Anti-inflammatory effects of Fritillaria ussuriensis maxim

Bulbs of Fritillaria ussuriensis Maxim., usually known as Bulbus Fritillariae ussuriensis, (BFU) has been used as antitussive, antiasthmatic and expectorant in traditional herbal medicine. In this study, the aqueous extract of BFU (BFUE) was evaluated for its anti-inflammatory activity. Meanwhile, the content of PGE2 and MDA in inflammatory exudates was measured to explore the anti-inflammatory mechanisms of BFUE. In order to identify the active components of BFU, the total alkaloids (TA), the total flavonoids (TF) and the total saponins (TS) were evaluated for their bioactivities. Results showed that BFUE inhibited carrageenin-induced paw edema, xylene-induced auricular edema and acetic acid-induced vascular permeation in a dose-dependent manner, and it revealed obvious inhibitory effects on the increase of PGE2 and MDA. TF showed the highest anti-inflammatory effects on auricular edema induced by xylene in mice, and TS at a dose of 400 and 200 mg/kg also showed good effects (P 2 and MDA levels, and TF and TS might be the active components for this activity.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Anti-inflammatory effects of Fritillaria ussuriensis maxim

Bulbs of Fritillaria ussuriensis Maxim., usually known as Bulbus Fritillariae ussuriensis, (BFU) has been used as antitussive, antiasthmatic and expectorant in traditional herbal medicine. In this study, the aqueous extract of BFU (BFUE) was evaluated for its anti-inflammatory activity. Meanwhile, the content of PGE2 and MDA in inflammatory exudates was measured to explore the anti-inflammatory mechanisms of BFUE. In order to identify the active components of BFU, the total alkaloids (TA), the total flavonoids (TF) and the total saponins (TS) were evaluated for their bioactivities. Results showed that BFUE inhibited carrageenin-induced paw edema, xylene-induced auricular edema and acetic acid-induced vascular permeation in a dose-dependent manner, and it revealed obvious inhibitory effects on the increase of PGE2 and MDA. TF showed the highest anti-inflammatory effects on auricular edema induced by xylene in mice, and TS at a dose of 400 and 200 mg/kg also showed good effects (P 2 and MDA levels, and TF and TS might be the active components for this activity.Colegio de Farmacéuticos de la Provincia de Buenos Aire

MeDReaders: a database for transcription factors that bind to methylated DNA

Understanding the molecular principles governing interactions between transcription factors (TFs) and DNA targets is one of the main subjects for transcriptional regulation. Recently, emerging evidence demonstrated that some TFs could bind to DNA motifs containing highly methylated CpGs both in vitro and in vivo. Identification of such TFs and elucidation of their physiological roles now become an important stepping-stone toward understanding the mechanisms underlying the methylation-mediated biological processes, which have crucial implications for human disease and disease development. Hence, we constructed a database, named as MeDReaders, to collect information about methylated DNA binding activities. A total of 731 TFs, which could bind to methylated DNA sequences, were manually curated in human and mouse studies reported in the literature. In silico approaches were applied to predict methylated and unmethylated motifs of 292 TFs by integrating whole genome bisulfite sequencing (WGBS) and ChIP-Seq datasets in six human cell lines and one mouse cell line extracted from ENCODE and GEO database. MeDReaders database will provide a comprehensive resource for further studies and aid related experiment designs. The database implemented unified access for users to most TFs involved in such methylation-associated binding actives. The website is available at http://medreader.org/

Extracellular Matrix Protein Tenascin C Increases Phagocytosis Mediated by CD47 Loss of Function in Glioblastoma.

Glioblastomas (GBM) are highly infiltrated by myeloid-derived innate immune cells that contribute to the immunosuppressive nature of the brain tumor microenvironment (TME). CD47 has been shown to mediate immune evasion, as the CD47-SIRPα axis prevents phagocytosis of tumor cells by macrophages and other myeloid cells. In this study, we established CD47 homozygous deletion (CD47-/-) in human and mouse GBM cells and investigated the impact of eliminating the "don't eat me" signal on tumor growth and tumor-TME interactions. CD47 knockout (KO) did not significantly alter tumor cell proliferation in vitro but significantly increased phagocytosis of tumor cells by macrophages in cocultures. Compared with CD47 wild-type xenografts, orthotopic xenografts derived from CD47-/- tumor cells grew significantly slower with enhanced tumor cell phagocytosis and increased recruitment of M2-like tumor-associated microglia/macrophages (TAM). CD47 KO increased tumor-associated extracellular matrix protein tenascin C (TNC) in xenografts, which was further examined in vitro. CD47 loss of function upregulated TNC expression in tumor cells via a Notch pathway-mediated mechanism. Depletion of TNC in tumor cells enhanced the growth of CD47-/- xenografts in vivo and decreased the number of TAM. TNC knockdown also inhibited phagocytosis of CD47-/- tumor cells in cocultures. Furthermore, TNC stimulated release of proinflammatory factors including TNFα via a Toll-like receptor 4 and STAT3-dependent mechanism in human macrophage cells. These results reveal a vital role for TNC in immunomodulation in brain tumor biology and demonstrate the prominence of the TME extracellular matrix in affecting the antitumor function of brain innate immune cells. SIGNIFICANCE: These findings link TNC to CD47-driven phagocytosis and demonstrate that TNC affects the antitumor function of brain TAM, facilitating the development of novel innate immune system-based therapies for brain tumors

Targeting UDP-α-D-glucose 6-dehydrogenase inhibits glioblastoma growth and migration

UDP-glucose 6-dehydrogenase (UGDH) produces UDP-α-D-glucuronic acid, the precursors for glycosaminoglycans (GAGs) and proteoglycans of the extracellular matrix. Elevated GAG formation has been implicated in a variety of human diseases, including glioblastoma (GBM). In our previous study, we found that Krüppel-like factor 4 (KLF4) promotes GBM cell migration by binding to methylated DNA, mainly methylated CpGs (mCpG) and transactivating gene expression. We identified UDGH as one of the downstream targets of KLF4-mCpG binding activity. In this study, we show that KLF4 upregulates UGDH expression in a mCpG-dependent manner, and UGDH is required for KLF4-induced cell migration in vitro. UGDH knockdown decreases GAG abundance in GBM cells, as well as cell proliferation and migration in vitro. In intracranial xenografts, reduced UGDH inhibits tumor growth and migration, accompanied by a decrease in the expression of extracellular matrix proteins such as tenascin C, brevican. Our studies demonstrate a novel DNA methylation-dependent UGDH upregulation by KLF4. Developing UGDH antagonists to decrease the synthesis of extracellular matrix components will be a useful strategy for GBM therapy

The effect of warming on grassland evapotranspiration partitioning using laser-based isotope monitoring techniques

Author's manuscript made available in accordance with the publisher's policy.The proportion of transpiration (T) in total evapotranspiration (ET) is an important parameter that provides insight into the degree of biological influence on the hydrological cycles. Studies addressing the effects of climatic warming on the ecosystem total water balance are scarce, and measured warming effects on the T/ET ratio in field experiments have not been seen in the literature. In this study, we quantified T/ET ratios under ambient and warming treatments in a grassland ecosystem using a stable isotope approach. The measurements were made at a long-term grassland warming site in Oklahoma during the May–June peak growing season of 2011. Chamber-based methods were used to estimate the δ2H isotopic composition of evaporation (δE), transpiration (δT) and the aggregated evapotranspiration (δET). A modified commercial conifer leaf chamber was used for δT, a modified commercial soil chamber was used for δE and a custom built chamber was used for δET. The δE, δET and δT were quantified using both the Keeling plot approach and a mass balance method, with the Craig–Gordon model approach also used to calculate δE. Multiple methods demonstrated no significant difference between control and warming plots for both δET and δT. Though the chamber-based estimates and the Craig–Gordon results diverged by about 12‰, all methods showed that δE was more depleted in the warming plots. This decrease in δE indicates that the evaporation flux as a percentage of total water flux necessarily decreased for δET to remain constant, which was confirmed by field observations. The T/ET ratio in the control treatment was 0.65 or 0.77 and the ratio found in the warming treatment was 0.83 or 0.86, based on the chamber method and the Craig–Gordon approach. Sensitivity analysis of the Craig–Gordon model demonstrates that the warming-induced decrease in soil liquid water isotopic composition is the major factor responsible for the observed δE depletion and the temperature dependent equilibrium effects are minor. Multiple lines of evidence indicate that the increased T/ET ratio under warming is caused mainly by reduced evaporation

Investigation of the anti-inflammatory and synergistic activities of bulbus Fritillariae ussuriensis and xuehua pear using acute inflammatory models

The combination of the bulb of Fritillaria ussuriensis Maxim. (Bulbus Fritillariae ussuriensis, BFU) and the fruit of Pyrus bretschneideri Rehd. (Xuehua pear, PBR), as folk medicine, is widely used in treatment with respiratory disease. In this study, three acute inflammatory models were used to estimate the anti-inflammatory activities and cooperative interactions of them. The data were dealt with the Tallarida's improved contouring method and the Q value method to evaluate the cooperative interactions of BFU and PBR more directly. All the treated groups showed well preventive effects on xylene-induced mouse auricular edema, acetic acid-induced mouse vascular permeation and carrageenin-induced rat paw edema in a dose-dependent manner. Combination of BFU and PBR (CBP) exhibited a higher inhibitory effect than the additive effect of individuals. These results indicated that BFU and PBR both had good antiinflammatory effects and the combination of them had synergistic effects on acute inflammation, which may support and supplement the civilian utilization of Bulbus Fritillariae and Fructus Pyri in treatment with the respiratory tract diseases, just like pharyngitis, laryngitis, tonsillitis, etc.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Anti-inflammatory effects of Fritillaria ussuriensis maxim

Bulbs of Fritillaria ussuriensis Maxim., usually known as Bulbus Fritillariae ussuriensis, (BFU) has been used as antitussive, antiasthmatic and expectorant in traditional herbal medicine. In this study, the aqueous extract of BFU (BFUE) was evaluated for its anti-inflammatory activity. Meanwhile, the content of PGE2 and MDA in inflammatory exudates was measured to explore the anti-inflammatory mechanisms of BFUE. In order to identify the active components of BFU, the total alkaloids (TA), the total flavonoids (TF) and the total saponins (TS) were evaluated for their bioactivities. Results showed that BFUE inhibited carrageenin-induced paw edema, xylene-induced auricular edema and acetic acid-induced vascular permeation in a dose-dependent manner, and it revealed obvious inhibitory effects on the increase of PGE2 and MDA. TF showed the highest anti-inflammatory effects on auricular edema induced by xylene in mice, and TS at a dose of 400 and 200 mg/kg also showed good effects (P 2 and MDA levels, and TF and TS might be the active components for this activity.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Differential responses of carbon-degrading enzyme activities to warming: implications for soil respiration

Extracellular enzymes catalyze rate‐limiting steps in soil organic matter decomposi-tion, and their activities (EEAs) play a key role in determining soil respiration (SR).Both EEAs and SR are highly sensitive to temperature, but their responses to cli-mate warming remain poorly understood. Here, we present a meta‐analysis on theresponse of soil cellulase and ligninase activities and SR to warming, synthesizingdata from 56 studies. We found that warming significantly enhanced ligninase activ-ity by 21.4% but had no effect on cellulase activity. Increases in ligninase activitywere positively correlated with changes in SR, while no such relationship was foundfor cellulase. The warming response of ligninase activity was more closely related tothe responses of SR than a wide range of environmental and experimental method-ological factors. Furthermore, warming effects on ligninase activity increased withexperiment duration. These results suggest that soil microorganisms sustain long‐term increases in SR with warming by gradually increasing the degradation of therecalcitrant carbon pool

Novel and Recurrent Mutations of WISP3 in Two Chinese Families with Progressive Pseudorheumatoid Dysplasia

BACKGROUND: The WNT1-inducible signaling pathway protein 3 (WISP3), which belongs to the CCN (cysteine-rich protein 61, connective tissue growth factor, nephroblastoma overexpressed) family, is a secreted cysteine-rich matricellular protein that is involved in chondrogenesis, osteogenesis and tumorigenesis. WISP3 gene mutations are associated with progressive pseudorheumatoid dysplasia (PPD, OMIM208230), an autosomal recessive genetic disease that is characterized by the swelling of multiple joints and disproportionate dwarfism. METHODOLOGY/PRINCIPAL FINDINGS: Four PPD patients from two unrelated Chinese families were recruited for this study. The clinical diagnosis was confirmed by medical history, physical examinations, laboratory results and radiological abnormalities. WISP3 mutations were detected by direct DNA sequence analysis. In total, four different mutations were identified, which consisted of two missense mutations, one deletion and one insertion that spanned exons 3, 5 and 6 of the WISP3 gene. One of the missense mutations (c.342T>G/p.C114W) and a seven-base pair frameshift deletion (c.716_722del/p.E239fs*16) were novel. The other missense mutation (c.1000T>C/p. S334P) and the insertion mutation (c.866_867insA/p.Q289fs*31) had previously been identified in Chinese patients. All four cases had a compound heterozygous status, and their parents were heterozygous carriers of these mutations. CONCLUSIONS/SIGNIFICANCE: The results of our study expand the spectrum of WISP3 mutations that are associated with PPD and further elucidate the function of WISP3