Traditional Chinese medicine invigorating the spleen and kidney promotes HBsAg seroclearance in the mouse model.

Traditional Chinese medicine (TCM) is often used as an adjuvant or alternative therapy for abnormal liver biochemistry or liver fibrosis associated with chronic hepatitis B (CHB). However, the role of TCM in HBsAg seroclearance remains unclear. We aimed at exploring the role and possible mechanisms of TCM in HBsAg seroclearance. Fifteen widely used TCM granules invigorating the spleen and kidneys were screened. C57BL/6J mice were administered daily with TCM granules by gavage for 1 week. The effect of TCM on the M1 polarization of macrophages was measured using a CD86 assay. According to the principles of formulating prescriptions, three single TCM with the most noticeable effect on M1 polarization, accompanied by two other TCM granules, were used to develop a TCM formula. The hepatitis B virus-expressing mouse model was constructed by hydrodynamic injection of the pAAV/HBV1.2 plasmid. Hepatitis B virus-expressing mice were gavaged daily with phosphate-buffered saline (PBS), TCM formula, or Codonopsis Radix, for 1 week. HBsAg, HBeAg, and hepatitis B virus DNA levels were measured. In addition, gut microbiota was profiled using 16S rDNA sequencing. Several TCM granules showed significant effects on M1 polarization. The TCM formula accelerated HBsAg seroclearance compared with the Codonopsis Radix and PBS groups. Intrahepatic M1 polarization, as indicated by flow cytometry and immunohistochemistry, was induced in the TCM formula and Codonopsis Radix groups. The abundance of Alloprevotella significantly increased in the TCM formula and Codonopsis Radix groups. These results demonstrate that the TCM formula for invigorating the spleen and kidney can accelerate HBsAg seroclearance. This effect can be attributed, at least in part, to M1 polarization of intrahepatic macrophages.

Natural Products-Based Botanical Bactericides Discovery: Novel Abietic Acid Derivatives as Anti-Virulence Agents for Plant Disease Management.

The discovery of natural product-based pesticides is critical for agriculture. In this work, a series of novel tricyclic diterpenoid derivatives decorated with an amino alcohol moiety were elaborately prepared from natural abietic acid, and their antibacterial behavior was explored. Bioassay results indicated that compound C2 exhibited the most promising bioactivity (EC50 = 0.555 µg mL-1) against Xanthomonas oryzae pv. oryzae (Xoo), about 73 times higher than the effect of commercial thiodiazole copper (TC). Results of in vivo bioassays showed that compound C2 displayed significantly higher control of rice bacterial leaf blight (curative activity: 63.8%; protective activity: 58.4%) than TC (curative activity: 43.6%; protective activity: 40.8%), and their bioactivity could be improved maximally 16% by supplementing the auxiliaries. Antibacterial behavior suggested that compound C2 could suppress various virulence factors. Overall, these findings suggested that new botanical bactericide candidates could control intractable plant bacterial diseases by suppressing virulence factors.

Yeast Culture Improves Egg Quality and Reproductive Performance of Aged Breeder Layers by Regulating Gut Microbes.

This study aimed to investigate the effects of dietary yeast culture (YC) supplementation on egg production, egg quality, reproductive performance, immune functions, antioxidant capacity, and intestinal microbial structure of aged hens. A total of 224 Hy-Line Brown layers (54 weeks old) were randomly assigned to two dietary treatments. The control group was fed a basal diet and the YC group was supplemented with YC at 2.0 g/kg of their diet. Each group had seven replicates with 16 hens each. The study was conducted over a period of 8 weeks. Results indicated that YC addition had no significant effect on laying performance. However, it significantly improved egg quality and hatching rate, enhanced ileum crude fat digestibility, increased the serum parameters of lysozyme (LZM) and total antioxidation capacity (T-AOC) (P < 0.05), and reduced serum aspartate aminotransferase (AST) levels (P < 0.05). Using 16S rRNA analysis, we found that addition of YC significantly altered ileum microbial composition. Linear discriminant analysis of effect size (LEfSe) showed significant enrichment of Bacilli and Lactobacilli in the YC group. PICRUSt analysis of the ileal microbiota found that glutathione metabolism, ubiquinone, and other terpenoid-quinone biosynthesis and lipopolysaccharide biosynthesis protein pathways were highly enriched in the YC group compared with the basal diet group. In summary, the addition of YC can improve egg quality, immune functions, antioxidant capacity, reproduction efficiency, and digestive absorption by increasing the abundance of Lactobacilli and Bacilli. Furthermore, it also improves the biosynthesis of lipopolysaccharide proteins, glutathione metabolism, and the synthesis of ubiquinone and other terpenoid-quinone metabolic pathways.

Targeting adenosinergic pathway enhances the anti-tumor efficacy of sorafenib in hepatocellular carcinoma.

BACKGROUND: Sorafenib is the most widely used first-line treatment for patients with advanced hepatocellular carcinoma (HCC), but such treatment provides only limited survival benefits that might be related to the immune status of distinct tumor microenvironments. A fundamental understanding of the distribution and phenotypes of T lymphocytes in tumors will undoubtedly lead to the development of novel immunotherapeutic strategies that could possibly enhance the efficacy of sorafenib treatments. METHODS: Flow cytometry, immunohistochemistry and immunofluorescence analyses were performed to detect the infiltration and distribution of various leukocyte populations, and the expression of different immune checkpoint molecules in fresh HCC tumor tissues. Correlations among indicating genes were calculated in 365 patients with HCC from The Cancer Genome Atlas (TCGA) data set, and the cumulative overall survival time was calculated using the Kaplan-Meier method. Moreover, role of adenosinergic pathway on sorafenib anti-tumor efficacy was investigated using both subcutaneous and orthotopic transplantation tumor model in immune competent C57BL/6 mice. RESULTS: We revealed that levels of CD3+ and CD8+ T cells were significantly downregulated in HCC tumor tissue, so were the infiltration of CD169+ cells (a Mφ subpopulation with T cell activation capacities) and their contact with CD8+ cells in tumor milieus. Moreover, levels of PD-1 and CD39 expression were significantly upregulated in human HCC-infiltrating CD4+ and CD8+ T cells, and CD39+CD8+ T cells exhibited a CD69+PD-1+perforinlowIFNγlow "exhausted" phenotype. Levels of both CD39+ T cells infiltration and adenosine receptor ADORA2B expression in tumor tissues were negatively correlated with overall survival of patients with HCC. Accordingly, mice treated with sorafenib in combination with adenosine A2B receptor blockage reagents exhibited significantly reduced tumor progression compared with control groups. CONCLUSIONS: These results suggest that adenosinergic pathway might represent an applicable target for sorafenib-combined-therapies in human HCC.

Polysaccharide extracts of Astragalus membranaceus and Atractylodes macrocephala promote intestinal epithelial cell migration by activating the polyamine-mediated K+ channel.

Astragalus membranaceus (Radix Astragali, RA) and Atractylodes macrocephala (Rhizoma Atractylodis Macrocephalae, RAM) are often used to treat gastrointestinal diseases. In the present study, we determined the effects of polysaccharides extracts from these two herbs on IEC-6 cell migration and explored the potential underlying mechanisms. A migration model with IEC-6 cells was induced using a single-edged razor blade along the diameter of cell layers in six-well polystyrene plates. The cells were grown in control media or media containing spermidine (5 µmol·L-1, SPD), alpha-difluoromethylornithine (2.5 mmol·L-1, DFMO), 4-Aminopyridine (40 µmol·L-1, 4-AP), the polysaccharide extracts of RA or RAM (50, 100, or 200 mg·L-1), DFMO plus SPD, or DFMO plus polysaccharide extracts of RA or RAM for 12 or 24 h. Next, cytosolic free Ca2+ ([Ca2+]cyt) was measured using laser confocal microscopy, and cellular polyamine content was quantified with HPLC. Kv1.1 mRNA expression was assessed using RT-qPCR and Kv1.1 and RhoA protein expressions were measured with Western blotting analysis. A cell migration assay was carried out using Image-Pro Plus software. In addition, GC-MS was introduced to analyze the monosaccharide composition of both polysaccharide extracts. The resutls showed that treatment with polysaccharide extracts of RA or RAM significantly increased cellular polyamine content, elevated [Ca2+]cyt and accelerated migration of IEC-6 cells, compared with the controls (P < 0.01). Polysaccharide extracts not only reversed the inhibitory effects of DFMO on cellular polyamine content and [Ca2+]cyt, but also restored IEC-6 cell migration to control level (P < 0.01 or < 0.05). Kv1.1 mRNA and protein expressions were increased (P < 0.05) after polysaccharide extract treatment in polyamine-deficient IEC-6 cells and RhoA protein expression was increased. Molar ratios of D-ribose, D-arabinose, L-rhamnose, D-mannose, D-glucose, and D-galactose was 1.0 : 14.1 : 0.3 : 19.9 : 181.3 : 6.3 in RA and 1.0 : 4.3 : 0.1 : 5.7 : 2.8 : 2.2 in RAM. In conclusion, treatment with RA and RAM polysaccharide extracts stimulated migration of intestinal epithelial cells via a polyamine-Kv1.1 channel activated signaling pathway, which facilitated intestinal injury healing.

Thermo-responsive magnetic liposomes for hyperthermia-triggered local drug delivery.

We prepared and characterised thermo-responsive magnetic liposomes, which were designed to combine features of magnetic targeting and thermo-responsive control release for hyperthermia-triggered local drug delivery. The particle size and zeta-potential of the thermo-responsive magnetic ammonium bicarbonate (MagABC) liposomes were about 210 nm and -14 mV, respectively. The MagABC liposomes showed encapsulation efficiencies of about 15% and 82% for magnetic nanoparticles (mean crystallite size 12 nm) and doxorubicin (DOX), respectively. The morphology of the MagABC liposomes was visualised using transmission electron microscope (TEM). The MagABC liposomes showed desired thermo-responsive release. The MagABC liposomes, when physically targeted to tumour cells in culture by a permanent magnetic field yielded a substantial increase in intracellular accumulation of DOX as compared to non-magnetic ammonium bicarbonate (ABC) liposomes. This resulted in a parallel increase in cytotoxicity for DOX loaded MagABC liposomes over DOX loaded ABC liposomes in tumour cells.

[Comparative Study on Effects of Anti-contusion Injury, Analgesia and Anti-inflammation of Root and Stem of Zanthoxylum nitidum].

OBJECTIVE: To provide the scientific evidence for expansion of medicinal parts of Zanthoxylum nitidum by comparing the effects of anti-contusion injury, analgesia and anti-inflammation of its root and stem. METHODS: The pharmacological effects between root and stem of Zanthoxylum nitidum were compared by observing the anti-injury effect in rats with injury struck by hammer. The analgesic effect in mice was evaluated by writhing test and hot plate test, and the anti-inflammatory effect on paw edema induced by carrageenan and granuloma induced by cotton pellet were investigated in rats. RESULTS: Both root and stem of Zanthoxylum nitidum relieved the exterior and histological symptoms of rats' injury legs struck by hammer, decreased the numbers of mice's writhing, enhanced pain threshold of mice on heat plate, inhibited the edema of rats induced by carrageenan, and suppressed the granuloma of rats induced by cotton pellet. CONCLUSION: Stem of Zanthoxylum nitidum has similar effects of anti-contusion injury, analgesia and anti-inflammation with root of Zanthoxylum nitidum.

Data analysis of iodine level in iodized salt from monitoring sites in Tibet in 2008 / 中国地方病学杂志

Objective To know the quality of iodized salt and the current situation of the salt coverage in Tibet,and to provide scientific basis for proposing proper prevention and control measures to Iodine dificiency disorders(IDD). Methods In 2008, according to the "Sampling Methods of the Main Products in the Salt Industry",one batch fifteen salt samples were collected in iodized salt processing factory in Tibet. Five townships were chosen in each county based on 5 different directions of east, south, west, north and center. If the monitoring county has less than five townships, then all of the townships were sampled. In each township, four villages were selected withrandom sampling and importance sampling. In each township, 15 households were selected for salt collection. Results A batch of 15 salt samples in a salt processing plant were tested, and all of them were qualified with salt iodine(34.6±1.58) mg/kg. A total of 21 107 edible salt samples were tested, and 11 203 of them were qualified iodized salt. These results meant that the provincial iodized salt coverage rate was 53.08%. Shannan iodized salt coverage rate was 94.31% (3395/3600) which was the highest in Tibet. Those of Nagqu, Changdu, Ngari were lower, they were 29.84% (897/3006), 24.94% (823/3300) and 17.08% (205/1200), respectively. Conclusions The quality of iodized salt in Tibet is up to the national standard, but the coverage rate of iodized salt is very low.We suggest that the strategy should be carried out according to the national overall program strategy and supplement iodized oil capsule for special groups.