Baicalin attenuated metabolic dysfunction-associated fatty liver disease by suppressing oxidative stress and inflammation via the p62-Keap1-Nrf2 signalling pathway in db/db mice.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the main cause of chronic liver disease. Baicalin (Bai), a bioactive molecule found in Scutellaria baicalensis Georgi, possesses antioxidant and antiinflammatory properties. These activities suggest Bai could be a promising therapeutic agent against NAFLD; however, its specific effects and underlying mechanism are still not clear. This study aims to explore the effect of Bai to attenuate MAFLD and associated molecular mechanisms. Bai (50, 100 or 200 mg/kg) was orally administered to db/db mice with MAFLD for 4 weeks or db/m mice as the normal control. Bai markedly attenuated lipid accumulation, cirrhosis and hepatocytes apoptosis in the liver tissues of MAFLD mice, suggesting strong ability to attenuate MAFLD. Bai significantly reduced proinflammatory biomarkers and enhanced antioxidant enzymes, which appeared to be modulated by the upregulated p62-Keap1-Nrf2 signalling cascade; furthermore, cotreatment of Bai and all-trans-retinoic acid (Nrf2 inhibitor) demonstrated markedly weakened liver protective effects by Bai and its induced antioxidant and antiinflammatory responses. The present study supported the use of Bai in attenuating MAFLD as a promising therapeutic agent, and its strong mechanism of action in association with the upregulating the p62-keap1-Nrf2 pathway.

Pien Tze Huang attenuated acetaminophen-induced liver injury by autophagy mediated-NLRP3 inflammasome inhibition.

ETHNOPHARMACOLOGICAL RELEVANCE: Pien Tze Huang is a classic traditional Chinese medicinal product, used for inflammatory diseases as stated in Chinese Pharmacopoeia. In particular, it is effective in treating liver diseases and pro-inflammatory conditions. Acetaminophen (APAP) is a widely used analgesic drug, but its over-dose is associated with acute liver failure where the clinical approved antidote treatment is limited. Inflammation has been considered as one of the therapeutic targets against APAP-induced liver injury. AIM OF THE STUDY: We aimed to explore the therapeutic potential of Pien Tze Huang tablet (PTH) on protecting liver against APAP-induced liver injury through its strong anti-inflammatory pharmacological action. MATERIALS AND METHODS: Wild-type C57BL/6 mice were given PTH (75, 150 and 300 mg/kg) by oral gavage 3 days before the APAP injection (400 mg/kg). The protective effect of PTH was assessed by aspartate aminotransferase (AST) and alanine transaminase (ALT) levels and pathological staining. The mechanisms underlying PTH's hepatoprotective effects were investigated in nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) knock-out (NLRP3-/-), over expression NLRP3 (oe-NLRP3) mice, and wild-type mice with the injection of autophagy inhibitor (3-methyladenine, 3-MA). RESULTS: APAP-exposed mice resulted in evident liver injury which was evidenced by hepatic necrosis and elevated levels of AST and ALT in the wild-type C57BL/6 mice. PTH dose-dependently reduced ALT, AST and upregulated autophagy activity. In addition, PTH significantly reduced elevated levels of proinflammatory cytokines and NLRP3 inflammasome. The liver protective effect of PTH (300 mg/kg) was still obvious in the oe-NLRP3 mice, however, it became insignificant in the NLRP3-/- mice. When PTH (300 mg/kg) was co-treated with 3-MA to the wild-type C57BL/6 mice, the NLRP3 inhibition were reversed when autophagy was blocked. CONCLUSION: PTH exerted a beneficial effect in protecting liver against APAP-induced liver injury. The underlying molecular mechanism was associated with the NLRP3 inflammasome inhibition which was likely driven by the upregulated autophagy activity. Our study underpins the traditional use of PTH in protecting liver through its anti-inflammatory action.

Phytochemical compositions and biological activities of the branches and leaves of Ormosia hosiei Hemsl. et Wils.

Ormosia hosiei Hemsl. et Wils. is an economical and medicinal plant, increasingly cultivated in China; however, its branches and leaves are often pruned as waste. This is the first study focused on the phytochemical profiles and antioxidant, anti-α-glucosidase, anti-tyrosinase, and anti-neuroinflammatory activities of the branches and leaves of O. hosiei. Herein, thirty-seven characteristic compounds were identified by UPLC-MS/MS and twelve were detected for the first time in O. hosiei. Twenty-seven phenolics were further quantified and significant differences in phenolic compositions between the branches and leaves of O. hosiei were observed. The ethanol extracts exhibited promising antioxidant, anti-α-glucosidase, anti-tyrosinase, and anti-neuroinflammatory effects, and the bioactivities significantly correlated with total phenolic content and twelve individual phenolics. Naringin, genistein, vitexin, vitexin-2-O-rhamnoside, syringaresinol and syringaresinol-4-O-ß-D-glucopyranoside can be considered potential quality markers of O. hosiei. Our results provided solid evidence that the branches and leaves of O. hosiei deserve more attention and exploitation, considering the potential to be developed as functional foods or herbal medicines.

Postoperative Adjuvant Hepatic Arterial Infusion Chemotherapy With FOLFOX in Hepatocellular Carcinoma With Microvascular Invasion: A Multicenter, Phase III, Randomized Study.

PURPOSE: To report the efficacy and safety of postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil and oxaliplatin (FOLFOX) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). PATIENTS AND METHODS: In this randomized, open-label, multicenter trial, histologically confirmed HCC patients with MVI were randomly assigned (1:1) to receive adjuvant FOLFOX-HAIC (treatment group) or routine follow-up (control group). The primary end point was disease-free survival (DFS) by intention-to-treat (ITT) analysis while secondary end points were overall survival, recurrence rate, and safety. RESULTS: Between June 2016 and August 2021, a total of 315 patients (ITT population) at five centers were randomly assigned to the treatment group (n = 157) or the control group (n = 158). In the ITT population, the median DFS was 20.3 months (95% CI, 10.4 to 30.3) in the treatment group versus 10.0 months (95% CI, 6.8 to 13.2) in the control group (hazard ratio, 0.59; 95% CI, 0.43 to 0.81; P = .001). The overall survival rates at 1 year, 2 years, and 3 years were 93.8% (95% CI, 89.8 to 98.1), 86.4% (95% CI, 80.0 to 93.2), and 80.4% (95% CI, 71.9 to 89.9) for the treatment group and 92.0% (95% CI, 87.6 to 96.7), 86.0% (95% CI, 79.9 to 92.6), and 74.9% (95% CI, 65.5 to 85.7) for the control group (hazard ratio, 0.64; 95% CI, 0.36 to 1.14; P = .130), respectively. The recurrence rates were 40.1% (63/157) in the treatment group and 55.7% (88/158) in the control group. Majority of the adverse events were grade 0-1 (83.8%), with no treatment-related death in both groups. CONCLUSION: Postoperative adjuvant HAIC with FOLFOX significantly improved the DFS benefits with acceptable toxicities in HCC patients with MVI.

Qishen Yiqi Dripping Pill Protects Diabetic Nephropathy by Inhibiting the PI3K-AKT Signaling Pathways in Rats.

This study aimed to explore the potential mechanisms of Qishen Yiqi dripping pill (QYDP) against diabetic nephropathy (DN) through network pharmacology and animal experiments. The components and targets of QYDP and DN-related targets were retrieved from public databases. A total of 116 compounds and 160 targets of QYDP anti-DN were obtained. The top 10 hub targets including AKT1, TNF, ALB, INS, PPARG, IL-6, IL-1B, VEGF-A, JUN, and MAPK3 were screened by Cytoscape software. Then, the key targets of QYDP were enriched in 1815 Gene Ontology (GO) entries (P < 0.01) and 159 Kyoto Encyclopedia of Genomes and Genomes (KEGG) pathways (P < 0.01), mainly including the AGE-RAGE signaling pathway in diabetic complications and the PI3K-AKT signaling pathway. In animal experiments, the results of an ELISA assay showed that QYDP could regulate the expression levels of kidney function-related indexes and reduce the expression of inflammatory factors. qRT-PCR and western blot results showed that QYDP regulated the expression of hub genes. In conclusion, this study shows that QYDP could treat DN by antioxidative and antiinflammatory activity and inhibiting the PI3K-AKT signaling pathway.

Antitumour effects of apatinib in progressive, metastatic differentiated thyroid cancer (DTC).

PURPOSE: Management of progressive, metastatic radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC) has been a great challenge due to its poor prognosis and limited treatment options. Recently, apatinib, an orally anti-angiogenic tyrosine kinase inhibitor (TKI) is reported to be useful for treatment of progressive RAIR-DIC. The aim of this study was to evaluate the antitumour effect of apatinib and the combination therapy with radioactive iodine (RAI) in patients with progressive metastatic DTC. METHODS: Five patients (all female, mean age 62 ± 8 years, ranged from 51 to 69 years) with distant metastatic DTC (dmDTC) after total thyroidectomy (TTE) and neck lymph node dissection were treated with apatinib at a dose 500 mg per day after 18F-Fluorodeoxyglucose (18F-FDG) PET/CT. The effects of apatinib on DTC were evaluated at 4 ± 1 months after treatment with apatinib. RAI therapy was then initiated. The response to apatinib and the combination therapy with RAI treatment was evaluated by Response Evaluation Criteria in Solid Tumours (RECIST, version 1.1) and metabolic activity using serum thyroglobulin (Tg) and 18F-FDG PET/CT. RESULTS: Positive 18F-FDG PET/CT results were found in all patients before apatinib therapy. The immunohistochemical analysis of primary tumour tissues showed high expression of vascular endothelial growth factor receptor-2 (VEGFR-2). Four patients with follicular thyroid carcinoma (FTC) showed partial response (PR) with significant decrease in tumour size and maximum standardized uptake value (SUVmax) after 4 ± 1 month's treatment with apatinib. Further significant reduction of tumour size and SUVmax were observed in three patients after combination therapy with apatinib and RAI. Only one patient with both FTC and papillary thyroid cancer (PTC) demonstrated progressive disease (PD) after treatment with apatinib alone, however, a decrease in tumour size and SUVmax as well as serum Tg levels was achieved after the combination with RAI therapy and apatinib. CONCLUSIONS: Apatinib had significant antitumour effects on progressive distant metastatic DTC. Moreover, beneficial synergistic and complementary effects were shown when apatinib combined with RAI therapy. CLINICAL TRIAL REGISTRATION: NCT04180007, Registered November 26, 2019.

Flavan-3-ols in Vitis seeds: Their extraction and analysis by HPLC-ESI-MS/MS.

An orthogonal L1643 × 22 test design was applied to select the optimum conditions for extracting flavan-3-ols in grape seeds. Highest yield of flavan-3-ols was achieved with 80% methanol, a ratio [1:30 (g/mL)] of sample-to-solvent, sonication for 20 min, and extraction at 25 °C for 12 h in darkness. The optimized analytical method for HPLC separation was a multistep gradient elution using 1% formic acid (A) and acetonitrile containing 1% formic acid (B), at a flow rate of 0.6 mL/min in 36 min. Moreover, fourteen flavan-3-ols were separated and identified using HPLC-ESI-MS/MS, including four monomers ((+)-catechin, (-)-epicatechin, epigallocatechin gallate and epicatechin gallate) and ten oligomers (three dimers, four trimers, two tetramers and one pentamer). The optimized method was used to determine flavan-3-ols content and compositions among ten representative cultivars. The new wine grape - Beihong, had higher flavan-3-ols content and polymerization than classic wine grapes - Cabernet Sauvignon, Merlot, Semillon and Riesling.

Effect of 1 Year of Qigong Exercise on Cognitive Function Among Older Chinese Adults at Risk of Cognitive Decline: A Cluster Randomized Controlled Trial.

Background: The rapidly aging Chinese population is showing an increase in age-related illnesses, including mild cognitive impairment and Alzheimer disease. The best types of physical activity for the improvement of cognition remain unknown. This study aimed to compare the effectiveness of a tailored qigong exercise with that of stretching exercise in the maintenance of cognitive abilities in Chinese elders at risk of cognitive decline. Methods: Seventy-four community-dwelling adults aged ≥60 years were screened for eligibility. Using a randomized control group design, participants with scores ≥19 on the Chinese version of the Montreal Cognitive Assessment-Basic (MoCA) were allocated to a 1-year qigong intervention (n = 33) and a stretching control exercise group (n = 33). The primary outcome was the MoCA score, as a measure of global cognitive function, and secondary outcomes were globe cognition and five domain scores on the Chinese version of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The MoCA and RBANS were administered at baseline and 1 year after intervention to assess the effect of the exercises on cognitive decline. Results: Twenty-five of 33 (75.8%) participants in the qigong group and 26 of 33 (78.8%) participants in the control group completed the 1-year exercise programs. A bivariate test revealed strong correlation between MoCA and RBANS total scores after the intervention (r = 0.517, p < 0.01). Generalized estimating equations revealed a lower risk of progression of cognitive decline at 1 year in the qigong group than in the control group (odds ratio, 0.314; 95% confidence interval, 0.103-0.961; p = 0.04). Two-way repeated-measures ANOVA followed by post hoc t tests with Bonferroni corrections indicated that MoCA and RBANS scores were significantly higher in the qigong group than in the control group (MoCA and RBANS global cognition, memory, visuospatial/constructional ability, and language, all p < 0.01), with the exception of RBANS attention score (p > 0.05). Conclusions: One year of qigong practice was significantly superior to stretching exercise not only for the prevention of cognitive decline progression, but also for the improvement of several cognitive functions, among older Chinese adults at risk of cognitive decline.

Temporal variation analysis and risk assessment of neonicotinoid residues from tea in China.

The extensive use of neonicotinoids (NEOs) has caused the release of wide-ranging of residues to the environment and food, and their potential health risks are now receiving more attention. In this study, three surveys were conducted to obtain the overall profiles of NEO residue levels (seven NEOs and one metabolite) in Chinese tea over a period of seven years. A total of 726 tea samples were tested, and nearly 87% of the samples were found to have detectable NEO residues. The overall average detection frequency of acetamiprid was the highest, reaching 73%. Imidacloprid residues in 4.6% of the samples exceeded the Chinese maximum residue limits, whereas clothianidin and nitenpyram had been detected in Chinese tea samples since 2014. The applications of thiacloprid and thiamethoxam gradually increased, and some tea samples with high residue levels appeared in China. These findings signal the replacement of new and old varieties of NEOs in China. Both long- and short-term cumulative exposures to NEOs were calculated based on optimistic and pessimistic models recommended in the EFSA guidelines. In the three survey periods, the average total imidacloprid-equivalent concentrations were 484.63, 1713.36, and 1148.34 µg/kg, respectively. Combined with the refined point estimates and probabilistic models used in this study, the hazard quotients of NEO residues in tea for Chinese tea consumers were found to be low and within the bounds of safety.

A highly-efficient and cost-effective pretreatment method for selective extraction and detection of perchlorate in tea and dairy products.

In view of the high polarity and ubiquitous occurrence of perchlorate, achieving an ultra-trace analysis has become a challenging task. The present study aimed to develop a simple and generic pretreatment protocol based on cold-induced liquid-liquid extraction to efficiently extract perchlorate from tea and dairy products and remarkably decrease potential matrix interferences and laborious cleanup. By optimizing the pretreatment conditions, the enrichment factor of perchlorate increased by 7.79 times under the compromise between the matrix effect and extraction recovery. The validated method presented satisfactory selectivity, linearity, accuracy, precision, and matrix effect, providing recoveries of 78.2%-106.2% with RSDr ranging from 1.2% to 7.9% and RSDR less than 10.7% for tea and dairy products. This pretreatment protocol depended only on shaking, freezing, and centrifugation in one step, without additional equipment or tedious operations, which will be explored to a greater extent in complex biological or food matrices.

Simultaneous determination of neonicotinoids and fipronils in tea using a modified QuEChERS method and liquid chromatography-high resolution mass spectrometry.

The widespread use of neonicotinoids (NEOs) and fipronils (FIPs) as insecticides in modern agriculture has been widely investigated because of their adverse effects on human health. This study aimed to develop an accurate quantitative approach to analyze NEOs and FIPs in tea by using a modified QuEChERS method based on dispersive solid-phase extraction procedure coupled with liquid chromatography-high resolution mass spectrometry. To minimize matrix interferences largely, we selected polyvinylpolypyrrolidone (PVPP) and strong cationic exchange adsorbent (PCX) as dispersive adsorbents to eliminate polyphenols and caffeine from tea extract, respectively. Under optimal conditions, a slight matrix effect was observed for NEOs and FIPs due to the highest reductions of polyphenols and caffeine (94% and 88%, respectively). The method was validated by the European Medicines Agency and Eurachem guidelines and was successfully applied to tea samples for NEOs and FIPs analysis. NEOs and FIPs were commonly detected in tea.

A novel treatment strategy using indocyanine green for transarterial chemoembolization in BCLC stage C hepatocellular carcinoma.

PURPOSE: The aim of our study was to propose a strategy based on indocyanine green (ICG) (SBI) to provide better clinical guidelines for transarterial chemoembolization (TACE) treatments for Barcelona clinic liver cancer (BCLC) stage C hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: From October 2005 to December 2012, 112 BCLC stage C HCC patients initially treated with TACE were investigated, randomly divided into a training cohort (n = 79) and validation cohort (n = 33). In training group, the patients were grouped based on their 15 minutes ICG retention rate (ICG R15), different chemo drugs and dose of lipidol in TACE. Overall survival (OS) and progression-free survival (PFS) were analyzed in subgroups. Strategy based on ICG was built and verified in validation group. RESULTS: For those patients with ICG R15 values >10%, the lipiodol ≤10 mL group showed better survival than the lipiodol >10 mL group. For those patients with ICG R15 values ≤10%, the group that received triple-drug chemotherapy treatments with lipiodol diameter ratio values between 1 and 3 showed better survival than the other group. Patients who conformed with the SBI had better survival times than those who did not conform with the SBI, in both the training cohort (median OS 10.3 vs 5.1 months; P < .001; median PFS, 3.3 vs 2.1 months; P = .006) and the validation cohort (median OS 8.9 vs 7.1 months; P = .087; median PFS, 6.6 vs 2.3 months; P < .001). CONCLUSIONS: The SBI is suitable and may provide survival benefits for TACE treatments in BCLC stage C HCC patients.

An enhanced sensitivity and cleanup strategy for the nontargeted screening and targeted determination of pesticides in tea using modified dispersive solid-phase extraction and cold-induced acetonitrile aqueous two-phase systems coupled with liquid chromatography-high resolution mass spectrometry.

At present, matrix interferences in tea are still a great challenge for analysis of multi-pesticide residues. Herein, a simple sample preparation method was developed based on the modified dispersive solid-phase extraction (DSPE) procedure and cold-induced acetonitrile aqueous two-phase systems (ATPS). In modified DSPE procedure, polyvinylpolypyrrolidone (PVPP) was selected as the matrix dispersive adsorbent to remove polyphenols from the tea with the removal rate of >98.3%. Using cold-induced acetonitrile ATPS, caffeine of the tea extract was sharply reduced by 81.2%, and a 0.798-3.167 of enrichment factor for the representative pesticides was achieved. In liquid chromatography-high resolution mass spectrometry analysis, a full scan/data independent acquisition approach was used for the nontargeted screening and targeted determination of pesticides. In data analysis, an in-house database of pesticides was constructed, and a simple accurate mass calibration method was used to correct the accurate mass variation, which was conducive to reduce the number of false detects.

Rapid Determination of Aconitum Alkaloids from Human Urine by UHPLC-HRMS.

Aconitum alkaloid poisoning is a type of poisoning caused by accidental ingestion and clinical use of herbal drugs in many countries. In this study, we developed an in-syringe dispersive micro solid-phase extraction (DMSPE) method for selective extraction of aconitine, benzoylaconine and aconine from human urine using a type of polymer material. All of the parameters influencing the extraction efficiency such as the type and amount of sorbent, the extraction time and the desorption solvent and volume in DMSPE were carefully investigated and optimized. Using DMSPE method, the absence of evaporation and centrifugation steps reduced the consuming time of sample preparation. Samples were analyzed by ultra high-performance liquid chromatography-high-resolution mass spectrometry on an HSS T3 analytical column. The results showed that the DMSPE method yielded fewer relative and absolute matrix effects, which reduced the sample to sample variability in human urine. The limits of detection and limits of quantitation of this method were determined to be 0.08-0.1 and 0.2-0.3 µg/L, respectively. The average recoveries of the analytes were between 88.6% and 107.2% with the intra- and interday precisions ranging from 2.1% to 6.4% and from 5.9% to 13.9%, respectively. The method presented here is an efficient, low-cost and selective extraction of aconitine, benzoylaconine and aconine from human urine.

Evaluation of safety of iridoids rich fraction from Valeriana jatamansi Jones: Acute and sub-chronic toxicity study in mice and rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Valeriana jatamansi Jones named Zhizhuxiang in China is one of the most popular traditional medicine for varied ailments related to malaise, abdominal distention, insomnia, and rheumatism. AIM OF THE STUDY: Evaluate the safety of iridoids rich fraction from V. jatamansi Jones (IRFV) and to provide data for clinical application. MATERIALS AND METHODS: The acute and sub-chronic toxicity of IRFV were investigated by employing established methods. The acute toxicity study was conducted through oral administration of a single dose (3,200 mg/kg body weight) of IRFV to adult mice. The vehicle used for dilution of the IRFV was a mixture of 0.5% CMC-Na and 99.5% water. The weight, diet, toxic reaction, and death after 14 days were observed. In the sub-chronic toxicity study, low doses (240 mg/kg bw), middle doses (960 mg/kg bw), and high doses (1,200 mg/kg bw) of IRFV were administered daily to adult rats for 6 days a week (except Sunday) for 3 months. The general behavior of the rats was observed and recorded daily. The weight and food consumption of rats were tested weekly. The effect on organs, the hematological and blood biochemical parameters, and the histopathology were assessed after 1.5 months (five males and five females) and after 3 months (10 males and 10 females).The remaining 10 rats (five males and five females) in each group were fed for 2 weeks to observe reversible and delayed toxicity after the medicine was administered. RESULTS: In the acute toxicity study, no significant difference was found in the body weight of the mice in the control group and those in the drug group (p>0.05). The maximum tolerated dose of IRFV on mice was 3,200 mg/kg, which is 2666 times of the clinical adult daily dose. In the sub-chronic toxicity study on rats, the daily single oral doses of the IRFV did not result in death nor affected the general behavior, including appearance, activities, discharge, and waste at all tested doses. Moreover, no significant difference was found (p>0.05) between the body weights of the rats from the drug groups and those from the control group. Food consumption was significantly affected (p<0.05) only in the first 3 weeks. No statistically significant differences (p>0.05) were observed in the hematological and blood biochemical parameters, and no abnormality of other organs were noted in both gross and histopathological examinations, except several animal transients (p<0.05) or spontaneous lesions (abnormality). CONCLUSION: IRFV is extremely safe in the usual clinical dose, and may not have any single dose toxicity. The lethal dose with 50% mortality rate (LD50) on mice is over 2,000 mg/kg bw. The no-observed adverse effects level is 1,200 mg/kg/day for rats. No direct correlation was found between the hematology, blood biochemical indexes, and organ coefficient of tested rats and the toxicity of IRFV.

Molecular weight and galloylation affect grape seed extract constituents' ability to cross-link dentin collagen in clinically relevant time.

OBJECTIVE: To investigate the relationship between the structures of polyphenolic compounds found in grape seed extract (GSE) and their activity in cross-linking dentin collagen in clinically relevant settings. METHODS: Representative monomeric and dimeric GSE constituents including (+)-catechin (pCT), (-)-catechin (CT), (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG), (-)-epigallocatechin gallate (EGCG), procyanidin B2 and a pCT-pCT dimer were purchased or synthesized. GSE was separated into low (PALM) and high molecular weight (PAHM) fractions. Human molars were processed into dentin films and beams. After demineralization, 11 groups of films (n=5) were treated for 1min with the aforementioned reagents (1wt% in 50/50 ethanol/water) and 1 group remained untreated. The films were studied by Fourier transform infrared spectroscopy (FTIR) followed by a quantitative mass spectroscopy-based digestion assay. Tensile properties of demineralized dentin beams were evaluated (n=7) after treatments (2h and 24h) with selective GSE species that were found to protect dentin collagen from collagenase. RESULTS: Efficacy of GSE constituents in cross-linking dentin collagen was dependent on molecular size and galloylation. Non-galloylated species with degree of polymerization up to two, including pCT, CT, EC, EGC, procyanidin B2 and pCT-pCT dimer were not active. Galloylated species were active starting from monomeric form, including ECG, EGCG, PALM, GSE and PAHM. PALM induced the best overall improvement in tensile properties of dentin collagen. SIGNIFICANCE: Identification under clinically relevant settings of structural features that contribute to GSE constituents' efficacy in stabilizing demineralized dentin matrix has immediate impact on optimizing GSE's use in dentin bonding.

Antiviral therapy in the improvement of survival of patients with hepatitis B virus-related hepatocellular carcinoma treated with sorafenib.

BACKGROUND AND AIM: To evaluate the role of antiviral therapy with nucleoside analogs (NAs) in sorafenib-treated patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: A retrospective cohort study was done in 151 HBV-related HCC patients treated with sorafenib at Sun Yat-sen University Cancer Center between 2007 and 2012. Overall survival (OS), progression-free survival and adverse events were compared in patients treated with/without NAs. Subgroup analysis and Cox regression analysis were performed to determine the efficiency of NAs and prognostic factors for OS. RESULTS: HBV-related HCC patients (n=151) were identified from our database of HCC patients treated with sorafenib. Patients treated with NAs (antiviral group, n=88) had significantly improved OS compared with the patients who received no NAs (non-antiviral group, n=63; median OS: 16.47 months vs 13.10 months, P=0.03). Patients in the antiviral group had a significant risk reduction of death compared with the non-antiviral group (hazard ratio: 0.67, 95% confidence interval: 0.46-0.98, P=0.04). By subgroup analysis, patients of Barcelona Clinic Liver Cancer (BCLC) stage C and patients with higher presorafenib HBV-DNA level achieved better survival improvement. Antiviral therapy with NAs was one of the independent prognostic factors for OS of HBV-related HCC patients who were treated with sorafenib. CONCLUSION: Antiviral therapy with NAs improved OS of HBV-related HCC patients treated with sorafenib, especially in patients with BCLC stage C disease and higher HBV-DNA level.

Resveratrols in grape berry skins and leaves in vitis germplasm.

BACKGROUND: Resveratrol is an important stilbene that benefits human health. However, it is only distributed in a few species including grape and is very expensive. At present, grape has been an important source resveratrol. However, the details are scarce on resveratrol distribution in different Vitis species or cultivars. METHODOLOGY/PRINCIPAL FINDING: The composition and content of resveratrols were investigated by HPLC for assessing genotypic variation in berry skins and leaves of 75 grape cultivars, belonging to 3 species and 7 interspecific hybrids. Trans-resveratrol, cis-piceid and trans-piceid were detected in berry skins and leaves, but cis-resveratrol was not. Resveratrol content largely varied with genetic background as well as usage. In most cultivars, total resveratrol including the above three compounds was higher in berry skins than leaves. In berry skins of most cultivars and leaves of almost all cultivars, cis-piceid was the most abundant resveratrol; trans-resveratrol and trans-piceid were minor components. Some specific cultivars were found with extremely high levels of trans-resveratrol, cis- piceid, trans-piceid or total resveratrols in berry skins or leaves. In skins and leaves, rootstock cultivars had a higher content of total resveratrols, and the cultivated European type cultivars and their hybrids with V. labrusca had relatively low totals. There were no significant correlations of the amounts of total resveratrols or any individual resveratrol between berry skins and leaves. All 75 cultivars can be divided into four groups based on the composition of resveratrols and their concentration by principal component analysis. CONCLUSION: Resveratrol content of grape berries and leaves varied largely with their genetic background and usage. Rootstock cultivars had a higher content of total resveratrols than the other germplasm. Total resveratrols were lower in leaves than berry skins in most cultivars. Cis-piceid was the most abundant resveratrol in most cultivars, and trans-res and trans-pd were minor components.

Simultaneous analysis of anthocyanin and non-anthocyanin flavonoid in various tissues of different lotus (Nelumbo) cultivars by HPLC-DAD-ESI-MS(n).

A validated HPLC-DAD-ESI-MS(n) method for the analysis of non-anthocyanin flavonoids was applied to nine different tissues of twelve lotus genotypes of Nelumbo nucifera and N. lutea, together with an optimized anthocyanin extraction and separation protocol for lotus petals. A total of five anthocyanins and twenty non-anthocyanin flavonoids was identified and quantified. Flavonoid contents and compositions varied with cultivar and tissue and were used as a basis to divide tissues into three groups characterized by kaempferol and quercetin derivatives. Influences on flower petal coloration were investigated by principal components analyses. High contents of kaempferol glycosides were detected in the petals of N. nucifera while high quercetin glycoside concentrations occurred in N. lutea. Based on these results, biosynthetic pathways leading to specific compounds in lotus tissues are deduced through metabolomic analysis of different genotypes and tissues and correlations among flavonoid compounds.