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Hyaluronic acid is widely present in the human body. It is an important component of extracellular matrix. It has unique hydrodynamic properties, good viscoelasticity and strain properties. At present, hyaluronic acid has been widely used in biomaterials, targeted-drug preparations, cosmetics and prevention of adhesion after abdominal surgery. With the expansion of the application scope of hyaluronic acid and the continuous emergence of new medical materials, the research on hyaluronic acid has been increasing in recent years. This paper reviews the clinical application of hyaluronic acid and its mechanism, in order to provide reference for the further development and safe application of hyaluronic acid products.
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Receptor activity-modulating proteins (RAMPs) are accessory molecules that form complexes with specific G protein-coupled receptors (GPCRs) and modulate their functions. It is established that RAMP interacts with the glucagon receptor family of GPCRs but the underlying mechanism is poorly understood. In this study, we used a bioluminescence resonance energy transfer (BRET) approach to comprehensively investigate such interactions. In conjunction with cAMP accumulation, Gα q activation and β-arrestin1/2 recruitment assays, we not only verified the GPCR-RAMP pairs previously reported, but also identified new patterns of GPCR-RAMP interaction. While RAMP1 was able to modify the three signaling events elicited by both glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), and RAMP2 mainly affected β-arrestin1/2 recruitment by GCGR, GLP-1R and glucagon-like peptide-2 receptor, RAMP3 showed a widespread negative impact on all the family members except for growth hormone-releasing hormone receptor covering the three pathways. Our results suggest that RAMP modulates both G protein dependent and independent signal transduction among the glucagon receptor family members in a receptor-specific manner. Mapping such interactions provides new insights into the role of RAMP in ligand recognition and receptor activation.
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Objective To develop a HPLC-MS/MS method for the absolute bioavailability study of salidroside in Beagle dogs. Methods Gastrodin was used as internal standard. Plasma samples were treated by protein precipitation and separated by Symmetry RP18 column (100 mm×4.6 mm, 3.5 μm). 0.1% formic acid in water(A) and 0.1% formic acid in acetonitrile: methanol (20 : 80, V/V) (B) were used as the mobile phase for isocratic elution with 35% mobile phase B. The flow rate was 0.4 ml/min. Column temperature was 40 ℃. Injection volume was 2 μl. By electrospray ionization source (ESI) and multi-reaction monitoring (MRM) mode, the MRM ion pairs of salidroside and gastrodin were identified as m/z 299.1→118.9 and m/z 285.1→122.9, separately. Blood samples were collected at different time points after oral or intravenous administration of salidroside. The harvested plasma samples were analyzed by HPLC-MS/MS method to assess the pharmacokinetics and absolute bioavailability of salidroside. Results Excellent linearity(r>0.998 6) was found in the concentration range of 10−10 000 ng/ml for salidroside and the lowest quantitative concentration was 10 ng/ml. The recovery was 89.5%−91.8%. The intra-day precision (RSD) was less than 9.7%, and the inter-day precision (RSD) was less than 7.3%. After a single oral dose of 15 mg/kg or an intravenous injection of 1.5 mg/kg of salidroside, cmax was (9 680±3725) and (9 310±1 645) ng/ml; tmax was (1.25±0.67) and (0.011±0.017) h, AUC0−t was (20 535.4±5 200.0) and (4 646.7±720.5) ng·h/ml, AUC0−∞ was (20 607.9±5 266.2) and (4 691.6±715.2) ng·h/ml; t1/2 was (1.31±0.63) and (0.98±0.13) h, respectively. Conclusion The LC-MS/MS method established in this study was simple, rapid, sensitive and reliable. It meets the regulatory requirements of biological analysis for pharmacokinetic properties of salidroside in Beagle dogs. The absolute bioavailability of salidroside in Beagle dogs is (43.9±11.2)%.
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Paeoniae Radix Rubra has the effects of clearing heat, cooling blood, dissipating blood stasis and pain relieving (in terms of Chinese medicine). Paeoniae Radix Rubra and its active ingredients have significant pharmacological effects in anti-tumor，protecting liver, nerve and heart. By reviewing the relevant literatures published in recent years, we found that the studies on Paeoniae Radix Rubra are mainly focused in the mechanism of action, drug development and clinical application. In this review, we summarize the research results of the pharmacological effects of Paeoniae Radix Rubra and its active ingredients in order to provide the reference for the future research and clinical application of Paeoniae Radix Rubra.
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Objective To investigate the effect of medical sodium hyaluronate gel (HA) on the growth and metastasis of abdominal and pelvic tumor cells in vitro and in nude mice. Methods Three tumor cells, Hela, CT26 and HCT116, were used to investigate the effects of different HA concentrations on the growth and migration of tumor cells in vitro by MTT assay and Transwell assay. An orthotopic transplantation model of colonic tumor in nude mice was established to investigate the effect on the proliferation of cell HCT116 by comparing the tumor volume and tumor mass 4 weeks after inoculation. The effects on the metastasis of cell CT26 were investigated by comparing the tumor metastasis rate and the number of metastatic lesions of lung and liver in nude mice among the different experimental groups 3 weeks after inoculation. Results HA did not promote the growth and metastasis of Hela, CT26 and HCT116 cells in vitro at different concentrations. Actually, HA exhibited a certain inhibitory activity at the concentration of 5 mg/ml. In the orthotopic transplantation model of colonic tumor-HCT116, HA did not promote the growth of cell HCT116. In the orthotopic transplantation model of colonic tumor-CT26, HA inhibited CT26 tumor metastasis. Conclusion Under the experimental conditions, HA did not promote the growth, migration or metastasis of abdominal and pelvic related tumor cells including Hela, CT26 and HCT116 in vitro and in vivo.
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Objective To detect the transcription factors of copper ion (Cu,2+) metabolism and oxidative stress by Candida albicans knocked down different transcription factors.Methods Spot assay, growth curve were used.Results The sensitivity to Cu,2+ in Cup2Δ/Δ was increasing and the growth of Cup2Δ/Δ was inhibited in 5 mmol /L Cu,2+ medium.The results showed that Cup2Δ/Δ also increased the sensitivity to H2O2, interestingly, Cu,2+and H2O2 played a synergistic antifungal effect.The tolerance of Cup2Δ/Δ and SN250 to H2O2 induced oxidative stress was increased after BCS chelating Cu,2+.In the fluconazole, miconazole and ketoconazole susceptibility experiments, Cup2Δ/Δ did not show susceptibility to azole drugs.Conclusion Knockout transcription factor Cup2, which could increase the sensitivity to Cu,2+ and H2O2in Candida albicans.Transcription factor Cup2 might be involved in the regulation and control of Candida albicansmetabolism on Cu,2+ and oxidative stress induced by H2O2, but not involved in the regulation and control of drug resistance to azole drugs.
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Objective To explore the in vitro fungistasis of nanometer silvers made by different methods on Candida al-bicans .Methods The minimal inhibitory concentrations (MICs) of Candida albicans strains stimulated to silver nanoparticles were determined by microdilution method .The combination effects of silver nanoparticles with fluconazole were determined by chess board check assay .Results The inhabitation effect of two kinds of silver nanoparticles were different on the growth of Candida albicans .Silver nanoparticles had a synergistic effect with fluconazole on Candida albicans .Conclusion The two kinds of silver nanoparticles had various antifungal activities in vitro and had a synergistic effect with fluconazole on Candida albicans .
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The chemical constituents of Rosa chinensis Jacq were diverse ,mainly including flavonoids ,flavonoid glyco-sides ,phenolic acids ,aromatic oils ,tannins and pigments .Its extract and some chemical constituents had shown multiple phar-macological activities ,such as antitumor ,antifungal ,anti-viral ,anti-oxidation etc ..The advances in the study on chemical com-ponents and pharmacological actions of Rosa chinensis Jacq were reviewed and its application prospect was prospected .
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Hepatotoxicity is one of the most common adverse reactions during anti -hyperlipidemia treatment .Mechanisms of anti-hyperlipidemia drug-induced hepatotoxicity are not clear yet , but most of the toxic reactions are dose-related hypersensitivity and could be released after drug withdrawal .It is accepted that clinical risk factors for the development of hepatotoxicity during anti -hyper-lipidemia treatment are high age and chronic illnesses .Treatment of anti-hyperlipidemia drug-induced hepatotoxicity has not been uni-fied and most of the treatments are non-specific and symptomatic .Researching hypotoxicity and hepatoprotection antihyperlipidemia drug, especially TCM and pharmaceutics will become a promising direction .
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The target of rapamycin ( TOR) , a Ser/Thr protein kinase of PIKKs ( phosphatidylinositol kinase-related kinases ) , is the central factor of a highly conserved signaling pathway in eukaryotes , and regulates cell growth in response to nutrients , hor-mones, and stresses.It controls temporal growth by activating anabolic processes such as translation , ribosome biogenesis , protein syn-thesis, transportation of amino acid and metabolic enzymes .The advances in TOR pathway in the most pervasive human fungal patho-gen Candida albicans.
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Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.
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With the wide use of azoles,drug tolerance and cross tolerance of Candida albicands has seriously hampered the clinical treatments of Candida albicands.New antifungal agents(potent and effective) have been developed over the past years based on the discovery of many new target sites of Candida albicands.For example,Echinocandins(caspofungin and micafungin),aiming at the cell wall of Candida albicands,showed strong antifungal activities to fluconazole resistant candidas and fungal biofilm.Moreover,because ?-glucan synthase does not exist on the cell membrane of mammalian cells,Echinocandins has a low toxicity and a promising clinical future.Though the mechanism of Histatin(targeting fungal membrane) is not clear,it has strong activity not only on candida resistant of polyene and azole,but also to Candida parapsilosis,Candida krusei and Cryptococcus neoformans.Berberine and Ocimum gratissimum L.were also found to have prominent anti-fungi activities.Berberine extract can intensively inhibit 24-SMT in a dose-depended manner;besides,it has more potent inhibitory activity against the growth of mycelia than against that of yeast.Various new methods can be used to increase the susceptibility of Candida albicands to antifungal agents,such as altering fungi membrane composition,changing some genes,adopting the photodynamic inactivation method,employing hypersensitization agents and combining antifungal agents.This article reviews the newly-developed antifungal agents and newly-proposed target sites of Candida albicands.
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Objective:To study the effects of several herbal medicines on SMMC-7721 liver cancer cells with Fourier transform infrared spectrometer(FTIR). Methods: FTIR was employed to determine the infrared spectra(IRs) of SMMC-7721 liver cancer cells cultivated for 20 h with the extracts of Spica prunellae, Herba houttuyniae, Radix bupleuri and Herba artemisiae scopariae. Cluster analysis of IRs was also performed. Results: IR spectral parameters such as band shape, intensity and frequency of the blank, control and herbal-extract-treated cells were compared. There existed obvious blue shift of ? s(PO 2 -), ? as (PO 2 -) bands, red shift of ? as (CH 3), ?(CH 2) bands on the herbal-extract-treated cells IRs. The decreasing ratio of ? as (CH 3) to ? s(CH 2) peak intensity and the increasing ratio of ? s(PO 2 -) to ?(N-H) peak area indicated the destructive effect of herbal extracts on the membrane structure of SMMU-7721 cells and inhibitory effect on the DNA replication respectively. Cluster analysis successfully discriminated the herbal-extract-treated cells from the blank cells and the liver-oriented medicines from the non-liver-oriented medicine. Conclusion: FTIR provides another fast and effective approach to analyze the changes of cells treated with Chinese herbal medicines, which may help to illuminate the functional mechanism of Chinese herbal medicines.
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The incidence of candidiasis caused by Candida albicans has increased dramatically in recent years. With the widespread use of antifungal agents, the emergence of drug resistant strains pose a major challenge to drug treatment. The overexpression of membrane proteins functioning as drug efflux pumps is one of the main mechanisms for multidrug resistance of Candida albicans. Membrane transporters associated with drug resistance in Candida albicans are reviewed in this article.
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By means of TLC-densitomery, the contents of oleanolic acid extracted from the fruits of Ligustrum lucidum were determined to be 8.04% (g/g) in the unriped fruit collected in August and 2.73% (g/g) in riped fruit gathered in December. This result showed that the oleanolic acid content in fructus L. Iucidum decreases gradually with growing until the fruit is fully riped.
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Cap1p, encoded by CAP1, is a basic region-leucine zipper (bZip) transcription factor in Candida albicans. It has been proven to play important roles in both drug resistance and oxidative stress. Within the AP-1 family, Cap1p belongs to the same subgroup which also includes Yap1p, Yap2p, and Pap1p. The function of Cap1p is regulated by a nuclear localization mechanism. In recent years, some target genes of Cap1p have been discovered and the differences as well as similarities between Cap1p and Yap1p have been revealed. However, the role of Cap1p in the drug resistance of Candida albicans still needs to be further investigated. Currently drug resistance and oxidative stress are the 2 focuses in the research of fungal pathogens, making Cap1p very important in the future study. The authors have been involved in Cap1p research for a long time and this review introduces the current progress in the area.
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ATP binding cassette transporter (ABCT),a membrane transporting protein existing in mammalian, bacterial, fungal and many other types of cells, is correlated with multidrug resistance in many cells. To date 10 ABCT have been described in Candida albicans , but only CDR1 and CDR2 genes were associated with multidrug resistance. Moreover, their encoding proteins Cdr1p and Cdr2p have many functions such as efflux pump and phospholipid translocator. The progress in the study of Cdr1p and Cdr2p proteins mediating multidrug resistance in Candida albicans was summarized in the paper.