Ginkgo biloba extract ameliorates hyperglycaemia-induced enteric glial cell injury via regulation of the TLR2-related pathway.

BACKGROUND: Diabetic gastrointestinal dysfunction (DGD) is a common complication in diabetic patients, and enteric glial cells (EGCs) found in the gastrointestinal tract have been shown to play an essential role in gastrointestinal dysfunction. Thus, targeting EGCs may be helpful for the control of DGD. This study aimed to evaluate the protective effect of Ginkgo biloba extract (GBE) from G. biloba dropping pills against hyperglycaemic stress-induced EGCs injury and its underlying mechanism. METHODS: In vitro, the protective effect of GBE on CRL-2690 cells was evaluated by MTT assay and TUNEL assay. The expression of related markers was evaluated by RNA sequencing and validated by using western blotting. In vivo, STZ-induced C57BL/6J WT mice were used as models to evaluate the effects of GBE on blood glucose, body weight, and EGCs' activity and relevant signalling pathways were validated by immunofluorescence. RESULTS: The results showed that GBE (25 µg/ml) treatment significantly attenuated hyperglycaemic stress-induced cytotoxicity and cell apoptosis in CRL-2690 cells, which was verified in an STZ-induced (100 mg/kg, 3 days) diabetic mouse model with continuous GBE administration (25/100 mg/kg/day, 6/12 weeks). Further mechanistic study based on transcriptomic data revealed that GBE exerted its beneficial effect by regulating immune-related pathways, and TLR2/BTK/NF-κB/IL-1α/IL-10 comprised the main targets of this drug. CONCLUSIONS: This study demonstrates the protective effect of GBE against hyperglycaemic stress-induced EGCs injury using both in vitro and in vivo models and further reveals that the effect was achieved by targeting TLR2 and its downstream molecules BTK/NF-κB/IL-1α/IL-10. This study may be helpful for expanding the clinical application of GBE in treating DGD.

Allometry of bud dynamic pattern and linkage between bud traits and ecological stoichiometry of Nitraria tangutorum under fertilizer addition.

Affected by the pressure and constraints of available resources, plant growth and development, as well as plant life history strategies, usually vary with environmental conditions. Plant buds play a crucial role in the life history of woody plants. Nitraria tangutorum is a common dominant woody species in desertified areas of northern China and its growth is critical to the desert ecosystem. Revealing the allometry of N. tangutorum aboveground bud fates and the linkage between bud traits and plant nutrient contents and stoichiometric ratios can be useful in understanding plant adaptation strategy. We applied seven nitrogen and phosphorus fertilizer addition treatments to natural N. tangutorum ramets in Ulan Buh Desert in three consecutive years. We surveyed three types of aboveground buds (dormant buds, vegetative buds, and reproductive buds) in each N. tangutorum ramet, then measured the plant carbon (C), nitrogen (N), and phosphorus (P) contents and ratios during three consecutive years. We specified that reserve growth potential (RGP), vegetative growth intensity (VGI) and sexual reproduction effort (SRE) are the three indices of bud dynamic pattern. The results showed that the bud dynamic pattern of N. tangutorum ramets differed significantly among different fertilizer addition treatments and sampling years. The allometry of RGP, VGI, and SRE was obvious, showing size dependence. The allometric growth relationship fluctuated among the sampling years. The linkage between bud traits and plant stoichiometric characteristics of N. tangutorum ramets showed close correlation with plant P content, C:P and N:P ratios, no significant correlation with plant C content, N content and C:N ratio. These results contribute to an improved understanding of the adaptive strategies of woody plants growing in desert ecosystems and provide insights for adoption of effective measures to restore and conserve plant communities in arid and semi-arid regions.

Xanthine dehydrogenase rewires metabolism and the survival of nutrient deprived lung adenocarcinoma cells by facilitating UPR and autophagic degradation.

Xanthine dehydrogenase (XDH) is the rate-limiting enzyme in purine catabolism by converting hypoxanthine to xanthine and xanthine to uric acid. The altered expression and activity of XDH are associated with the development and prognosis of multiple types of cancer, while its role in lung adenocarcinoma (LUAD) remains unknown. Herein, we demonstrated that XDH was highly expressed in LUAD and was significantly correlated with poor prognosis. Though inhibition of XDH displayed moderate effect on the viability of LUAD cells cultured in the complete medium, it significantly attenuated the survival of starved cells. Similar results were obtained in XDH-knockout cells. Nucleosides supplementation rescued the survival of starved LUAD cells upon XDH inhibition, while inhibition of purine nucleoside phosphorylase abrogated the process, indicating that nucleoside degradation is required for the XDH-mediated survival of LUAD cells. Accordingly, metabolic flux revealed that ribose derived from nucleoside fueled key carbon metabolic pathways to sustain the survival of starved LUAD cells. Mechanistically, down-regulation of XDH suppressed unfolded protein response (UPR) and autophagic flux in starved LUAD cells. Inhibition of XDH decreased the level of amino acids produced by autophagic degradation, which was accompanied with down-regulation of mTORC1 signaling. Supplementation of amino acids including glutamine or glutamate rescued the survival of starved LUAD cells upon knockout or inhibition of XDH. Finally, XDH inhibitors potentiated the anti-cancer activity of 2-deoxy-D-glucose that induced UPR and/or autophagy in vitro and in vivo. In summary, XDH plays a crucial role in the survival of starved LUAD cells and targeting XDH may improve the efficacy of drugs that induce UPR and autophagy in the therapy of LUAD.

New triterpenoids from the Cyclocarya paliurus (Batalin) Iljinskaja and their anti-fibrotic activity.

Cyclocarya paliurus, a Chinese herbal medicine and new food resource, contains a triterpenic-acid-rich extract that demonstrated ameliorative effect on diabetic nephropathy (DN). A more in-depth discovery of functional components led to the isolation of seven new triterpenoids including two pentacyclic triterpenes, 1α,2α,3ß,23-tetrahydroxyolean-12-en-28-oic acid and 2α,3ß,22α-tirhydroxyurs-12-en-28-oic acid 28-O-ß-D-glucopyranoside, and five tetracyclic triterpenoid glycosides (cypaliurusides N-R), together with twelve known compounds from the leaves of C. paliurus. Their structures were determined using a comprehensive analysis of chemical and spectroscopic data. Partial compounds were assessed for anti-fibrotic activities in high-glucose and TGF-ß1 induced HK-2 cells. Compound 16 remarkably decreased the level of fibronectin with an inhibition rate of 37.1%. Furthermore, 16 effectively alleviated the epithelial-mesenchymal transformation (EMT) process by upregulating E-cadherin expression and downregulating α-SMA expression, and it significantly decreased the level of the transcriptional inhibitors (Snail and Twist) of E-cadherin. The discovery of anti-fibrotic compounds from C. paliurus provides the potential utilization and functional candidates for the DN prevention.

Two new triterpenoids from the leaves of Cyclocarya paliurus (Batalin) Iljinskaja.

Two previously undescribed triterpenoids (1-2), along with thirteen known compounds (3-15) were isolated from a CHCl3-soluble extract of the leaves of Cyclocarya paliurus. Their structures were established on the basis of chemical and spectroscopic approaches. These compounds were assessed for their therapeutic effects on diabetic nephropathy (DN)-evoked fibrosis through High-Glucose and transforming growth factor-ß1 (TGF-ß1) challenged HK-2 cells. Among them, compounds 3, 5 and 8 could remarkedly decrease the level of fibronectin to relieve DN with 27.66 ± 2.77%, 6.09 ± 0.57% and 17.74 ± 5.83% inhibition rate at 10 µM, 10 µM and 1 µM, respectively.

All-trans retinoic acid plus high-dose dexamethasone as first-line treatment for patients with newly diagnosed immune thrombocytopenia: a multicentre, open-label, randomised, controlled, phase 2 trial.

BACKGROUND: High-dose dexamethasone is the standard initial treatment for patients with immune thrombocytopenia, but many patients still relapse and require further treatments. All-trans retinoic acid has been shown to exert immunomodulatory effects and promote thrombopoiesis, and so we aimed to assess the activity and safety of all-trans retinoic acid plus high-dose dexamethasone as a first-line treatment for newly diagnosed patients with immune thrombocytopenia. METHODS: This multicentre, open-label, randomised, controlled, phase 2 trial was done at six different tertiary medical centres in China. Eligible participants were adults (aged >18 years) with treatment-naive, newly diagnosed, primary immune thrombocytopenia who had either a platelet count of less than 30 × 109 platelets per L or a platelet count of less than 50 × 109 platelets per L and clinically significant bleeding. We randomly assigned (1:1) participants to receive either all-trans retinoic acid (10 mg orally twice daily for 12 weeks) plus high-dose dexamethasone (40 mg/day intravenously for 4 consecutive days) or high-dose dexamethasone alone using a central, web-based randomisation system. If patients did not respond by day 14, the 4-day course of dexamethasone was repeated. The primary endpoint was 6-month sustained response, defined as the maintenance of a platelet count of at least 30 × 109 platelets per L and at least 2-times higher than the baseline count and the absence of bleeding, with no need for rescue medication at this time. The primary endpoint was analysed by intention-to-treat and safety was assessed in all participants who received at least one dose of the study drug. This trial is registered with ClinicalTrials.gov, NCT04217148, and is now completed. FINDINGS: Between Jan 1, 2020, and June 30, 2020, 132 patients were randomly assigned to either all-trans retinoic acid plus high-dose dexamethasone (n=66) or high-dose dexamethasone alone (n=66). Three patients did not receive their allocated treatment, leaving 129 in the safety analysis set. At 6 months, a significantly higher proportion of participants in the all-trans retinoic acid plus high-dose dexamethasone group (45 [68%] of 66) than in the high-dose dexamethasone monotherapy group (27 [41%] of 66) had a sustained response (OR 3·095, 95% CI 1·516-6·318; p=0·0017). The most common adverse events were dry skin (31 [48%] of 64 patients), headaches (12 [19%]), and insomnia (12 [19%]) in the combination group, and insomnia (ten [15%] of 65 patients) and anxiety or mood disorders (eight [12%]) in the monotherapy group. Both treatments were well tolerated and no grade 4 or worse adverse events occurred. There were no treatment-related deaths. INTERPRETATION: The combination of all-trans retinoic acid and high-dose dexamethasone was safe and active in newly diagnosed patients with primary immune thrombocytopenia, providing a sustained response. This regimen represents a potential first-line treatment in this setting, but further studies are needed to validate its efficacy and safety. FUNDING: The Beijing Municipal Science and Technology Commission, the National Natural Science Foundation of China, the Beijing Natural Science Foundation, the National Key Research and Development Program of China, and the Foundation for Innovative Research Groups of the National Natural Science Foundation of China.

Saponins from Panax japonicus attenuate cognitive impairment in ageing rats through regulating microglial polarisation and autophagy.

CONTEXT: Panax japonicus is the dried rhizome of Panax japonicus C.A. Mey. (Araliaceae). Saponins from Panax japonicus (SPJ) exhibit anti-inflammatory and antioxidative effects. OBJECTIVE: To explore the neuroprotective effect of SPJ on natural ageing of rat. MATERIALS AND METHODS: Sprague-Dawley (SD) rats 18-month-old were divided into ageing control, ageing treated with SPJ 10 or 30 mg/kg (n = 8). Five-month-old rats were taken as the adult control (n = 8). Rats were fed regular feed or feed containing SPJ for 4 months. Cognitive level was evaluated by Morris water maze (MWM) test. The mechanisms of SPJ's neuroprotection were evaluated by transmission electron microscope, western blot analysis, and immunofluorescence in vivo and in vitro. RESULTS: SPJ attenuated ageing-induced cognitive impairment as indicated by elevated number of times crossing the target platform (from 1.63 to 3.5) and longer time spent in the target platform quadrant (from 1.33 to 1.98). Meanwhile, SPJ improved the morphology of microglia and synapse, and activated M2 microglia polarisation including increased hippocampus levels of CD206 (from 0.98 to 1.47) and YM-1 (from 0.67 to 1.1), and enhanced autophagy-related proteins LC3B (from 0.48 to 0.82), Beclin1 (from 0.32 to 0.51), Atg5 (from 0.22 to 0.89) whereas decreased p62 level (from 0.71 to 0.45) of ageing rats. In vitro study also showed that SPJ regulated the microglial polarisation and autophagy. DISCUSSION AND CONCLUSIONS: SPJ improved cognitive deficits of ageing rats through attenuating microglial inflammation and enhancing microglial autophagy, which could be used to treat neurodegenerative disorders.

Quality analysis of Citri Trifoliatae Fructus in different harvest time by HPLC combined with electronic eye technology / 中国中药杂志

As a local variety of medicinal material, Citri Trifoliatae Fructus is widely used in many places, whereas its harvest time remains unclear. Therefore, studying its harvest time can make more reasonable use of this medicinal material. In this study, we determined the flavonoids content and compared the color of Citri Trifoliatae Fructus harvested in different time, aiming to guide the harvest of this medicinal material. The fresh fruits of Citrus trifoliata were collected from Xinxiang city, Henan province, graded according to the diameter range, and then dried. The contents of isonaringin, naringen, and poncirin in Citri Trifoliatae Fructus were determined by HPLC, and the color values of the samples were detected by electronic eye. The correlation analysis of the obtained data was carried out to explore the relationships of color and diameter with quality. The results showed that the contents of isonaringin, naringen, and poncirin varied significantly in different harvest time, within the ranges of 0.21-1.20, 2.21-11.59, and 3.73-23.16 mg·g~(-1), respectively. With the delay of harvest time, Citri Trifoliatae Fructus showed the color changing from green to yellow, gradually increased diameter, and gradually decreased contents of isonaringin, naringen, and poncirin. The contents of isonaringin, naringen, and poncirin were negatively correlated with the degree of red and green(a~*) and positively correlated with the degree of yellow and blue(b~*). The contents of naringen and poncirin had significantly negative correlations with the diameter. This study indicates that the quality of Citri Trifoliatae Fructus can be judged by its diameter and skin color, which provides a theoretical basis for the rational harvest of this medicinal material.

Development of a Simple In Vitro Assay To Identify and Evaluate Nucleotide Analogs against SARS-CoV-2 RNA-Dependent RNA Polymerase.

Nucleotide analogs targeting viral RNA polymerase have been proved to be an effective strategy for antiviral treatment and are promising antiviral drugs to combat the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In this study, we developed a robust in vitro nonradioactive primer extension assay to quantitatively evaluate the efficiency of incorporation of nucleotide analogs by SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Our results show that many nucleotide analogs can be incorporated into RNA by SARS-CoV-2 RdRp and that the incorporation of some of them leads to chain termination. The discrimination values of nucleotide analogs over those of natural nucleotides were measured to evaluate the incorporation efficiency of nucleotide analog by SARS-CoV-2 RdRp. In agreement with the data published in the literature, we found that the incorporation efficiency of remdesivir-TP is higher than that of ATP and incorporation of remdesivir-TP caused delayed chain termination, which can be overcome by higher concentrations of the next nucleotide to be incorporated. Our data also showed that the delayed chain termination pattern caused by remdesivir-TP incorporation is different for different template sequences. Multiple incorporations of remdesivir-TP caused chain termination under our assay conditions. Incorporation of sofosbuvir-TP is very low, suggesting that sofosbuvir may not be very effective in treating SARS-CoV-2 infection. As a comparison, 2'-C-methyl-GTP can be incorporated into RNA efficiently, and the derivative of 2'-C-methyl-GTP may have therapeutic application in treating SARS-CoV-2 infection. This report provides a simple screening method that should be useful for evaluating nucleotide-based drugs targeting SARS-CoV-2 RdRp and for studying the mechanism of action of selected nucleotide analogs.

[Occurrence regularity and integrated control of leaf miner in safflower].

Leaf miner is one of the major pests on safflower, which causes yield loss and poor quality seriously. "Weihonghua", "nine safflower varieties" and "three chemical insecticides" as materials that used to evaluate variety and regularity of leaf miner, safflower resistant level, and different proportions insecticides in field efficiency test. The results showed that Liriomyza sativae and L. huidobrensis accounted for 80%, the peak period of two pests was all in July; but Phytomyza horticola is relative less, its peak period occured in June. Three were great difference of resistance to leaf miner among safflower varieties, FQ12 and YJ65 expressed higher resistibility to leaf miner by ratio method. With abamectin 2% emulsifiable concentrate diluted for 2 000 times, or the mixture three insecticides(bifenthrin 20% water emulsions, thiamethoxam 25% water dispersible granule, abamectin 2% emulsifiable concentrate=1∶1∶1) diluted for 3 000 times, which were sprayed on leaves at squaring stage and lethal rate was 96% after 48 h in the study. Through comparative study on the variety and regularity of leaf miner, screen for resistant varieties to leaf miner and for high efficiency pesticide. The study provides theoretical basis and reference for integrated pest management of leaf miner.

Autophagy in endothelial cells regulates their haematopoiesis-supporting ability.

BACKGROUND: Endothelial cells (ECs) function as an instructive platform to support haematopoietic stem cell (HSC) homeostasis. Our recent studies found that impaired bone marrow (BM) ECs are responsible for the defective haematopoiesis in patients with poor graft function (PGF), which is characterised by pancytopenia post-allotransplant. Although activated autophagy was reported to benefit ECs, whether EC autophagy plays a critical role in supporting HSCs and its effect on PGF patients post-allotransplant remain unclear. METHODS: To evaluate whether the autophagy status of ECs modulates their ability to support haematopoiesis, human umbilical vein endothelial cells (HUVECs) and primary BM ECs derived from healthy donors were subjected to knockdown or overexpression of Beclin-1 (an autophagy-related protein). Moreover, BM ECs derived from PGF patients were studied. FINDINGS: Beclin-1 knockdown significantly reduced the haematopoiesis-supporting ability of ECs by suppressing autophagy, which could be restored by activating autophagy via Beclin-1 upregulation. Moreover, autophagy positively regulated haematopoiesis-related genes in HUVECs. Subsequently, a prospective case-control study demonstrated that defective autophagy reduced Beclin-1 expression and the colony-forming unit (CFU) plating efficiency in BM ECs from PGF patients compared to matched patients with good graft function. Rapamycin, an autophagy activator, quantitatively and functionally improved BM ECs from PGF patients in vitro and enhanced their ability to support HSCs by activating the Beclin-1 pathway. INTERPRETATION: Our results suggest that the autophagy status of ECs modulates their ability to support haematopoiesis by regulating the Beclin-1 pathway. Defective autophagy in BM ECs may be involved in the pathogenesis of PGF post-allotransplant. Rapamycin provides a promising therapeutic approach for PGF patients. FUNDING: Please see funding sources.

Interactive effects of temperature and nutrients on the phytoplankton community in an urban river in China.

Understanding the relative impact sizes of environmental factors and nutrients on the high annual variation of phytoplankton abundance in eutrophic rivers is important for aquatic ecosystem management efforts. In this study, we used phytoplankton dynamic datasets in the eutrophic Fenhe River to show the variations and drivers of phytoplankton abundance under complex, fluctuating environmental conditions during 2012-2017. The temporal and spatial variations of nutrients in the river depicted that the total phosphorus (TP) concentration was higher in the wet season and in downstream. There were increases in total nitrogen (TN) concentration in the normal season and in upstream. The structural equation model (SEM) showed that the phytoplankton abundance increased during the wet season despite the decrease in the TN:TP ratio and was reduced upstream due to the highest TN:TP ratio. Among the environmental variables, water temperature (WT) was an important predictor and positively correlated temporally and spatially to phytoplankton. The interaction of nutrients with the phytoplankton community at different temperature levels indicated that different phytoplankton groups have different nutrient requirements. We can conclude that enhances in temperature and TP concentration will significantly increase phytoplankton abundance and dominance of cyanobacteria and green algae in the future, whereas there was insignificant effect on diatoms. These data indicated that temperature and TP content were the important abiotic factors influencing the phytoplankton growth of the water body, which could provide a reference for the evaluation of environmental alterations in the future.

Supercritical fluid CO2 extraction of three polymethoxyflavones from Citri reticulatae pericarpium and subsequent preparative separation by continuous high-speed counter-current chromatography.

Polymethoxyflavones (PMFs) are widely found in Citri Reticulatae Pericarpium (CRP) and have been investigated with a broad spectrum of biological activities as well as health promoting properties. However, separation of the PMFs from a complex sample, especially preparative separation of these PMFs with high purity, remains challenging. In the present study, an efficient method based on supercritical fluid extraction (SFE) and continuous high-speed counter-current chromatography (HSCCC) has been developed for extracting and preparative purification PMFs from CRP. Various experimental conditions were investigated to optimize the SFE and HSCCC processes. Under these optimized conditions, crude extract of CRP (extract I) was obtained with a maximum contents of nobiletin, 3,5,6,7,8,3',4'-heptamethoxyflavone and tangeretin. Further extraction of crude extract I was carried out to obtain crude extract II, which was further isolated and purified by HSCCC. It was worth mentioned that continuous injection HSCCC process were realized without lost of separation efficiency, which allowed for multiple purification cycles and therefore saved a lot of labor and time. Furthermore, high-performance liquid chromatography (HPLC) was employed to analyze the fractions separated by HSCCC, which revealed that the purities of the three PMFs were all above 98%. The structures of the three PMFs were identified by LC-MS and 1H NMR spectroscopy.

[Research on regional distribution and industrial status analysis of genuine medicinal resources of flowers in Henan province].

Flower medicinal materials usually refer to Chinese medicinal materials with a complete flower,inflorescence,or part of a flower as the different medicinal parts,they have an important share in the Chinese herbal medicine market and appeared frequently in Chinese medicine prescriptions. Firstly,the species and regional distribution of the flower medicinal materials resources in China were briefly summarized. Secondly,the characteristics,yield,producing area and origin distribution of the main flower medicinal materials in Henan province were discussed. Finally,the present situation and the main problems of the flower medicinal materials industry in Henan province were comprehensively analyzed,and the corresponding industrial development countermeasures were put forward.This research was intended to provide decision-making demonstration and scientific basis for the rational exploitation and utilization of resources,breeding of new varieties,planting division,production layout and the healthy and sustainable development of the flower medicinal materials industry in Henan province.

A systematic review and a dose-response meta-analysis of coffee dose and nonalcoholic fatty liver disease.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is the most predominant chronic liver disease worldwide. Effect of coffee on NAFLD risk and its potential dose-response patterns were explored in the study. DESIGN: PubMed, Web of Science, MEDLINE, Cochrane and Embase were searched up to 10 April 2018. We performed pair-wise meta-analysis of <1 cup per day vs. 1-2 cups per days or >2 cups per day to pool the relative risks (RRs) and corresponding 95% confidence intervals (CIs). And dose-response analysis was used to estimate relationship of NAFLD occurrence with coffee intake. RESULTS: Seven articles were included with 4825 cases and 49,616 non-cases. Compared with <1 cup, 1-2 cups or >2 cups of coffee consumption per day were not significantly associated with NAFLD occurrence, and RR were 0.97 (95% CI: 0.85-1.11) and 0.88 (95%CI: 0.72-1.06). However, the summary RR of the highest versus lowest coffee consumption was 0.94 (95% CI: 0.92-0.97). Dose-response meta-analysis presented a non-linearity curve relationship of coffee and NAFLD occurrence while coffee consumption >3 cups per day reduced NAFLD significantly. CONCLUSION: Coffee intake level more than 3 cups was observed lower risk of NAFLD than <2 cups per day. Although the risk of NAFLD was inversely associated with coffee consumption, while relevance may not be very close and more observational studies would be needed to verify the relationship of coffee and NAFLD.

A Novel Human Papillomavirus 16 L1 Pentamer-Loaded Hybrid Particles Vaccine System: Influence of Size on Immune Responses.

Cervical cancer remains the second-most prevalent female malignancy around the world, leading to a great majority of cancer-related mortality that occurs mainly in developing countries. Developing an effective and low-cost vaccine against human papillomavirus (HPV) infection, especially in medically underfunded areas, is urgent. Compared with vaccines based on HPV L1 viruslike particles (VLPs) in the market, recombinant HPV L1 pentamer expressed in Escherichia coli represents a promising and potentially cost-effective vaccine for preventing HPV infection. Hybrid particles comprising a polymer core and lipid shell have shown great potential compared to conventional aluminum salts adjuvant and is urgently needed for HPV L1 pentamer vaccines. It is well-reported that particle sizes are crucial in regulating immune responses. Nevertheless, reports on the relationship between the particulate size and the resultant immune response have been in conflict, and there is no answer to how the size of particles regulates specific immune response for HPV L1 pentamer-based candidate vaccines. Here, we fabricated HPV 16 L1 pentamer-loaded poly(d,l-lactide- co-glycolide) (PLGA)/lecithin hybrid particles with uniform sizes (0.3, 1, and 3 µm) and investigated the particle size effects on antigen release, activation of lymphocytes, dendritic cells (DCs) activation and maturation, follicular helper CD4+ T (TFH) cells differentiation, and release of pro-inflammatory cytokines and chemokines. Compared with the other particle sizes, 1 µm particles induced more powerful antibody protection and yielded more persistent antibody responses, as well as more heightened anamnestic responses upon repeat vaccination. The superior immune responses might be attributed to sustainable antigen release and robust antigen uptake and transport and then further promoted a series of cascade reactions, including enhanced DCs maturation, increased lymphocytes activation, and augmented TFH cells differentiation in draining lymph nodes (DLNs). Here, a powerful and economical platform for HPV vaccine and a comprehensive understanding of particle size effect on immune responses for HPV L1 pentamer-based candidate vaccines are provided.

[Effect of fluidized bed technology on micromeritics properties of Leonurus Herba extract].

Based on different binders, the Leonurus Herba extract powders were fluidized and modified. The physical properties such as hygroscopicity, flowability, filling property and compression property were studied by various micromeritics methods before and after modification. The results showed that the physical properties of Leonurus Herba extract were close to those of microcrystalline cellulose, and its comprehensive flow index was between 61-75. Fluidization process can improve hygroscopicity, so the moisture absorption indexes of the samples were significantly lower than those of the original Leonurus Herba extract samples. With the plastic constant, compression ratio and yield stress, Heckel equation and Kawakita equation as the the investigation indicators, results showed that fluidization process based on binder water was superior to other methods in increasing the compressibility of the extracts. In low and medium pressure, the fluidized and modified extract can form the tablets with a certain strength. Fluidized transformation had a greater influence on the properties of original Leonurus Herba extracts, which was instructive to guide significance for the surface modification of pharmaceutical powders and provide the basis for the development of extract tablet.

Sodium butyrate ameliorates S100/FCA-induced autoimmune hepatitis through regulation of intestinal tight junction and toll-like receptor 4 signaling pathway.

BACKGROUND AND AIM: Recent investigation revealed that dysbiosis in the gut flora and disruption of permeability of intestinal barrier are possible causes for the development of autoimmune hepatitis. Supplementation of sodium butyrate has been suggested to protect liver injury from disrupted permeability of small intestine. In current study, we employed S100/Freund's complete adjuvant induced autoimmune hepatitis to investigate therapeutic efficacy of sodium butyrate and its mechanism in the liver and upper small intestine. METHODS: C57BL/6 mice were employed and divided into three groups - control group (n=8), autoimmune hepatitis group (n=12) and autoimmune hepatitis with treatment of sodium butyrate group (n=12). Histological staining and western blot analyses were employed to evaluate liver and upper small intestine morphology and gene expression respectively. RESULTS: The findings revealed that S100/Freund's complete adjuvant caused liver injury and disruption of upper small intestine villi. Sodium butyrate attenuated the injuries and prevented migration of Escherichia coli into the liver. Moreover, the effect of sodium butyrate on protection of injuries of the liver and upper small intestine could be due to inhibition of toll-like receptor 4 signaling pathway, as well as its down-regulation of inflammatory cytokines - interleukin-6 and tumor necrosis factor-a. CONCLUSIONS: Sodium butyrate can prevent liver injury by maintaining the integrity of small intestine and inhibiting inflammatory response in S100/Freund's complete adjuvant induced autoimmune hepatitis.

Triterpenoids from Cyclocarya paliurus and their inhibitory effect on the secretion of apoliprotein B48 in Caco-2 cells.

Five previously undescribed compounds including two triterpenoid aglycones, 3ß,23-dihydroxy-1,12-dioxo-olean-28-oic acid and 3ß,23,27-trihydroxy-1-oxo-olean-12-ene-28-oic acid, and three triterpenoid glucosides cyclocarioside L-N, along with 17 known compounds were isolated from a CH3Cl-soluble extract of the leaves of Cyclocarya paliurus. Two 27-nor-triterpenoid glycosides were isolated from the genus for the first time. Furthermore, the characterized compounds were tested for the inhibitory effects on apoliprotein B48 secretion in Caco-2 cells. Seven triterpenoid aglycones together with four triterpenoid saponins significantly decreased the apoliprotein B48 oversecretion induced by oleic acid in Caco-2 cells.