[Mechanism of Xinshubao Tablets in exerting anti-inflammatory, vasodilation, and cardioprotective effects based on network pharmacology].

This study aims to explore the anti-inflammatory, vasodilation, and cardioprotective effects of the intestinal absorption liquids containing Xinshubao Tablets or single herbs, and to elucidate the potential mechanism based on network pharmacology. Western blot was then conducted to validate the expression changes of core proteins. Lipopolysaccharide(LPS)-stimulated RAW264.7 cells were used to observe the anti-inflammatory effect. The vasodilation activity was examined by the microvessel relaxation assay in vitro. Oxygen-glucose deprivation(OGD)-induced H9c2 cells were used to investigate the cardioprotective effect. The chemical components were retrieved from Herb databases and composition of Xinshubao Tablets drug-containing intestinal absorption solution. Drug targets were retrieved from SwissTargetPrediction databases. GeneCards was searched for the targets associated with the anti-inflammatory, vasodilation, and cardioprotective effects. The common targets shared by the drug and the effects were used to establish the protein-protein interaction(PPI) network, from which the core targets were obtained. Finally, the core targets were imported into Cytoscape 3.9.1 for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses. The anti-inflammatory experiment showed that both Xinshubao Tablets and the single herbs constituting this formula had anti-inflammatory effects. Curcumae Radix had the strongest inhibitory effect on the production of tumor necrosis factor-α(TNF-α), and Salviae Miltiorrhizae Radix et Rhizoma had the strongest inhibitory effect on the generation of interleukin-6(IL-6). Xinshubao Tablets, Curcumae Radix, and Crataegi Fructus had vasodilation effect, and Crataegi Fructus had the strongest effect. Xinshubao Tablets, Salviae Miltiorrhizae Radix et Rhizoma, Acanthopanacis Senticosi Radix et Rhizoma seu Caulis, and Paeoniae Radix Alba had cardioprotective effects, and Salviae Miltiorrhizae Radix et Rhizoma had the strongest cardioprotective effect. Network pharmacology results demonstrated that except the whole formula, Salviae Miltiorrhizae Radix et Rhizoma had the most components with anti-inflammatory effect, and Curcumae Radix had the most components with vasodilation and cardioprotective effects, followed by Salviae Miltiorrhizae Radix et Rhizoma. The nitric oxide synthase 3(NOS3) was predicted as the core target for the anti-inflammatory, vasodilation, and cardioprotective effects. Western blot results showed that Xinshubao Tablets significantly up-regulated the expression of NOS3 in OGD-induced H9c2 cells. GO enrichment analysis showed that the effects were mainly related to lipid exported from cell, regulation of blood pressure, and inflammatory response. KEGG pathway enrichment predicted AGE-RAGE and HIF-1 signaling pathways as the key pathways.

Effect the accumulation of bioactive constituents of a medicinal plant (Salvia Miltiorrhiza Bge.) by arbuscular mycorrhizal fungi community.

BACKGROUND: Arbuscular mycorrhizal fungi (AMF) form symbiotic relationships with various terrestrial plants and have attracted considerable interest as biofertilizers for improving the quality and yield of medicinal plants. Despite the widespread distribution of AMFs in Salvia miltiorrhiza Bunge's roots, research on the impact of multiple AMFs on biomass and active ingredient accumulations has not been conducted. In this study, the effects of five native AMFs (Glomus formosanum, Septoglomus constrictum, Rhizophagus manihotis, Acaulospora laevis, and Ambispora gerdemannii) and twenty-six communities on the root biomass and active ingredient concentrations of S. miltiorrhiza were assessed using the total factor design method. RESULTS: Thirty-one treatment groups formed symbiotic relationships with S. miltiorrhiza based on the pot culture results, and the colonization rate ranged from 54.83% to 89.97%. AMF communities had higher colonization rates and total phenolic acid concentration than single AMF, and communities also appeared to have higher root fresh weight, dry weight, and total phenolic acid concentration than single inoculations. As AMF richness increased, there was a rising trend in root biomass and total tanshinone accumulations (ATTS), while total phenolic acid accumulations (ATP) showed a decreasing trend. This suggests that plant productivity was influenced by the AMF richness, with higher inoculation benefits observed when the communities contained three or four AMFs. Additionally, the affinities of AMF members were also connected to plant productivity. The inoculation effect of closely related AMFs within the same family, such as G. formosanum, S. constrictum, and R. manihotis, consistently yielded lower than that of mono-inoculation when any combinations were applied. The co-inoculation of S. miltiorrhiza with nearby or distant AMFs from two families, such as G. formosanum, R. manihotis, and Ac. laevis or Am. gerdemannii resulted in an increase of ATP and ATTS by more than 50%. AMF communities appear to be more beneficial to the yield of bioactive constituents than the single AMF, but overall community inoculation effects are related to the composition of AMFs and the relationship between members. CONCLUSION: This study reveals that the AMF community has great potential to improve the productivity and the accumulation of bioactive constituents in S. miltiorrhiza, indicating that it is an effective way to achieve sustainable agricultural development through using the AMF community.

Ethnopharmacology, Phytochemistry, and Pharmacology of Pyrethrum tatsienense (Bureau & Franch.) Ling ex C. Shih: A Comprehensive Review.

BACKGROUND: Pyrethrum tatsienense (Bureau & Franch.) Ling ex C. Shih (PTLCS) belongs to the family Compositae, which is a perennial medicinal plant mainly distributed in the Qinghai-Tibet Plateau of China. This review provides a comprehensive summary of the ethnopharmacology, phytochemistry, and pharmacology of PTLCS. This review offers valuable references and guidance for researching PTLCS in depth. METHODS: The related references of PTLCS were retrieved from an online database, such as Web of Science, Google Scholar, SciFinder, PubMed, SpringLink, Elsevier, Willy, CNKI, and so on. RESULTS: PTLCS is widely reported for treating headaches, head injuries, traumatic injuries, anabrosis, impetigo, hepatitis, and other diseases in the medical field. Phytochemical research revealed that this plant contained flavonoid aglycones, flavonoid glycosides, xanthones, triterpenoids, coumarins, polyacetylenes, volatile oils, and other compounds. Meanwhile, PTLCS exhibited extensive pharmacological activities including anti-cardiac ischemia, anti-hypoxia, hepatoprotective, anti- inflammatory and analgesic, and antioxidant activities. CONCLUSIONS: PTLCS is widely used as a Tibetan medicine, which has a variety of chemicals with diverse bioactivities. Therefore, further studies are necessary to perform on the PTLCS to assay biological activities, discover their bioactive constituents, and reveal pharmacological mechanisms. This review may supply an important theoretical basis and valuable reference for in-depth research and exploitations of PTLCS.

Ethnopharmacology, Phytochemistry, and Pharmacology of Highland Barley Monascus purpureus Went: A Comprehensive Review.

BACKGROUND: Highland barley Monascus purpureus Went, a traditional Tibetan medicine with food functions, which is fermented by Monascus purpureus with highland barley as substrate. It possesses various medical functions of promoting blood circulation and removing blood stasis, invigorating spleen and promoting digestion in folk of the Qinghai-Tibet Plateau in China. This review provides a comprehensive overview of ethnopharmacology, phytochemistry, and pharmacology of highland barley Monascus purpureus Went. METHODS: The references of highland barley Monascus purpureus Went were retrieved from the online database, such as Web of Science, Google Scholar, SciFinder, PubMed, SpringLink, Elsevier, Willy, CNKI, and so on. RESULTS: Phytochemical research revealed that highland barley Monascus purpureus Went contained multiple chemical components, including Monascus pigments, monacolins, lactones, and other compounds. The reported pharmacological activities of highland barley Monascus purpureus Went included hypolipidemic, anti-nonalcoholic fatty liver disease, and hepatoprotective activities. CONCLUSION: In a word, botany, ethnopharmacology, phytochemistry and pharmacology of highland barley Monascus purpureus Went were reviewed comprehensively in this paper. In the future, highland barley Monascus purpureus Went needs further study, such as paying more attention to quality control and utilization of medicine. Therefore, this review may provide a theoretical basis and valuable data for future studies and exploitations on highland barley Monascus purpureus Went.

Polydatin alleviates traumatic brain injury: Role of inhibiting ferroptosis.

Secondary injury is the main cause of high mortality and poor prognosis of TBI, which has recently been suggested to be related to ferroptosis. Polydatin, a monocrystalline compound extracted from the rhizome of Polygonum, has been shown to exert potential neuroprotective effects. However, its role and mechanism in the secondary injury of TBI has not been elucidated. In this study, the inhibition of Polydatin on ferroptosis was observed both in the hemoglobin treated Neuro2A cells in vitro and in TBI mouse model in vivo, characterized by reversion of accumulation or deposition of free Fe2+, increased content of MDA, decreased activity of key REDOX enzyme GPx4, cell death and tissues loss. Although Polydatin corrected the increased mRNA levels of ferroptosis signaling molecules GPX4, SLC7A11, PTGS2, and ATP5G3 after TBI, TBI and Polydatin treatment had no significant effect on their protein expression. Notably, Polydatin could completely reverse the decrease of GPx4 activity after TBI in vivo and in vitro, and the effect was stronger than that of the classical ferroptosis inhibitor FER-1 in vitro. Further, Polydatin has been shown to reduce the severity of acute neurological impairment and significantly improve subacute motor dysfunction in TBI mice. Our findings provided translational insight into neuroprotection with Polydatin in TBI by inhibiting ferroptosis mainly depending on the maintenance of GPx4 activity.

Role of ethylene in the regulatory mechanism underlying the abortion of ovules after fertilization in Xanthoceras sorbifolium.

KEY MESSAGE: Genes related to the MAPK cascade, ethylene signaling pathway, Pi starvation response, and NAC TFs were differentially expressed between normal and abortive ovules. Receptor-mediated ethylene signal perception and transmission play an important role in regulating fruit and ovule development. Xanthoceras sorbifolium, a small to medium-sized tree endemic to northern China, is an emerging dedicated oilseed crop designed for applications in advanced biofuel, engine oil, and functional food, as well as for pharmaceutical and cosmetic applications. Despite the importance of Xanthoceras seed oil, low seed productivity has constricted commercial exploitation of the species. The abortion of developing seeds (ovules after fertilization) is a major factor limiting fruit and seed production in the plant. To increase fruit and seed yields, a better understanding of the mechanisms underlying the abortion of fertilized ovules is critical. This study revealed differences in nucellus degeneration, endosperm development, and starch grain content between normally and abnormally developing ovules after fertilization. We constructed 6 RNA-sequencing (RNA-seq) libraries from normally and abnormally developing ovules at the onset of their abortion process. Comparative transcriptome analysis between the normal and abnormal ovules identified 818 differentially expressed genes (DEGs). Among DEGs, many genes involved in mitogen-activated protein kinase (MAPK) cascades, ethylene signaling pathway, and NAC transcription factor genes showed up-regulated expression in abnormal ovules. The RNA-seq data were validated using quantitative reverse-transcription PCR. Using virus-induced gene silencing (VIGS) methods, evaluation of an ethylene receptor gene (XsERS) function indicated that the gene was closely related to early development of fruits and seeds. Based on the data presented here, we propose a model for a MAPK-ethylene signaling-NAC2 gene regulatory cascade that plays an important role in the regulation of the ovule abortion process in X. sorbifolium. The present study is imperative for understanding the mechanisms of ovule abortion after fertilization and identifying the critical genes and gene networks involved in determining the fate of ovule development.

Intrathoracic infusion therapy with Lentinan and chemical irritants for malignant pleural effusion: a systematic review and meta-analysis of 65 randomized controlled trials.

BACKGROUND: Aderivative of Shiitake mushrooms, Lentinan is used to control malignant pleural effusion (MPE) through intrathoracic infusion. PURPOSE: To determine the clinical response, survival and safety of Lentinan plus chemical irritants, and the optimal combinations with chemical irritants, indication, threshold and optimal regimen for achieving the desired responses. STUDY DESIGN: We performed a new systematic review and meta-analysis following the PRISMA guidelines. METHODS: We collected all randomized controlled trials (RCTs) regarding Lentinan plus chemical irritants from Chinese and English electronic databases (from inception until March 2019). We evaluated their bias risk, synthesized data using meta-analysis, and summarized evidence quality following the Grades of Recommendation Assessment, Development and Evaluation approach. RESULTS: We included 65 RCTs involving 4,080 patients and nine chemical irritants. Most trials had unclear bias risk. Lentinan with cisplatin significantly improved complete response [Risk ratio (RR) = 1.68, 95% confidence intervals (CI) (1.51 to 1.87), p < 0.00001, Fig.3a] and quality of life [RR = 1.51 95% CI (1.41 to 1.62), p < 0.00001, Fig.4], and decreased the risk of treatment failure, myelosuppression, gastrointestinal reaction, and chest pain. For patients with moderate to large volume of the pleural effusion, primary treatment, KPS score ≥ 50-60, or anticipated survival time ≥ 3months, Lentinan (3-4 mg/time, once a week for three to four times) withcisplatin (30-40 mg/m2 or 50-60 mg/m2) significantly improved complete response and decreased failure. Most results were robust and moderate quality. CONCLUSION: The results suggest that Lentinan with chemical irritants, especially cisplatin is beneficial to the patient with MPE, and provide evidence for the indication, threshold, and optimal regimen that may achieve success and decrease failure.

Dual-Controlled Release of Icariin/Mg2+ from Biodegradable Microspheres and Their Synergistic Upregulation Effect on Bone Regeneration.

Current scaffolds applied for bone tissue engineering are still lacking sufficient osteogenic capacity to induce efficient bone regeneration. Biodegradable microsphere-type scaffolds are designed to achieve the dual-controlled release of a Chinese medicine (i.e., icariin, ICA) and a bioactive ion (i.e., Mg2+ ), in order to achieve their synergistic effect on inducing osteogenesis. The hydrophobic icariin is preloaded onto MgO/MgCO3 (1:1 in weight ratio) particles at different amounts and then the particles are encapsulated into biodegradable poly(lactide-co-glycolide) (PLGA) microspheres (PMI) at a fixed fraction (20 wt%). Continuous releases of Mg2+ ion and icariin from the microspheres are detected, showing dependence on icariin amounts. At an optimized moderate loading amount, the resulting PMI-M microspheres display the strongest activation effect on cell biological behaviors among all the designs. By implanting the PMI-M microspheres into rat calvarial defects for 16 weeks, it is found that they can effectively enhance new bone formation, presenting significantly higher capacity in inducing osteogenesis than PMg (containing MgO/MgCO3 but without icariin) and blank PLGA microspheres. Clearly, the released Mg2+ ions are beneficial to osteogenesis, and the coincorporation of icariin exerts supplemental effects in inducing new bone formation, which suggest a promising strategy to regenerate severe bone injuries by designing a dual-release system.

The Traditional Chinese Medicine Fufang Shatai Heji (STHJ) Enhances Immune Function in Cyclophosphamide-Treated Mice.

Fufang Shatai Heji (STHJ) is a mixture of traditional Chinese medicines, such as Radix Adenophorae, Radix Pseudostellariae, and Radix Astragali. STHJ is commonly used to treat diseases caused by low immune function, for example, Sjögren's syndrome (SS). The primary objective of this study was to assess the immunopotentiating effect of STHJ using an immunosuppressive mouse model receiving cyclophosphamide (CTX). Following CTX treatment, STHJ was administered by oral gavage for 30 consecutive days. The percentage of specific lymphocyte subpopulations in the spleen was measured by flow cytometry. Levels of inflammatory factors in serum were detected by enzyme-linked immunosorbent assays (ELISAs). The administration of STHJ significantly elevated thymus and spleen indices, increased B cell and natural killer (NK) cell activities, and decreased CD8+ T, CD8+CD122+ T, NKT, and γδT cell activities in the CTX-treated mice. In addition, STHJ upregulated the expression of interleukin- (IL-) 2, IL-6, and tumor necrosis factor-α (TNF-α) and downregulated IL-10 expression in CTX-treated mice. In conclusion, STHJ effectively remitted CTX-induced immunosuppression by modulating the balance of lymphocyte subsets and cytokines. Our results suggest STHJ treatment could be used as an effective therapeutic approach to improve immune function in patients with low immunity.

Biopharmaceutical characters and bioavailability improving strategies of ginsenosides.

Deglycosylation is the most important gastrointestinal metabolism in which ginsenosides are split off from glycosyl moieties by the enzymes secreted from intestinal microflora, and two possible metabolic pathways of protopanaxdiol-type ginsenosides (PPD-type ginsenosides) and protopanaxtriol-type ginsenosides (PPT-type ginsenosides) have been concluded. The former is deglycosylated at C-3 and/or C-20, and transformed to protopanaxdiol (PPD). By comparison, the latter is deglycosylated at C-6 and/or C-20, and eventually transformed to protopanaxtriol (PPT) instead. The pharmacokinetic behavior of PPD-type ginsenosides and PPT-type ginsenosides is different, mainly in a faster absorption and elimination rate of PPT-type ginsenosides, but almost all of ginsenosides have a low oral bioavailability, which is relevant to the properties, the stability in the gastrointestinal tract, membrane permeability and the intestinal and hepatic first-pass effect of ginsenosides. Fortunately, its bioavailability can be improved by means of pharmaceutical strategies, including nanoparticles, liposomes, emulsions, micelles, etc. These drug delivery systems can significantly increase the bioavailability of ginsenosides, as well as controlling or targeting drug release. Ginsenosides are widely used in the treatment of various diseases, the most famous one is the Shen Yi capsule, which is the world's first clinical application of tumor neovascularization inhibitors. Hence, this article aims to draw people's attention on ocotillol-type ginsenosides, which have prominent anti-Alzheimer's disease activity, but have been overlooked previously, such as its representative compound-Pseudoginsenoside F11(PF11), and then provide a reference for the druggability and further developments of ocotillol-type ginsenosides by utilizing the homogeneous structure between dammarane-type ginsenosides and ocotillol-type ginsenosides.

Efficacy and safety of Kangfuxin liquid combined with aminosalicylic acid for the treatment of ulcerative colitis: A systematic review and meta-analysis.

BACKGROUND: To systematically evaluate the clinical efficacy and safety of Kangfuxin liquid (KFXL) combined with aminosalicylic acid (ASA) in treating ulcerative colitis (UC). METHODS: The PubMed, Cochrane Library, Embase, CBM, Wan fang, the Chinese Scientific Journal Database (VIP), and Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched for randomized controlled trials of KFXL combined with ASA for UC from the inception dates to March 3, 2017. Two researchers independently screened the literature, extracted data, and evaluated the methodological quality according to the inclusion criteria. The meta-analysis was performed using Review Manager software (RevMan, Version 5.3, Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014), and the risk of bias was assessed using the Cochrane Collaboration Tool. RESULTS: A total of 39 randomized controlled trials (RCTs) involving 3204 patients fulfilled the inclusion criteria. Compared with ASA alone, KFXL combined with ASA significantly improved the clinical effectiveness rate [RR = 1.19, 95% CI: (1.16, 1.23), P < .00001], reduced the relapse rate [RR = 0.26, 95% CI: (0.18, 0.38), P < .00001], reduced the inflammation factor levels of TNF-a, IL-1, IL-6, IL-8, and C-reactive protein, reduced the coagulation index of fibrinogen, increased the coagulation index of prothrombin time, and mean platelet volume, and reduced the clinical symptoms of abdominal pain, diarrhoea, pus and bloody stool, and tenesmus. However, KFXL combined with ASA did not increase the adverse event incidence [RR = 0.74, 95% CI (0.42, 1.32), P = .31], and no severe adverse events were reported. CONCLUSION: KFXL combined with ASA has good therapeutic effect for UC and might be a safe approach in managing UC. More high-quality, multicenter randomized, double-blind trials with a large sample size are required to generate a high level of clinical evidence.

Potato native and wound periderms are differently affected by down-regulation of FHT, a suberin feruloyl transferase.

Potato native and wound healing periderms contain an external multilayered phellem tissue (potato skin) consisting of dead cells whose cell walls are impregnated with suberin polymers. The phellem provides physical and chemical barriers to tuber dehydration, heat transfer, and pathogenic infection. Previous RNAi-mediated gene silencing studies in native periderm have demonstrated a role for a feruloyl transferase (FHT) in suberin biosynthesis and revealed how its down-regulation affects both chemical composition and physiology. To complement these prior analyses and to investigate the impact of FHT deficiency in wound periderms, a bottom-up methodology has been used to analyze soluble tissue extracts and solid polymers concurrently. Multivariate statistical analysis of LC-MS and GC-MS data, augmented by solid-state NMR and thioacidolysis, yields two types of new insights: the chemical compounds responsible for contrasting metabolic profiles of native and wound periderms, and the impact of FHT deficiency in each of these plant tissues. In the current report, we confirm a role for FHT in developing wound periderm and highlight its distinctive features as compared to the corresponding native potato periderm.

Effects of Ca/P molar ratios on regulating biological functions of hybridized carbon nanofibers containing bioactive glass nanoparticles.

Biological functions of hybridized carbon nanofibers (CNFs) depend closely on the incorporated bioactive components. For hybridized CNFs containing bioactive glass (BG) nanoparticles (CNF/BG), chemical compositions of BG nanoparticles might have decisive effects on their cell affinity and osteocompatibility. Herein, three hybridized CNF/BGs were produced by incorporating 68S-type BG nanoparticles with different Ca/P molar ratios (1.0, 1.67 or 2.5) into CNFs via a sol-gel/electrospinning and carbonization method. Structural evolution of these hybridized CNF/BGs was studied in relation to their Ca/P molar ratios. Crystalline wollastonite was found to be the dominant phase at a high feeding Ca/P molar ratio (i.e. 2.5), but weak crystallized hydroxyapatite was the main phase at the low feeding Ca/P molar ratio (i.e. 1.0). These findings were correlated to the biological functions of the resulted CNF/BG hybrids including apatite formation ability in simulated body fluid and osteoblast behaviors in in vitro culture. All the CNF/BG hybrids displayed a strong affinity for inducing apatite deposition, showing insignificant difference after the initial nucleation stage, while they behaved differently in promoting the proliferation and osteogenic differentiation of osteoblasts. The fastest proliferation rate and the highest expression of alkaline phosphatase activity was found on the CNF/BG (Ca/P = 1.0). The results suggested a feasible way to upregulate osteoblast behaviors is by changing the feeding Ca/P molar ratios in the preparation of CNF/BG hybrids for potential bone repairing applications.

Polysaccharides from Ganoderma lucidum attenuate microglia-mediated neuroinflammation and modulate microglial phagocytosis and behavioural response.

BACKGROUND: Ganoderma lucidum (GL) has been widely used in Asian countries for hundreds of years to promote health and longevity. The pharmacological functions of which had been classified, including the activation of innate immune responses, suppression of tumour and modulation of cell proliferations. Effective fractions of Ganoderma lucidum polysaccharides (GLP) had already been reported to regulate the immune system. Nevertheless, the role of GLP in the microglia-mediated neuroinflammation has not been sufficiently elucidated. Further, GLP effect on microglial behavioural modulations in correlation with the inflammatory responses remains to be unravelled. The aim of this work was to quantitatively analyse the contributions of GLP on microglia. METHODS: The BV2 microglia and primary mouse microglia were stimulated by lipopolysaccharides (LPS) and amyloid beta42 (Aß42) oligomer, respectively. Investigation on the effect of GLP was carried by quantitative determination of the microglial pro- and anti-inflammatory cytokine expressions and behavioural modulations including migration, morphology and phagocytosis. Analysis of microglial morphology and phagocytosis modulations was confirmed in the zebrafish brain. RESULTS: Quantitative results revealed that GLP down-regulates LPS- or Aß-induced pro-inflammatory cytokines and promotes anti-inflammatory cytokine expressions in BV-2 and primary microglia. In addition, GLP attenuates inflammation-related microglial migration, morphological alterations and phagocytosis probabilities. We also showed that modulations of microglial behavioural responses were associated with MCP-1 and C1q expressions. CONCLUSIONS: Overall, our study provides an insight into the GLP regulation of LPS- and Aß-induced neuroinflammation and serves an implication that the neuroprotective function of GLP might be achieved through modulation of microglial inflammatory and behavioural responses.

Neurogenesis-Promoting Natural Product α-Asarone Modulates Morphological Dynamics of Activated Microglia.

α-Asarone is an active constituent of Acori Tatarinowii, one of the widely used traditional Chinese Medicine to treat cognitive defect, and recently is shown to promote neurogenesis. Here, we demonstrated that low level (3 µM) of α-asarone attenuated LPS-induced BV2 cell bipolar elongated morphological change, with no significant effect on the LPS-induced pro-inflammatory cytokine expressions. In addition, time-lapse analysis also revealed that α-asarone modulated LPS-induced BV2 morphological dynamics. Consistently a significant reduction in the LPS-induced Monocyte Chemoattractant Protein (MCP-1) mRNA and protein levels was also detected along with the morphological change. Mechanistic study showed that the attenuation effect to the LPS-resulted morphological modulation was also detected in the presence of MCP-1 antibodies or a CCR2 antagonist. This result has also been confirmed in primary cultured microglia. The in vivo investigation provided further evidence that α-asarone reduced the proportion of activated microglia, and reduced microglial tip number and maintained the velocity. Our study thus reveals α-asarone effectively modulates microglial morphological dynamics, and implies this effect of α-asarone may functionally relate to its influence on neurogenesis.

In situ photoimmunotherapy for cutaneous granuloma caused by itraconazole-resistant Candida guilliermondii.

Cutaneous granulomas caused by Candida guilliermondii are difficult to cure. In situ photoimmunotherapy (ISPI) is a novel method composed of local photothermal therapy and immunoadjuvant. In this study, ISPI was used the first time clinically for cutaneous granuloma caused by itraconazole-resistant C.guilliermondii. A 10-week cycle of ISPI was composed of (1) 5% imiquimod applied topically every other day and (2) irradiation of lesions with an 808-nm diode laser at Days 14, 28, 42, and 56. Here we report our first case. A patient was treated with ISPI for four cycles. After the treatment, the lesions were eliminated without recurrence during a 12-month follow-up. Our results demonstrate that ISPI can be used as an effective treatment modality for cutaneous fungal granuloma.

[Effect of Low Molecular Weight Organic Acids on the Chemical Speciation and Activity of Mercury in the Soils of the Water-Level-Fluctuating Zone of the Three Gorges Reservoir].

To investigate the effect of low molecular weight organic acids ( LMWOA) on the ability of migration and the species of mercury in the soil of the Water-Level-Fluctuating Zone of the Three Gorges Reservoir, citric acid, tartaric acid and oxalic acid were dded into the soil to conduct simulation experiments. The results showed that the percentage of exchangeable mercury increased with the increase of the concentration of citric acid, but the value declined slightly as the concentration of tartaric acid and oxalic acid increased. While all three acids elevated the bioavailability of mercury, which increased with the increase of the concentration of acids. Vhen the concentration of citric acid reached 15 mmol x L(-1), the activation effect was the best. But for oxalic acid and citric acid, 10 mmol x L(-1) was the optimal concentration. In general, the effect of three organic acids on the activation of mercury in the soil followed the trend of citric acid > tartaric acid > oxalic acid. In the soil supplemented with 15 mmol x L(-1) citric acid, the change of mercury pecies was more and more striking with the prolonged incubation, and the conversion did not stop until 14 d, at that time the stomach cid dissolved mercury increased obviously, which was mainly converted from elemental mercury.

[Total nitrogen and total phosphorus thresholds for epilithic diatom assemblages in inflow tributaries of the Three Gorges Reservoir, China.] / åŸºäºŽé™„çŸ³ç¡ è—»çš„ä¸‰å³¡æ°´åº“å ¥åº“æ”¯æµæ°®ã€ç£·é˜ˆå€¼.

To study the relationships between in-stream total nitrogen (TN) and phosphorus (TP) loads and responses of epilithic algal metrics, nonparametric change-point analysis (nCPA) and thresholds indicator taxa analysis (TITAN) were used to detect possible TN and TP thresholds for algal chlorophyll a, diatom richness, Shannon diversity index, and diatom community composition for tributary rivers of the Three Gorges Reservoir (TGR). We found that nCPA simulated similar TP thresholds for all the four algal metrics (-0.03 mg·L-1), with similar TN thresholds (-0.8 mg·L-1) for all metrics but community composition. In contrast, TITAN provided specific nutrient thresholds for both sensitive and tolerant taxa within the whole community, and the threshold ranges covered thresholds for the other metrics. Additionally, nine (one sensitive and eight tolerant taxa) and ten indicator taxa (five sensitive and five tolerant taxa) for TN and TP were detected by TITAN, respectively. Therefore, we used the results of TITAN to define nutrient thresholds for the study rivers. That is, when in-stream TN concentration exceeded 0.382 mg·L-1 or TP concentration exceeded 0.016 mg·L-1(i.e. negative response threshold), sensitive taxa within river epilithic diatom assemblages would respond with decrease in density. When TN exceeded 1.298 mg·L-1 or TP exceeded 0.065 mg·L-1(i.e. positive response threshold), even tolerant taxa would be influenced and the whole assemblage would be changed significantly. Based on such criteria, we found that 87% sites had TN concentrations higher than the negative response threshold, with 22% sites being higher than the TN positive response threshold. As for TP, 94% and 14% sites exceeded the negative and positive response threshold, respectively. Our findings suggest that although most of the inflow tributaries of Three Gorges Reservoir were disturbed by human disturbance, yet the disturbance was not so extensive. Our findings provided significant information for managing river ecosystems of the TGR region.

Red Light Combined with Blue Light Irradiation Regulates Proliferation and Apoptosis in Skin Keratinocytes in Combination with Low Concentrations of Curcumin.

Curcumin is a widely known natural phytochemical from plant Curcuma longa. In recent years, curcumin has received increasing attention because of its capability to induce apoptosis and inhibit cell proliferation as well as its anti-inflammatory properties in different cancer cells. However, the therapeutic benefits of curcumin are severely hampered due to its particularly low absorption via trans-dermal or oral bioavailability. Phototherapy with visible light is gaining more and more support in dermatological therapy. Red light is part of the visible light spectrum, which is able to deeply penetrate the skin to about 6 mm, and directly affect the fibroblast of the skin dermis. Blue light is UV-free irradiation which is fit for treating chronic inflammation diseases. In this study, we show that curcumin at low concentrations (1.25-3.12 µM) has a strong anti-proliferative effect on TNF-α-induced psoriasis-like inflammation when applied in combination with light-emitting-diode devices. The treatment was especially effective when LED blue light at 405 nm was combined with red light at 630 or 660 nm, which markedly amplified the anti-proliferative and apoptosis-inducing effects of curcumin. The experimental results demonstrated that this treatment reduced the viability of human skin keratinocytes, decreased cell proliferation, induced apoptosis, inhibited NF-κB activity and activated caspase-8 and caspase-9 while preserving the cell membrane integrity. Moreover, the combined treatment also down-regulated the phosphorylation level of Akt and ERK. Taken together, our results indicated that the combination of curcumin with LED blue light united red light irradiation can attain a higher efficiency of regulating proliferation and apoptosis in skin keratinocytes.

The transportation and accumulation of arsenic, cadmium, and phosphorus in 12 wheat cultivars and their relationships with each other.

Pot experiments were conducted to investigate the difference in arsenic (As), cadmium (Cd), and phosphorus (P) uptake, accumulation, and translocation among 12 wheat cultivars and their relationships with each other in soil "naturally" contaminated with both As and Cd. As, Cd, and P concentrations in wheat grain, straw, and root differed significantly (p<0.05) among the 12 wheat cultivars. The grain As concentration was not correlated with straw and root As, or the total As content in plants, but was significantly (p<0.05) correlated with As translocation factors (TFs), i.e., TFs(Grain/Root) and TFs(Grain/Straw). The grain Cd concentration was positively correlated with the total Cd content and TFs(Grain/Straw). The grain P concentration was positively correlated with straw and root P. Both As and Cd concentrations in wheat grains were correlated with P in wheat straw and grain. Compared with As, Cd was more easily transported to the wheat grain, and the rachis played a key role in ensuring this difference. A significant positive correlation was observed between root As and Cd, but no significant relationship was detected between grain As and Cd concentrations. The lack of a relationship between grain As and Cd suggests the possibility of selecting cultivars in which little As and Cd accumulation occurs in the wheat grain.