glucose excursion and average daily risk range. Homeostasis model analysis (HOMA)% ß, corrected insulin response and insulin-to-glucose ratio were significantly higher in the responder group compared with the non-responder. There was no episode of severe hypoglycemia. CONCLUSIONS: Nateglinide and acarbose are equally effective in type 2 diabetes for postprandial glucose excursions during basal insulin treatment. The markers of beta cell function might be used for predicting response. (Clinical trial reg. no. NCT 00437918, clinicaltrial.gov.).

A Phase II study of anti-epidermal growth factor receptor radioimmunotherapy in the treatment of glioblastoma multiforme.

OBJECT: This single-institution Phase II study tests the efficacy of adjuvant radioimmunotherapy with (125)I-labeled anti-epidermal growth factor receptor 425 murine monoclonal antibody ((125)I-mAb 425) in patients with newly diagnosed glioblastoma multiforme (GBM). METHODS: A total of 192 patients with GBM were treated with (125)I-mAb 425 over a course of 3 weekly intravenous injections of 1.8 GBq following surgery and radiation therapy. The primary end point was overall survival, and the secondary end point was toxicity. Additional subgroup analyses were performed comparing treatment with (125)I-mAb 425 (RIT, 132 patients), (125)I-mAb 425 and temozolomide (TMZ+RIT, 60 patients), and a historical control group (CTL, 81 patients). RESULTS: The median age was 53 years (range 19-78 years), and the median Karnofsky Performance Scale score was 80 (range 60-100). The percentage of patients who underwent debulking surgery was 77.6% and that of those receiving temozolomide was 31.3%. The overall median survival was 15.7 months (95% CI 13.6-17.8 months). The 1- and 2-year survivals were 62.5 and 25.5%, respectively. For subgroups RIT and TMZ+RIT, the median survivals were 14.5 and 20.2 months, respectively. No Grade 3 or 4 toxicity was seen with the administration of (125)I-mAb 425. The CTL patients lacked Karnofsky Performance Scale scores, had poorer survival, were older, and were less likely to receive radiation therapy. On multivariate analysis, the hazard ratios for RIT versus CTL, TMZ+RIT versus CTL, and TMZ+RIT versus RIT were 0.49 (p < 0.001), 0.30 (p < 0.001), and 0.62 (p = 0.008), respectively. CONCLUSIONS: In this large Phase II study of 192 patients with GBM treated with anti-epidermal growth factor receptor (125)I-mAb 425 radioimmunotherapy, survival was 15.7 months, and treatment was safe and well tolerated.

Effect of dietary ascorbate on lipogenesis and lipolysis activities in black sea bream, Acanthopagrus schlegelii.

To assess the effect of dietary ascorbate on lipid metabolism, 1-year black sea bream (Acanthopagrus schlegelii) were reared on a casein-based purified diet and an ascorbate fortified diet (1,100 mg of L: -ascorbyl-2- monophosphate-Mg/kg diet). The fortified ascorbate was effectively incorporated into the fish body and elevated muscle carnitine content. Fortifications of dietary ascorbate depressed activities of glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase as lipogenic enzymes in the hepatopancreas and intraperitoneal fat body. Starvation after feeding experiment activated carnitine palmitoyltransferase as a lipolysis enzyme in the hepatopancreas in both control and vitamin C(VC) groups, while the lipolysis activity was significantly higher in VC group. These results confirmed that dietary ascorbate depressed lipogenesis and activated lipolysis, i.e., influenced the lipid metabolism of black sea bream.

Structure of lasiansine from Aconitumnagarum var. lasiandrum.

A new C19-diterpenoid alkaloid, lasiansine (1), was isolated from the roots of Aconitu nagarum var. lasiandrum (Ranunculaceae) together with six known diterpenoid alkaloids. The structure of 1 was elucidated by spectral methods (1H-NMR, 13C-NMR, 2D-NMR, HRMS, IR), and the 13C-NMR spectrum of 16-epipyroaconine (3) and the single-crystal X-ray analysis of its derivative (5) are reported for the first time.

Use of vitamins, minerals, and other dietary supplements by 17- and 18-year-old students in Korea.

Various types of dietary supplements (DS) are popularly taken by young individuals. We surveyed 1,190 Korean senior high school third grade students for their DS use, motivational factors for this use, and potential dietary consequences of vitamin/mineral supplement (VMS) use. The use prevalence of DS-including VMS, tonic medicines, manufactured health food supplements, cordial food supplements, and drink rehabilitators-was 54%. VMS were taken most frequently, followed by tonic medicines and manufactured health food supplements. VMS use was highest in individuals who had a significant concern for their overall health and in those from families with a high socioeconomic level and with parental use of DS. Total daily study time of DS users was only slightly longer than that of nonusers. The VMS most frequently used were vitamin C and multivitamins. More than 46% of other DS users, and 58% of VMS users, had increased their intake of supplements during third grade relative to the previous year. VMS users had a more positive view of the potential health benefit of VMS than did nonusers. Vitamin and mineral intakes from VMS occurred over a wide range, with mean intakes typically exceeding the Korean and Canadian-U.S. Recommended Dietary Allowances. For a significant number of individuals, intakes of vitamin A, niacin, folic acid, vitamin C, calcium, iron, and zinc exceeded the Tolerable Upper Intake Levels. Given the widespread use of DS by older teenagers, the contribution of these supplements to their overall health and well-being is a subject that clearly merits additional study.

TRANCE/RANKL knockout mice are protected from bone erosion in a serum transfer model of arthritis.

There is considerable evidence that osteoclasts are involved in the pathogenesis of focal bone erosion in rheumatoid arthritis. Tumor necrosis factor-related activation-induced cytokine, also known as receptor activator of nuclear factor-kappaB ligand (TRANCE/RANKL) is an essential factor for osteoclast differentiation. In addition to its role in osteoclast differentiation and activation, TRANCE/RANKL also functions to augment T-cell dendritic cell cooperative interactions. To further evaluate the role of osteoclasts in focal bone erosion in arthritis, we generated inflammatory arthritis in the TRANCE/RANKL knockout mouse using a serum transfer model that bypasses the requirement for T-cell activation. These animals exhibit an osteopetrotic phenotype characterized by the absence of osteoclasts. Inflammation, measured by clinical signs of arthritis and histopathological scoring, was comparable in wild-type and TRANCE/RANKL knockout mice. Microcomputed tomography and histopathological analysis demonstrated that the degree of bone erosion in TRANCE/RANKL knockout mice was dramatically reduced compared to that seen in control littermate mice. In contrast, cartilage erosion was present in both control littermate and TRANCE/RANKL knockout mice. These results confirm the central role of osteoclasts in the pathogenesis of bone erosion in arthritis and demonstrate distinct mechanisms of cartilage destruction and bone erosion in this animal model of arthritis.

Cantilever-based optical deflection assay for discrimination of DNA single-nucleotide mismatches.

Characterization of single-nucleotide polymorphisms is a major focus of current genomics research. We demonstrate the discrimination of DNA mismatches using an elegantly simple microcantilever-based optical deflection assay, without the need for external labeling. Gold-coated silicon AFM cantilevers were functionalized with thiolated 20- or 25-mer probe DNA oligonucleotides and exposed to target oligonucleotides of varying sequence in static and flow conditions. Hybridization of 10-mer complementary target oligonucleotides resulted in net positive deflection, while hybridization with targets containing one or two internal mismatches resulted in net negative deflection. Mismatched targets produced a stable and measurable signal when only a four-base pair stretch was complementary to the probe sequence. This technique is readily adaptable to a high-throughput array format and provides a distinct positive/negative signal for easy interpretation of oligonucleotide hybridization.

[The contents and their change of nucleosides from natural Cordyceps sinensis and cultured cordyceps mycelia].

AIM: To compare the content of nucleosides from natural Cordyceps sinensis and cultured Cordyceps mycelia, and the effect of humidity and heat on the contents of nucleosides. METHODS: The contents of nucleosides were determined using high performance capillary electrophoresis (HPCE). Beckman P/ACE System 5010 apparatus equipped with a UV detector and a Beckman untreated fused-silica capillary (57 cm x 75 microns, 50 cm effective length) were used. Before sample injection, the capillary was rinsed with 1 mol.L-1 sodium hydroxide and running buffer for 5 minutes, respectively. 20 kV was applied during separation. Pressure injection was 586 kPa for 6 seconds, and the wavelength of detector was 254 nm. The running time was 20 minutes at 20 degrees C. The effect of humidity and heat on the content of nucleosides from natural Cordyceps sinensis and cultured Cordyceps mycelia was observed for 1, 3, 5 and 10 days at temperature 40 degrees C, and relative humidity 75%. RESULTS: The contents of nucleosides from cultured Cordyceps mycelia were higher than that of those from natural Cordyceps sinensis. The contents of nucleosides from freshly collected natural Cordyceps sinensis, were under the detection limit. The contents of nucleosides from natural Cordyceps sinensis were significantly increased by effect of humidity and heat, the phenomenon was not observed in cultured Cordyceps mycelia. CONCLUSION: There are difference in nucleosides content between natural Cordyceps sinensis and cultured Cordyceps mycelia. The nucleosides in natural Cordyceps sinensis may be derived from the degradation of macro-molecular nucleic acids. That means it is probably controversial that adenosine was used for quality control of natural Cordyceps sinensis.