The combination of EGCG with warfarin reduces deep vein thrombosis in rabbits through modulating HIF-1α and VEGF via the PI3K/AKT and ERK1/2 signaling pathways.

Deep venous thrombosis (DVT) poses a major challenge to public health worldwide. Endothelial cell injury evokes inflammatory and oxidative responses that contribute to thrombus formation. Tea polyphenol (TP) in the form of epigallocatechin-3-gallate (EGCG) has anti-inflammatory and oxidative effect that may ameliorate DVT. However, the precise mechanism remains incompletely understood. The current study was designed to investigate the anti-DVT mechanism of EGCG in combination with warfarin (an oral anticoagulant). Rabbits were randomly divided into five groups. A DVT model of rats was established through ligation of the inferior vena cava (IVC) and left common iliac vein, and the animals were orally administered with EGCG, warfarin, or vehicle for seven days. In vitro studies included pretreatment of human umbilical vein endothelial cells (HUVECs) with different concentrations of EGCG for 2 h before exposure to hydrogen peroxide. Thrombus weight and length were examined. Histopathological changes were observed by hematoxylin-eosin staining. Blood samples were collected for detecting coagulation function, including thrombin and prothrombin times, activated partial thromboplastin time, and fibrinogen levels. Protein expression in thrombosed IVCs and HUVECs was evaluated by Western blot, immunohistochemical analysis, and/or immunofluorescence staining. RT-qPCR was used to determine the levels of AGTR-1 and VEGF mRNA in IVCs and HUVECs. The viability of HUVECs was examined by CCK-8 assay. Flow cytometry was performed to detect cell apoptosis and ROS generation was assessed by 2',7'-dichlorofluorescein diacetate reagent. In vitro and invivo studies showed that EGCG combined with warfarin significantly reduced thrombus weight and length, and apoptosis in HUVECs. Our findings indicated that the combination of EGCG and warfarin protects HUVECs from oxidative stress and prevents apoptosis. However, HIF-1α silencing weakened these effects, which indicated that HIF-1α may participate in DVT. Furthermore, HIF-1α silencing significantly up-regulated cell apoptosis and ROS generation, and enhanced VEGF expression and the activation of the PI3K/AKT and ERK1/2 signaling pathways. In conclusion, our results indicate that EGCG combined with warfarin modifies HIF-1α and VEGF to prevent DVT in rabbits through anti-inflammation via the PI3K/AKT and ERK1/2 signaling pathways.

Melatonin induces the rejuvenation of long-term ex vivo expanded periodontal ligament stem cells by modulating the autophagic process.

BACKGROUND: Stem cells that have undergone long-term ex vivo expansion are most likely functionally compromised (namely cellular senescence) in terms of their stem cell properties and therapeutic potential. Due to its ability to attenuate cellular senescence, melatonin (MLT) has been proposed as an adjuvant in long-term cell expansion protocols, but the mechanism underlying MLT-induced cell rejuvenation remains largely unknown. METHODS: Human periodontal ligament stem cells (PDLSCs) were isolated and cultured ex vivo for up to 15 passages, and cells from passages 2, 7, and 15 (P2, P7, and P15) were used to investigate cellular senescence and autophagy change in response to long-term expansion and indeed the following MLT treatment. Next, we examined whether MLT could induce cell rejuvenation by restoring the autophagic processes of damaged cells and explored the underlying signaling pathways. In this context, cellular senescence was indicated by senescence-associated ß-galactosidase (SA-ß-gal) activity and by the expression of senescence-related proteins, including p53, p21, p16, and γ-H2AX. In parallel, cell autophagic processes were evaluated by examining autophagic vesicles (by transmission electronic microscopy), autophagic flux (by assessing mRFP-GFP-LC3-transfected cells), and autophagy-associated proteins (by Western blot assay of Atg7, Beclin-1, LC3-II, and p62). RESULTS: We found that long-term in vitro passaging led to cell senescence along with impaired autophagy. As expected, MLT supplementation not only restored cells to a younger state but also restored autophagy in senescent cells. Additionally, we demonstrated that autophagy inhibitors could block MLT-induced cell rejuvenation. When the underlying signaling pathways involved were investigated, we found that the MLT receptor (MT) mediated MLT-related autophagy restoration by regulating the PI3K/AKT/mTOR signaling pathway. CONCLUSIONS: The present study suggests that MLT may attenuate long-term expansion-caused cellular senescence by restoring autophagy, most likely via the PI3K/AKT/mTOR signaling pathway in an MT-dependent manner. This is the first report identifying the involvement of MT-dependent PI3K/AKT/mTOR signaling in MLT-induced autophagy alteration, indicating a potential of autophagy-restoring agents such as MLT to be used in the development of optimized clinical-scale cell production protocols.

Change in late sodium current of atrial myocytes in spontaneously hypertensive rats with allocryptopine treatment.

AIM: We aimed to study the effect of allocryptopine (All) on the late sodium current (INa,Late) of atrial myocytes in spontaneously hypertensive rats (SHR). METHODS: The enzyme digestion method was used to separate single atrial myocytes from SHR and Wistar-Kyoto (WKY) rats. INa,Late was recorded using the patch-clamp technique, and the effect of All was evaluated on the current. RESULTS: Compared with WKY rat cells, an increase in the INa,Late current in SHR myocytes was found. After treatment with 30 µM All, the current densities were markedly decreased; the ratio of INa,Late/INa,peak of SHR was reduced by 30 µM All. All reduced INa,Late by alleviating inactivation of the channel and increasing the window current of the sodium channel. Furthermore, INa,Late densities of three SCN5A mutations declined substantially with 30 µM All in a concentration-dependent manner. CONCLUSIONS: The results clearly show that an increase in INa,Late in SHR atrial myocytes was inhibited by All derived from Chinese herbal medicine.

[Fire-needle Acupuncture Intervention Relieves Ankle-joint Inflammatory Reactions Possibly by Down-regulating Serum TNF-α and Anti-cyclic Citrullinated Peptide Antibody Levels in Collagen-induced Arthritis Rats].

OBJECTIVE: To observe the effect of fire-needle acupuncture of "Zusanli" (ST 36) and "Kunlun" (BL 60) on ankle-joint swelling and serum tumor necrosis factor-α (TNF-α) and anti-cyclic citrullinated peptide antibody (ACPA) contents in collagen-induced arthritis (CIA) rats, so as to study its mechanism underlying improvement of rheumatoid arthritis (RA)．. METHODS: Thirty-two male Wistar rats were randomized into control, model, medication (Methotrexate) and fire-needling groups (n＝8 in each). The RA model was established by injecting type Ⅱ chicken collagen (0.1 mol/L) plus Freund's complete adjuvant (primary immunization) and Freund's incomplete adjuvant (immunization once more) into the subcutaneous tissues of the right foot bottom, back and tail root of rats. Fire-needling was applied to the left and right "Zusanli" (ST 36) and "Kunlun" (BL 60) alternatively for 3 times in each acupoint, once daily for 10 days. For rats of the medication group, Methotrexate sodium chloride solution (0.1 mg/100 g) was administrated by gavage, once every 5 days, twice together. The rats' right hind ankle diameter was measured before and after the treatment. The X-ray film of the right ankle was taken, and the contents of serum TNF-α and ACPA were assayed by ELISA. RESULTS: The ankle diameter and serum concentrations of TNF-α and ACPA were significantly increased in the model group compared to the control group (P<0.05), and X-ray film showed swollen and deformed tarsus joints, and narrowing of the joint space. After the intervention, the ankle diameter, serum TNF-α and ACPA levels were considerably decreased in both medication and fire-needle groups compared with the model group (P<0.05). Meanwhile, the joint swelling and bone deformity became relatively milder. There were no significant differences between the medication and fire-needling groups in the ankle diameter and the contents of serum TNF-α and ACPA (P>0.05). CONCLUSION: Fire-needling stimulation of ST 36 and BL 60, similar to Methotrexate, can relieve the inflammatory reactions of hind-ankle joint in CIA rats, which may be related to its effect in down-regulating ACPA and TNF-α levels.

Comparative Effectiveness of Neoadjuvant Treatments for Resectable Gastroesophageal Cancer: A Network Meta-Analysis.

Background: Several neoadjuvant treatments are available for patients with resectable gastroesophageal cancer. We did a Bayesian network meta-analysis (NMA) to compare available treatments, summarizing the direct and indirect evidence. Method: We searched relevant databases for randomized controlled trials of neoadjuvant treatments for resectable gastroesophageal cancer which compared two or more of the following treatments: surgery alone, perioperative docetaxel, oxaliplatin, leucovorin, and fluorouracil (FLOT), and neoadjuvant treatments listed in National Comprehensive Cancer Network guideline. Then we performed a NMA to summarize the direct and indirect evidence to estimate the relative efficacy for outcomes including overall survival (OS), progression-free survival and R0 resection rate. We calculated odds ratio (OR) and hazard ratio (HR) with 95% credible intervals (CrI) for dichotomous data and time-to-event data, respectively. We also calculated the surface under the cumulative ranking curve (SUCRA) value of each intervention to obtain a hierarchy of treatments. Result: Eight eligible trials (2434 patients) were included in our NMA. The treatment with the highest probability of benefit on OS as compared with surgery alone was perioperative FLOT [HR = 0.58 with 95% CrI: (0.43, 0.78), SUCRA = 93%], followed by preoperative radiotherapy, paclitaxel, and carboplatin (RT/PC) [HR = 0.68 with 95% CrI: (0.53, 0.87), SUCRA = 72%], perioperative cisplatin with fluorouracil (CF) [HR = 0.70 with 95% CrI: (0.51, 0.95), SUCRA = 68%], and perioperative epirubicin, cisplatin, and fluorouracil or capecitabine (ECF/ECX) [HR = 0.75 with 95% CrI: (0.60, 0.94), SUCRA = 56%]. Conclusion: Compared with surgery alone, perioperative CF, perioperative ECF/ECX, perioperative FLOT, and preoperative RT/PC significantly improved survival. Perioperative FLOT is likely to be the most effective neoadjuvant treatment for the disease. Further clinical studies are needed and justified.

Comparative effectiveness of hyperthermic intraperitoneal chemotherapy for gastric cancer: A systematic review and network meta-analysis protocol.

BACKGROUND: Comparative efficacy and safety of different hyperthermic intraperitoneal chemotherapies (HIPEC) in patients with advanced gastric cancer who underwent gastrectomy is unclear. To investigate this question, we conduct a systematic review and network meta-analysis. METHODS: The protocol followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. PubMed, Embase, and the Cochrane Library will be searched systematically for eligible randomized controlled trials without language restriction. The primary outcome is overall survival. The second outcomes are postoperative complications. The surface under the cumulative ranking curve value will be calculated to establish a hierarchy of the treatments. RESULTS: The results will provide useful information about the effectiveness and safety of HIPEC regimens in patients with resected gastric cancer. CONCLUSION: The findings of the study will be disseminated through peer-reviewed journal.

Comparative effectiveness of adjuvant treatments for resected gastric cancer: a network meta-analysis.

BACKGROUND: Different adjuvant treatments are available for patients with gastric cancer, but conventional meta-analyses performing direct comparisons between two alternative treatments did not have enough power to compare all the adjuvant treatments. Thus, we did a network meta-analysis summarizing the direct and indirect comparisons to identify the optimum treatment. METHODS: We systematically searched for RCTs of adjuvant treatments for gastric cancer comparing two or more of the following treatments: surgery alone, radiotherapy with fluoropyrimidine, S-1-based regimens, and XELOX. The treatments offering available indirect evidence to investigate the comparative effectiveness of adjuvant treatments mentioned above were also included. Then we performed a Bayesian network meta-analysis to summarize the direct and indirect comparisons. We estimated hazard ratios with 95% credible intervals (CrI) for OS and DFS. RESULTS: 11 eligible RCTs (5620 patients) were included in the network meta-analysis. Radiotherapy with fluorouracil (5-FU/RT), S-1-based regimens, and XELOX significantly improved OS as compared with surgery alone [(HR = 0.75 with 95% CrI: 0.63-0.89), (HR = 0.63 with 95% CrI: 0.52-0.76), and (HR = 0.66 with 95% CrI: 0.51-0.85), respectively]. No treatment was clearly superior to others; however, S-1-based regimes and XELOX showed a statistically non-significant trend to better survival as compared with 5-FU/RT. CONCLUSIONS: S-1-based chemotherapy and XELOX are likely to be the most effective adjuvant treatments for patients with resected gastric cancer. 5-FU alone provided little survival benefits as compared with surgery alone. Further clinical trials may be required to investigate S-1-based and XELOX-based adjuvant treatment strategies.

Curcumin exerts a protective effect against premature ovarian failure in mice.

This study was designed to investigate the protective effect of curcumin against d-galactose (d-gal)-induced premature ovarian failure (POF) in mice. A mouse POF model was induced by subcutaneous injection of d-gal (200 mg/kg/day) daily for 42 days. Mice in the curcumin group received both d-gal treatment and intraperitoneal injection of curcumin (100 mg/kg/day) for 42 days. Ovarian function, oxidative stress and apoptosis were evaluated. The P, E2 and SOD levels were higher, and the FSH, LH and MDA levels were significantly lower in the curcumin group than those in the d-gal group. The proportion of primordial follicles was also significantly higher in the curcumin group than that in the d-gal group. In addition, curcumin treatment after d-gal administration resulted in significantly lower Sod2, Cat, 8-OhdG, 4-HNE, NTY and senescence-associated protein P16 expression levels, higher Amh expression levels and less apoptosis in granulosa cells than was observed in the d-gal group. Moreover, the p-Akt, Nrf2 and HO-1 protein expression levels were significantly higher and the apoptosis-related cleaved caspase-3 and -9 protein expression levels were markedly lower in the curcumin group than in the d-gal group. In conclusion, curcumin effectively inhibited d-gal-induced oxidative stress, apoptosis and ovarian injury via a mechanism involving the Nrf2/HO-1 and PI3K/Akt signaling pathways, suggesting that curcumin is a potential protective agent against POF.

[Effect of Moxibustion on Serum IL-17 and TNF-α Levels in Collagen-induced Arthritis Rats].

OBJECTIVE: To observe the influence of moxibustion on serum interleukin -17 (IL-17) and tumor necrosis factor alpha (TNF-α) levels in collagen-induced arthritis (CIA) rats, so as to study its mechanism underlying improvement of rheumatoid arthritis. METHODS: A total of 40 male Wistar rats were used in the present study, and 8 rats were randomly selected as a normal control group. The other 32 rats were modeled. The primary immunity emulsion was made with mixed Type Ⅱ chicken collagen and complete Freund's adjuvant, and 0.3 mL emulsion (containing 0.3 mg collagen) was injected equally into left pelma, tail root and the back. Seven days after the primary immune, the same procedure was conducted to induce the secondary immunity, and the emulsion was made with mixed Type Ⅱ chicken collagen and incomplete Freund's adjuvant. The whole course of mo-deling lasted 21 days. And then 24 CIA rats were randomly divided into model group, medication group and moxibustion group (n=8 in each group). For those of the moxibustion group, suspended moxibustion with 20 mm distance above "Zusanli"(ST 36)and "Kunlun" (BL 60) was performed for 20 min/acupoint, once daily, alternately on left and right hind limbs for 10 consecutive days. For those of the medication group, gavage of methotrexate (0.1 mg/100 g) was administrated once every 5 days, and totally two times. Left ankle joint diameter and body weight were detected, and X-ray of left tarsus was observed in each group before and after modeling or after treatment. Serum levels of IL-17 and TNF-α were determined by ELISA kits. RESULTS: After modeling, the left ankle diameter and serum concentrations of IL-17 and TNF-α increased (P<0.05), and the body weight decreased (P<0.05) in the model group compared to the control group, combined with the tarsus soft tissue swelling, joint space narrowing, bone destruction seen from the tarsal X-ray. After intervention, the ankle diameter, the serum IL-17 and TNF-α levels decreased (P<0.05), and the body weight increased (P<0.05) in both medication and moxibustion groups compared to the model group; meanwhile the tarsus soft tissue swelling and the bone deformity turned to be improved. There were no significant differences between the medication group and the moxibustion group in above mentioned indexes (P>0.05). CONCLUSIONS: Moxi-bustion is effective in CIA rats, and the mechanism may be related to the reduction of serum IL-17 and TNF-α levels.

Effect of curcumin on glycerol-induced acute kidney injury in rats.

The aim of this study was to investigate the protective role and underlying mechanisms of curcumin on glycerol-induced acute kidney injury (AKI) in rats. Glycerol (10 ml/kg BW, 50% v/v in sterile saline, i.m.) was used to induce AKI, followed by curcumin (200 mg/kg/day, p.o.) administration for 3 days. To confirm renal damage and the effects of curcumin on AKI, serum BUN, Scr, and CK as well as renal SOD, MDA, GSH-Px were measured. Additionally, morphological changes were identified by H&E staining and transmission electron microscopy. The expression of several factors including chemotactic factor MCP-1, proinflammatory cytokines including TNF-α and IL-6, as well as the kidney injury markers, as Kim-1 and Lipocalin-2 were also assessed using q-PCR. Finally, cell apoptosis in renal tissue was detected using in situ TUNEL apoptosis fluorescence staining and expression of proteins associated with apoptotic, oxidative stress and lipid oxidative related signaling pathways were detected using immunohistochemical staining and western blot. The results showed that curcumin exerts renoprotective effects by inhibiting oxidative stress in rhabdomyolysis-induced AKI through regulation of the AMPK and Nrf2/HO-1 signaling pathways, and also ameliorated RM-associated renal injury and cell apoptosis by activating the PI3K/Akt pathway.

Platelet lysate supports the in vitro expansion of human periodontal ligament stem cells for cytotherapeutic use.

Human platelet lysate (PL) produced under optimal conditions of standardization and safety has been increasingly suggested as the future 'gold standard' supplement to replace fetal bovine serum (FBS) for the ex vivo propagation of mesenchymal stem cells for translational medicine and cell therapy applications. However, the multifaceted effects of PL on tissue-specific stem cells remain largely unexplored. In the present study, we investigated the stem cell behaviours of human periodontal ligament stem cells (PDLSCs) in media with or without PL. Our data indicate that human PL, either as an adjuvant for culture media or as a substitute for FBS, supports the proliferation and expansion of human PDLSCs derived from either 'young' or 'old' donors to the same extent as FBS, without interfering with their immunomodulatory capacities. Although PL appears to inhibit the in vitro differentiation of 'young' or 'old' PDLSCs, their decreased osteogenic potential may be restored to similar or higher levels compared with FBS-expanded cells. PL- and FBS-expanded PDLSCs exhibited a similar potential to form mineralized nodules and expressed similar levels of osteogenic genes. Our data indicate that large clinically relevant quantities of PDLSCs may be yielded by the use of human PL; however, further analysis of its precise composition and function will pave the way for determining optimized, defined culture conditions. In addition to the potential increase in patient safety, our findings highlight the need for further research to develop the potential of PL-expanded PDLSCs for clinical use. Copyright © 2016 John Wiley & Sons, Ltd.

Chinese herbal medicine, Jianpi Ligan decoction, improves prognosis of unresectable hepatocellular carcinoma after transarterial chemoembolization: a retrospective study.

OBJECTIVE: This study aimed to investigate the efficacy of Jianpi Ligan decoction (JLD) as an adjuvant therapy for patients with unresectable hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE). METHODS: From March 2007 to March 2013, 103 patients with unresectable HCC who underwent TACE in our center were included in this retrospective study. Among the 103 patients, 53 patients accepted JLD along with TACE (JLD group) and 50 patients accepted TACE alone (control group). Indices including complication, toxicity, treatment success rate, and long-term survival were obtained for analysis and comparison. RESULTS: There was no significant difference in patient characteristics between the two groups. No procedure-related deaths or encephalopathy occurred. Fewer patients from the JLD group experienced constipation (7/53 vs 15/50, P=0.0377), abdominal bloating (5/53 vs 12/50, P=0.0466), and lack of appetite (35/53 vs 42/50, P=0.0360). The JLD group had lesser and lighter hepatic toxicity (P=0.0265) and gastrointestinal toxicity (P=0.0445) such as nausea and vomiting. The JLD group had a significantly higher treatment success rate than the control group (51/53 vs 40/50, P=0.0103). Three-year overall survival probability was significantly higher in the JLD group than in the control group (37.74% vs 26.00%; hazard ratio [HR] 0.6171; 95% confidence interval [CI], 0.3832-0.9938; P=0.0365 by log-rank test). No significant difference was found in 3-year overall survival probability (39.22% vs 32.50%; HR, 0.7449; 95% CI, 0.4398-1.2614; P=0.2491 by log-rank test) or 3-year intrahepatic recurrence-free survival probability in patients who achieved treatment success (37.25% vs 30.00%; HR, 0.7280; 95% CI, 0.4332-1.2233; P=0.2087 by log-rank test) between the two groups. CONCLUSION: Application of JLD was effective for reduction of side effects and improvement of long-term survival for patients with unresectable HCC treated by TACE.

[Effect of Electroacupuncture on Serum TNF-α, IL-1ß and Intercellular adhesion molecule 1 Levels in Rheumatoid Arthritis Rats].

OBJECTIVE: To observe the influence of electroacupuncture (EA) on serum TNF-α, IL-1ß and Intercellular adhesion molecule 1 (ICAM-1) levels in rheumatoid arthritis (RA) rats so as to explore its mechanism in relieving RA. METHODS: Eight Wistar rats were used as the normal control group in this study. The RA model was established by injecting mixture solution of incomplete Freund's adjuvant and type II chicken collagen into the left paw. The 24 successful RA rats were randomly divided into model, medication (Prednisolone) and EA groups (n = 8 in each group). EA(2 Hz /100 Hz,1-2 mA)was applied to "Zusanli"(ST 36) and "Kunlun" (BL 60) for 30 min, once daily for 10 days. For rats of the medication group, Prednisolone acetate (0. 1 mL/10 g) was intragastric infused daily. The rats' left ankle diameter was measured before and after the treatment, and the contents of serum TNF-α, IL-1ß and ICAM-1 were assayed by ELISA. RESULTS: In comparison with the normal control group, the rats' ankle diameter, serum TNF-α, IL-1ß and ICAM-1 contents were remarkably increased in the model group (P < 0.05); while compared with the model group, the increased ankle diameter, and serum TNF-α, IL-1ß and ICAM-1 contents were obviously reversed in both medication and EA groups ( P < 0.05), without significant differences between the medication and EA groups (P > 0.05). CONCLUSION: EA intervention is effective in relieving RA rats' inflammatory reactions by down-regulating the levels of serum TNF-α, IL-1ß and ICAM-1.

Treatment of periodontal intrabony defects using autologous periodontal ligament stem cells: a randomized clinical trial.

BACKGROUND: Periodontitis, which progressively destroys tooth-supporting structures, is one of the most widespread infectious diseases and the leading cause of tooth loss in adults. Evidence from preclinical trials and small-scale pilot clinical studies indicates that stem cells derived from periodontal ligament tissues are a promising therapy for the regeneration of lost/damaged periodontal tissue. This study assessed the safety and feasibility of using autologous periodontal ligament stem cells (PDLSCs) as an adjuvant to grafting materials in guided tissue regeneration (GTR) to treat periodontal intrabony defects. Our data provide primary clinical evidence for the efficacy of cell transplantation in regenerative dentistry. METHODS: We conducted a single-center, randomized trial that used autologous PDLSCs in combination with bovine-derived bone mineral materials to treat periodontal intrabony defects. Enrolled patients were randomly assigned to either the Cell group (treatment with GTR and PDLSC sheets in combination with Bio-oss(®)) or the Control group (treatment with GTR and Bio-oss(®) without stem cells). During a 12-month follow-up study, we evaluated the frequency and extent of adverse events. For the assessment of treatment efficacy, the primary outcome was based on the magnitude of alveolar bone regeneration following the surgical procedure. RESULTS: A total of 30 periodontitis patients aged 18 to 65 years (48 testing teeth with periodontal intrabony defects) who satisfied our inclusion and exclusion criteria were enrolled in the study and randomly assigned to the Cell group or the Control group. A total of 21 teeth were treated in the Control group and 20 teeth were treated in the Cell group. All patients received surgery and a clinical evaluation. No clinical safety problems that could be attributed to the investigational PDLSCs were identified. Each group showed a significant increase in the alveolar bone height (decrease in the bone-defect depth) over time (p < 0.001). However, no statistically significant differences were detected between the Cell group and the Control group (p > 0.05). CONCLUSIONS: This study demonstrates that using autologous PDLSCs to treat periodontal intrabony defects is safe and does not produce significant adverse effects. The efficacy of cell-based periodontal therapy requires further validation by multicenter, randomized controlled studies with an increased sample size. TRIAL REGISTRATION: NCT01357785 Date registered: 18 May 2011.

Increasing Selenium and Yellow Pigment Concentrations in Foxtail Millet (Setaria italica L.) Grain with Foliar Application of Selenite.

Although addition of selenium (Se) is known to increase Se in crops, it is unclear whether exogenous Se is linked to nutritional and functional components in foxtail millet (Setaria italica L.). In this study, we examined the potential of increasing Se and yellow pigment (YP) in foxtail millet grain by foliar application of Se. Field experiments were conducted during the growing season of foxtail millet in 2013 and 2014 to assess the effects of foliar spray of sodium selenite (10-210 g Se ha(-1)) on the yield, Se uptake and accumulation, total YP, and microminerals in the grain. Average grain yields with Se application were 5.60 and 4.53 t ha(-1) in the 2 years, showing no significant differences from the unfertilized control. However, grain Se concentration increased linearly with Se application rate, by 8.92 and 6.09 µg kg(-1) in the 2 years with application of 1 g Se ha(-1) (maximum grain recovery rates of Se fertilizer, 52 and 28 %). Likewise, total grain YP concentration markedly increased by 0.038 and 0.031 mg kg(-1) in the 2 years with application of 1 g Se ha(-1). Grain Mn, Cu, Fe, and Zn concentrations were not significantly affected by Se application. This study indicated that foliar application of Se effectively and reliably increased the concentrations of Se and YP in foxtail millet grain without affecting the yield or mineral micronutrient concentrations. Thus, foliar-applied selenite has a significant potential to increase the concentrations of selenium and YP (putative lutein (Shen, J Cereal Sci 61:86-93, 2015; Abdel-Aal, Cereal Chem 79:455-457, 2002; Abdel-Aal, J Agric Food Chem 55:787-794, 2007)) of foxtail millet and, thus, the health benefits of this crop.

[Effect of electroacupunctu-e intervention on serum IL-17 and IL-23 contents in rheumatoid arthritis rats].

OBJECTIVE: To observe the influence of electroacupuncture (EA) stimulation of "Zusanli" (ST 36) and "Kunlun" (BL 60) on serum and knee-joint IL-17 and IL-23 contents in rheumatoid arthritis (RA) rats so as to study its underlying mechanism in improving RA. METHODS: Male Wistar rats were randomly allocated to normal control, RA model, EA and Prednisolone groups (n = 8 in each group). The RA model was established by intra-planta injection of incomplete Freund's adjuvant and type II collagen. EA (2 Hz/100 Hz,1-2 mA)was applied to bilateral "Zusanli"(ST 36) and "Kunlun"(BL 60) for 30 min, once daily for 10 days. The rats' ankle diameter was measured, and IL-17 and IL-23 contents in the serum and the knee-joint cavity were assayed by ELISA and Western blot, respectively. RESULTS: In comparison with the normal control group, the rats' ankle diameter, serum IL-17 and IL-23 contents and knee-joint IL-17 and IL-23 protein expression levels were significantly increased in the model group (P < 0.05). After EA and Prednisolone treatment, compared with the model group, all the rats' ankle diameter, serum IL-17 and IL-23 contents and knee-joint IL-17 and IL-23 protein expression levels were decreased remarkably (P < 0.05). No obvious differences were found between the EA and Prednisolone groups in the aforementioned indexes (P > 0.05), except IL-17 protein expression level (being markedly lower in the Prednisolone group than in the EA group). CONCLUSION: EA intervention can reduce inflammatory reaction of the ankle-joint in RA rats, which may be related to its effects in down-regulating serum and knee-joint IL-17 and IL-23 levels.

Hepatic arterial infusion chemotherapy reduced hepatic metastases from pancreatic cancer after pancreatectomy.

BACKGROUND/AIMS: This study aims to investigate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) on liver metastases from pancreatic cancer after pancreatectomy. METHODOLOGY: We randomly assigned 106 patients with pancreatic cancer after pancreatectomy between 2005 and 2010 to receive 2 cycles of HAIC plus 4 cycles of systemic chemotherapy (Combined Therapy) or 6 cycles of systemic chemotherapy alone (Monotherapy). Both the HAIC and systemic chemotherapy regimen consisted of a 5-hour infusion of 5-fluorouracil 1000 mg/m2 on day 1 followed by gemcitabine 800 mg/m2 as an over 30-min infusion on day 1 and day 8. The treatment was started on an average of 21.2 days after surgery and repeated every 4 weeks. The disease-free survival, overall survival and liver metastases-free survival were compared. RESULTS: There was no significant difference in adverse effects between two groups. Significant differences were found in 3-year overall survival (Combined Therapy, 23.08 %; Monotherapy, 14.81%; P=0.0473) and liver metastases-free survival (Combined Therapy, 80.77%; Monotherapy, 55.56%; P=0.0014). CONCLUSIONS: HAIC effectively and safely prevents liver metastases and improves the prognosis of patients with pancreatic cancer after pancreatectomy.

[Simultaneous determination of seven constituents in Euodiae Fructus and two related species by HPLC].

This study is to develop a HPLC method for quality evaluation of Euodiae Fructus and related species by simultaneous determination limonin, indole alkaloids (14-fomyldihydroxyrutaecarpine, evodiamine, rutaecarpine), and quinolone alkaloids [1-methyl-2-undecyl-4 (1H)-quinolone, evocarpine, dihydroevocarpine] in the fruits of five Evodia species. Samples were analyzed on a YMC C18 column (4.6 mm x 250 mm, 5 microm) eluted with mobile phases of acetonitrile (A), tetrahydrofuran (B), and a buffer solution of 5 mmol x L(-1) ammonium acetate (pH 3.8) (C) in a linear gradient mode. The column temperature was 30 degrees C and the flow rate was 1.0 mL x min(-1). The PDA detector wavelengths were set at 220 and 250 nm. The seven compounds were well separated and showed good linearity (r = 0.999 9) within the concentration ranges tested. The mean recoveries were between 96.7%-102.4% (RSD 1.4%-3.1%). Through the validation, the method was proved to be accurate and repeatable. All the seven constituents were detected in the fruits of five species, but the contents of them varied widely in different samples. The total contents of seven constituents in 16 batches of Euodiae Fructus were 9.46-69.9 mg x g(-1), and the mean content was 28.2 mg x g(-1). The total content of seven constituents in E. compacta and E. fargesii was 25.8, 7.69 mg x g(-1), respectively.

Prophylactic adjuvant hepatic arterial infusion chemotherapy reduced hepatic metastases from Stage III colorectal cancer after curative resection.

BACKGROUND/AIMS: This study aims to investigate the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) on liver metastases of Stage III colorectal cancer patients after curative resection. METHODOLOGY: We randomly assigned 287 Stage III colorectal cancer patients after curative resection between 2002 and 2008 to receive 2 cycles of HAIC plus 4 cycles of systemic chemotherapy (combined therapy) or 6 cycles of systemic chemotherapy alone (monotherapy). Both the HAIC and systemic chemotherapy regimen consisted of a 2-hour infusion of Oxaliplatin (85mg/m2) on day 1 followed by folinic acid 200mg/m2 as a 2-hour infusion on days 2 and 3 and by 5-fluorouracil 2400mg/m2 as a 48-hour infusion on days 2 and 3. The treatment repeated every 4 weeks. The disease-free survival, overall survival and liver metastases-free survival were compared. RESULTS: There was no significant difference in adverse effects between two groups. Significant differences were found in 3-year disease-free survival (Combined therapy, 75.00%; Monotherapy, 63.27%; p=0.0035), overall survival (Combined therapy, 84.29%; Monotherapy, 65.31%; p=0.0006) and liver metastases-free survival (Combined therapy, 80.00%; Monotherapy, 69.39%; p=0.0451). CONCLUSIONS: HAIC effectively and safely prevents metachronous liver metastases and improves the prognosis of patients with Stage III colorectal cancer after curative resection.